Binap-silver salts as chiral catalysts for the enantioselective 1,3-dipolar cycloaddition of azomethine ylides and alkenes

Binap-AgSbF6 catalyzed 1,3-dipolar cycloadditions between azomethine ylides and electrophilic alkenes are described and compared with analogous transformations mediated by other Binap-silver(I) salt complexes. Maleimides and 1,2-bis(phenylsulfonyl)ethylene are suitable dipolarophiles for obtaining very good enantioselectivities, even better values are generated by a multicomponent version. There are some very interesting applications of the disulfonylated cycloadducts in the total synthesis of cis-2,5-disubstituted pyrrolidines, precursors of natural products, or valuable intermediates in the synthesis of antiviral compounds.

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Methyl (1S,3R,3aS,6aR)-5-methyl-3-phenyl-4,6-dioxooctahydro pyrrolo[3,4-c]pyrrole-1-carboxylateC15H16N2O4[α]D20=+140 (c 0.5, CHCl3) >99% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

Ethyl (1S,3R,3aS,6aR)-5-methyl-3-phenyl-4,6-dioxooctahydro pyrrolo[3,4-c]pyrrole-1-carboxylateC16H18N2O4[α]D20=+74 (c 1, CHCl3) 92% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

Isopropyl (1S,3R,3aS,6aR)-5-methyl-3-phenyl-4,6-dioxoocta hydropyrrolo[3,4-c]pyrrole-1-carboxylateC17H20N2O4[α]D20=+63 (c 1, CHCl3) 87% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

tert-Butyl (1S,3R,3aS,6aR)-5-methyl-3-phenyl-4,6-dioxoocta hydropyrrolo[3,4-c]pyrrole-1-carboxylateC18H22N2O4[α]D20=+33.9 (c 0.8, CHCl3) 91% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

Methyl (1S,3R,3aS,6aR)-5-methyl-3-(2-naphthyl)-4,6-dioxoocta hydropyrrolo[3,4-c]pyrrole-1-carboxylateC19H18N2O4[α]D20=+109.4 (c 1, CHCl3) >99% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

Methyl (1S,3R,3aS,6aR)-5-methyl-4,6-dioxo-3-o-tolyloctahydropyrrolo[3,4-c]pyrrole-1-carboxylateC16H18N2O4[α]D20=+50.8 (c 0.6, CHCl3) 70% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

Methyl (1S,3R,3aS,6aR)-3-(2-chlorophenyl)-5-methyl-4,6-dioxooctahydropyrrolo[3,4-c]pyrrole-1-carboxylateC15H15ClN2O4[α]D20=+27.1 (c 1, CHCl3) >99% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

Methyl (1S,3R,3aS,6aR)-5-methyl-3-(4-methylphenyl)-4,6-dioxooctahydropyrrolo[3,4-c]pyrrole-1-carboxylateC16H18N2O4[α]D20=+89 (c 0.4, CHCl3) 99% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

Methyl (1S,3R,3aS,6aR)-3-(4-chlorophenyl)-5-methyl-4,6-dioxooctahydropyrrolo[3,4-c]pyrrole-1-carboxylateC15H15ClN2O4[α]D20=+39 (c 0.8, CHCl3) 94% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

Methyl (1S,3R,3aS,6aR)-3-(3-pyridyl)-5-methyl-4,6-dioxooctahydropyrrolo[3,4-c]pyrrole-1-carboxylateC14H15N3O4[α]D20=+8 (c 0.5, CHCl3) 40% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

Methyl (1S,3R,3aS,6aR)-5-methyl-4,6-dioxo-3-(2-thienyl)octahydropyrrolo[3,4-c]pyrrole-1-carboxylateC13H14N2O4S[α]D20=+48 (c 0.6, CHCl3) 93% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

Methyl (1S,3R,3aS,6aR)-5-ethyl-4,6-dioxo-3-phenyloctahydropyrrolo[3,4-c]pyrrole-1-carboxylateC15H18N2O4[α]D20=+58.7 (c 0.5, CHCl3) 99% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

Methyl (1S,3R,3aS,6aR)-4,6-dioxo-3,5-diphenyloctahydropyrrolo[3,4-c]pyrrole-1-carboxylateC15H16N2O4[α]D20=+40.2 (c 0.5, CHCl3) 82% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

Methyl (1S,3R,3aS,6aR)-5-benzyl-4,6-dioxo-3-phenyloctahydropyrrolo[3,4-c]pyrrole-1-carboxylateC21H20N2O4[α]D20=+69.4 (c 1, CHCl3) 98% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

Methyl (1S,3R,3aS,6aR)-1,5-dimethyl-4,6-dioxo-3-phenyloctahydro pyrrolo[3,4-c]pyrrole-1-carboxylateC16H18N2O4[α]D20=+108.6 (c 1, CHCl3) 99% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

