Feb 17, 2016 - Incorporation of a single methoxy group in the benzene nucleus as in 12 did not .... (2.050 g, 13.67 mmol) and methallyl bromide (3.663 g, 27.33 mmol). ..... 137.6, 127.6, 113.6 (CH), 112.8 (CH2), 110.54 (CH), 56.3 (CH3), 56.2.
Tetrahedron 72 (2016) 1758e1772
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Intramolecular carbonyl-ene reactions in the synthesis of peri-oxygenated hydroaromatics Shyam Basak, Dipakranjan Mal * Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur 721302, India
a r t i c l e i n f o
a b s t r a c t
Article history: Received 11 January 2016 Received in revised form 12 February 2016 Accepted 15 February 2016 Available online 17 February 2016
2-Methallyl aromatic aldehydes, synthesized by Suzuki coupling of 2-formylphenylboronic acids, are shown to provide cycloalkylidene ene products under acidic conditions. Susceptibility of the products to aromatization is manoeuvred by varying the reaction conditions and catalysts including binol-derived Brønsted acid catalysts. A peri-effect is identified as a controlling factor for the aromatizations. Several oxidative transformations of an ene product are carried out as model studies of hydroaromatic polyketide natural products. Ó 2016 Elsevier Ltd. All rights reserved.
Keywords: Intramolecular Carbonyl-ene Hydroaromatics Anthracyclines
1. Introduction The ene reaction is a fundamentally important carbonecarbon single bond forming reaction.1 It has been a key step in many classic syntheses including asymmetric syntheses.2 Studied in depth by many researchers, it continues to attract attention of the organic chemists due to its enormous applicability in organic synthesis. Among the various subclasses of the ene reactions, type-II intramolecular carbonyl-ene reaction (ICE) (Scheme 1) is more elaborately studied.1 H2C
n
H
H2C
O
n OH
Scheme 1. Typical type-II carbonyl-ene reaction of an alicyclic compound.
Like the general ene reaction, type-II ICE reaction has facilitated many total syntheses in atom-economic manner and made their ways to the industries. Examples of the total syntheses are those of natural products (þ)-cassiol, laulimalide, (þ)-azaspiracid-1 etc.3 The mechanistic aspects of the reaction have thoroughly been examined.4 However, its scope is largely confined to the alicyclic compounds.1
* Corresponding author. Fax: þ91 3222282252; e-mail address: dmal@chem. iitkgp.ernet.in (D. Mal). http://dx.doi.org/10.1016/j.tet.2016.02.033 0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.
The present report stems from the seminal work of Hauser and Mal on carbonyl-ene reaction in the construction of hydroaromatic ring A of anthracyclines. Treatment of a methallylanthraquinone carboxaldehyde with SnCl4$5H2O in DCM resulted in the formation of a tetracycle.5 It is presumably the first report of a type-II ICE reaction in the formation of a hydroaromatic system. The applications of such reactions, however, are limited to few methoxyanthraquinone-embedded precursors.6 In view of the wide occurrence7 of hydroaromatics, especially the m-cresol unit in natural products 1e9 (Fig. 1), we intended to validate the potential of the reaction for a general synthesis of oxygenated hydroaromatics. Herein, we report regiocontrolled construction of oxygenated hydroaromatics with naphthalene, anthracene and naphthacene nuclei, as well as their ene precursors. Susceptibility of the ene products to aromatization has been correlated with their structures.8 Oxidation chemistry of an ene product has been briefly explored as models, for the terminal ring in the natural products. 2. Results and discussion Synthesis of the aldehyde-ene precursors: The majority of the ene-precursors of this study are not reported in the literature. In general, the synthesis of methallylarenes is scarcely reported.9a The Suzuki coupling9b,9c was adopted as the key step for the synthesis of ene-precursors 10e16 (109b, 119d, 129e, 149feh) and boronic acids 17e26 (1810a,10b, 2210c) were employed for this coupling reactions (Scheme 2). Initial attempt of the coupling of 17 with methallyl bromide in presence of PdCl2(PPh3)2 gave the desired product 10 in
S. Basak, D. Mal / Tetrahedron 72 (2016) 1758e1772 OH OH H3CO
O
O
OH
OH O
OH
O
OH
Balticol C (1)
6-Methylxanthopurpurin3-O-methyl ether (2)
O
OH
O
O
Altersolanol P (3)
O
HO HO HO
OH
H3CO
OH
O
1759
OH
OH
HO OH O
O
OH
O
OH OH
OH O
O
OH
O
O
HO
HO OH Galtamycinone (4)
O
O
OH
Nocatriones A (5)
Aranciamycin l (6)
O OHO
O OH HO HO
OH OH
O
OH
O OH
OH
O OH
Idarubicinone (7)
O
O
Aquayamycin (8)
Tetrangomycin (9)
Fig. 1. Structures of selected natural products with oxygenated tetralin skeletons.
R1 R2
R1 B(OH)2
R3
R2 or R3
CHO R4
R4
R5 OH B O
Br
2.5 mol% PdCl2(PPh3)2 aq. Na2CO3, THF inert atmosphere
R5
R3
OH
CHO R4
10 R1 = R2 = R3 = R4 = R5 = H; 71%
17 R1 = R2 = R3 = R4 = H
19 R1 = R2 = R4 = H, R3 = OMe
18 R1 = R2 = R4 = H, R3 = OMe
21 R1 = R4 = OMe, R2 = R3 = H
20 R1 = R4 = OMe, R2 = R3 = H
24 R1, R2=
22 R1 = R4 = H, R2 = R3 = OMe
26 R1 = R2 = H, R3, R4 =
23 R1, R2 =
R1 R2
, R3 = R4 = H
11 R1 = R2 = R3 = R4 = H, R5 = Me; 73% 12 R1 = R2 = R4 = R5 = H, R3 = OMe; 60% 13 R1 = R4 = OMe, R2 = R3 = R5 = H; 80% 14 R1 = R4 = R5 = H, R2 = R3 = OMe; 71%
, R3 = R4 = H
15 R1, R2=
25 R1 = R2 = H, R3, R4 =
, R3 = R4 = R5 = H; 50%
16 R1 = R2= R5 = H, R3, R4 =
;68%
Scheme 2. Synthesis of ene-precursors by Suzuki reaction.
40% yield. However, the yield could be significantly improved i.e. up to 71% by adding the boronic acid 17 portion wise as well as increasing the amount of the methallyl bromide. This modification was applied for the synthesis of all other compounds (11e16). This modification allowed minimum formation of the biphenyl dicarboxaldehyde. Ene precursor 27 was synthesized in four steps from isovanillin derivative 2811. It was reduced to 29 with NaBH4, which was thermally rearranged to give 30. O-methylation of compound 30 followed by MnO2 oxidation of 31 furnished aldehyde 27 (Scheme 3). Keeping in the mind the structural features of altersolanol P7b (3) as well as truncated anthracyclines12a, naphthaldehyde 32 was chosen as the model substrate. It was prepared in seven steps as shown in Scheme 4. Hauser annulation12ced of cyanophthalide 3312e with methyl acrylate was performed to give 1,4-naphthoquinol 34, which was selectively monomethallylated to give 35.
After O-methylation of 35, the resulting ether 36 was subjected to Claisen rearrangement in refluxing DMF followed by methylation to give naphthalene derivative 37. LAH reduction of 37 to alcohol 38 followed by PCC oxidation of 38 provided ene precursor 32 (Scheme 4). Alkylidene malonate 39 was prepared by Knoevenagel reaction of 10 with dimethyl malonate in the presence of piperidine and OR
O i) DMF, reflux 53% ii) MeI, K2CO3 acetone 99%
O R
28 R = CHO 29 R = CH2OH
NaBH4, 79%
MnO2 DCM
O
O O
95%
CHO
OH 30 R = H 31 R = Me
Scheme 3. Synthesis of metthallylbenzaldehyde 27.
27
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S. Basak, D. Mal / Tetrahedron 72 (2016) 1758e1772
O
OH
95%
COOCH3
O
O
Br
i) LiOBu-t, THF -78 °C, ii) H3O+
CN
CO2CH3 O
33
O
K2CO3, acetone, 0 °C_rt
NaH, Me2SO4, THF
55%
OH
CO2CH3 O
34
85%
OH 35
i) DMF, reflux,12 h ii) Me2SO4, K2CO3, acetone
O
O
70% CO2CH3 O
O
LAH, THF, rt 30 h, 86% CO2CH3
O
O
36
R
O
O
O PCC DCM, rt 88%
38 R = CH2OH 32 R = CHO
37
Scheme 4. Model studies on the synthesis of altersolanol-p.
acetic acid in benzene. Ene substrate 40 was prepared from 10 by Wittig reaction with carbethoxymethylenetriphenylphosphorane. Ene substrate 41 was prepared from 2-bromobenzaldehyde following literature procedure (Fig. 2).13
involving dry ethyl acetate (EA) containing 50 mol% SnCl4$5H2O were most effective. The isolated yields of the ene products 42 and 43 were 82% and 9% respectively under these conditions (Table 3).
2.3. Scope of substrates
CHO MeO2C
CO2Me
39
CO2Et 40
41
Fig. 2. Ene precursors 39e41.
Following the optimization study, we examined substrates 11, 12, 15, 16 for the ICE as detailed in Table 3. Our primary goal was to intercept hydroaromatic products of the reactions. From the inspection of the results in Table 3, it is apparent that such objectives are achievable to great extent by changing the reaction conditions. Application of the optimized conditions (SnCl4$5H2O in EA) to ethyl analogue of 10 i.e. 11 also delivered nonaromatized desired
2.1. Preliminary studies with SnCl4$5H2O Preliminary studies were conducted with 109b under Hauser conditions (SnCl4$5H2O in DCM). When it was treated with 50 mol% SnCl4$5H2O5, the desired methylidene tetrahydronaphthol 42 was obtained in 39% yield along with 2-methylnaphthalene (43)14 in 50% yield. The structure of 42 was established by its characteristic 1 H NMR signals at d 4.99 (s, 1H) and 4.92 (s, 1H) due to exocyclic olefinic protons. The generation of a double bond exocyclic to the new ring in 42 suggests that the ene cyclization is a concerted one as shown in the proposed T.S. (Fig. 3). For the corresponding stepwise process, a product with an endocyclic double bond is expected due to conjugative stability of the product. Ene precursors 12, 13, 16 were also employed for the ICE reaction under same reaction conditions, and in all the cases aromatized products (44, 45, 46) were exclusively obtained (Table 1).
Table 1 ICE reaction of selected substrates with SnCl4$5H2O, DCM at rt (Hauser protocol)a Substrates
Non-aromatized ene products (%yield)
d
2.2. Model studies In order to optimize the conditions, precursor 10 was chosen. To minimize the formation of aromatized product 43, the reaction conditions were optimized as shown in Table 2. Conditions
d
d
Half chair conformation H Chair conformation
H
O
LA or BA a
Fig. 3. Proposed T.S.
All reactions were carried out for 1e2 h.
Aromatized ene products (%yield)
S. Basak, D. Mal / Tetrahedron 72 (2016) 1758e1772 Table 2 Optimization studies for intramolecular-ene reaction of 10e42a,b Solvent
Ratio of 42: 43
Time
%yield
Toluene Chloroform DCM Diethyl ether Ethyl acetate 1,4-Dioxane Acetone
0: 100 81: 19 45: 55 85: 15 90: 10 0: 100 50: 17
1.5 d 3.5 h 2h 4d 1.5 d 3.5 d 3 dc
91 85 89 89 91 83 55c
a b c
Ratio of the products was determined by 1H NMR analysis. All reactions were carried out with 50 mol% SnCl4$5H2O at rt. 33% starting aldehyde recovered.
ene product 47 in 86% yield with a small amount of aromatized product 4815 (7%). These conditions worked well with naphthalene substrates 15 and 16 affording ene products 49 and 50 in 85% and 88% yield respectively along with aromatized products 51 and 46 respectively. Thus the above conditions are well-suited for unsubstituted aromatic aldehyde precursors 10, 11, 15, 16. Incorporation of a single methoxy group in the benzene nucleus as in 12 did not alter the course of the ene cyclization. When it was treated under optimized conditions, the expected ene product 52 was obtained in 78% yield along with aromatized product 44 as the minor product (Table 3). Since peri-oxygenated hydroaromatics commonly occur in many naturally occurring quinones,16 we evaluated ICE reaction of few
1761
other methoxy substituted ene-precursors. Under the optimized conditions i.e. SnCl4$5H2O in EA, compound 13 exclusively furnished aromatized product (45) (Table 4). Others Lewis acids such as Sc(OTf).3xH2O, CuCl.22H2O, InCl3 also led to the aromatized product in major amounts (see SI). This susceptibility of aromatization may be due to the presence of activating methoxy groups attached to the benzene ring. As an alternative, we tried with BINOL-derived Brønsted acids as catalysts in view of their applicability in asymmetric reactions.17 After an extensive optimization study (see SI), 10 mol% BINOL-derived phosphoric acid (BINOLPO2H) in CHCl3 at rt was found to be the best for 13 affording ene product 53 in 80% yield, although it took 5 days for completion of the reaction (Table 4). Like 13, the ene reactions of substrates 14 and 27 in the presence of SnCl4$5H2O in EA resulted in exclusive formation of aromatized products 54 and 55. On contrary, under the influence of BINOL-derived phosphoramide (BINOL-PONHTf) the reaction afforded some nonaromatized products. However, these products 56 and 57 appeared to form from dimerization of the initial ene products as proposed in the mechanism (vide SI) (Table 4). Compounds 14 and 27 are more susceptible to aromatization than 13. This can be explained by considering destabilaization of incipient carbocation 58 due to peri-effect of the methoxy group with the indicated hydrogen (Scheme 5). When 32 was treated with SnCl4$5H2O in ethyl acetate, expected ene product 59 was not obtained. Instead, anthracene derivatives 60 and 61 were obtained. The compound 60 seemed
Table 3 ICE reaction of ortho propenyl aromatic carboxaldehydes with 50 mol% SnCl4$5H2O, EA at room temperature Substrates
Non-aromatized ene products (%yield)
Aromatized ene products (%yield)
Time
1.5 d
1.5 d
1.5 d
1.5 d
2d
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S. Basak, D. Mal / Tetrahedron 72 (2016) 1758e1772
Table 4 Optimized conditions of ICE reactions of substrates having aromatic methoxy groups
O
O
O -H3
O
O+
H O 13
O
O
OH
53 (80%)
O
H 58
O 45 (15%)
Scheme 5. Explanation for the differential reactivities of 13, 14 and 27.
to form via aromatization of putative ICE product 59, which could not be isolated. Formation of the anthraquinone 61 is interesting and unprecedented (vide SI). It was obtained as the sole product with 10 mol% BINOL-PO2H in CHCl3 at room temperature (Table 5). Formation of the abnormal product 61 can be explained by the mechanism shown in Scheme 6. The aromaized ene product 60 acting as a photosensitizer forms singlet oxygen and then reacts with it to form cycloaddition adduct 62. Fragmentation of 62 forms a bisoxocarbenium ion 63, which upon reaction with moisture furnishes 64. Elimination of methanol from 64 gives 61.
