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Mechanistic Evidence for a Novel Rearrangement Sequence in the Synthesis of 4-Aryl-5,6-dihydro-1,2-oxathiine-2,2-dioxides from Homopropargyl Benzosulfonates 1 MechanistcEvidenceforaNovelRear angemenZhang,* Wei t Georgia Pugh
Lead Discovery, DuPont Crop Protection, Stine-Haskell Research Center, Newark, DE 19714, USA Fax +1(412)8263053; E-mail:
[email protected] Received 12 February 2002
Abstract: Under similar literature conditions, tributyltin hydridepromoted free radical reaction of homopropargyl benzosulfonates 1 initiated a novel rearrangement sequence and led to formation of two kinds of cyclic sultones: 4-aryl-5,6-dihydro-1,2-oxathiin-2,2dioxides 2 and 4-aryl-3-tributyltin-1,2-oxathiane-2,2-dioxides 7. Isolation and X-ray structure characterization of previously unreported cyclic a-tributyltin sultones 7 provided evidence for a cyclization-fragmentation-cyclization mechanism proposed by Motherwell. Key words: 4-aryl-5,6-dihydro-1,2-oxathiin-2,2-dioxides, 4-aryl3-tributyltin-1,2-oxathiane-2,2-dioxides, a,b-unsaturated sultones, ipso substitutions, free radicals
With a simple cyclization-fragmentation sequence, intramolecular homolytic ipso substitutions can be designed for 1,2-, 1,4-, and 1,5-phenyl migration reactions and used for biaryl synthesis (Scheme 1).2,3 Numerous examples involving cleavage of C-C, C-N, C-O, C-P, C-S, C-Si, and C-Sn bonds have been reported.4 Further applications for making fused tricyclics, such as phenanthridinones,4m,5 benzochromenes4k,6 and benzoazacoumarins7 have also been developed. The process of intramolecular homolytic ipso substitutions has been well recognized. The mechanistic insight, however, has not been fully understanded since the postulated spirocyclohexadienyl radicals could not be identified so far.3 Studies on mechanism of homolytic ipso substitution and related reactions thus attract the attention of organic chemists. Herein we describe our investigation on a novel rearrangement reaction involving homolytic ipso substitution originally reported by Motherwell research group. In a study of radical reactions of homopropargyl benzosulfonates 1, Motherwell and coworkers discovered an unusual rearrangement sequence leading to the formation of cyclic a,b-unsaturated sultones (Scheme 2).8 A mechanistic account for this novel process has been proposed (Scheme 3). It is believed that the vinyl radical generated by addition of a tributyltin radical to the alkyne first attacks the benzene ring via 1,6-ipso substitution. However, the sequential extrusion of sulfur dioxide from radical 5, a facile Synlett 2002, No. 5, 03 05 2002. Article Identifier: 1437-2096,E;2002,0,05,0778,0780,ftx,en;S09501ST.pdf. © Georg Thieme Verlag Stuttgart · New York ISSN 0936-5214
Scheme 1 Intramolecular homolytic ipso substitutions via spirocyclohexadienyl radicals.
process known in biaryl synthesis,9 does not occurred. The surviving radical undergoes a 6-endo addition followed by a b-elimination of the tributyltin radical to provide 4-aryl-5,6-dihydro-1,2-oxathiin-2,2-dioxide 2. This reaction is not only mechanistically unique, but also provides novel synthetic routes to b-aryl cyclic a,b-unsaturated sultones and sultams.
Scheme 2
Motherwell’s synthesis of cyclic sultone 2.
In a related research project, we had the opportunity to use Motherwell’s procedure for making b-aryl cyclic a,b-unsaturated sultones and sultams. Thus, under similar reaction conditions that involve adding tributyltin hydride in 10 h (15 h described in the literature, both ended with 33 mM of tin), we observed the formation of the a,b-unsaturated cyclic sultone 2 along with previously unreported cyclic a-tributyltin substituted sultone 7 (Scheme 4).10 Two kinds of sultones (2 and 7) are obtained from the same in-
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Scheme 3 sultone 2.
Mechanistic Evidence for a Novel Rearrangement
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A proposed mechanism for the formation of cyclic Scheme 5 and 7.
A mechanism for the formation of cyclic sultones 2
termediate radical 6 via a competition between the tin radical elimination (6 ® 2) and the tin hydride reduction (6 ® 7) (Scheme 5). For these two routes, the former is an intramolecular process, whereas the latter is a tin hydride dependent intermolecular process. The tin radical elimination is usually faster than the tin hydride reduction. However, in this case, radical 6 is stabilized by the phenyl group and the rate of radical elimination is significantly slowed down. Faster addition of tributyltin hydride results in relatively higher concentration of tributyltin hydride in the reaction mixture and thus favors the reduction of radical 6. The structures of both 7a and 7b have been confirmed by single crystal X-ray diffraction studies (Figure). The X-ray structures also provide the stereochemical information: the cis substituents on the sultone rings suggest that tin hydride reduction of radical 6 to 7 occurred stereoselectively in trans fashion.
