Synthesis of substituted

Download PDF
5 downloads 0 Views 1MB Size Report
Comment
Aug 15, 2011 - Synthesis of substituted [3]dendralenes and their unique cycloaddition ... including their conversion to a new class of hydrocarbons, the.
ChemComm

Dynamic Article Links

Cite this: Chem. Commun., 2011, 47, 10809–10811 www.rsc.org/chemcomm

COMMUNICATION

Synthesis of substituted [3]dendralenes and their unique cycloaddition reactionsw Rekha Singh and Sunil K. Ghosh* Received 13th July 2011, Accepted 15th August 2011 DOI: 10.1039/c1cc14211a Dimethylsulfonium methylide mediated olefination of 2-phenylethenylidene phosphonoacetate followed by the Horner– Wadsworth–Emmons reaction with aromatic aldehydes provided access to reactive 1,5-diaryl-2-ethoxycarbonyl [3]dendralenes which in situ underwent Diels–Alder cyclodimerisation leading to highly functionalised cyclohexenes with very high regio- and stereoselectivity. Acyclic cross-conjugated polyolefins, also known as [n]dendralenes 1 (Fig. 1), have received renewed attention. Besides their attracted interest in polymer chemistry1 and theoretical chemistry,2 they have high synthetic potential3 especially in sequential cycloaddition reactions for easy access to polycyclic systems.4–6 Various approaches such as metal-catalysed coupling reactions,6–8 Peterson type elimination,9 thermal decomposition of vinyl sulfolene,10 pyrolysis,11 Mitsunobu dehydration12 and Hofmann elimination13 have provided access to types of [n]dendralenes. Recent success of the Sherburn group for practical syntheses8,14 of several unsubstituted dendralenes [n = 3–8] and efforts from Hopf and Yildizhan,15 Fallis5,12 and others16,17 also brought significant advancement in this area of research. These synthetic methodologies helped in the study of the reactivity of unsubstituted [n]dendralenes including their conversion to a new class of hydrocarbons, the ivyanes.18 Unlike unsubstituted dendralenes, very little effort has

Fig. 1 Various dendralenes. Bio-Organic Division, Bhabha Atomic Research Centre, Trombay, Mumbai, India. E-mail: [email protected]; Fax: +91-22-25505151; Tel: +91-22-25595012 w Electronic supplementary information (ESI) available: Typical experimental procedure, full characterisation data, copies of 1H and 13 C NMR. CCDC 833098. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c1cc14211a

This journal is

c

The Royal Society of Chemistry 2011

Fig. 2 Carbene anion.

been made to make a substituted version of these cross-conjugated molecules. Only a handful of methods can introduce substituents like alkyl groups at specific positions such as at the termini of the central double bond 2 and 2-substituted 3 or 1,4-disubstituted [3]dendralenes19 4 (Fig. 1). Highly functionalised compounds such as 1,2,5-trialkyl substituted cross-conjugated trienes 5 have also been reported by metal-catalysed dimerisation of allenes.20 As a continuation of our work on versatile olefin synthesis using dimethylsulfonium methylide 6,21 we have reported22 an interesting observation that 6 in excess or in the presence of a base undergoes a tandem ylide addition–eliminative olefination on various activated olefins thus acts as an equivalent of the carbene anionz (Fig. 2). This strategy has been used for the preparation of 1-substituted vinyl silanes, styrenes and products derived from them.23 The methodology has been applied for sequential tandem double olefination of vinyl phosphonates and aldehydes to provide di and tri-substituted 1,3-dienes with very high regio and stereoselectivity.24 This strategy has also been used25 for the olefination of extended conjugated systems like 1,3-diendioates or 1,3,5-trienedioates leading to 1,3-butadien2-yl- or 1,3,5-hexatriene-2-yl-malonates. We report herein a sequential double olefination process for the synthesis of 1,5diaryl-2-alkoxycarbonyl [3]dendralenes. The unique reactivity of these specially substituted cross-conjugated trienes for a highly regio- and stereoselective Diels–Alder cyclodimerisation leading to complex cyclohexenes has also been presented. Knoevenagel condensation of ethyl bis-(2,2,2-trifluroethyl)phosphonoacetate with cinnamaldehyde in the presence of piperidinium benzoate provided the desired 2-phenylethenylidene phosphonoacetate 7 in 84% yield (Scheme 1). When this phosphonoacetate 7 was added to ylide 6, generated25 using Me3SI and n-BuLi in THF and the intermediate was quenched with p-bromobenzaldehyde, the desired [3]dendralene 8a was formed. The triene 8a must have formed via the dienic ylide 9 followed by a Horner–Wadsworth–Emmons reaction (Scheme 2) with the added aldehyde. The formation of the triene 8a could be monitored by TLC, but could not be isolated because of its high reactivity. Under the reaction conditions, it underwent an in situ Diels–Alder (D–A) cyclodimerisation to Chem. Commun., 2011, 47, 10809–10811