Our next objective was to evaluate the reactivity of a polarized carbonecarbon double bond as an enophile in the ene reaction. Treatment of the alkylidene malonate 39 with SnCl4$5H2O, provided a 42:49 mixture of 43 and 65. It was inert to BINOL-derived phosphoric acid. No reaction of 39 took place even at elevated temperature (up to 100 C). However, BINOLPONHTf promoted the reaction, but it was very slow at room temperature. When it was conducted at 80 C, the reaction was complete in 3 d giving 65 in 94% yield. However, substrate 40 with an acrylate functionality, resisted cyclization with catalysts like SnCl4$5H2O or BINOL-PO2H. With BF3$OEt2 in DCM, it underwent intramolecular RauhuteCurrier like reaction resulting in a mixture of products 66 (35%) and 67 (57%). This type of cyclization has some resemblance with recent publication on formation of five-membered ring.18a Formation of hydrolysed product 67 was confirmed by transforming it into its methyl ester derivative by DBU-MeI.18b In view of extending scope of the ICE reaction to formation of a five-membered ring, substrate 41 was treated under 10 mol% BINOL-PONHTf.19 Within 1 d at room temperature, it gave indenol 68 in 96% yield (Table 6).
S. Basak, D. Mal / Tetrahedron 72 (2016) 1758e1772
1763
Table 5 ICE reaction of 32, an intermediate for the synthesis of Altersolanol-p Products (%yield)A,B
Substrates
A: 50 mol% SnCl4$5H2O, ethyl acetate, rt, 1 d.; B: 10 mol% BINOL-PO2H, CHCl3, rt, 4 d.
Brønsted acid catalyst CHCl3, rt
O
O
O O2
CHO O
O2*
hν O
O 32
OH2
O
OH
O
59 H
O
O
O
60 (photosensitizer) O
O
O H
O O O
O2
O
O OH2
62
63
O
H
O
O H
CH3OH
64
O
O 61
Scheme 6. Proposed mechanism for the formation of 61.
Table 6 ICE reaction of ene precursors containing an olefinic double bond
2.4. Elaboration of ICE product 42 With a view to paving the synthetic route to altersolanol P (3), galtamycinone (4) and aranciamycin I (6), few model elaborations were briefly studied. Regioselective transposition of the exocyclic
double bond of the ene products without aromatization of the new cyclohexane ring was envisaged for facile entry to altersolanol P (3) and aranciamycin I (6). Since 42 is readily aromatized in acidic conditions, it was derivatized to its acetate 69 with Ac2O-pyridine. However, the acetate 69 slowly decomposed on standing.
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S. Basak, D. Mal / Tetrahedron 72 (2016) 1758e1772
Alternatively, ene product 42 was silylated with TBSCl-imidazole to give ether 70. Transposition of the double bond in 70 was initially attempted with BF3$Et2O and TsOH. But, none were successful. However, on reaction with [Rh(PPh3)3Cl] and DBU (10 equiv), 70 smoothly isomerized to 71 without any aromatization.20 For epoxidation of 71 to 72, a few standard epoxidations with m-CPBA were attempted. The best procedure was Oxone based method.21 When treated with Oxone, sodium bicarbonate in acetone, H2O, EA (5:1:1), compound 71 delivered epoxide 72 in 70% yield. The relative stereochemistry of the cyclohexane ring of 72 was established by analysis of coupling constants and a NOESY experiment. As a model study on the A ring formation of galtamycinone (4), which features an m-cresol unit, tetralin 42 was submitted to PDC in DCM. The desired oxidized product a-naphthol 73 was obtained. On the contrary, when it was treated with PCC in DCM, it gave unexpectedly menadione (74), perhaps resulting from overoxidation of possible alkylidene ketone 75 (Scheme 7).22 Oxone, acetone, water, ethyl acetate rt, 45 min
RhCl(PPh3)3 (10 mol%) DBU, EtOH, reflux 10 d
O
69%
73%
OTBS
OTBS
OR 71
69 R = COCH3 70 R = TBS
OH
73
PCC, DCM, rt 81%
OH O
O 75
3.2. Preparation of the ene-precursors 3.2.1. General procedure to prepare ene-substrate from different 2formylphenylboronic acids.9b To a solution of methallyl bromide (2 equiv) in THF (0.2 M) in a two neck round bottom flask were added PdCl2(PPh3)2 (2.5 mol%) and aq Na2CO3 (1 M, 2 equiv). This solution was degassed with inert gas. To this, a degassed solution of 2-formylphenylboronic acid (0.25 equiv) was added and the resulting mixture was heated at reflux. After 1 h, the reaction mixture was cooled to rt, and another 0.25 equiv degassed solution of the boronic acid was added. After 6e7 h, the reaction mixture was cooled and quenched with water (3 mL/mmol) and extracted with DCM (310 mL/mmol). The combined organic layer was washed with brine, dried over MgSO4, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel.
72
PDC, DCM, rt 83%
42
FTIR instrument using a KBr pellet. The phrase ‘usual work-up’ or ‘worked up in the usual manner’ refers to washing of the organic phase with water (21/4 of the volume of the organic phase) and brine (11/4 of the volume of the organic phase), drying (Na2SO4), filtration, and concentration under reduced pressure.
O 74 Menadione (Vit K3)
Scheme 7. Functional group modifications of ene product 42.
3. Conclusion We have successfully developed an efficient synthesis of omethallylbenzaldehyde and demonstrated their utilities in intramolecular carbonyl-ene reaction to provide a regiodefined synthesis of oxygenated hydroaromatics. In this study, we have reported synthesis of hydroaromatics containing anthracene, phenanthrene and naphthacene nuclei. Isolation of the nonaromatized ene products is delicately sensitive to the nature of substituents, catalysts and reaction conditions. Peri-effects seem to play important roles to prevent dehydrative aromatization of the products. This fact will be under further scrutiny. Ene products are amenable to useful functionalizations especially transposition of the new double bond. Studies on the total synthesis of altersolanol P (3), aranciamycin I (6) etc. are underway. 3.1. Experimental section All reactions utilizing moisture-sensitive reagents were performed under an inert atmosphere. All solvents namely DMF, DCM, THF, MeOH etc. were dried prior to use, according to the standard protocols. Melting points were determined in open capillary tubes and are reported as uncorrected. TLC was carried out on precoated plates (silica gel 60 F254), and the spots were visualized with UV and fluorescent lights. Column chromatography was performed on silica gel (60e120 or 230e400 mesh). 1H and 13C NMR spectra for all the compounds were recorded at 200/400/600 and 50/100/ 150 MHz (Bruker AVANCE 200, Bruker UltrashieldÔ 400, AscendÔ 600), respectively. IR spectra were recorded with a PerkineElmer
3.2.2. 2-(2-Methallyl)benzaldehyde (10).9b,9c General procedure A was followed for coupling between 2-formylphenylboronic acid (2.050 g, 13.67 mmol) and methallyl bromide (3.663 g, 27.33 mmol). The crude product was purified by flash column chromatography on silica gel with hexane to afford the desired product 10 (1.554 g, 9.70 mmol) in 71% yield and unwanted yellowish, liquid [1,10 -Biphenyl]-2,20 -dicarboxaldehyde (0.689 g, 3.28 mmol) in 24% yield. 3.2.3. Data for 10. Yellowish liquid; Rf (hexane) 0.5; 1H NMR (400 MHz, CDCl3): d 10.25 (s, 1H), 7.87 (dd, J¼1.0, 7.6 Hz, 1H), 7.53 (dt, J¼1.0, 7.6 Hz, 1H), 7.39 (t, J¼7.6, 1H), 7.28 (d, J¼7.6 Hz, 1H), 4.84 (s, 1H), 4.46 (s, 1H), 3.74 (s, 2H), 1.78 (s, 3H); 13C NMR (100 MHz, CDCl3): d 192.3 (CH), 145.4, 142.3, 134.6, 134.0 (CH), 131.8 (CH), 130.8 (CH), 127.2 (CH), 112.7 (CH2), 40.4 (CH2), 23.1 (CH3). 3.3. Preparation of ethallyl bromide23 3.3.1. 2-Methylenebutyraldehyde. This was prepared according to the literature procedure. 1H NMR (400 MHz, CDCl3): d 9.46 (s, 1H), 6.17 (s, 1H), 5.91 (s, 1H), 2.17 (q, J¼7.6 Hz, 2H), 0.98 (t, J¼7.6 Hz, 3H); 13 C NMR (100 MHz, CDCl3): d 194.8 (CH), 151.8, 133.2 (CH2), 20.9 (CH2), 11.9(CH3). 3.3.2. 2-Methylenebutan-1-ol. To a stirred solution of 2-methylenebutyraldehyde (3.7 g, 44 mmol) in MeOH (50 mL) was added CeCl3$7H2O (19.7 g, 53 mmol). Then NaBH4 (2.01 g, 53 mmol) was added portion wise and reaction mixture was stirred for 3.0 h. MeOH was evaporated under vacuum. Usual work-up of the mixture using diethyl ether afforded 2-methylenebutan-1-ol (2.70 g, 31.4 mmol) in 71% yield. Colourless liquid; 1H NMR (200 MHz, CDCl3): d 4.97 (s, 1H), 4.83 (s, 1H), 4.03 (s, 2H), 2.37 (bs, 1H), 2.04 (q, J¼7.4 Hz, 2H), 1.03 (t, J¼7.4 Hz, 3H); 13C NMR (50 MHz, CDCl3): d 150.8, 108.1 (CH2), 65.9 (CH2), 25.8 (CH2), 12.2 (CH3). 3.3.3. 2-Bromomethyl-but-1-ene. 2-Bromomethyl-but-1-ene was prepared from 2-methylene-butan-1-ol following the reported procedure. 1H NMR (200 MHz, CDCl3): d 5.14 (s, 1H), 4.94 (s, 1H), 3.97 (s, 2H), 2.22 (q, J¼7.4 Hz, 2H), 1.06 (t, J¼7.4 Hz, 3H); 13C NMR (50 MHz, CDCl3): d 147.3, 114.0 (CH2), 37.1 (CH2), 26.4 (CH2), 12.1 (CH3). 3.3.4. 2-(2-Methylenebutyl)benzaldehyde (11). General procedure A was followed for coupling between 2-formylphenylboronic acid
S. Basak, D. Mal / Tetrahedron 72 (2016) 1758e1772
