Chiral Auxiliaries

Abstract

This chapter deals with the use of chiral auxiliaries for the asymmetric induction through a DKR process. In the last fifteen years, a wide number of various chiral auxiliaries have been employed in DKR processes occurring in different types of reactions, such as substitution reactions involving configurationally-labile alkyl halides or configurationally-labile anions, esterification and transesterification reactions, cyclocondensation reactions, reductions, cycloaddition reactions, and miscellaneous reactions. One of the most studied reactions has been the nucleophilic substitution on configurationally-labile alkyl halides, involving compounds with a bromo or iodo atom in the α-position with respect to a carboxylic acid derivative, in which the SN2 reaction is governed by a chiral auxiliary placed in the carboxylic moiety. Remarkable diastereoselectivities were particularly obtained by Caddick for nucleophilic substitution reactions of α-bromoacyl-imidazolidinones with nitrogen nucleophiles, together with those reported by Park for nucleophilic substitutions of α-bromo amides derived from chiral amino acids with nitrogen nucleophiles, allowing the synthesis of chiral di-, tri-, and tetrapeptides to be achieved. Several excellent results were also reported for esterification and transesterification reactions, such as the first example of DKR involving an intramolecular transesterification developed by Ishii, which provided a chiral 4-hydroxymethyl-2-oxazolidinone with an excellent diastereoselectivity starting from a serinol derivative. On the other hand, Bosch has developed highly diastereoselective DKR processes on the basis of cyclocondensation reactions of chiral aminoalcohols with δ-oxoacid derivatives, providing chiral bicyclic polysubstituted lactams. In addition, Ward has developed the synthesis of lairdinol A on the basis of a diastereoselective epoxidation of a (R)-carvone-derivative.