Highly Enantioselective Phase-Transfer-Catalyzed Alkylation of Protected α-Amino Acid Amides toward Practical Asymmetric Synthesis of Vicinal Diamines, α-Amino Ketones, and α-Amino Alcohols
- 17 March 2005
- journal article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 127 (14) , 5073-5083
- https://doi.org/10.1021/ja0459328
Abstract
Highly enantioselective alkylation of protected glycine diphenylmethyl (Dpm) amide 1 and Weinreb amide 10 has been realized under phase-transfer conditions by the successful utilization of designer chiral quaternary ammonium salts of type 4 as catalyst. Particularly, remarkable reactivity of the chiral ammonium enolate derived from 1b and 4c allowed the reaction with less reactive simple secondary alkyl halides with high efficiency and enantioselectivity. An additional unique feature of this chiral ammonium enolate is its ability to recognize the chirality of β-branched primary alkyl halides, which provides impressive levels of kinetic 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 the corresponding amino ketone by a simple treatment with Grignard reagents. In addition, reduction and alkylation of the optically active α-amino ketone into both syn and anti α-amino alcohols with almost complete relative and absolute stereochemical control have been achieved. With (S,S)- and (R,R)-4 in hand, the present approach renders both enantiomers of α-amino amides including Weinreb amides readily available with 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.Keywords
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