(1.025 g, 6.80 mmol) and ethallylbromide (2.022 g, 13.66 mmol). The crude was purified by flash column chromatography on silica gel with hexane to afford the desired product 11 (1.120 g, 5.00 mmol) in 73% yield, unwanted yellowish liquid [1,10 -Biphenyl]2,20 -dicarboxaldehyde (0.214 g, 1.02 mmol) in 15% yield. 3.3.5. Data for 11.9d Yellowish liquid; Rf (1:20 EA/hexane) 0.4; 1H NMR (200 MHz, CDCl3): d 10.23 (s, 1H), 7.77 (dd, J¼1.2, 7.4 Hz, 1H), 7.53 (dt, J¼1.6, 7.4 Hz, 1H), 7.39 (t, J¼7.4 Hz, 1H), 7.28 (d, J¼7.4 Hz, 1H), 4.85 (d, J¼1.2 Hz, 1H), 4.41 (d, J¼1.2 Hz, 1H), 3.75 (s, 2H), 2.10 (q, J¼7.4 Hz, 2H), 1.08 (t, J¼7.4 Hz, 3H); 13C NMR (50 MHz, CDCl3): d 192.3 (CH), 151.2, 142.5, 134.5, 134.0 (CH), 131.9 (CH), 130.6 (CH), 127.1 (CH), 110.7 (CH2), 39.0 (CH2), 29.5 (CH2), 12.4 (CH3); HRMS (ESI): m/z calculated for C12H14O: requires: 175.1123 for [MþH]þ, 157.1017 for [MH2OþH]þ; found: 175.1129, 157.1040. 3.3.6. 2-formyl-4-methoxyphenylboronic acid (18) and its hemiacetal form 19.10a,10b Mixture of boronic acid 18 and its hemiacetal 19 was prepared according to the literature procedure. Peaks of 18 were only detectable from the spectra. 1
3.3.7. Data for 18. H NMR (400 MHz, DMSO-d6) d 10.22 (s, 1H), 7.62 (d, J¼8.4 Hz, 1H), 7.38 (d, J¼2.8 Hz, 1H), 7.19 (dd, J¼2.8, 8.4 Hz), 3.81 (s, 3H); 13C NMR (100 MHz, DMSO-d6) d 194.9 (CH), 160.7, 142.1, 136.3 (CH), 119.8 (CH), 113.2 (CH), 55.9 (CH3). 3.3.8. Data for 5-methoxy-2-(2-methallyl)benzaldehyde (12). 9e General procedure A was performed on mixture of boronic acid 18 and its hemiacetal 19 (0.567 g, 3.15 mmol) and methallyl bromide (0.844 g, 6.30 mmol). The reaction mixture was purified by flash column chromatography on silica gel (1:10 EA/hexane) to afford the desired colourless product 12 (0.360 g, 1.89 mmol) in 60% yield along with the dimeric product [4,40 -dimethoxybiphenyl]-2,20 -dicarboxaldehyde24 (0.270 g, 0.54 mmol) in 17% yield. Rf (1:10 EA/hexane) 0.4; 1H NMR (400 MHz, CDCl3): d 10.22 (s, 1H), 7.39 (d, J¼2.8 Hz, 1H), 7.17 (d, J¼8.4 Hz, 1H), 7.08 (dd, J¼2.8, 8.4 Hz, 1H), 4.82 (s, 1H), 4.44 (s, 1H), 3.85 (s, 3H), 3.64 (s, 2H), 1.76 (s, 3H); 13C NMR (100 MHz, CDCl3): d 191.7 (CH), 158.7, 145.8, 135.2, 134.9, 133.0 (CH), 121.3 (CH), 112.7 (CH), 112.6 (CH2), 55.7 (CH3), 39.5 (CH2), 23.0 (CH3). 3.3.9. Boronic acid 20 and 21.25 2-(2,5-dimethoxy phenyl)-1,3dioxane (1.120 g, 5.00 mmol) was dissolved in hexane (34 mL) and the reaction was cooled to 25 C. To the cooled solution was added freshly distilled benzene (11 mL) followed by drop wise addition of n-BuLi (1.6 M, 5.3 mL, 8.50 mmol). After 12 h, trimethylborate (2.2 mL, 9.35 mmol) in THF (11.2 mL) was added and the reaction was stirred at the same temperature for 2 h. Then it was allowed to warm to rt and stirred for 12 h. The reaction mixture was quenched with 2 (M) HCl (7.5 mL) and stirred for 3 h. It was then extracted with EA (350 mL). Solvent was evaporated. Crude material was dissolved in 2 (M) NaOH (10 mL) and was thoroughly washed with ether (310 mL). Aqueous part was acidified with conc. HCl to pH 2e3. This was extracted with EA (325 mL). The combined organic layers was dried over Na2SO4 and evaporated to afford a mixture of 20 and its hemiacetal form 21 (4:1) (630 mg, 3.00 mmol) in 60% yield. Yellowish solid; mp 130e135 C; 11B NMR (128 MHz, CDCl3): d 28.4. IR (KBr): ~v¼3527, 1657, 1426, 1382, 1326, 1289, 1249, 1193, 1062, 942, 714 cm1. HRMS (ESI): m/z calculated for C9H11BO5: requires: 193.0672 for [MH2OþH]þ, 233.0623 for [MþNa]þ; found: 193.0720, 233.0623. 1H NMR signals of individual components were predicted from 1H NMR spectrum of the mixture; Data for boronic acid 20. 1H NMR (400 MHz, DMSO-d6) d 10.28 (s, 1H), 7.51 (s, 2H), 7.18 (d, J¼8.8 Hz, 1H), 7.04 (d, J¼8.8 Hz, 1H), 3.82 (s, 3H), 3.67 (s, 3H); 13C NMR (100 MHz, DMSO-d6) d 190.6 (CH), 156.4, 155.4, 127.4, 119.0 (CH), 112.8 (CH), 56.7 (CH3), 56.6
1765
(CH3); Data for hemiacetal form 21. 1H NMR (400 MHz, DMSO-d6)
d 8.83 (s, 1H), 6.97 (d, J¼8.8 Hz, 1H), 6.82 (d, J¼8.8 Hz, 1H), 6.71 (d, J¼8.4 Hz, 1H), 6.07 (d, J¼8.4 Hz, 1H), 3.71 (s, 3H). 3.3.10. 3,6-Dimethoxy-2-(2-methallyl)benzaldehyde (13). Coupling reaction between mixture of boronic acid 20 and its hemiactal form 21 (0.420 g, 2.00 mmol) and methallyl bromide (0.535 g, 4.00 mmol) was performed following the general procedure A. The crude product was purified by flash column chromatography on silica gel with 1:20 EA/hexane solvent to afford the desired yellowish liquid product 13 (0.352 g, 1.60 mmol) in 80% yield. Rf (1:20 EA/hexane) 0.3; 1H NMR (200 MHz, CDCl3): d 10.52 (s, 1H), 7.07 (d, J¼9.0 Hz, 1H), 6.84 (d, J¼9.0 Hz, 1H), 4.64 (q, J¼1.8 Hz, 1H), 4.31e3.98 (m, 1H), 3.86 (s, 3H), 3.79 (s, 3H), 3.71 (s, 2H), 1.90e1.65 (m, 3H); 13C NMR (50 MHz, CDCl3): d 192.6 (CH), 157.0, 152.3, 145.5, 131.8, 124.8, 117.5 (CH), 110.2 (CH), 109.3 (CH), 57.0 (CH3), 56.4 (CH3), 32.8 (CH2), 23.8 (CH3); nmax (KBr, cm1): 2938, 1687, 1592, 1477, 1263, 1085, 887, 717; HRMS (ESI): m/z calculated for C13H16O3: requires: 221.1178 for [MþH]þ; found: 221.1180. 3.3.11. Boronic acid 22. 10cLiterature procedure was followed to prepare the boronic acid 22. Dark brown crystal; mp 96e98 C; 1H NMR (400 MHz, CDCl3) d 9.77 (s, 1H), 8.22e7.86 (m, 2H), 7.81 (s, 1H), 7.37 (s, 1H), 4.02 (d, J¼16.2 Hz, 6H); 13C NMR (100 MHz, CDCl3) d 196.8 (CH), 153.5, 150.6, 133.8, 121.0 (CH), 120.9 (CH), 56.5 (CH3), 56.3 (CH3). 11B NMR (128 MHz, CDCl3): d 28.2. 3.3.12. 4,5-Dimethoxy-2-(2-methallyl)benzaldehyde (14). General procedure A was performed on 22 (0.577 g, 2.75 mmol) and methallyl bromide (0.737 g, 5.50 mmol). The crude product was purified by flash column chromatography on silica gel with 1:15 EA/ hexane to afford the desired product 14 (0.430 g, 1.95 mmol) in 71% yield along with dimeric product [4,5,40 ,50 -Tetramethoxybiphenyl]2,20 -dicarboxaldehyde in (0.091 g, 0.28 mmol) 10% yield. 3.3.13. Data for 14. Colourless liquid; Rf (1:15 EA/hexane) 0.45; 1H NMR (400 MHz, CDCl3): d 10.14 (s, 1H), 7.40 (s, 1H), 6.70 (s, 1H), 4.84 (s, 1H), 4.49 (s, 1H), 3.93 (s, 3H), 3.92 (s, 3H), 3.65 (s, 2H), 1.76 (s, 3H); 13C NMR (50 MHz, CDCl3): d 190.0 (CH), 154.0, 148.2, 145.5, 137.6, 127.6, 113.6 (CH), 112.8 (CH2), 110.54 (CH), 56.3 (CH3), 56.2 (CH3), 39.7 (CH2), 22.9 (CH3); IR (KBr): ~v¼3447, 2931, 1676, 1597, 1512, 1458, 1404, 1354, 1271, 1227, 1101, 1000, 882, 757 cm1; HRMS (ESI): m/z calculated for C13H16O3: requires: 203.1072 for [MH2OþH]þ, 221.1178 for [MþH]þ; found: 203.1099, 221.1249. 3.3.14. 2-Formyl-1-naphthylboronic acid 23 and its hemiacetal form 24. To a stirred solution of 2-(1-bromonaphthalen-2-yl)-[1,3]dioxane26, (10.9 g, 37.33 mmol) in dry THF (120 mL) was added n-BuLi (2.5 (M) in hexane, 19.4 mL, 48.53 mmol) drop wise under inert atmosphere at 78 C. The reaction mixture was stirred for 1 h. Then B(OCH3)3 (6 mL, 53.4 mmol) was added and stirred for 2 h at the same temperature. The resulting mixture was allowed to warm to room temperature and stirred for 12 h. 2 M HCl (56 mL) was added at 0 C and stirred for 3 h. The mixture was extracted with EA (3100 mL). Solvent was evaporated. Crude material was dissolved in 2 M NaOH (80 mL) and was thoroughly washed with ether (350 mL). The aqueous part was acidified with conc. HCl to pH 2e3. This was extracted with EA (310 mL). The combined organic layers was dried over Na2SO4 and was evaporated to get mixture of boronic acid 23 and its hemiacetal form 24 (2:1) (4.1 g, 20.5 mmol) in 50% yield. 3.3.15. Data for 2-(1-bromonaphthalen-2-yl)-[1,3]dioxane. 1H NMR (400 MHz, CDCl3): d 8.39 (d, J¼8.4 Hz, 1H), 7.82e7.87 (m, 3H), 7.52e7.62 (m, 2H), 6.12 (s, 1H), 4.30e4.34 (m, 2H), 4.07e4.14 (m, 2H), 2.25e2.37 (m, 1H), 1.46e1.50 (m, 1H); 13C NMR (100 MHz,
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CDCl3): d 135.7, 135.0, 132.2, 128.3 (CH), 128.2 (CH), 127.9 (CH), 127.5 (CH), 127.2 (CH), 124.8 (CH), 123.1 (CH), 102.2 (CH), 67.8 (2 CH2), 26.0 (CH2); IR (KBr): ~v¼3446, 2963, 2854, 2370, 1654, 1560, 1542, 1507, 1459, 1375, 1342, 1275, 1231, 1148, 1103, 995, 958, 816, 745 cm1; HRMS (ESI): m/z calculated for C14H13BrO2: requires: 295.0157 for [MþH]þ; found: 295.0187. 3.3.16. Data for mixture of boronic acid 23 and its hemiacetal form 24. Yellow solid; 11B NMR (128 MHz, DMSO-d6): d 30.9; IR (KBr): ~v¼3367, 3048, 1520, 1500, 1472, 1452, 1394, 1372, 1337, 1270, 1220, 1199, 1140, 1101, 1063, 944, 733 cm1; HRMS (ESI): m/z calculated for C11H9O2B: requires: 183.0617 for [MH2OþH]þ; found: 183.0640. 1H NMR peaks of individual components were predicted from 1H NMR spectrum of the mixture; Data for boronic acid 23. 1 H NMR (400 MHz, DMSO-d6): d 10.18 (s, 1H), 8.34 (d, J¼8.0 Hz, 1H), 8.06e7.54 (m, 7H); 13C NMR (100 MHz, DMSO-d6): d 194.2 (CH), 135.9, 135.8, 134.7, 130.9 (CH), 129.3 (CH), 128.9 (CH), 128.9 (CH), 127.4 (CH), 124.8 (CH); Data for hemiacetal form 24. 1H NMR (400 MHz, DMSO-d6): d 8.06e7.54 (m, 8H), 6.31 (s, 1H). 13C NMR (100 MHz, DMSO-d6): d 155.8, 134.3, 133.6, 132.3 (CH), 129.0 (CH), 127.6 (CH), 127.5 (CH), 126.7 (CH), 121.4 (CH), 97.8 (CH). 3.3.17. 1-(2-Methallyl)naphthalene-2-carboxaldehyde (15). General procedure A was followed to perform coupling reaction between mixture of boronic acid 23 and its hemiacetal form 24 (0.610 g, 3.05 mmol) and methallyl bromide (0.817 g, 6.10 mmol). Reaction mixture was purified by flash column chromatography on silica gel with 1:25 EA/hexane solvent to afford the desired product 15 (0.320 g, 1.53 mmol) in 50% yield. Yellowish liquid; Rf (1:25 EA/ hexane) 0.35; 1H NMR (400 MHz, CDCl3): d 10.52 (s, 1H), 8.14 (d, J¼8.2 Hz, 1H), 7.97 (d, J¼8.2 Hz, 1H), 7.82e7.88 (m, 2H), 7.55e7.62 (m, 2H), 4.86 (t, J¼1.2 Hz, 1H), 4.28 (s, 1H), 4.20 (s, 2H), 1.94 (s, 3H); 13 C NMR (50 MHz, CDCl3): d 192.2 (CH), 144.8, 141.7, 136.5, 132.8, 131.9, 129.0 (CH), 128.8 (CH), 127.9 (CH), 127.1 (CH), 125.7 (CH), 124.0 (CH), 113.2 (CH2), 34.6 (CH2), 23.7 (CH3); IR (KBr): ~v¼3458, 1678, 1649, 1452, 1345, 1227, 885, 810, 763, 747 cm1; HRMS (ESI): m/z calculated for C15H14O: requires: 193.1017 for [MH2OþH]þ, 211.1123 for [MþH]þ; found: 193.1058, 211.1142. 