Solvent effects on diastereoselective intramolecular [2 + 2] photocycloadditions. Reversal of selectivity through intramolecular hydrogen bonding

The intramolecular [2 + 2] enone-alkene photocycloaddition has been established as a powerful reaction in the rapid construction of advanced intermediates for the synthesis of complex natural products.1,2 The diastereocontrol that is available through intramolecular processes is a result of geometric constraints imposed both by the intramolecular nature of the process and by the conformational bias on the transition states which can be invoked by substituents on the tether between the reactive functional groups. We and others have previously demonstrated the asymmetric induction imposed on the product by a single stereogenic center on the tether proximal to the enone function in an intramolecular [2 + 2] photocycloaddition.1-3 The normal mode of cycloaddition4 for 1 (Scheme 1) results in high diastereoselectivity for the product 2, which has the proximal substituent (OSiEt3 in 2) cis to the substituent on the internal carbon of the alkene (Me in 2). Conformation A (see Figure 1) for initial bond formation is the lowest energy conformation by approximately 1.8 kcal/mol (7.53 kJ/mol) and accurately predicts the stereochemistry of the product 2. We report here additional examples which illustrate the ability to reverse the normal diastereoselectivity by taking advantage of hydrogen bonding between a hydroxyl group and a proximal carbonyl oxygen, as well as a dependence of the diastereoselectivity on the reaction solvent. Hydrogen bonding in a [4 + 4] photocycloaddition of pyridones has been postulated for an explanation of diastereoselectivity5 and hydrogen bonding plays an important role in photocycloadditions of â-dicarbonyl compounds6 (the de Mayo reaction). However, to our knowledge, these are the first examples which demonstrate the effects of hydrogen bonding, both intramolecular and intermolecular, on the diastereoselectivity in intramolecular [2 + 2] enoneolefin photocycloadditions.7 The synthesis of photosubstrate 1 and the corresponding amide 3 is illustrated in Scheme 1. The addition of ethynyl magnesium bromide to 4-methyl-4-pentenal8 in THF at 0 °C resulted in the formation of the acetylenic alcohol, which was then protected (Et3SiCl, Et3N, catalytic DMAP, CH2Cl2) to give silyl ether 5 in 58% yield (Scheme 1).9 The protected acetylene 5 was then acylated with either ethyl chloroformate (n-BuLi, THF, -78 °C) to give the acetylenic ester or amide, which was converted to the cyclopentenone 1 with use of our zinc homoenolate procedure reported previously.10 Irradiation of a hexane solution of ester 1 produced a single detectable diastereomer 2 in 95% yield (Table 1).9 These 2-carboalkoxycyclopentenone chromophores typically undergo (1) Crimmins, M. T.; Reinhold, T. L. Org. React. 1993, 44, 297-588 and references therein. Crimmins, M. T. In ComprehensiVe Organic Synthesis; Trost, B. M., Ed.; Pergamon: Oxford, England, 1991; Vol. 5, pp 123-150. Crimmins, M. T. Chem. ReV. 1988, 88, 1453-1473. For earlier reviews on photocycloadditions see: Horspool, W. M. In Photochemistry in Organic Synthesis; Coyle, J. D., Ed.; Royal Society of Chemistry: London, 1986; p 210. Wender, P. A. In Photochemistry in Organic Synthesis; Coyle, J. D., Ed.; Royal Society of Chemistry: London, 1986; p 163. Weedon, A. C. In Synthetic Organic Photochemistry; Horspool, W. M., Ed.; Plenum: New York, 1984; p 61. Oppolzer, W. Acc. Chem. Res. 1982, 15, 135. Baldwin, S. W. Org. Photochem. 1981, 5, 123. (2) De Keukeleire, D.; He, S.-L. Chem. ReV. 1993, 93, 359-380. (3) Crimmins, M. T.; DeLoach, J. A. J. Am. Chem. Soc. 1986, 108, 800806. Crimmins, M. T.; DeLoach, J. A. J. Org. Chem. 1984, 49, 20762077. Crimmins, M. T.; Thomas, J. B. Tetrahedron Lett. 1989, 30, 59976000. See: Crimmins, M. T. Chem. ReV. 1988, 88, 1453-1473. Crimmins, M. T.; Huang, S.; Guise-Zawacki, L. E. Tetrahedron Lett. 1996, 37, 65196522. (4) For recent discussions of the mechanism of [2 + 2] enone-olefin photocycloadditions see: Schuster, D. I.; Lem, G.; Kaprinidis, N. A. Chem. ReV. 1993, 93, 3-22. Andrew, D.; Hastings, D. J.; Weedon, A. C. J. Am. Chem. Soc. 1994, 116, 10870-10882. Maradyn, D. J.; Weedon, A. C. Tetrahedron Lett. 1994, 35, 8107-8110. Maradyn, D. J.; Weedon, A. C. J. Am. Chem. Soc. 1995, 117, 5359-5360. (5) Sieburth, S. M.; Joshi, P. V. J. Org. Chem. 1993, 58, 1661-1663. Sieburth, S. M.; Hiel, G.; Lin. C.-H.; Huan, D. P. J. Org. Chem. 1994, 59, 80-87. (6) de Mayo, P. Acc. Chem. Res. 1971, 4, 41.. (7) Photoisomerizations which rely on the effects of hyrdogen bonds have also been reported. Lewis, F. D.; Yoon, B. A.; Arai, T.; Iwasaki, T.; Tokumaru, K. J. Am. Chem. Soc. 1995, 117, 3029-3036. Lewis, F. D.; Yoon, B. A. J. Org. Chem. 1994, 59, 2537-2545. (8) Cresson, P. Bull. Soc. Chim. Fr. 1964, 2618-2628. Rhoads, S. J.; Raulins, N. R. Org. React. 1975, 22, 2-252. (9) All new compounds gave consistent 1H, 13C, and IR spectra as well as satisfactory C, H combustion analyses or HRMS. All yields are for homogeneous, chromatographically pure products unless otherwise indicated. (10) Crimmins, M. T.; Nantermet, P. G. J. Org. Chem. 1990, 55, 42354237. Crimmins, M. T.; Nantermet, P. G.; Trotter, B. W.; Vallin, I. M.; Watson, P. S.; McKerlie, L. A.; Reinhold, T. L.; Cheung, W.-H.; Stetson, K. A.; Dedopoulou, D.; Gray, J. L. J. Org. Chem. 1993, 58, 1038-1047. Scheme 1