10809

Scheme 1

Synthesis of 2-phenylethylidene phosphonoacetate.

Scheme 3 Crossover experiment.y

give the cyclohexene 10a as a racemic compound wherein one molecule of the triene 8a behaved as a diene and another as a dienophile. The overall process proceeded with moderate (ca. 33%) yield but with excellent regio- and stereoselectivity. A racemic but single diastereoisomer 10a was obtained from the reaction whose structure was confirmed by X-ray crystallographyw (Fig. 3). The D–A reaction was very unique in the sense that the 3-methylene group of the triene 8a exclusively participated as the dienophile component. Looking through the structure of 8a, it was not so apparent that this double bond is the most electronically deactivated. More interestingly, this 3-methylene group and the 4-position double bond of the triene together acted as the diene component. The orientation of the diene component and the dienophile component was such that bonding took place between the unsubstituted carbons of the 3-methylene groups (from diene and dienophile, both) and two substituted carbons, at 3-position (dienophile) and 5-position (diene) leading to one regio-isomer only with the generation of a quaternary stereogenic centre. Although, Sherburn et al.14 have shown

the similar regioselectivity in D–A cyclodimerisation of unsubstituted [3]dendralene which has been explained by the biradical mechanism proposed by Dewar et al.26 To interrupt this D–A homodimerisation of the triene 8a, we added dienophiles such as N-phenylmalemide or dimethyl acetylene dicarboxylate after 15 min of the addition of p-bromobenzaldehyde. We did not find any D–A adduct from these dienophiles, only the cyclohexene 10a was obtained. Interruption of the homodimerisation also failed with the addition of an external diene such as isoprene. We have also carried out crossover experiments to confirm the intermediacy of [3]dendralene in this reaction. For this, phosphonoacetate 7 was added to ylide 6 and quenched with an equimolar mixture of p-bromobenzaldehyde and pyridine-3-carboxaldehyde. After usual workup, we obtained all four possible D–A adducts (Scheme 3) (35% combined yield). The cyclohexenes 10a and 10b were formed by D–A homodimerisation of trienes 8a and 8b, respectively. The cyclohexenes 11a and 11b were formed by the cross D–A reaction of the trienes 8a and 8b wherein triene 8a acted as diene and triene 8b acted as dienophile or vice versa. No other regio- and stereoisomers were obtained. The observed yield was poor. But, considering the number of elementary steps and complexity of the process, the yield at this stage was acceptable.