3.3.18. 2-(2-Methallyl)-naphthalene-1-carboxaldehyde (16). A mixture of boronic acid 25 and its hemiacetal 26 was prepared from 2(2-bromonaphthalen-1-yl)-[1,3]dioxane26 (1.460 g, 5 mmol) following the same process as the preparation of mixture of boronic acid 23 and its hemiacetal form 24 from 2-(2-bromonaphthalen-1yl)-[1,3]dioxane. The crude product (0.68 g, w3.4 mmol) was sufficiently pure to carry out the Suzuki coupling reaction with methallyl bromide (0.91 g, 6.8 mmol) following the general procedure A. The crude product was purified by flash column chromatography on silica gel with 1:10, EA/hexane to afford the desired product 16 (0.48 g, 2.3 mmol) in 68% yield along with dimerized product [1,20 -binaphthalenyl]-2,10 -dicarboxaldehyde27 (0.294 g, 0.95 mmol) in 19% yield. 3.3.19. Data for 2-(2-bromonaphthalen-1-yl)-[1,3]dioxane. 1H NMR (200 MHz, CDCl3): d 9.03 (d, J¼8.2 Hz, 1H), 7.79 (d, J¼8.2 Hz, 1H), 7.47e7.69 (m, 4H), 6.55 (s, 1H), 4.39 (dd, J¼4.6, 11.2 Hz, 2H), 4.12 (t, J¼11.6 Hz, 2H), 2.38e2.63 (m, 1H), 1.54 (d, J¼13.6, 1H); 13C NMR (50 MHz, CDCl3): d 133.7, 132.3, 132.0, 131.1 (CH), 130.0 (CH), 128.3 (CH), 126.9 (CH), 126.7 (CH), 126.3 (CH), 122.0, 105.0 (CH), 68.3 (2 CH2), 26.2 (CH2). IR (KBr): ~v¼3458, 2967, 2852, 1636, 1413, 1370, 1144, 1120, 1104, 997, 947, 809, 776, 745, 469 cm1. HRMS (ESI): m/z calculated for C15H14O: requires: 193.1017 for [MH2OþH]þ, 211.1123 for [MþH]þ; found: 193.1058, 211.1142. 3.3.20. Data for 16. Yellowish liquid; Rf (1:10 EA/hexane) 0.4; 1H NMR (400 MHz, CDCl3): d 10.80 (s, 1H), 9.04 (d, J¼8.8, 1H), 7.98 (d,
J¼8.4 Hz, 1H), 7.85 (d, J¼8.0 Hz, 1H), 7.61e7.65 (m, 1H), 7.51e7.54 (m, 1H), 7.36 (d, J¼8.4 Hz, 1H), 4.90 (s, 1H), 4.50 (s, 1H), 3.82 (s, 2H), 1.81 (s, 3H). 13C NMR (100 MHz, CDCl3): d 193.8 (CH), 145.2, 144.2, 134.5 (CH), 133.0, 131.3, 129.6 (CH), 129.3, 129.0 (CH), 128.5 (CH), 126.5 (CH), 125.3 (CH), 113.4 (CH2), 41.2 (CH2), 23.2 (CH3). IR (KBr): ~v¼2919, 1685, 1428, 1220, 1062, 893, 812, 670 cm1; HRMS (ESI): m/ z calculated for C15H14O: requires: 193.1017 for [MH2OþH]þ, 211.1123 for [MþH]þ; found: 193.1013, 211.1130. 3.3.21. 4-Methoxy-3-(2-methallyloxy)benzaldehyde (28). 11To a stirred solution of isovanillin (8.8 g, 57.9 mmol) in dry acetone (300 mL) was added solid K2CO3 (8.0 g, 57.9 mmol) at 0 C followed by addition of methallyl bromide (8.8 mL, 86.9 mmol). The reaction mixture was stirred for 24 h. Acetone was evaporated. The mixture was extracted with EA (250 mL) and the organic layer was washed with H2O (3100 mL) and brine (100 mL). The combined organic layer was dried over Na2SO4 and evaporated under vacuum to afford the crude material. It was purified by performing flash column chromatography on silica gel with 1:5 EA/hexane solvent to afford 28 (10.9 g, 52.7 mmol) in 91% yield. Yellow oil; Rf (1:5 EA/hexane) 0.55; 1H NMR (200 MHz, CDCl3) d 9.75 (s, 1H), 7.41e7.32 (m, 2H), 6.91 (d, J¼8.2 Hz, 1H), 5.06 (s, 1H), 4.94 (s, 1H), 4.49 (s, 2H), 3.88 (s, 3H), 1.77 (s, 3H); 13C NMR (50 MHz, CDCl3) d 190.8 (CH), 154.9, 148.7, 140.1, 130.0, 126.7 (CH), 113.2 (CH2), 111.2, 110.8 (CH), 72.5 (CH2), 56.1 (CH3), 19.3 (CH3); IR (KBr): ~v¼3422, 2936, 1686, 1611, 1582, 1508, 1438, 1270, 1220, 1162, 1134, 1017, 905, 642 cm1. 3.3.22. [4-Methoxy-3-(2-methyl-allyloxy)phenyl]methanol (29). To a stirred solution of compound 28 (5.15 g, 25 mmol) in THF (50 mL) and MeOH (16 mL) at 0 C was added NaBH4 (1.04 g, 27.5 mmol) in portions. The resulting mixture was stirred at rt for overnight. Then it was quenched with saturated NH4Cl. Extraction of the reaction mixture with EA (375 mL) followed by drying over Na2SO4 and removal of solvent gave a residue. Flash column chromatography of the residue on silica gel with 1:5 EA/hexane solvent afforded product 29 (4.1 g, 19.7 mmol) in 79% yield. Colourless liquid; Rf (1:5 EA/hexane) 0.45; 1H NMR (400 MHz, CDCl3) d 6.86e6.78 (m, 2H), 5.07 (s, 1H), 4.95 (s, 1H), 4.51 (d, J¼2.4 Hz, 2H), 4.54 (s, 2H), 3.81 (s, 3H), 2.50 (bs, 1H), 1.80 (s, 3H); 13C NMR (50 MHz, CDCl3) d 149.0, 148.3, 140.8, 133.7, 119.8 (CH), 112.9 (CH2), 112.7 (CH), 111.8 (CH), 72.6 (CH2), 65.0 (CH2), 56.1 (CH3), 19.4 (CH3); IR (KBr): ~v¼3411, 2920, 2847, 2361, 1592, 1515, 1427, 1261, 1157, 1136, 1021, 903, 807 cm1. HRMS (ESI): m/z calculated for C12H16O3: requires: 191.1072 for [MH2OþH]þ; found: 191.1080. 3.3.23. 3-Hydroxymethyl-6-methoxy-2-(2-methallyl)phenol (30). A solution of compound 29 (3.0 g, 14.4 mmol) in DMF (15 mL) was heated at reflux for 28 h. DMF was evaporated under reduced pressure. Flash column chromatography of the residue on silica gel with 1:3 EA/hexane solvent afforded 30 (1.58 g, 7.6 mmol) in 53% yield and its ether (1.33 g, 6.5 mmol) 45% yield. White crystalline solid; Rf (1:3 EA/hexane) 0.5; mp 82e84 C; 1H NMR (400 MHz, CDCl3) d 6.88 (d, J¼8.0 Hz, 1H), 6.74 (d, J¼8.0 Hz, 1H), 5.89 (s, 1H), 4.76 (s, 1H), 4.55 (s, 2H), 4.44 (s, 1H), 3.87 (s, 3H), 3.48 (s, 2H), 2.04 (bs, 1H), 1.82 (s, 3H); 13C NMR (50 MHz, CDCl3) d 146.2, 145.8, 144.1, 133.1, 123.9, 120.1 (CH), 110.2 (CH2), 108.5 (CH), 63.4 (CH2), 56.1 (CH3), 33.5 (CH2), 23.1 (CH3); IR (KBr): ~v¼3434, 3185, 1618, 1491, 1440, 1272, 1090, 890, 792 cm1; HRMS (ESI): m/z calculated for C12H16O3: requires: 191.1072 for [MH2OþH]þ, 381.2066 for [(MH2O)2þH]þ; found: 191.1080, 381.2052. 3.3.24. [3,4-Dimethoxy-2-(2-methyl-allyl)-phenyl]methanol (31). To a stirred solution of compound 30 (0.370 mg, 1.78 mmol) in acetone (20 mL) were added potassium carbonate (1.23 g, 8.9 mmol) and MeI (0.34 mL, 5.34 mmol). The reaction mixture was stirred for 48 h. Usual work-up was done with EA. Flash column
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chromatography of the crude product on silica gel with 1:5 EA/ hexane solvent afforded product 31 (0.392 g, 1.88 mmol) in 99% yield. White solid; Rf (1:5 EA/hexane) 0.4; mp 46e48 C; 1H NMR (400 MHz, CDCl3) d 7.07 (d, J¼8.4 Hz, 1H), 6.78 (d, J¼8.4 Hz, 1H), 4.73 (s, 1H), 4.50 (s, 2H), 4.31 (s, 1H), 3.83 (s, 3H), 3.76 (s, 3H), 3.42 (s, 2H), 2.21 (bs, 1H), 1.81 (s, 3H); 13C NMR (50 MHz, CDCl3) d 152.3, 147.5, 146.2, 132.7, 131.9, 124.4 (CH), 110.5 (CH2), 110.3 (CH), 63.1 (CH2), 60.8 (CH3), 55.7 (CH3), 33.6 (CH2), 22.4 (CH3); IR (KBr): ~v¼3393, 2935, 1490, 1452, 1274, 1220, 1084, 1023, 889 cm1; HRMS (ESI): m/z calculated for C13H17O2: requires: 205.1229 for [MH2OþH]þ; found: 205.1205. 3.3.25. Preparation of 3,4-dimethoxy-2-(2-methallyl)benzaldehyde (27). To a stirred solution of 31 (0.353 g, 1.6 mmol) in dry DCM (10 mL) was added activated MnO2 (0.910 g, 16.0 mmol). The reaction mixture was stirred for 4 d and filtered. Removal of the solvent followed by flash column chromatography on silica gel with 1:10 EA/haxane afforded 27 (0.335 g, 1.52 mmol) in 95% yield. Rf (1:10 EA/hexane) 0.5; 1H NMR (400 MHz, CDCl3) d 9.98 (s, 1H), 7.65 (d, J¼8.4 Hz, 1H), 6.70 (d, J¼8.4 Hz, 1H), 4.74 (t, J¼1.2 Hz, 1H), 4.24 (s, 1H), 3.91 (s, 3H), 3.77 (s, 3H), 3.73 (s, 2H), 1.83 (s, 3H); 13C NMR (50 MHz, CDCl3) d 190.9 (CH), 157.6, 147.5, 145.8, 136.3, 128.4, 128.0 (CH), 111.2 (CH2), 110.1 (CH), 61.1 (CH3), 55.9 (CH3), 32.3 (CH2), 23.6 (CH3); IR (KBr): ~v¼2919, 2849, 1686, 1589, 1490, 1456, 1282, 1258, 1078, 890, 809 cm1; HRMS (ESI): m/z calculated for C13H16O3: requires: 221.1178 for [MþH]þ; found: 221.1168. 3.3.26. Methyl 1,4-dihydroxy-8-methoxynaphthalene-2-carboxylate (34). A solution of 3-cyanophthalide 33 (189 mg, 1 mmol) in dry THF (5 mL) was added to stirred suspension of LTB (240 mg, 3 mmol) in dry THF (15 mL) at 60 C under an inert atmosphere. The resulting solution was stirred at 60 C for 30 min after which a solution of methyl acrylate (0.18 mL, 2 mmol) in dry THF (5 mL) was added. The reaction mixture was stirred for another 30 min at 60 C followed by 6e8 h stirring at room temperature. The reaction was then quenched with saturated ammonium chloride solution and THF was evaporated under reduced pressure. The residue was then extracted with ethyl acetate (320 mL). The combined extracts were washed with brine (31/ 3 vol), dried (Na2SO4) and concentrated to afford crude product. This crude product was purified by column chromatography on silica gel with ethyl acetateepetroleum ether (1:3) as solvent to obtain pure compound 34 in 95% yield (236 mg, 0.95 mmol). Yellow solid; Rf (1:3 EA/hexane) 0.55; mp 175e176 C; 1H NMR (400 MHz, DMSO-d6): d 11.45 (s, 1H), 9.70 (bs, 1H), 7.67 (d, J¼8.4 Hz, 1H), 7.51 (t, J¼8.4 Hz, 1H), 7.12 (s, 1H), 7.01 (d, J¼7.6 Hz, 1H), 3.91 (s, 3H), 3.88 (s, 3H); 13C NMR (100 MHz, DMSO-d6): d 170.7, 158.9, 154.7, 145.0, 131.8, 129.8 (CH), 116.5, 115.1 (CH), 107.9 (CH), 106.4 (CH), 106.3, 56.7 (CH3), 53.0 (CH3); IR (KBr): ~v¼3414, 1636, 1438, 1364, 1289, 1251, 1192, 1114, 1042, 984, 806, 750 cm1; HRMS (ESI): m/z calculated for C13H13O5: requires: 249.0763 for [MþH]þ, 217.0486 for [MCH3OHþH]þ; found: 249.0747, 217.0486. 3.3.27. Methyl 1-hydroxy-8-methoxy-4-(2-methyl-allyloxy)naphthalene-2-carboxylate (35). To a stirred solution of compound 34 (0.496 g, 2 mmol) in acetone (15 mL) was added K2CO3 (1.38 g, 10 mmol) at 0 C and stirred for 5 min followed by addition of methallyl bromide (0.4 mL, 4 mmol) at 0 C. The reaction mixture was warmed to rt and stirred for overnight. Acetone was evaporated. The reaction mixture was extracted with 100 mL ethyl acetate and was successively washed with (325 mL) H2O and brine (150 mL). Organic layer was dried over Na2SO4 and evaporated to afford crude product. Flash column chromatography on silica gel was carried out with 1:5 EA/hexane solvent to furnish 35 (0.332 g, 1.10 mmol) in 55% yield. Yellow oil; Rf (1:5 EA/hexane) 0.35; 1H
