Asymmetric transfer hydrogenation amino acid derivatives

Metal-based asymmetric phase-transfer catalysts have mainly been used to catalyze two carbon-carbon bond-forming reactions (1) the asymmetric alkylation of amino acid-derived enolates and (2) Darzens condensations [5]. The alkylation ofprochiral glycine or alanine derivatives [3] is a popular and successful strategy for the preparation of acyclic a-amino acids and a-methyl-a-amino acids respectively (Scheme 8.1). In order to facilitate the generation of these enolates and to protect the amine substituent, an imine moiety is used to increase the acidity of the a-hydrogens, and therefore allow the use of relatively mild bases (such as metal hydroxides) to achieve the alkylation. In the case of a prochiral glycine-derived imine (Scheme 8.1 R3 = H), if monoalkylation is desired, the new chiral methine group... 

Antilla and coworkers also developed asymmetric transfer hydrogenation reaction by means of 50, derived from VAPOL (Scheme 11.13) [24]. They realized the highly enantioselective transfer hydrogenation of acyclic a-imino ester 51 by the combination of 39 and 50 to furnish synthetically useful a-amino acid derivatives 52 in excellent enantioselectivities (94—99% ee). They also achieved reductive ami-nation of alkyl-substituted kettmines (R = alkyl) in the presence of dehydrating agent (4A MS). 

Fig. 19 Amino acid-derived tridentate click chelators, 86, used as ligands in asymmetric transfer hydrogenation (ATH) reactions...

Ahlford K, Ekstrom J, Zaitsev AB, Ryherg P, Eriksson L, Adolfsson H. Asymmetric transfer hydrogenation of ketones catalyzed by amino acid derived rhodium complexes on the origin of enantioselectivity and enantioswitchabihty. Chemistry. 2009 15(42) 11197-11209. 

SCHEME 31.32. The a- and (3-amino acid derivatives synthesis through an asymmetric hydrogen transfer. 

The scope of this reaction was expanded with the development of the asymmetric transfer hydrogenation of P-y-alkynyl a-imino esters. In this reaction, both imine and aUcyne undergo reduction to yield synthetically challenging franx-alkenyl amino acid derivatives [65]. It was shown that conjugate hydride transfer to the alkyne takes place first, as propargyl a-amino esters failed to undergo reduction under the reaction conditions. 

Secondary Amines.—The reduction of imines to the corresponding secondary amines can be effected by various methodologies. New additions are the sodium triacyloxyborohydrides (easily obtainable from sodium borohydride and AT-acyl derivatives of optically active amino-acids), which are used for the asymmetric reduction of cyclic imines. Also now available is a highly stereoselective reduction of N-benzylimines derived from substituted cyclohexanones, with alkali-metal borohydrides, in particular L-selectride. A fiuther addition is the first report of the reduction of aldimines by hydrogen transfer from propan-2-ol,... 

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