Figure
Scheme 4
Reactions for the formation of cyclic sultones 2 and 7.
X-ray structures of sultones 7a and 7b.
An alternative route to cyclic a-tributyltin sultone 7 could be hydrostannylation of a,b-unsaturated sultone 2 (2 ® 6 ® 7) (Scheme 5). However, this possibility was ruled out by a control experiment in which 2b was reacted with 1.0 equiv. of tributyltin hydride and 1.0 equiv. of AIBN in benzene (33 mM). After heating at 80 °C for 18 h, no atributyltin sultone 7b but only unreacted starting materials were detected by 1H NMR.
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W. Zhang, G. Pugh
In summary, we have obtained some mechanistic information on the free radical rearrangement of homopropargyl benzosulfonate 1. Isolation of cyclic a-tributyltin sultone 7 provided evidence to support radical 6 as an intermediate in the proposed cyclization-fragmentation-cyclization rearrangement sequence.
(5) (6) (7) (8)
Acknowledgement The authors thank William Marshall for providing the X-ray structural analysis of compounds 7a and 7b.
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References (1) Current address: Fluorous Technologies, Inc., 970 William Pitt Way, Pittsburgh, PA 15238, USA (2) (a) Beckwith, A. L. J.; Ingold, K. U. In Rearrangement in Ground and Excited States; de Mayo, P., Ed.; Academic Press: New York, 1980, 170. (b) Freidlina, R. K. h.; Terent’ev, A. B. In Advanced in Free Radical Chemistry; Williams, G. H., Ed.; Heyden & Son: London, 1980, 32. (3) Studer, A.; Bossart, M. In Radicals in Organic Synthesis, Vol. 2; Renaud, P.; Sibi, M. P., Eds.; Wiley-VCH: Weinheim, 2001, 62. (4) Some representative references on intramolecular homolytic ipso substitutions: (a) Ryokawa, A.; Togo, H. Tetrahedron 2001, 57, 5915. (b) Leardini, R.; McNab, H.; Minozzi, M.; Nanni, D. J. Chem. Soc. Perkin Trans 1 2001, 1072. (c) Amrein, S.; Bossart, M.; Vasella, T.; Studer, A. J. Org. Chem. 2000, 65, 4281. (d) Bonfand, E.; Forslund, L.; Motherwell, W. B.; Vazquez, S. Synlett 2000, 475. (e) Caddick, S.; Shering, C. L.; Wadman, S. N. Tetrahedron 2000, 56, 465. (f) Miranda, L. D.; Cruz-Almanza, R.; Alvarez-Garcia, A.; Muchowski, J. M. Tetrahedron Lett. 2000, 41, 631. (g) Clive, D. L.; Kang, S. Tetrahedron Lett. 2000, 41, 1315. (h) Wakabayashi, K.; Yorimitsu, H.; Shinokubo, H.; Oshima, K. Org. Lett. 2000, 2, 1899. (i) Clark, A. J.; De Campo, F.; Deeth, R. J.; Filik, R. P.; Gatard, S.; Hunt, N. A.; Lastecoueres, D.; Thomas, G. H.; Verlhac, J.-B.; Wongtap, H. J. Chem. Soc. Perkin Trans 1 2000, 671. (j) Senboku, H.; Hasegawa, H.; Orito, K.; Tokuda, M. Tetrahedron Lett. 2000, 41, 5699. (k) Bowman, W. R.; Mann, E.; Parr, J. J. Chem. Soc. Perkin Trans 1 2000, 2991. (l) Alcaide, B.; Rodriguez-Vicente, A. Tetrahedron Lett. 1998, 39, 6589. (m) Crich, D.; Hwang, J.-T. J. Org. Chem. 1998, 63, 2765. (n) Amii, H.; Kondo, S.; Uneyama, K. Chem. Commun. 1998, 1845. (o) Rosa, A. M.; Lobo, A. M.; Branco, P. S.; Prabhakar, S. Tetrahedron 1997, 53, 285. (p) Giraud, L.; Lacote, E.; Renaud, P. Helv. Chim. Acta 1997, 80, 2148. (q) Mander, L. N.; Sherburn, M. S. Tetrahedron Lett. 1996, 37, 4255. (r) Lee, E.; Whang, H. S.; Chung, C. K. Tetrahedron Lett. 1995, 36, 913. (s) Black,