1767
NMR (400 MHz, CDCl3): d 12.18 (s, 1H), 7.88 (d, J¼8.4 Hz, 1H), 7.52 (d, J¼8.4 Hz, 1H), 7.12 (s, 1H), 6.94 (d, J¼7.6 Hz, 1H), 5.20 (s, 1H), 5.04 (s, 1H), 4.54 (s, 2H), 4.03 (s, 3H), 3.97 (s, 3H), 1.91 (s, 3H); 13C NMR (100 MHz, CDCl3): d 171.3, 159.0, 157.1, 146.2, 141.2, 132.8, 129.7 (CH), 116.9, 114.9 (CH), 112.9 (CH2), 107.5 (CH), 105.2, 103.9 (CH), 72.4 (CH2), 56.6 (CH3), 52.5 (CH3), 19.9 (CH3); IR (KBr): ~v¼3380, 2936, 1654, 1364, 1253, 1070, 772 cm1; HRMS (ESI): m/z calculated for C17H18O5: requires: 303.1232 for [MþH]þ; found: 303.1238. 3.3.28. Methyl 1,8-dimethoxy-4-(2-methyl-allyloxy)-naphthalene-2carboxylate (36). To a stirred solution of compound 35 (190 mg, 0.63 mmol) in THF (5 mL) was added NaH (60% in oil, 75.6 mg, 1.83 mmol) at 0 C followed by addition of Me2SO4 (0.5 mL, 5.04 mmol). The reaction mixture was stirred for 12 h. Then it was quenched with H2O and the reaction mixture was extracted with ethyl acetate (325 mL). Combined organic layers was washed with H2O (225 mL) and brine (125 mL). Organic layer was dried over Na2SO4. Triethylamine (0.44 mL, 3.15 mmol) was added to it and stirred for 30 min. Then this solution was washed with 1 (N) HCl solution (125 mL) followed by washing with (125 mL) brine solution. Organic layer was dried over Na2SO4 and evaporated under vacuum to afford the crude product. Flash column chromatography was done on silica gel with 1:10 (EA/ hexane) solvent to afford 36 (169 mg, 0.54 mmol) in 85% yield. Colourless liquid; Rf (1:10 EA/hexane) 0.45; 1H NMR (600 MHz, CDCl3): d 7.93 (dd, J¼1.1, 8.4 Hz, 1H), 7.47 (t, J¼8.1 Hz, 1H), 7.10 (s, 1H), 6.95 (d, J¼7.7 Hz, 1H), 5.20 (s, 1H), 5.05 (s, 1H), 4.59 (s, 2H), 4.00 (s, 3H), 3.95 (s, 3H), 3.88 (s, 3H), 1.91 (s, 3H); 13C NMR (100 MHz, CDCl3): d 167.8, 157.4, 151.9, 150.2, 140.9, 131.2, 128.1 (CH), 121.1, 121.0, 115.0 (CH), 113.0 (CH2), 107.9 (CH), 105.7 (CH), 72.4 (CH2), 63.7 (CH3), 56.5 (CH3), 52.5 (CH3), 19.8 (CH3); IR (KBr): ~v¼2926, 2853, 2369, 1724, 1586, 1364, 1220, 1178, 1070, 1009, 902, 667 cm1; HRMS (ESI): m/z calculated for C18H20O5: requires: 317.1389 for [MþH]þ, 285.1127 for [MCH3OHþH]þ; found: 317.1392, 285.1117. 3.3.29. Methyl 1,4,8-trimethoxy-3-(2-methallyl)naphthalene-2carboxylate (37). 33Stirred solution of compound 36 (150 mg, 0.47 mmol) in 2.5 mL DMF was refluxed for 12 h at 180 C. DMF was evaporated under vacuum and dissolved in ethyl acetate (100 mL). It was then washed with brine solution (520 mL). Combined organic layers were washed with brine solution and dried over Na2SO4. Solvent was evaporated under vacuum to afford the crude product. Without purification, crude material was dissolved in dry acetone (5 mL). K2CO3 (324 mg, 2.35 mmol) was added to it at 0 C followed by addition of Me2SO4 (0.13 mL, 1.41 mmol). The reaction mixture was refluxed for 12 h. Acetone was evaporated reaction mixture was extracted with ethyl acetate (325 mL). Combined organic layers was washed with H2O (225 mL) and brine (125 mL). Organic layer was dried over Na2SO4. Triethylamine (0.33 mL, 2.35 mmol) was added to it and stirred for 30 min. Then this solution was washed with 1 (N) HCl solution (125 mL) followed by washing with (125 mL) brine solution. Organic layer was dried over Na2SO4. Crude product was obtained after evaporation of ethyl acetate under vaccum. Flash column chromatography was done on silica gel with 1:10 EA/hexane solvent to afford 37 (108 mg, 0.33 mmol) in 70% yield. Colourless liquid; Rf (1:10 EA/hexane) 0.5; 1 H NMR (400 MHz, CDCl3): d 7.69 (d, J¼8.4 Hz, 1H), 7.46 (t, J¼8.0 Hz, 1H), 6.89 (d, J¼7.6 Hz, 1H), 4.81 (s, 1H), 4.55 (s, 1H), 4.00 (s, 3H), 3.87e3.83 (m, 9H), 3.54 (s, 2H), 1.74 (s, 3H); 13C NMR (100 MHz, CDCl3): d 168.7, 156.9, 150.6, 150.4, 143.9, 131.9, 127.6 (CH), 127.3, 126.2, 119.7, 115.3 (CH), 112.1 (CH2), 106.5 (CH), 64.1 (CH3), 62.3 (CH3), 56.3 (CH3), 52.2 (CH3), 35.2 (CH2), 22.9 (CH3); IR (KBr): ~v¼2933, 2842, 1726, 1573, 1448, 1371, 1341, 1272, 1251, 1190, 1072, 1048, 891 cm1; HRMS (ESI): m/z calculated for C19H22O5: requires:
1768
S. Basak, D. Mal / Tetrahedron 72 (2016) 1758e1772
331.1546 for [MþH]þ, 353.1365 for [MþNa]þ, [MMeOHþH]þ; found: 331.1543, 353.1367, 299.1283.
299.1283
3.3.30. 1,4,8-Trimethoxy-3-(2-methallyl)-naphthalen-2-yl-methanol (38). Compound 37 (100 mg, 0.30 mmol) in THF (3 mL) was added drop wise to a stirred suspension of LAH (34.2 mg, 0.9 mmol) in THF (5 mL) at rt. Reaction mixture was stirred at rt for 30 h. When the reaction is complete, excess LAH was quenched with saturated Na2SO4 solution. Then it was filtered through Celite pad. Residue part was thoroughly washed with ethyl acetate. Crude product was obtained after removal of solvent. Flash column chromatography was done on silica gel with 1:1 EA/hexane to afford 38 (77.9 mg, 0.26 mmol) in 86% yield. Yellowish oil; Rf (1:1 EA/hexane) 0.45; 1H NMR (400 MHz, CDCl3): d 7.70 (d, J¼8.4 Hz, 1H), 7.42 (t, J¼8.4 Hz, 1H), 6.89 (d, J¼7.6 Hz, 1H), 4.82 (d, J¼1.2 Hz, 1H), 4.76 (s, 2H), 4.32 (s, 1H), 4.03 (s, 3H), 3.90 (s, 3H), 3.85 (s, 3H), 3.64 (s, 2H), 2.37 (bs, 1H), 1.91 (s, 3H); 13C NMR (100 MHz, CDCl3): d 156.4, 152.1, 150.6, 146.5, 131.3, 131.0, 128.7, 126.7 (CH), 120.0, 115.4 (CH), 111.2 (CH2), 106.2 (CH), 63.4 (CH3), 62.3 (CH3), 58.2 (CH2), 56.3 (CH3), 34.5 (CH2), 23.8 (CH3); IR (KBr): ~v¼2919, 2848, 1638, 1566, 1443, 1220, 1069, 681 cm1; HRMS (ESI): m/z calculated for C18H22O4: requires: 325.1416 for [MþNa]þ; found: 325.1417. 3 . 3 . 31. 1, 4 , 8 -Tr i m e t h o x y- 3 - ( 2 - m e t h a l l yl ) - n a p h t h a l e n e- 2 carboxaldehyde (32). To a stirred solution of compound 38 (130 mg, 0.43 mmol) in 10 mL DCM was added PCC (185 mg, 0.86 mmol) at 0 C and stirred at rt for 3 h. Reaction mixture was passed through basic alumina to remove PCC. Then flash column chromatography was done on silica gel with 1:10 EA/hexane solvent to afford 32 (113.5 mg, 0.38 mmol) in 88% yield. Yellow liquid; Rf (1:10 EA/ hexane) 0.35; 1H NMR (600 MHz, CDCl3) d 10.62 (s, 1H), 7.72 (dd, J¼1.0, 8.4 Hz, 1H), 7.59e7.53 (m, 1H), 6.94 (dd, J¼0.9, 7.8 Hz, 1H), 4.68e4.63 (m, 1H), 4.11 (m, 1H), 4.06 (s, 3H), 3.92 (s, 3H), 3.86 (d, J¼0.8 Hz, 2H), 3.85 (s, 3H), 1.96e1.86 (m, 3H); 13C NMR (150 MHz, CDCl3) d 193.0, 160.5, 157.5, 151.0, 146.5, 134.3, 129.8 (CH), 128.6, 126.1, 119.5, 115.5 (CH), 109.5 (CH2), 106.8 (CH), 65.3 (CH3), 62.4 (CH3), 56.4 (CH3), 33.3 (CH2), 24.2 (CH3); IR (KBr): ~v¼2922, 2851, 1685, 1366, 1265, 1063, 913, 744 cm1; HRMS (ESI): m/z calculated for C18H20O4: requires: 301.1440 for [MþH]þ; found: 301.1424. 3.3.32. Dimethyl 2-[2-(2-methallyl)-benzylidene]malonate (39).28 A stirred solution of 10 (330 mg, 2.06 mmol), dimethyl malonate (300 mg, 2.26 mmol), piperidine (0.02 mL, 0.206 mmol), and acetic acid (0.012 mL, 0.206 mmol) in 10 mL benzene was heated at reflux with a DeaneStark attachment for 9 h until no water was extracted. The reaction mixture was diluted with EA and washed with HCl (5% in water, 310 mL) and NaHCO3 (5% in water, 310 mL). The organic layer was dried over Na2SO4, and the solvent was removed under vacuum. Column chromatography of the residue with flash silica gel and 2% EA in hexane afforded product 39 (395 mg, 1.44 mmol) 70% yield. Colourless oil; Rf (1:50 EA/hexane) 0.25; 1H NMR (400 MHz, CDCl3) d 8.04 (s, 1H), 7.32e7.30 (m, 2H), 7.23e7.20 (m, 2H), 4.84 (s, 1H), 4.57 (s, 1H), 3.84 (s, 3H), 3.70 (s, 3H), 3.38 (s, 2H), 1.71 (s, 3H). 13C NMR (100 MHz, CDCl3) d 167.0, 164.6, 143.9, 143.0 (CH), 139.3, 133.2, 130.8 (CH), 130.4 (CH), 128.1 (CH), 127.2, 126.8 (CH), 112.9 (CH2), 52.8 (CH3), 52.6 (CH3), 42.2 (CH2), 22.7 (CH3). IR (KBr): ~v¼2923, 1735, 1612, 1435, 1261, 1219, 1068 cm1. HRMS (ESI): m/z calculated for C16H18O4: requires: 297.1103 for [MþNa]þ, 275.1283 for [MþH]þ; found: 297.1100, 275.1264. 3.3.33. Ethyl 3-[2-(2-methallyl)phenyl]acrylate (40). To a stirred solution of aldehyde 10 (280 mg, 1.75 mmol) in DCM (7 mL) was added (carbethoxymethylene)triphenylphosphorane (822 mg, 2.4 mmol) at 0 C under inert atmosphere. This mixture was allowed to warm to rt and stirred at the same temperature for 24 h. The mixture was concentrated and slurried with silica gel. Column
chromatography with silica gel and 2% EA in pet ether solvent afforded compound 40 (350 mg, 1.52 mmol) in 87% yield. Colourless liquid; Rf (1:50 EA/hexane) 0.3; 1H NMR (400 MHz, CDCl3) d 7.98 (d, J¼15.8 Hz, 1H), 7.58 (dd, J¼1.4, 7.8 Hz, 1H), 7.32 (dt, J¼1.4, 7.5 Hz, 1H), 7.27e7.22 (m, 1H), 7.21 (dd, J¼1.4, 7.6 Hz, 1H), 6.34 (d, J¼15.8 Hz, 1H), 4.86e4.81 (m, 1H), 4.54 (dd, J¼1.1, 2.1 Hz, 1H), 4.26 (q, J¼7.1 Hz, 2H), 3.45 (s, 2H), 1.74 (t, J¼1.1 Hz, 3H), 1.33 (t, J¼7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 167.2, 144.5, 142.6 (CH), 139.3, 134.0, 131.1 (CH), 130.1 (CH), 127.0 (CH), 126.7 (CH), 119.6 (CH), 112.8 (CH2), 60.7 (CH2), 41.8 (CH2), 22.9 (CH3), 14.5 (CH3); IR (KBr): ~v¼2923, 2853, 1718, 1459, 1311, 1268, 1175, 1038, 979, 891, 768; HRMS (ESI): m/z calculated for C15H18O2: requires: 231.1385 for [MþH]þ, 157.1017 for [MC3H4O2þH]þ; found: 231.1387, 157.1017.