Fig. 3 ORTEP plot of racemic 10a.z

Scheme 4 Improved synthesis of cyclohexene 10a.y

Scheme 2 Synthesis of cyclohexene 10a.y

10810

Chem. Commun., 2011, 47, 10809–10811

This journal is

c

The Royal Society of Chemistry 2011

4

5 6

Scheme 5 Synthesis of cyclohexenes 10a–h.y

A significant improvement of the overall yield for 10a starting from phosphonoacetate 7 was observed when the reaction was performed in two stages instead of one-pot. Thus the phosphonoacetate 7 was added to ylide 6 and then quenched with water to give the 1,3-butadien-2-ylphosphonoacetate 12 in 88% yield. This phosphonate was then mixed with 1 equiv. of p-bromobenzaldehyde and reacted with NaH in THF which resulted in the formation of the D–A homodimerisation product 10a (Scheme 4) in 72% yield (63%) overall from dienic phosphonoacetate 7. To show the generality of the process, dienyl phosphonate 12 was reacted with sodium hydride and various aromatic aldehydes as described for 10a. The reaction of substituted benzaldehydes (Scheme 5) proceeded well with varying substituents and patterns. Heteroaromatic aldehyde such as 3-pyridine carboxaldehyde also reacted well to give the D–A dimer. In each case, the isolated product was found to be the cyclohexene, resulted from the D–A homodimerisation of the corresponding [3]dendralene. The cyclohexenes 10a–h were formed with very high regio- and stereoselectivity and only one diastereoisomer was obtained in each case. In conclusion, a novel route to functionalised [3]dendralenes has been developed. Interestingly, the substituents on these dendralenes made them reactive enough to undergo a facile intermolecular D–A cyclodimerisation at room temperature giving highly substituted cyclohexenes with very high regio- and stereoselectivity. Efforts are ongoing to interrupt this self-dimerisation and also to induce asymmetry for enhancement of the utility of the present method.

7

8 9

10 11

12

13 14 15 16

17

18 19 20

Notes and references z For the use of this terminology; see: T. Cohen and L. C. Yu, J. Org. Chem., 1984, 49, 605. y The products 10a–h or 11a,b are obtained as racemic compounds only. z X-Ray crystallographic data were collected at the X-ray diffraction facility, Department of Chemistry, IIT, Mumbai. 1 W. J. Bailey, J. Economy and M. E. Hermes, J. Org. Chem., 1962, 27, 3295; R. C. Blume, U.S. Pat. 3,860,669 (Chem. Abstr., 1975, 82, 172295j). 2 U. Fleischer, W. Kutzelnigg, P. Lazzeretti and V. Muhlenkamp, J. Am. Chem. Soc., 1994, 116, 5298. 3 H. Hopf, Nature, 2009, 460, 183; H. Hopf, in Organic Synthesis Highlights V, ed. H.-G. Schmalz and T. Wirth, Wiley-VCH, Weinheim, 2003, p. 419; H. Hopf, Classics in Hydrocarbon