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M.; Cadogan, J. I. G.; McNab, H. J. Chem. Soc., Chem. Commun. 1990, 395. (t) Kohler, J. J.; Speckamp, W. N. Tetrahedron Lett. 1977, 631. (u) Kohler, J. J.; Speckamp, W. N. Tetrahedron Lett. 1977, 635. Bowman, W. R.; Heaney, H.; Joadan, B. M. Tetrahedron 1991, 48, 10119. Harrowven, D. C.; Nunn, M. I. T.; Newman, N. A.; Fenwick, D. R. Tetrahedron Lett. 2001, 42, 961. Zhang, W.; Pugh, G. Tetrahedron Lett. 2001, 42, 5613. (a) Bonfand, E.; Motherwell, W. B.; Pennell, A. M. K.; Uddin, M. K.; Ujjainwalla, F. Heterocycles 1997, 46, 523. (b) Motherwell, W. B.; Pennell, A. M. K.; Ujjainwalla, F. J. Chem. Soc. Chem. Commun. 1992, 1067. (a) da Mata, M. L. E. N.; Motherwell, W. B.; Ujjainwalla, F. Tetrahedron Lett. 1997, 38, 137. (b) da Mata, M. L. E. N.; Motherwell, W. B.; Ujjainwalla, F. Tetrahedron Lett. 1997, 38, 141; see also ref.4d. Procedure for tinhydride reaction of homopropargyl benzosulfonate 1: A solution of Bu3SnH (4.6 mmole) and AIBN (4.6 mmole) in 50 mL of dry benzene was added to a refluxing solution of 2 (4.6 mmole) in 90 mL of dry benzene over a period of 10 h via a syringe pump. After an additional 4–6 h, the reaction mixture was concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (gradient elution; 10% EtOAc–hexanes then 100% EtOAc) furnished in order of elution, the cyclic atributyltin substituted sultone 7 and a,b-unsaturated cyclic sultone 2. 1H NMR, IR and MS spectra of 2a and 2b are identical with those provided in the literature (ref.8) Analytical data for 7a: 1H NMR (300 MHz, CDCl3) d 0.73 (t, 3 CH3), 0.40–1.30 (3 ´ 3 CH2), 2.17 (br dd, 1 H), 2.41 (qd, 1 H), 4.57 (d, 1 H), 4.66 (m, 1 H), 4.80 (td, 1 H), 5.21 (dt, 1 H), 7.43 (dd, 1 H), 7. 53 (t, 1 H), 7.68 (d, 1 H), 7.79 (d, 1 H), 8.18 (d, 1 H), 8.99 (d, 1 H). 13C NMR (75 MHz, CDCl3) d 9.9 (t, 3 CH2), 12.0 (q, 3 CH3), 25.6 (t, 3 CH2), 27.0 (t, 3 CH2), 27.3 (t), 37.1 (d), 1.4 (d), 69.6 (t), 119.9 (d), 124.6 (d), 124.9 (d), 126.2 (d), 127.0 (s), 134.9 (d), 137.6 (s), 144.6 (s), 148.3 (d). IR(neat)1334 (SO2), 1150 (SO2) cm–1. MS m/e (rel. intensity) 552 (M+–1, 10), 405(40), 361(97), 294(70), 262 (M+–SnBu3, 100). Analytical data for 7b: 1H NMR (300 MHz, CDCl3) d 0.74 (t, 3 CH), 0.50–1.30 (3 ´ 3 CH2), 2.11 (br d, 1 H), 2.51 (qd, 1 H), 2.88 (s, 2 CH3), 3.78 (dd, 1 H), 4.63 (dd, 1 H), 4. 81 (m, 2 H), 7.15 (d, 1 H), 7.35 (d, 1 H), 7. 43 (t, 1 H), 7.51 (t, 1 H), 7.77 (d, 1 H), 8.24 (d, 1 H). 13C NMR (75 MHz, CDCl3) d 10.2 (t, 3 CH2), 12.0 (q, 3 CH3), 25.6 (t, 3 CH2), 27.0 (t, 3 CH2), 27.6 (t), 43.8 (d), 43.8 (q, 2 CH3), 52.4 (d), 70.1 (t), 112.9 (d), 115.9 (d), 121.3 (d), 122.8 (d), 123.1 (d), 125.5 (d), 128.1 (s), 130.5 (s), 135.1 (s), 150.5 (s). IR(neat)1340 (SO2), 1153 (SO2) cm–1. MS m/e (rel. intensity) 594 (M+ + 1, 25), 538(25), 332(24), 240(100).