3.4. 2-Isopropenylbenzaldehyde (41)13 Compound 41 was prepared following the literature procedure. Only modification was quenching of last Grignard reaction with saturated NH4Cl solution (5 mL/mmol). Colourless liquid; 1H NMR (400 MHz, CDCl3) d 10.13 (s, 1H), 7.84 (d, J¼7.6 Hz, 1H), 7.48e7.44 (m, 1H), 7.33e7.25 (m, 2H), 5.34 (S, 1H), 4.83 (s, 1H), 2.09 (s, 3H); 13C NMR (50 MHz, CDCl3) d 192.4 (CH), 147.8, 141.9, 133.6 (CH), 133.6, 128.7 (CH), 128.0 (CH), 127.6 (CH), 119.1 (CH2), 25.2 (CH3). General procedures to perform the ene reactions: 3.4.1. With SnCl4$5H2O. A stirred solution of an O-propenyl arene aldehyde (1 equiv) in dry solvent (10 mL/mmol) was stirred with SnCl4$5H2O (50 mol%) in stoppered reaction flask. After completion of the reaction, as monitored by TLC, it was quenched with saturated solution of sodium bicarbonate (5 mL/mmol). Usual work-up of the reaction mixture with EA or DCM furnished the mixture of products. Products were purified by column chromatography on basic alumina. 3.4.2. With BINOL-PO2H. A particular mol% of BINOL-PO2H was added to a stirred solution of O-propenyl arene aldehyde (1 equiv) in dry solvent (10 mL/mmol) in a stoppered reaction flask. Reaction was monitored by TLC. After completion of reaction, it was slurried with basic alumina and products were purified by column chromatography on basic alumina. 3.4.3. With BINOL-PONHTf. A stirred solution of O-propenyl arene aldehyde (1 equiv) in dry solvent (10 mL/mmol) was stirred with a particular mol% of BINOL-PONHTf in a stoppered reaction flask. By TLC reaction was monitored. After completion of reaction, it was slurried with basic alumina and products were purified by column chromatography. 3.4.4. 3-Methylene-1,2,3,4-tetrahydronaphthalen-1-ol (42) and 2methylnaphthalene (43). General procedure A was followed to perform the ene-reaction on 10 (0.600 g, 3.75 mmol) with SnCl4$5H2O (0.657 g, 1.87 mmol) in 37 mL dry EA at rt for 1.5 d. Compound 43 (0.048 g, 0.34 mmol) was obtained as a white solid in 9% yield after column chromatography on basic alumina with hexane. More polar product was eluted with 1:3 EA/n-hexane solvent to give 42 (0.492 g, 3.08 mmol) as a white solid in 82% yield. 3.4.5. Data for 42. White solid; Rf (1:3 EA/hexane) 0.4; mp 43e45 C; 1H NMR (600 MHz, CDCl3) d 7.42 (dd, J¼1.8, 7.3 Hz, 1H), 7.26e7.19 (m, 2H), 7.13 (dd, J¼1.4, 7.4 Hz, 1H), 5.07 (t, J¼1.5 Hz, 1H), 5.00 (q, J¼1.4 Hz, 1H), 4.83 (dt, J¼4.6, 8.6 Hz, 1H), 3.57 (s, 2H), 2.73 (dd, J¼4.3, 13.2 Hz, 1H), 2.61 (dd, J¼4.8, 13.2 Hz, 1H), 1.89 (d, J¼8.5 Hz, 1H); 13C NMR (150 MHz, CDCl3): d 141.1, 138.6, 136.2, 129.1 (CH), 128.8 (CH), 128.2 (CH), 126.5 (CH), 112.3 (CH2), 69.8 (CH), 41.2 (CH2), 37.2 (CH2); IR (KBr): ~v¼3448, 2067, 1637, 673 cm1; HRMS
S. Basak, D. Mal / Tetrahedron 72 (2016) 1758e1772
(ESI): m/z calculated for C11H12O: [MH2OþH]þ; found: 143.0832.
requires:
143.0861
for
3.4.6. Data for 43. 14White solid; Rf (hexane) 0.55; mp 35e40 C; 1 H NMR (200 MHz, CDCl3): d 7.73e7.82 (m, 3H), 7.62 (s, 1H), 7.23e7.48 (m, 3H), 2.52 (s, 3H). 3.4.7. 3-Ethylidene-1,2,3,4-tetrahydronaphthalen-1-ol (47) and 2ethylnaphthalene (48). General procedure A was followed to perform ene-reaction of 11 (0.200 g, 1.15 mmol) with SnCl4$5H2O in dry EA (6 mL) for 1.5 d. Two products formed. The less polar product 4815 (0.012 g, 0.08 mmol) was separated after column chromatography on basic alumina with hexane in 7% yield. More polar product 47 (0.172 g, 0.99 mmol) was eluted with 1:3 EA/hexane solvent in 86% yield. 3.4.8. Data for 47. Colourless liquid; Rf (1:3 EA/hexane) 0.45; 1H NMR (400 MHz, CDCl3): d 7.41e7.40 (m, 1H), 7.26e7.11 (m, 3H), 5.64e5.50 (m, 1H), 4.84e4.77 (m, 1H), 3.70e3.42 (m, 2H), 2.77e2.50 (m, 2H), 1.89 (bs, 1H), 1.71 (t, J¼5.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): d 139.2, 139.2, 137.0, 136.0, 131.6, 131.1, 129.1 (CH), 128.8 (CH), 128.3 (CH), 128.1 (CH), 128.1 (CH), 128.0 (CH), 126.3 (CH), 126.3 (CH), 121.6 (CH), 120.7 (CH), 69.8 (CH), 69.6 (CH), 42.2 (CH2), 38.8 (CH2), 34.9 (CH2), 31.2 (CH2), 13.3 (CH3), 13.1 (CH3); IR (KBr): ~v¼3433, 2067, 1636, 673 cm1; HRMS (ESI): m/z calculated for C12H14O: requires: 155.0861 for [MH2OþH]þ, 173.0966 for [MþH]þ; found: 155.0889, 173.0987. 3.4.9. 3-Methylene-1,2,3,4-tetrahydrophenanthren-1-ol (49) and 3methylphenanthrene (51). General procedure A was adopted for the ene-reaction of 15 (0.221 g, 1.05 mmol) with SnCl.45H2O (0.184 g, 0.53 mmol) in dry EA (10 mL) at rt for 1.5 d. Column chromatography on basic alumina with hexane afforded 51 (0.016 g, 0.084 mmol) 8% yield. More polar product 49 (0.188 g, 0.89 mmol) was obtained in 85% yield after eluting with 1:3 EA/ hexane solvent. 3.4.10. Data for 49. White low melting solid; Rf (1:3 EA/hexane) 0.35; mp 50e54 C; 1H NMR (400 MHz, CDCl3): d 7.98 (d, J¼8.0 Hz, 1H), 7.84 (d, J¼8.0 Hz, 1H), 7.74 (d, J¼8.0 Hz, 1H), 7.57e7.49 (m, 3H), 5.20 (s, 1H), 5.10 (s, 1H), 4.96 (t, J¼4.2 Hz, 1H), 3.90 (ABq, J¼18.4 Hz, 2H), 2.83 (dd, J¼4.4, 12.8 Hz, 1H), 2.72 (dd, J¼4.4, 12.8 Hz, 1H), 1.92 (d, J¼9.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 141.04, 135.6, 133.4, 131.8, 131.7, 128.8 (CH), 127.3 (CH), 127.1 (CH), 126.5 (CH), 126.2 (CH), 123.5 (CH), 112.9 (CH2), 70.2 (CH), 41.2 (CH2), 34.6 (CH2); IR (KBr): ~v¼3434, 2067, 1637, 672 cm1; HRMS (ESI): m/z calculated for C15H14O: requires: 193.1017 for [MH2OþH]þ, 211.1123 for [MþH]þ; found: 193.1011, 211.1113. 3.4.11. Data for 51.29 White solid; Rf (hexane) 0.4; mp 62e64 C;1H NMR (200 MHz, CDCl3): d 8.68 (d, J¼7.4 Hz, 1H), 8.48 (s, 1H), 7.87 (d, J¼7.4 Hz, 1H), 7.79 (d, J¼7.8 Hz, 1H), 7.69 (s, 2H), 7.62 (d, J¼6.8 Hz, 1H), 7.59 (d, J¼6.2 Hz, 1H), 7.43 (d, J¼8.0 Hz, 1H), 2.63 (s, 3H). 3.4.12. 2-Methylene-1,2,3,4-tetrahydrophenanthren-4-ol (50) and 2methylphenanthrene (46). General procedure A was followed for the ene-reaction on 16 (0.262 mmol, 1.25 mmol) with SnCl4$5H2O (0.219 g, 0.63 mmol) in dry EA (12 mL) at rt for 1.5 d. Column chromatography was done on basic alumina with hexane to afford 46 (0.01 g, 0.05 mmol) in 4% yield. Compound 50 (0.231 g, 1.10 mmol) was obtained after eluting with 1:3 EA/hexane solvent in 88% yield. 3.4.13. Data for 50. White solid; Rf (1:3 EA/hexane) 0.4; mp 70e72 C; 1H NMR (400 MHz, CDCl3): d 8.27 (d, J¼8.4 Hz, 1H), 7.81 (d, J¼8.4 Hz, 1H), 7.74 (d, J¼8.4 Hz, 1H), 7.57 (t, J¼7.6 Hz, 1H), 7.46 (t,
1769
J¼7.6 Hz, 1H), 7.22 (d, J¼8.4 Hz, 1H), 5.57 (s, 1H), 5.14 (s, 1H), 5.09 (s, 1H), 3.69 (ABq, J¼18.8 Hz, 2H), 2.66 (ABq, J¼13.2 Hz, 2H), 1.92 (bs, 1H). 13C NMR (100 MHz, CDCl3): d 140.7, 134.3, 132.7, 132.5, 132.5, 128.9 (CH), 128.7 (CH), 127.3 (CH), 127.0 (CH), 125.5 (CH), 123.7 (CH), 112.3 (CH2), 65.5 (CH), 41.0 (CH2), 38.3 (CH2). IR (KBr): ~v¼2922, 2065, 1634, 675 cm1. HRMS (ESI): m/z calculated for C15H14O: requires: 193.1017 for [MH2OþH]þ; found: 193.1011. 3.4.14. Data for 46.29 White solid; Rf (hexane) 0.55; mp 55e57 C. 1 H NMR (400 MHz, CDCl3): d 8.65 (d, J¼8.4 Hz, 1H), 8.58 (d, J¼8.4 Hz, 1H), 7.87 (d, J¼8.4 Hz, 1H), 7.55e7.73 (m, 5H), 7.49 (d, J¼8.4 Hz, 1H), 2.57 (s, 3H). 3.4.15. 7-Methoxy-3-methylene-1,2,3,4-tetrahydronaphthalen-1-ol (52) and 2-methoxy-6-methylnaphthalene (44). General procedure A was followed for the ICE of 12 (0.190 g, 1.00 mmol) with SnCl4$5H2O (0.175 g, 0.50 mmol) at rt in 10 mL dry EA for 2 d. Column chromatography on basic alumina afforded 52 (0.150 g, 0.78 mmol) in 78% yield and 44 (0.026 g, 0.15 mmol) in 15% yield. 3.4.16. Data for 52. Yellow oil; Rf (1:2 EA/hexane) 0.45; 1H NMR (600 MHz, CDCl3): d 7.04 (d, J¼8.4 Hz, 1H), 6.96 (d, J¼2.4 Hz, 1H), 6.82 (dd, J¼2.4, 8.4 Hz, 1H), 5.05 (s, 1H), 4.98 (s, 1H), 4.78 (t, J¼4.6 Hz, 1H), 3.80 (s, 3H), 3.5 (s, 2H), 2.72 (dd, J¼4.2, 13.0 Hz, 1H), 2.58 (dd, J¼5.0, 13.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 158.3, 141.4, 139.7, 129.7 (CH), 128.1, 115.1 (CH), 113.1 (CH), 112.1 (CH2), 70.0 (CH), 55.6 (CH3), 41.3 (CH2), 36.5 (CH2); IR (KBr): ~v¼3421, 2923, 2852, 1669, 1608, 1498, 1464, 1430, 1267, 1160, 1034, 878, 811 cm1; HRMS (ESI): m/z calculated for C12H14O: requires: 173.0966 for [MH2OþH]þ, 191.1072 for [MþH]þ; found: 173.0976, 191.1064. 3.4.17. Data for 44. 30Colourless liquid; Rf (hexane) 0.4; 1H NMR (400 MHz, CDCl3): d 7.67e7.64 (m, 2H), 7.55 (s, 1H), 7.30e7.27 (m, 1H), 7.13e7.11 (m, 2H), 3.91 (s, 3H), 2.48 (s, 3H); 13C NMR (50 MHz, CDCl3): d 157.2, 133.2, 132.9, 129.4, 128.9 (CH), 128.8 (CH), 126.9 (CH), 126.8 (CH), 118.8 (CH), 105.9 (CH), 55.5 (CH3), 21.7 (CH3). 3.4.18. 5,8-Dimethoxy-3-methylene-1,2,3,4-tetrahydronaphthalen-1ol (53) and 1,4-dimethoxy-6-methylnaphthalene (45). General procedure B was followed for the ene-reaction of 13 (0.286 g, 1.30 mmol) with 10 mol% BINOL-PO2H (0.045 g, 0.13 mmol) in CHCl3 (13 mL) at rt for 5 d. Two products were formed. Column chromatography of the crude product on basic alumina with hexane afforded aromatized product 45 (0.040 g, 0.20 mmol) in 15% yield. More polar product 53 (0.229 g, 1.04 mmol) was obtained upon eluting with 1:2 EA/hexane solvent in 80% yield. 3.4.19. Data for 53. Yellowish liquid; Rf (1:2 EA/hexane) 0.45; 1H NMR (400 MHz, CDCl3): d 6.71 (ABq, J¼8.8 Hz, 2H), 5.17 (t, J¼4.4 Hz, 1H), 5.05 (s, 1H), 5.0 (s, 1H), 3.84 (s, 3H), 3.80 (s, 3H), 3.40 (ABq, J¼19.2 Hz, 2H), 2.61 (m, 2H),1.62 (bs,1H); 13C NMR (100 MHz, CDCl3): d 152.0, 151.2, 141.1, 128.2, 127.1, 111.9 (CH2), 109.3 (CH), 108.0 (CH), 64.7 (CH), 56.1 (CH3), 55.9 (CH3), 39.7 (CH2), 32.3 (CH2); IR (KBr): ~v¼3439, 2063, 1636, 1219, 772 cm1; HRMS (ESI): m/z calculated for C13H16O3: requires: 243.0997 for [MþNa]þ; found: 243.0995. 3.4.20. Data for 45. 31Yellowish liquid; Rf (hexane) 0.55; 1H NMR (400 MHz, CDCl3): d 8.12 (d, J¼8.8 Hz, 1H), 8.01 (s, 1H), 7.35 (dd, J¼2.0, 8.4 Hz, 1H), 6.66 (ABq, J¼8.2 Hz, 2H), 3.97 (s, 3H), 3.96 (s, 3H), 2.54 (s, 3H); 13C NMR (100 MHz, CDCl3): d 149.8, 149.3, 135.8, 128.1 (CH), 126.7, 124.7, 121.9 (CH), 121.0 (CH), 103.5 (CH), 102.5 (CH), 55.9 (CH3), 55.9 (CH3), 22.1 (CH3). 3.4.21. Compound 56 and 2,3-dimethoxy-6-methylnaphthalene (54). General procedure C was followed for the ene-reaction of 14 (0.242 g, 1.10 mmol) with 1 mol% BINOL-PONHTf (0.005 g,
