| Abstract
| - Highly enantioselective alkylation of protected glycine diphenylmethyl (Dpm) amide 1 and Weinrebamide 10 has been realized under phase-transfer conditions by the successful utilization of designer chiralquaternary ammonium salts of type 4 as catalyst. Particularly, remarkable reactivity of the chiral ammoniumenolate derived from 1b and 4c allowed the reaction with less reactive simple secondary alkyl halides withhigh efficiency and enantioselectivity. An additional unique feature of this chiral ammonium enolate is itsability to recognize the chirality of β-branched primary alkyl halides, which provides impressive levels ofkinetic resolution and double stereodifferentiation during the alkylation, allowing for two α- and γ-stereocenters to be controlled. Combined with the subsequent reduction using LiAlH4 in cyclopentyl methyl ether(CPME), this system offers a facile access to structurally diverse optically active vicinal diamines.Furthermore, the optically active α-amino acid Weinreb amide 11 can be efficiently converted to thecorresponding amino ketone by a simple treatment with Grignard reagents. In addition, reduction andalkylation of the optically active α-amino ketone into both syn and anti α-amino alcohols with almost completerelative and absolute stereochemical control have been achieved. With (S,S)- and (R,R)-4 in hand, thepresent approach renders both enantiomers of α-amino amides including Weinreb amides readily availablewith enormous structural variation and also establishes a general and practical route to vicinal diamines,α-amino ketones, and α-amino alcohols with the desired stereochemistry.
|