This journal is

c

The Royal Society of Chemistry 2011

21 22 23

24

25 26

Chemistry: Syntheses, Concepts, Perspectives, Wiley-VCH, Weinheim, 2000, p. 253; H. Hopf, Angew. Chem., Int. Ed., 2001, 40, 705; H. Hopf, Angew. Chem., Int. Ed. Engl., 1984, 23, 948. O. Kwon, S. B. Park and S. L. Schreiber, J. Am. Chem. Soc., 2002, 124, 13402; K. M. Brummond and L. You, Tetrahedron, 2005, 61, 6180. M. D. Clay, D. Riber and A. G. Fallis, Can. J. Chem., 2005, 83, 559. A. D. Payne, A. C. Willis and M. S. Sherburn, J. Am. Chem. Soc., 2005, 127, 12188; T. A. Bradford, A. D. Payne, A. C. Willis, M. N. Paddon-Row and M. S. Sherburn, Org. Lett., 2007, 9, 4861; G. Bojase, A. D. Payne, A. C. Willis and M. S. Sherburn, Angew. Chem., Int. Ed., 2008, 47, 910. H.-M. Chang and C.-H. Cheng, J. Org. Chem., 2000, 65, 1767; C. S. Chin, H. Lee, H. Park and M. Kim, Organometallics, 2002, 21, 3889; N. A. Miller, A. C. Willis, M. N. Paddon-Row and M. S. Sherburn, Angew. Chem., Int. Ed., 2007, 46, 937; S. Kim, D. Seomoon and P. H. Lee, Chem. Commun., 2009, 1873. A. D. Payne, G. Bojase, M. N. Paddon-Row and M. S. Sherburn, Angew. Chem., Int. Ed., 2009, 48, 4836. J. Le Noˆtre, A. A. Martinez, P. H. Dixneuf and C. Bruneau, Tetrahedron, 2003, 59, 9425; S. Park and D. Lee, Synthesis, 2007, 2313. S. Fielder, D. D. Rowan and M. S. Sherburn, Angew. Chem., Int. Ed., 2000, 39, 4331. A. T. Blomquist and J. A. Verdol, J. Am. Chem. Soc., 1955, 77, 81; W. J. Bailey and J. Economy, J. Am. Chem. Soc., 1955, 77, 1133; A. T. Blomquist and J. A. Verdol, J. Am. Chem. Soc., 1955, 77, 1806; H. Priebe and H. Hopf, Angew. Chem., Int. Ed. Engl., 1982, 21, 286. S. Woo, N. Squires and A. G. Fallis, Org. Lett., 1999, 1, 573; S. Woo, S. Legoupy, S. Parra and A. G. Fallis, Org. Lett., 1999, 1, 1013. H.-D. Martin, M. Eckert-Maksic´ and B. Mayer, Angew. Chem., Int. Ed. Engl., 1980, 19, 807. T. A. Bradford, A. D. Payne, A. C. Wills, M. N. Paddon-Row and M. S. Sherburn, J. Org. Chem., 2010, 75, 491. H. Hopf and S. Yildizhan, Eur. J. Org. Chem., 2011, 2029. S. Brase, H. Wertal, D. Frank, D. Vidovic and A. D. Meijere, Eur. J. Org. Chem., 2005, 4167; M. Shi and L.-X. Shao, Synlett, 2004, 807; C. J. Reider, K. J. Winberg and F. G. West, J. Org. Chem., 2011, 76, 50. H. L. Shimp, A. Hare, M. McLaughlin and G. C. Micalizio, Tetrahedron, 2008, 64, 3437; K. M. Brummond, H. Chen, P. Sill and L. You, J. Am. Chem. Soc., 2002, 124, 6180; B. Kang, D.-H. Kim, Y. Do and S. Chang, Org. Lett., 2003, 5, 3041. G. Bojase, T. V. Nguyen, A. D. Payne, A. C. Wills and M. S. Sherburn, Chem. Sci., 2011, 2, 229. K. Beydoun, H.-J. Zhang, B. Sundararaju, B. Demerseman, M. Achard, Z. Xi and C. Bruneau, Chem. Commun., 2009, 6580. M. Arisawa, T. Sugihara and M. Yamaguchi, Chem. Commun., 1998, 2615; T. Miura, T. Biyajima, T. Toyoshima and M. Murakami, Beilstein J. Org. Chem., 2011, 7, 578. E. J. Corey and M. Chaykovsky, J. Am. Chem. Soc., 1965, 87, 1353. S. K. Ghosh, R. Singh and S. M. Date, Chem. Commun., 2003, 636. S. M. Date, R. Singh and S. K. Ghosh, Org. Biomol. Chem., 2005, 3, 3369; R. Singh, G. C. Singh and S. K. Ghosh, Tetrahedron Lett., 2005, 46, 4719; R. Singh, G. C. Singh and S. K. Ghosh, Eur. J. Org. Chem., 2007, 5376; S. K. Ghosh, R. Singh and G. C. Singh, Eur. J. Org. Chem., 2004, 4141. S. M. Date and S. K. Ghosh, Angew. Chem., Int. Ed., 2007, 46, 386; S. M. Date and S. K. Ghosh, Bull. Chem. Soc. Jpn., 2004, 77, 2099; R. Chowdhury and S. K. Ghosh, Eur. J. Org. Chem., 2008, 3868. R. Singh and S. K. Ghosh, Org. Lett., 2007, 9, 5071; R. Singh and S. K. Ghosh, Tetrahedron, 2010, 66, 2284. M. J. S. Dewar, S. Olivella and J. J. P. Stewert, J. Am. Chem. Soc., 1986, 108, 5771.

Chem. Commun., 2011, 47, 10809–10811

10811