Conjugate glycine imine esters

Scheme 12.7 Asymmetric phase-transfer catalytic conjugate addition of glycine imine esters to o, l-unsaturated carbonyl compounds and its application to the synthesis of functionalized prolines.

Several conjugate addition protocols of glycine imine esters have been applied to the synthesis of natural products. In this context, Shibasaki and coworkers designed... 

Recently, Park and coworkers [112] described an efficient phase-transfer-catalyzed conjugate addition of the glycine imine ester 65a to ethyl 2-(phenylselanyl)acrylate 83. In the presence of catalyst 13b, the adduct 84 was obtained in almost qtxan-titative yield with 96% ee (Scheme 12.10). The potential application of this addition reaction was demonstrated as an important step in the synthesis of (-l-)-polyoxamic acid. 

The simplest amino acid, glycine, would be an ideal starting material for the synthesis of more complicated amino acids but it does not easily form enols or enoiates. The methyl ester of the ben-zaldehyde imine has two electro n-withdra wing groups to help stabilization of the enolate and conjugate addition of acrylonitrile is now possible. The base used was solid potassium carbonate with a quaternary ammonium chloride as phase transfer catalyst. Simple hydrolysis of the alkylated product leads to the extended amino acid. 

A short synthesis of (-f)-monomorine (1562) by Maruoka and coworkers used the chiral phase-transfer catalyst (R)-1672 to mediate an enantioselective conjugate addition between enone 1673 and the imine-protected glycine ester 1674 (Scheme 213). In a remarkable one-pot reaction, the intermediate adduct 1675 was then treated with Hantzsch ester (diethyl 2,6-dimethyl-l,4-dihydropyridine-3,5-dicarboxylate) in mildly acidic medium, which brought about deprotection of the acetal and imine as well as a double reductive amination in which the dihydropyridine acted as the hydrogen transfer agent. The resulting indolizidine ester (—)-1676 was... 

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