Glycine imine esters

Glycine imine esters, Ph2C=N-CH2-C02R, undergo asymmetric Michael addition to enones using an ether-water phase-transfer system.218 A chiral ammonium salt, in conjunction with cesium carbonate, gives high ees. 

KOH/kaolin combined with a chiral catalyst was used for asymmetric alkylation of glycine imine esters, and recycled for subsequent reactions without loss of activity over three times [55, 56]. 

FIG. 7 Asymmetric phase transfer catalysis alkylation of glycine imine esters. 

Scheme 16.10 Enantioselective phase-transfer catalytic diallq lation using polymer-supported glycine imine esters 15 and 17.

Recently, Sirit and co-workers [45] developed calixarene-based chiral phase-transfer catalysts derived from cinchona alkaloids successfully used for alkylation of glycine-imine esters. In 2010, Itsuno et al. [46] published quartemary ammonium sulfonate polymers used for a-alkylation reaction of a glycine imine ester with high yields and enantioselectivity. 

Based on the catalyst design limitation arising from their synthesis, other chiral quaternary ammonium salts were developed, such as Ca-symmetrical PTC catalysts XXVIII [53], spermidine- and spermine-based catalysts XXIX [54], bis-biphenyl quaternary ammonium salts XXX [55], and other chiral quaternary ammonium salts of types XXXI and XXXII [56]. V-spiro chiral ammonium salt XXXI and XXXII (the later, readily available from gallic acid) possessing flexible alkyl chains showed high catalytic efficiency in alkylations of glycine-imine esters even in the presence of 0.01-0.05 mol% of XXXI or XXXII (Scheme 8.6) [57]. 

Readily available chiral cyclopropenimine (13) catalyses Mannich reactions of A-Boc-aldimines (14) and glycine imines (15), with yields/rZe/ee up to 97/98/95%." The vicinal diamino stereoarray of the products (16) allows access to many useful derivatives, and the t-butyl ester of the product (16, = BuO is amenable to acidic deprotection. In the... 

Scheme 12.1 Asymmetric phase-transfer catalytic alkylation of glycine imine ester 65a.

Scheme 12.5 Asymmetric double alkylation of glycine imine ester 72 under phase-transfer conditions.

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... 

By using the catalyst (S)-37b, Maruoka s group reported the asymmetric addition of glycine imine ester 65c to a,p-enone 81 to afford the corresponding adduct 82 [111]. Subsequently, the one-pot transformation including intramolecular reductive amination, acetal hydrolysis, and second reductive amination was effected with the Hantzsch ester and trifluoroacetic acid in aqueous ethanol to furnish the octahydropyrrolizine core structure with excellent enantioselectivity. This product was further converted into (-I-) -monomorine in three additional steps (Scheme 12.9). 

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. 

Maruoka and coworkers described a direct phase-transfer-catalyzed Mannich reaction of the glycine imine ester 65a with a-imino ester. N-spiro quaternary ammonium bromide (S,S)-31c was identified as an efficient catalyst under LL (aqueous NaOH-mesitylene) phase-transfer conditions (Scheme 12.12) [114]. The usefulness of the Mannich adduct 86 was further demonstrated by the conversion into an optically pure precursor 87 of streptolidine lactam. 

Scheme 12.11 Asymmetric phase-transfer catalytic aldol condensation of glycine imine ester 6Sa with aldehyde and its application to the synthesis of p-hydroxy-a-amino ester 85.

By using tartrate-derived bisammonium salts as chiral phase-transfer catalysts, Shibasaki and coworkers developed the asymmetric Mannich condensation of glycine imine ester 65a with N-Boc-protected aldimines [82,115]. The condensation products were obtained with high diastereoselectivities and moderate to good enantioselectivities. This method could be applied to access the enantiomerically enriched 3-amino pyrrolidine intermediate 88 for the further synthesis of (-1-)-nemonapride (Scheme 12.13). 

Scheme 12.12 Asymmetric phase-transfer catalytic Mannich reaction of glycine imine ester 65a with a-amino ester and its further conversion into streptolidine lactam precursor 87.

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