Binap–silver-catalyzed enantioselective multicomponent 1,3-dipolar cycloaddition of azomethines ylides derived from ethyl glyoxylate

The enantioselective binap–silver catalyzed multicomponent 1,3-dipolar cycloaddition using ethyl glyoxylate, phenylalanine ethyl ester, and maleimides is described. The employment of basic silver carbonate allows the reaction to take place in the absence of an extra base giving high yields and ee. In addition, low-level calculations regarding the importance of the benzyl substituent at the α-position of the amino ester justify the expected absolute configuration of the final cycloadducts and the observed high enantiodiscrimination.

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Diethyl (1S,3R,3aS,6aR)-1-benzyl-5-methyl-4,6-dioxooctahydropyrrolo[3,4-c]pyrrole-1,3-dicarboxylateC20H24N2O6Ee = 90% from HPLC[α]D20 = −23.8 (c 1, CHCl3)Source of chirality: (Sa)-binap

Diethyl (1S,3R,3aS,6aR)-1-benzyl-4,6-dioxooctahydropyrrolo[3,4-c]pyrrole-1,3-dicarboxylateC19H22N2O6Ee = 30% from HPLC[α]D20 = −12.8 (c 1, CHCl3)Source of chirality: (Sa)-binap

Diethyl (1S,3R,3aS,6aR)-1-benzyl-5-ethyl-4,6-dioxooctahydropyrrolo[3,4-c]pyrrole-1,3-dicarboxylateC21H26N2O6Ee = 88% from HPLC[α]D20 = −17.7 (c 1, CHCl3)Source of chirality: (Sa)-binap

Diethyl (1S,3R,3aS,6aR)-1,5-dibenzyl-4,6-dioxooctahydropyrrolo[3,4-c]pyrrole-1,3-dicarboxylateC26H28N2O6Ee = 80% from HPLC[α]D20 = −36.9 (c 1, CHCl3)Source of chirality: (Sa)-binap

Diethyl (1S,3R,3aS,6aR)-1-benzyl-4,6-dioxo-5-phenyl octahydropyrrolo[3,4-c]pyrrole-1,3-dicarboxylateC25H26N2O6Ee = 90% from HPLC[α]D20 = −28.0 (c 1, CHCl3)Source of chirality: (Sa)-binap

Diethyl (1S,3R,3aS,6aR)-1-benzyl-5-(4-bromophenyl)-4,6-dioxooctahydropyrrolo[3,4-c]pyrrole-1,3-dicarboxylateC25H25BrN2O6Ee = 92% from HPLC[α]D20 = −32.6 (c 1, CHCl3)Source of chirality: (Sa)-Binap