Asymmetric Synthesis of Functionalized Tertiary Homoallyl Alcohols by Diastereoselective Allylation of Chiral α-Keto Amides Derived from (S)-Proline Esters. Control of Stereochemistry Based on Saturated Coordination of Lewis Acid

Article abstract of DOI:10.1021/jo00367a008

Diastereoselective additions of allylsilanes and -stannanes to chiral α-keto amides 1a-c derived from esters of (S)-proline in the persence of Lewis acids afforded optically active tertiary homoallyl alcohols of high diastereomeric excesses (up to 92percent de).Reaction conditions were examined in detail.The order of the effectiveness of Lewis acids on diastereoselectivity was SnBr4 > SnCl4 > TiCl4 > BF3*OEt2 >> AlCl3.At least 3 mol equiv of SnCl4 were required to achieve the high diastereoselection.The coordination of Lewis acids with the oxygen atom(s) of 1 may be one of the resonans for the high diastereoselectivity.When SnCl4 as used, dichloromethane was the best solvent.In the case of TiCl4, a heterogeneous reaction mixture in n-hexane and CH2Cl2 led to higher diastereoselectivity than a homogeneous solution in CH2Cl2 alone.Both allylsilane and -stannane led to homoallyl alcohols of predominant R configuration.The reaction was faster with allylstannane than with allylsilane.Allylation with allylmagnesium bromide showed the opposite diastereoselectivity.From a study of the effect of temperature, the enthalpy factor was found to be more important than the entropy factor.Some of the diastereomers (3a,b) were found to cyclize spontaneously to afford the corresponding lactones (5a,b).This lactonization process was highly stereoselective.Compounds 5a,b were separed from 4a,b, respectively, by preparative TLC.Removal of the chiral auxiliaries by methyllithium afforded essentially enantiomerically pure acyloins (6 and 9) (>98percent ee) of both enantiomers.