Room Temperature and Highly Enantioselective Additions of Alkyltitanium Reagents to Aldehydes Catalyzed by a Titanium Catalyst of (R)-H8-BINOL

Three alkyltitanium reagents of RTi(O-i-Pr)(3) (R = Cy (1a), i-Bu (1b), and n-Bu (1c)) were prepared in good yields. The high-resolution mass spectroscopy showed that 1b and 1c in the gas phase are monomeric species. However, the solid state of 1a revealed a dimeric structure. Asymmetric additions of 1a-1c to aldehydes catalyzed by a titanium catalyst of (R)-H-8-BINOL were studied at room temperature. The reactions produced desired secondary alcohols in good yields with good to excellent enantioselectivities of up to 94% ee. Reactivity and enantioselectivity differences, in terms of steric bulkiness of the R nucleophiles, are herein described. The addition reactions of secondary c-hexyl to aldehydes were slower than the reactions of primary i-butyl or n-butyl nucleophiles. For the primary alkyls, lower enantioselectivities were obtained for products from addition reactions of the linear n-butyl as compared with the enantioselectivities of products from the addition reactions of the branched i-butyl group. The same stereochemistry of RTi(O-i-Pr)(3) addition reactions as the addition reactions of organozinc, organoaluminum, Grignard, or organolithium reagents directly supports the argument of that titanium- catalyzed addition reactions of aldehydes involve an addition of an organotitanium nucleophile. Chirality 23:929-939, 2011. (C) 2011 Wiley-Liss, Inc.