Mechanisms of nucleophilic substitutions of acetals

Abstract

The nucleophilic substitution of (+)-(R)-benzaldehyde methyl isopropyl acetal (αR)-1 (93% ee) and (+)-(R)-o-anisaldehyde methyl isopropyl acetal (αR)-2 (homochiral) with Me₂CuLi–BF₃·OEt₂ occurs completely chemoselectively to afford (+)-(αR)-α-methyl(benzyl) isopropyl ether (+)-(αR)-3 (40% ee) and (+)-(αR)-α-methyl(o-methoxybenzyl) isopropyl ether (+)-(αR)-4 (34% ee) respectively, demonstrating that the mechanism of the former reaction involves a free oxonium ion to the extent of 56% and the latter to the extent of 66%.

References

1. (a) For recent reviews see: J. March, Advanced Organic Chemistry, 4th edn., Wiley Interscience, 1992, p. 461; (b) D. Seebach, R. Imwinkelreid and T. Weber, Modern Synthetic Methods, Vol. 4, Springer Verlag, 1986; (c) A. Alexakis and P. Mangeney, Tetrahedron: Asymmetry, 1990, 1, 477; (d) E. Mash, Studies in Natural Products Chemistry, Vol. 1, ed. Atta-ur-Rahman, Elsevier, 1988.
2. For recent examples see: T. L. Underiner and L. A. Paquette, J. Org. Chem., 1992, 57, 5438; K. Ishihara, N. Hanaki and H. Yamamoto, Synlett, 1993, 127; Y. Kondo, J. R. Green and J. Ho, J. Org. Chem., 1993, 58, 6182; O. Riant, O. Samuel and H. B. Kagan, J. Am. Chem. Soc., 1993, 115, 5835; N. M. Loim, M. A. Kondratenko and V. I. Sokolov, J. Org. Chem., 1994, 59, 7485; P. V. Fish and W. S. Johnson, J. Org. Chem., 1994, 59, 2324; T. Yuan, S. Yeh, Y. Hsieh and T. Luh, J. Org. Chem., 1994, 59, 8192; Y. D. Vankar, M. V. Reddy and N. C. Chaudhuri, Tetrahedron, 1994, 50, 37, 11 057; I. Kadota, K. Miura and Y. Yamamoto, J. Chem. Soc., Chem. Commun., 1994, 1953; H. Pellissier and M. Santelli, J. Chem. Soc., Chem. Commun., 1995, 607; K. Ishihara, N. Hanaki and H. Yamamoto, J. Chem. Soc., Chem. Commun., 1995, 1117.
3. (a) P. A. Bartlett, W. S. Johnson and J. D. Elliot, J. Am. Chem. Soc., 1983, 105, 2088; (b) V. M. F. Choi, J. D. Elliot and W. S. Johnson, Tetrahedron Lett., 1984, 25, 6, 591; (c) A. Mori, J. Fujiwara, K. Maruoka and H. Yamamoto, J. Organomet. Chem., 1985, 285, 83; (d) W. Richter, J. Org. Chem., 1981, 46, 5119.
4. (a) J. F. Normant, A. Alexakis, A. Ghribi and P. Mangeney, Tetrahedron, 1989, 45, 2, 507; (b) S. G. Davies, R. F. Newton and J. M. J. Williams, Tetrahedron Lett., 1989, 30, 2967.
5. Aklavinone: J. M. McNamara and Y. Kishi, J. Am. Chem. Soc., 1982, 104, 7371 calcitriol lactone: W. S. Johnson, J. D. Elliot and G. J. Hanson, J. Am. Chem. Soc., 1984, 106, 1138; W. S. Johnson and M. F. Chan, J. Org. Chem., 1985, 50, 2598 (–)-dihydromyo-porone: W. S. Johnson, P. H. Crackett, J. D. Elliot, J. C. Jagodzinski, S. D. Lindell and (in part) S. Natarajan, Tetrahedron Lett., 1984, 25, 3951 (R)-(+)-α-Lipoic acid: J. D. Elliott, J. Steele and W. S. Johnson, Tetrahedron Lett., 1985, 26, 2535 mevinolin analogues: W. S. Johnson, A. B. Kelson and J. D. Elliott, Tetrahedron Lett., 1988, 29, 3757.
6. (a) Y. Yamamoto, S. Nihhii and J. Yamada, J. Am. Chem. Soc., 1986, 108, 7116; (b) Y. Yamamoto and J. Yamada, J. Chem. Soc., Chem. Commun., 1987, 1218; (c) S. E. Denmark and N. G. Almstead, J. Org. Chem., 1991, 56, 6485; (d) T. Sammakia and R. S. Smith, J. Org. Chem., 1992, 57, 2997.
7. (a) S. E. Denmark and T. J. Wilson, J. Am. Chem. Soc., 1989, 11, 3475; (b) R. C. Corcoran, Tetrahedron Lett., 1990, 31, 2101; (c) I. Mori, K. Ishiara, L. A. Flippin, K. Nozaki, H. Yamamoto, P. A. Bartlett and C. H. Heathcock, J. Org. Chem., 1990, 55, 6107; (d) S. E. Denmark and N. G. Almstead, J. Org. Chem., 1991, 56, 6458; (e) S. E. Denmark and N. G. Almstead, J. Am. Chem. Soc., 1991, 113, 8089; (f) T. Sato and J. Otera, J. Organomet. Chem., 1994, 473, 55.
8. S. E. Denmark, T. J. Wilson and N. G. Almstead, J. Am. Chem. Soc., 1989, 111, 9258.
9. (a) T. Sammakia and R. S. Smith, J. Am. Chem. Soc., 1992, 114, 10 998; (b) T. Sammakia and R. S. Smith, J. Am. Chem. Soc., 1994, 116, 7915.
10. S. G. Davies and L. M. A. R. B. Correia, Chem. Commun., 1996, 796.
11. L. A. Bromley, S. G. Davies and C. L. Goodfellow, Tetrahedron: Asymmetry, 1991, 2, 139.
12. S. G. Davies, C. L. Goodfellow and K. H. Sutton, Tetrahedron: Asymmetry, 1992, 3, 1303.