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0.01 mmol) in CHCl3 (11 mL) at rt for 8 d. Two products were formed. Column chromatography of crude products on basic alumina with hexane afforded the aromatized product 54 (0.127 g, 0.63 mmol) in 57% yield. More polar product 56 (0.093 g, 0.44 mmol) was obtained upon eluting with 1:2 EA/hexane solvent in 40% yield. 3.4.22. Data for 56. Yellow liquid; Rf (1:2 EA/hexane) 0.35; 1H NMR (400 MHz, CDCl3): d 7.58 (d, J¼5.6 Hz, 1H), 7.47 (s, 1H), 7.23 (dd, J¼1.2, 5.6 Hz, 1H), 7.08 (s, 1H), 7.02 (s, 1H), 6.48 (s, 1H), 6.43 (s, 1H), 5.04 (t, J¼4.0 Hz, 1H), 3.98 (s, 3H), 3.83 (s, 3H), 3.64 (s, 3H), 3.22e3.20 (m, 2H), 2.60 (d, J¼10.0 Hz, 1H), 2.33 (d, J¼10.0 Hz, 1H), 1.35 (s, 3H), 1.13 (s, 3H); 13C NMR (100 MHz, CDCl3): d 149.6, 149.2, 147.6, 147.1, 134.8, 129.3, 128.8, 127.9, 127.3 (CH), 127.2 (CH), 126.2, 125.9 (CH), 111.7 (CH), 108.3 (CH), 106.3 (2CH), 72.9 (CH), 71.3, 56.2 (CH3), 56.0 (CH3), 56.0 (CH3), 55.9 (CH3), 44.1 (CH2), 40.3 (CH2), 30.5 (CH3), 23.5 (CH3); IR (KBr): ~v¼2922, 1489, 1255, 1220 cm1; HRMS (ESI): m/z calculated for C26H30O5: requires: 445.1991 for [MþNa]þ, 405.2066 for [MþH]þ, 221.1178 for [MC13H14O2þH]þ; found: 445.1987, 405.2057, 221.1173. 3.4.23. Data for 54. 32White solid; Rf (hexane) 0.55; mp 55e57 C; 1 H NMR (400 MHz, CDCl3): d 7.59 (d, J¼8.2 Hz, 1H), 7.47 (s, 1H), 7.17 (dd, J¼1.6, 8.2 Hz, 1H), 7.09 (s, 1H), 7.05 (s, 1H), 3.99 (s, 6H), 2.47 (s, 3H), 2.47 (s, 3H); 13C NMR (50 MHz, CDCl3): d 149.8, 149.1, 133.9, 129.6, 127.4, 126.5, 126.4 (CH), 125.8 (CH), 106.5 (CH), 106.1 (CH), 56.0 (2 OCH3), 21.7 (CH3); IR (KBr): ~v¼2964, 1608, 1511, 1493, 1455, 1414, 1256, 1206, 1161, 1127, 1013, 884, 855, 799, 749 cm1; HRMS (ESI): m/z calculated for C13H14O2: requires: 203.1072 for [MþH]þ; found: 203.1080. 3.4.24. Compound 57 and 1,2-dimethoxy-7-methylnaphthalene (55). General procedure C was followed for the ene-reaction of 27 (0.220 g, 1.00 mmol) with 1 mol% BINOL-PONHTf (0.005 g, 0.01 mmol) in CHCl3 (10 mL) at rt for 7 d. Two products were formed. Column chromatography was done by basic alumina with hexane to afford the aromatized product 55 (0.115 g, 0.57 mmol) in 57% yield. Compound 57 (0.089 g, 0.42 mmol) was obtained in 42% after eluting with 1:2 EA/hexane solvent. 3.4.25. Data for 57. Yellow liquid; Rf (1:2 EA/hexane) 0.4; 1H NMR (600 MHz, CDCl3) d 7.89e7.84 (m, 1H), 7.63 (d, J¼8.3 Hz, 1H), 7.54 (d, J¼8.9 Hz, 1H), 7.26e7.23 (m, 1H), 7.21 (d, J¼8.9 Hz, 1H), 6.90 (d, J¼8.4 Hz, 1H), 6.77 (d, J¼8.4 Hz, 1H), 5.11e5.03 (m, 1H), 3.98 (s, 3H), 3.92 (s, 3H), 3.84 (s, 3H), 3.69 (s, 3H), 3.35 (dd, J¼4.2, 14.1 Hz, 1H), 3.18 (dd, J¼6.6,14.1 Hz, 1H), 2.68 (d, J¼16.0 Hz,1H), 2.37 (d, J¼16.0 Hz,1H), 1.35 (s, 3H), 1.08 (s, 3H); 13C NMR (150 MHz, CDCl3) d 150.9, 148.5, 146.3, 142.8, 137.0, 130.4, 129.0, 128.7, 128.6, 127.3 (CH), 127.1 (CH), 124.1 (CH), 121.7 (CH), 120.5 (CH), 114.4 (CH), 110.0 (CH), 72.3 (CH), 70.9, 61.3 (CH3), 60.4 (CH3), 57.1 (CH3), 55.9 (CH3), 44.0 (CH2), 34.5 (CH2), 30.7 (CH3), 23.8 (CH3); IR (KBr): ~v¼3442, 2920, 2850, 1633, 1462, 1276, 1219, 1066 cm1; HRMS (ESI): m/z calculated for C26H30O5: requires: 445.1991 for [MþNa]þ, 405.2066 for [MþH]þ, 221.1178 for [MC13H14O2]þ; found: 445.1991, 405.2067, 221.1171. 3.4.26. Data for 55. Yellowish liquid; Rf (hexane) 0.5; 1H NMR (400 MHz, CDCl3): d 7.88 (s, 1H), 7.67 (d, J¼8.4 Hz, 1H), 7.55 (d, J¼8.4 Hz, 1H), 7.24e7.17 (m, 2H), 3.99 (s, 6H), 2.52 (s, 3H); 13C NMR (100 MHz, CDCl3): d 148.4, 135.8, 134.0, 129.1, 128.0, 127.5 (CH), 126.4 (CH), 123.9 (CH), 120.0 (CH), 114.1 (CH), 61.0 (CH3), 56.8 (CH3), 22.0 (CH3); IR (KBr): ~v¼2925, 2372, 1720, 1656, 1511, 1461, 1259, 1101, 771, 674 cm1. HRMS (ESI): m/z calculated for C13H14O2: requires: 203.1072 for [MþH]þ; found: 203.1069. 3.4.27. 1-Methoxy-6-methylanthraquinone (61). General procedure B was followed for the ene reaction of 32 (0.240 g, 0.80 mmol) with
10 mol% BINOL-PO2H (0.028 g, 0.08 mmol) in CHCl3 (8 mL) at rt for 5 d. Exclusively 61 (0.198 g, 0.78 mmol) was obtained after column chromatography on basic alumina with 1:3 EA/hexane solvent in 98% yield. Yellow solid; Rf (1:3 EA/hexane) 0.45; mp 137e138 C; 1H NMR (600 MHz, CDCl3) d 8.17 (d, J¼7.9 Hz, 1H), 8.04e8.00 (m, 1H), 7.96 (dd, J¼1.1, 7.7 Hz, 1H), 7.72 (t, J¼8.0 Hz, 1H), 7.57 (dd, J¼1.7, 7.9 Hz, 1H), 7.35 (dd, J¼1.0, 8.4 Hz, 1H), 4.05 (s, 3H), 2.51 (s, 3H); 13C NMR (150 MHz, CDCl3) d 184.0, 182.8, 160.6, 144.5, 136.1, 135.4 (CH), 135.1 (CH), 133.1, 132.6, 127.7 (CH), 127.0 (CH), 121.8, 120.0 (CH), 118.2 (CH), 56.8 (CH3), 22.0 (CH3); IR (KBr): ~v¼2921, 2851, 1672, 1584, 1459, 1306, 1270, 1219 cm1; HRMS (ESI): m/z calculated for C16H13O3: requires: 253.0865 for [MþH]þ, 193.1017 for [MCHO3þH]; found: 253.0852, 193.1011. 3.4.28. 1,9,10-Trimethoxy-6-methylanthracene (60). General procedure A was followed for the ene-reaction of 32 (0.270 g, 0.90 mmol) with SnCl4$5H2O (0.158 g, 0.50 mmol) in dry ethyl acetate (9 mL). Column chromatography on basic alumina with hexane afforded 60 (0.086 g, 0.31 mmol) in 34% yield. More polar product 61 (0.141 g, 0.56 mmol) was obtained after eluting with 1:3 EA/hexane solvent in 62% yield. 3.4.29. Data for 60. Yellowish semisolid; Rf (1:3 EA/hexane) 0.5; 1H NMR (600 MHz, CDCl3) d 8.30 (d, J¼9.0 Hz, 1H), 7.99 (s, 1H), 7.87 (d, J¼8.4, 1H), 7.36e7.32 (m, 2H), 6.76 (d, J¼7.2 Hz, 1H), 4.07 (s, 6H), 4.01 (s, 3H), 2.51 (s, 3H); 13C NMR (150 MHz, CDCl3) d 156.8, 149.4, 147.4, 135.9, 128.3 (CH), 127.5, 125.7, 125.3 (CH), 125.0, 123.5 (CH), 120.5 (CH), 117.8, 115.1 (CH), 103.5 (CH), 63.7 (CH3), 62.9 (CH3), 56.3 (CH3), 22.4 (CH3); IR (KBr): ~v¼2932, 1685, 1555, 1450, 1266, 1215, 1066, 911, 678 cm1; HRMS (ESI): m/z calculated for C18H18O3: requires: 253.0865 for [MC2H6þH]þ; found: 253.0868. 3.4.30. Dimethyl 2-(3-methyl-1,2-dihydronaphthalen-1-yl)malonate (65). General procedure C was followed for the ene-reaction of 39 (0.342 g, 1.25 mmol) with 20 mol% BINOL-PONHTf (0.120 g, 0.25 mmol) in toluene (12 mL) at 80 C for 80 h. Column chromatography of the crude product on silica gel afforded compound 65 (0.322 g, 1.17 mmol) in 94% yield. Colourless oil; Rf (1:7 EA/hexane) 0.35; 1H NMR (400 MHz, CDCl3) d 7.12e7.07 (m, 1H), 7.03e6.96 (m, 2H), 6.91 (d, J¼7.6, 1H), 6.19 (s, 1H), 3.67 (s, 3H), 3.65e3.59 (m, 1H), 3.55e3.53 (m, 1H), 3.40 (s, 3H), 2.51e2.46 (m, 1H), 2.04e2.00 (m, 1H), 1.80 (s, 3H); 13C NMR (100 MHz, CDCl3) d 169.1, 168.9, 135.7, 134.7, 133.2, 128.2 (CH), 127.9 (CH), 126.3 (CH), 125.9 (CH), 122.8 (CH), 58.6 (CH), 52.7 (CH3), 52.4 (CH3), 38.4 (CH), 32.7 (CH2), 23.9 (CH3); IR (KBr): ~v¼2927, 1736, 1437, 1261, 1220, 1152, 1023 cm1; HRMS (ESI): m/z calculated for C16H18O4: requires: 297.1103 for [MþNa]þ, 143.0861 for [M-dimethyl malonateþH]þ; found: 297.1115, 143.0878. General procedure A was also for the ene-reaction on 39 with 50 mol% SnCl4$5H2O in dry DCM. Column chromatography of the crude products afforded product 65 and 43 in 49% and 42% yield respectively. 3.4.31. Ethyl 3,3-dimethyl-3,4-dihydronaphthalene-2-carboxylate (66) and 3,3-dimethyl-3,4-dihydronaphthalene-2-carboxylic acid (67). General procedures A, B, C were followed for the ene-reaction of 40 with SnCl4$5H2O, BINOL-PO2H, BINOL-PONHTf. Cyclization didn’t occur at rt. Double bond of 40 isomerized in presence of 20 mol% rac-BINOL-phosphoramide in toluene at 100 C. After dissolving the compound 40 (0.060 g, 0.26 mmol) in 3 mL dry DCM, catalytic amount of BF.3OEt2 was added at 0 C under inert atmosphere and the reaction mixture was allowed to warm and stirred at rt for 48 h. Usual work-up procedure was done to get the crude material. Flash column chromatography of the crude product on silica gel with 1:5 EA/hexane solvent afforded the compounds 66 (0.020 g, 0.09 mmol) in 35% yield. More polar product 67 (0.030 g,
S. Basak, D. Mal / Tetrahedron 72 (2016) 1758e1772