Methyl (1S,3R,3aS,6aR)-1-isobutyl-5-methyl-4,6-dioxo-3-(2-thienyl)octahydropyrrolo[3,4-c]pyrrole-1-carboxylateC17H22N2O4S[α]D20=+24.7 (c 1, CHCl3) 91% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

Methyl (1S,3R,3aS,6aR)-1-benzyl-5-methyl-4,6-dioxo-3-phenyl octahydropyrrolo[3,4-c]pyrrole-1-carboxylateC22H22N2O4[α]D20=-75.8 (c 0.8, CHCl3) 99% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (1S,3R,3aS,6aR)

Methyl (2R,3R,4R,5S)-5-phenyl-3,4-bis(phenylsulfonyl)pyrrolidine-2-carboxylateC24H23NO6S2[α]D20=+1.2 (c 1, CHCl3) 90% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (2R,3R,4R,5S)

Methyl (2R,3R,4R,5S)-5-(naphth-2-yl)-3,4-bis(phenylsulfonyl) pyrrolidine-2-carboxylateC28H25NO6S2[α]D20=+17.1 (c 0.5, CHCl3) 92% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (2R,3R,4R,5S)

Methyl (2R,3R,4R,5S)-2-methyl-5-(naphth-2-yl)-3,4-bis(phenyl sulfonyl)pyrrolidine-2-carboxylateC29H25NO6S2[α]D20=+5.2 (c 1, CHCl3) 24% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (2R,3R,4R,5S)

Methyl (2R,3R,4R,5S)-3,4-bis(phenylsulfonyl)-5-(o-tolyl)pyrrolidine-2-carboxylateC25H25NO6S2[α]D20=+1.7 (c 0.8, CHCl3) 18% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (2R,3R,4R,5S)

Methyl (2R,3R,4R,5S)-3,4-bis(phenylsulfonyl)-5-(p-tolyl)pyrrolidine-2-carboxylateC25H25NO6S2[α]D20=+2.3 (c 1, CHCl3) 88% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (2R,3R,4R,5S)

Methyl (2R,3R,4R,5S)-5-(4-methoxyphenyl)-3,4-bis(phenylsulfonyl)pyrrolidine-2-carboxylateC25H25NO7S2[α]D20=-4.5 (c 1, CHCl3) 12% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (2R,3R,4R,5S)

Methyl (2R,3R,4R,5S)-5-(4-chlorophenyl)-3,4-bis(phenylsulfonyl)pyrrolidine-2-carboxylateC24H22ClNO6S2[α]D20=+91.6 (c 1, CHCl3) 45% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (2R,3R,4R,5S)

Isopropyl (2R,3R,4R,5S)-5-(4-chlorophenyl)-3,4-bis(phenylsulfonyl) pyrrolidine-2-carboxylateC26H26ClNO6S2[α]D20=+37.0 (c 0.7, CHCl3) 40% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (2R,3R,4R,5S)

Methyl (2R,3R,4R,5S)-3,4-bis(phenylsulfonyl)-5-(pyrid-3-yl) pyrrolidine-2-carboxylateC23H22N2O6S2[α]D20=-63.9 (c 1.2, CH2Cl2) 93% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (2R,3R,4R,5S)

Methyl (2R,3R,4R,5S)-2-isobutyl-3,4-bis(phenylsulfonyl)-5-(thien-2-yl)pyrrolidine-2-carboxylateC22H20NO6S3[α]D20=+7.1 (c 1, CHCl3) 70% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (2R,3R,4R,5S)

Methyl (2R,3R,4R,5S)-2-isobutyl-3,4-bis(phenylsulfonyl)-5-(thiazol-2-yl)pyrrolidine-2-carboxylateC21H19N2O6S3[α]D20=+4.1 (c 1, CH2Cl2) 10% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (2R,3R,4R,5S)

Methyl (2S,5R)-5-phenylpyrrolidine-2-carboxylateC12H15NO2[α]D20=+19.0 (c 1, CH2Cl2) 90% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (2S,5R)

Methyl (2R,3S,4S,5S)-5-[2-(2-acetoxyethyl)-4,5-dimethoxyphenyl]-3,4-bis(phenylsulfonyl)pyrrolidine-2-carboxylateC30H33NO10S2[α]D20=-25.3 (c 1, CHCl3) 50% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration (2R,3S,4S,5S)

Methyl (2R,3R,4R,5S)-5-{3-[2-((tert-butyldimethylsilyl)oxy)ethyl]-1-(phenylsulfonyl)-1H-indol-2-yl}-3,4-bis(phenylsulfonyl)pyrrolidine-2-carboxylateC40H46N2O9S3Si[α]D20=-4.5 (c 1, CHCl3) 12% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (2R,3S,4S,5S)

tert-Butyl methyl (2S,4S,5R)-2-isobutyl-5-(thiazol-2-yl)pyrrolidine-2,4-dicarboxylateC18H28N2O4S[α]D20=+38.0 (c 1, CH2Cl2) 88% ee from HPLCSource of chirality: (Sa)-BinapAbsolute configuration: (2S,4S,5R)