0.15 mmol) was obtained after eluting with 1:1 EA/hexane solvent in 57% yield. Formation of 67 was confirmed by transforming it into its methyl ester. 3.4.32. Data for 66. Yellowish liquid; Rf (1:5 EA/hexane) 0.4; 1H NMR (600 MHz, CDCl3) d 7.28 (s, 1H), 7.24 (m, 1H), 7.22e7.16 (m, 2H), 7.13 (d, J¼7.4 Hz, 1H), 4.26 (q, J¼6.9 Hz, 2H), 2.74 (s, 2H), 1.36 (t, J¼7.0 Hz, 3H), 1.25 (s, 6H); 13C NMR (150 MHz, CDCl3) d 167.9, 138.7, 136.3, 135.1 (CH), 132.2, 129.5 (CH), 128.1 (CH), 127.9 (CH), 126.8 (CH), 60.4 (CH2), 45.1 (CH2), 34.5, 26.1 (3CH3), 14.5 (CH3); IR (KBr): ~v¼2924, 2852, 1709, 1458,1254,1217, 1052, 717 cm1; HRMS (ESI): m/z calculated for C15H18O2: requires: 231.1385 for [MþH]þ; found: 231.1394. 3.4.33. Data for 67. White solid; Rf (1:1 EA/hexane) 0.3; mp 146e148 C; 1H NMR (600 MHz, CDCl3) d 7.52 (s, 1H), 7.28e7.26 (m, 1H), 7.23e7.22 (m, 2H), 7.16 (d, J¼6.8 Hz, 1H), 2.77 (s, 2H), 1.29 (s, 6H). 13C NMR (150 MHz, CDCl3) d 173.3, 137.9 (CH), 137.2, 136.7, 131.9, 130.1 (CH), 128.4 (CH), 128.2 (CH), 126.9 (CH), 45.2 (CH2), 34.4, 26.1 (2CH3). IR (KBr): ~v¼2959, 1672, 1413, 1270, 1220, 1033, 913. HRMS (ESI): m/z calculated for C13H14O2: requires: 203.1072 for [MþH]þ; found: 203.1054. 3 . 4 . 3 4 . M e t h yl 3 , 3 - d i m e t h yl - 3 , 4 - d i h y d r o n a p h t h a l e n e - 2 carboxylate. Yellowish liquid; Rf (1:5 EA/hexane) 0.45; 1H NMR (600 MHz, CDCl3) d 7.29 (s, 1H), 7.26e7.22 (m, 1H), 7.22e7.16 (m, 2H), 7.15e7.12 (m, 1H), 3.80 (s, 3H), 2.74 (s, 2H), 1.24 (s, 6H); 13C NMR (150 MHz, CDCl3) d 168.2, 138.3, 136.4, 135.5 (CH), 132.1, 129.6 (CH), 128.1 (CH), 128.0 (CH), 126.8 (CH), 51.6 (CH3), 45.1 (CH2), 34.5, 26.1 (2CH3); IR (KBr): ~v¼2925, 1710, 1445, 1256, 1219, 1052; HRMS (ESI): m/z calculated for C14H16O2: requires: 217.1229 for [MþH]þ; found: 217.1243. 3.4.35. 3-Methyl-1H-inden-1-ol (68).19 General procedure C was performed on 41 (0.219 g, 1.50 mmol) with 10 mol% BINOL-PONHTf (0.072 g, 0.15 mmol) in dry toluene (15 mL) at rt for 12 h. Product 68 (0.210 g, 1.44 mmol) was found in 96% yield. Yellow oil; Rf (1:2 EA/ hexane) 0.4; 1H NMR (400 MHz, CDCl3): d 7.47 (d, J¼7.6 Hz, 1H), 7.29e7.33 (m, 1H), 7.19e7.24 (m, 2H), 6.04 (d, J¼1.6 Hz, 1H), 5.08 (s, 1H), 2.21 (bs, 1H), 2.09 (t, J¼1.6 Hz, 3H); 13C NMR (50 MHz, CDCl3): d 146.3, 144.0, 141.5, 132.6 (CH), 128.4 (CH), 126.2 (CH), 123.3 (CH), 119.3 (CH), 76.4 (CH), 13.0 (CH3). IR (KBr): ~v¼3354, 2928, 1615, 1410, 1220, 1077, 1044 cm1. HRMS (ESI): m/z calculated for C10H10O: requires: 129.0704 for [MH2OþH]þ, 145.0653 for [M2HþH]þ; found: 129.0692, 145.0643. 3.4.36. 3-Methylene-1,2,3,4-tetrahydronaphthalen-1-ylacetate (69). To a stirred solution of 42 (100 mg, 0.6 mmol) in Ac2O (0.3 mL, 3.12 mmol) was added pyridine (0.29 mL, 3.43 mmol). It was stirred for 18 h. Then reaction mixture was diluted with EA (30 mL) and successively washed with CuSO4 solution (310 mL) to remove pyridine. Organic layers was washed with brine (10 mL) and dried over Na2SO4. Solvent was evaporated to get crude product. Flash column chromatography was done on silica gel with 1:10 EA/hexane to afford pure product 69 (61 mg, 0.3 mmol) in 50% yield. Yellow liquid; Rf (1:10 EA/hexane) 0.35; 1H NMR (400 MHz, CDCl3): d 7.31e7.25 (m, 2H), 7.22e7.14 (m, 2H), 6.02 (t, J¼4.8 Hz, 1H), 5.02 (s, 1H), 4.95 (s, 1H), 3.61 (ABq, J¼18.4, 2H), 2.70 (d, ABq, J¼4.8, 14.0 Hz, 2H), 2.07 (s, 3H); 13C NMR (100 MHz, CDCl3): d 170.9, 140.4, 137.2, 134.5, 129.2 (CH), 128.8 (CH), 128.7 (CH), 126.4 (CH), 111.8 (CH2), 71.6 (CH), 37.7 (CH2), 36.8 (CH2), 21.6 (CH3); HRMS (ESI): m/z calculated for C13H14O2: requires: 222.0895 for [MCH3CHOþCH3CNþNa]þ; found: 222.0866. 3.4.37. Tert-butyl-dimethyl-(3-methylene-1,2,3,4-tetrahydronaph thalen-1-yloxy)silane (70). Imidazole (850.9 mg, 12.5 mmol) was
1771
added to a stirred solution of compound 42 (400 mg, 2.5 mmol) in 20 mL DCM at 0 C. After 5 min stirring at 0 C, TBDMSeCl (452.2 mg, 3 mmol) was added. Reaction completed in 12 h. Usual work up done with DCM to get the crude product. Flash column chromatography was done on basic alumina with hexane to afford pure silyl protected product 70 (560 mg, 2.3 mmol) in 93% yield. Colourless liquid; Rf (hexane) 0.55; 1H NMR (600 MHz, CDCl3): d 7.47e7.40 (m, 1H), 7.25e7.17 (m, 2H), 7.13e7.06 (m, 1H), 4.97 (t, J¼1.7 Hz, 1H), 4.92 (d, J¼1.6 Hz, 1H), 4.84 (dd, J¼5.0, 8.8 Hz, 1H), 3.63 (d, J¼18.4 Hz, 1H), 3.49 (d, J¼18.4 Hz, 1H), 2.73 (dd, J¼5.0, 13.2 Hz, 1H), 2.54e2.46 (m, 1H), 0.98 (s, 9H), 0.18 (s, 3H), 0.17 (s, 3H); 13C NMR (150 MHz, CDCl3): d 142.3, 140.4, 135.8, 128.1 (CH), 127.4 (CH), 126.7 (CH), 126.1 (CH), 110.5 (CH2), 70.8 (CH), 42.2 (CH2), 37.1 (CH2), 26.1 (3CH3), 18.4, 4.0 (CH3), 4.4 (CH3); IR (KBr): ~v¼3433, 2955, 2857, 2091, 1637, 1255, 1116, 1082, 887, 836, 774, 742; HRMS (ESI): m/z calculated for C17H26OSi: requires: 143.0861 [MeTBSOHþH]þ, 145.1017 for [MeTBSOHþ3H]þ, 146.1096 for [MeTBSOHþ4H]þ; found: 143.0855, 145.1005, 146.1046. 3.4.38. Tert-butyl-dimethyl-(3-methyl-1,2-dihydronaphthalen-1yloxy)silane (71).20 To a stirred solution of compound 70 (145 mg, 0.53 mmol) in a 5 mL dry ethanol were added 10 mol% Rh(PPh3)3Cl (48.9 mg, 0.053 mmol) and DBU (0.79 mL, 5.3 mmol) under inert atmosphere. Reaction was run for 10 days. Reaction mixture was passed through basic alumina to separate catalyst. Column chromatography was done on basic alumina and eluted with only hexane to get 71 (102 mg, 0.37 mmol) in 73% yield. Colourless liquid; Rf (hexane) 0.55; 1H NMR (600 MHz, CDCl3) d 7.38 (q, J¼4.7 Hz, 1H), 7.16 (m, 2H), 6.97 (dd, J¼3.3, 5.9 Hz, 1H), 6.20 (d, J¼4.6 Hz, 1H), 4.93 (m, 1H), 2.39 (t, J¼13.9 Hz, 1H), 2.29 (dd, J¼6.4, 16.3 Hz, 1H), 1.92 (s, 2H), 0.96 (s, 9H), 0.13 (s, 3H), 0.12 (s, 3H); 13C NMR (150 MHz, CDCl3) d 137.2, 136.0, 134.4, 127.4 (CH), 126.6 (CH), 125.3 (CH), 124.7 (CH), 122.8 (CH), 69.8 (CH), 39.2 (CH2), 26.1 (3CH3), 23.7, 18.5, 4.6 (CH3), 4.3 (CH3); IR (KBr): ~v¼3448, 2955, 2929, 2857, 1459, 1255, 1220, 1111, 1078, 836, 812, 676, 474 cm1; HRMS (ESI): m/z calculated for C17H26OSi: requires: 145.1017 for [MeTBSOHþ3H]þ, 146.1096 for [MeTBSOHþ4H]þ; found: 145.1005, 146.1070. 3.4.39. Tert-butyl-dimethyl-(1a-methyl-1a,2,3,7b-tetrahydro-1-oxacyclopropa[a]naphthalen-3-yloxy)silane (72).21 To a stirred solution of 71 (100 mg, 0.36 mmol) in 4 mL acetone were added 0.8 mL EA, 0.8 mL water and solid NaHCO3 (91.7 mg, 2.16 mmol) and the reaction mixture was stirred for 10 min. To this was added solid oxone (448.6 mg, 0.728 mmol) and contents were stirred at room temperature for 45 min. After completion of the reaction, the excess acetone evaporated under vacuum and remaining reaction mixture was portioned between water and EA (20 mL each). The organic layer was separated and the aqueous layer extracted with EA (220 mL). Combined organic layer was dried (Na2SO4) and concentrated under reduced pressure. Column chromatography of the crude product was done on silica gel with hexane to afford the corresponding epoxide 72 (73.1 mg, 0.252 mmol) in 69% yield. Colourless liquid; Rf (hexane) 0.45; 1H NMR (600 MHz, CDCl3) d 7.52 (td, J¼1.0, 7.2 Hz, 1H), 7.37 (dt, J¼1.3, 7.4 Hz, 2H), 7.24 (td, J¼1.0, 7.4 Hz, 1H), 4.86 (tdd, J¼1.0, 6.4, 10.7 Hz, 1H), 3.67 (s, 1H), 2.47 (dd, J¼6.5, 13.8 Hz, 1H), 1.79 (dd, J¼10.9, 13.8 Hz, 1H), 0.99 (s, 9H), 0.17 (s, 3H), 0.16 (s, 3H); 13C NMR (150 MHz, CDCl3) d 140.6, 132.3, 129.0 (CH), 128.9 (CH), 126.9 (CH), 124.7 (CH), 66.6 (CH), 60.7 (CH), 59.0, 37.6 (CH2), 26.1 (3CH3), 21.9 (CH3), 18.4, 4.3 (CH3), 4.7 (CH3); IR (KBr): ~v¼2925, 2853, 1461, 1253, 1220, 1121, 1092, 873, 839 cm1; HRMS (ESI): m/z calculated for C17H26O2Si: requires: 131.0861 for [MeTBSOHeHCHOþH]þ, 159.0801 for [MeTBSOHþH]þ, 299.1436 for [2M2TBSOHeH2OþH]þ, 431.2406 for [2MeTBSOHeH2OþH]þ,
1772
563.3377 for [MþMeH2OþH]þ; 299.1445, 431.2404, 563.3361.
S. Basak, D. Mal / Tetrahedron 72 (2016) 1758e1772
found:
131.0860, 159.0810,
3.4.40. 3-Methylnaphthalen-1-ol (73).33 To a stirred solution of compound 42 (100 mg, 0.63 mmol) in dry DCM was added PDC (406 mg, 1.89 mmol) and stirred for 5 h until the starting material vanished. After completion of the reaction, reaction mixture was directly passed through basic alumina and eluted with 1:5 EA/ hexane to afford oxidized product 73 (84 mg, 0.53 mmol) in 83% yield. Yellowish solid; Rf (1:5 EA/hexane) 0.4; 1H NMR (400 MHz, CDCl3): d 8.13 (d, J¼8.0 Hz, 1H), 7.74 (d, J¼8.0 Hz, 1H), 7.42e7.50 (m, 2H), 7.25 (s, 1H), 6.7 (s, 1H), 2.47 (s, 3H); 13C NMR (50 MHz, CDCl3): d 151.1, 135.8, 134.9, 127.0 (CH), 126.5 (CH), 124.3 (CH), 122.6, 121.3 (CH), 119.7 (CH), 110.8 (CH), 21.7 (CH3). 3.4.41. 2-Methyl-1,4-naphthoquinone (74).34 To a stirred solution of compound 42 (100 mg, 0.63 mmol) in dry DCM (6 mL) was added PCC (406.4 mg, 1.89 mmol) and stirred for 5 h until the starting material vanished. After completion of the reaction, the mixture was directly passed through basic alumina and eluted with 1:5 EA/ hexane solvent to furnish over-oxidized product 74 (81%). Red solid; Rf (1:5 EA/hexane) 0.35; 1H NMR (400 MHz, CDCl3): d 8.05e8.12 (m, 2H), 7.72e7.75 (m, 2H), 6.85 (d, J¼1.2 Hz, 1H), 2.20 (d, J¼1.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): d 185.8, 185.2, 148.4, 135.9 (CH), 133.9 (CH), 133.8 (CH), 132.5, 132.4, 126.8 (CH), 126.3 (CH), 16.7 (CH3).
8. 9.
10.
11. 12.
Acknowledgements We gratefully acknowledge the Council of Scientific and Industrial Research (CSIR) for financial support (02(0183)/14/EMRII), and the Department of Science and Technology for instrumental facilities. S. B. thanks CSIR for his research fellowship (09/081(1177)/2012-EMR-I).
13. 14. 15. 16. 17.
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