A novel diastereoselective 1,3-dipolar cycloaddition approach to cis-fused bispyrrolidines

The intramolecular cycloaddition reactions of non-stabilized azomethine ylides generated by the condensation of N-aryl glycines and an enantiopure N-allyl-tethered alkenyl aldehyde derived from (S)-phenyl alanine were investigated. The stereoselective reactions led to the formation of novel cis-fused enantiomerically pure octahydropyrrolo[3,4-b]pyrroles, and the strategy was expanded to the synthesis of enantiopure novel heterotricyclic skeletons, perhydrothiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroles.

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(S)-3-Phenyl-2-(tosylamino)propan-1-olC16H19NO3S[α]D29=-21.4 (c 1, CHCl3)Source of chirality: chiral starting materialAbsolute configuration: (S)

(S)-2-(N-Allyl-N-tosylamino)-3-phenylpropan-1-olC19H23NO3S[α]D29=-1.2 (c 1, CHCl3)Source of chirality: chiral starting materialAbsolute configuration: (S)

(S)-2-(N-Allyl-N-tosylamino)-3-phenylpropanalC19H21NO3S[α]D29=-0.2 (c 1, CHCl3)Source of chirality: chiral starting materialAbsolute configuration: (S)

(3aR,6S,6aR)-cis-1-Phenyl-5-tosyl-6-benzyl-octahydropyrrolo[3,4-b]pyrroleC26H28N2O2S[α]D28=+6.6 (c 1, CHCl3)Source of chirality: chiral starting materialAbsolute configuration: (3aR,6S,6aR)

(3aR,6S,6aR)-cis-1-(4-Methyl)-phenyl-5-tosyl-6-benzyl-octahydropyrrolo[3,4-b]pyrroleC27H30N2O2S[α]D29=27.5 (c 1, CHCl3)Source of chirality: chiral starting materialAbsolute configuration: (3aR,6S,6aR)

(3aR,6S,6aR)-cis-1-(4-Methoxy)-phenyl-5-tosyl-6-benzyl-octahydropyrrolo[3,4-b]pyrroleC27H30N2O3S[α]D29=+24.6 (c 1, CHCl3)Source of chirality: chiral starting materialAbsolute configuration: (3aR,6S,6aR)

(3aR,6S,6aR)-cis-1-(4-Chloro)-phenyl-5-tosyl-6-benzyl-octahydropyrrolo[3,4-b]pyrroleC26H27ClN2O2S[α]D28=+27.0 (c 1, CHCl3)Source of chirality: chiral starting materialAbsolute configuration: (3aR,6S,6aR)

(3aR,6S,6aR)-cis-1-(4-Bromo)-phenyl-5-tosyl-6-benzyl-octahydropyrrolo[3,4-b]pyrroleC26H27BrN2O2S[α]D29=+29.8 (c 1, CHCl3)Source of chirality: chiral starting materialAbsolute configuration: (3aR,6S,6aR)

(3aR,6S,6aR)-cis-1-(4-Fluoro)-phenyl-5-tosyl-6-benzyl-octahydropyrrolo[3,4-b]pyrroleC26H27FN2O2S[α]D27=+2.5 (c 1, CHCl3)Source of chirality: chiral starting materialAbsolute configuration: (3aR,6S,6aR)

(2S,3aR,4S,6aR,7aR)-cis-2-Phenyl-4-benzyl-5-N-(p-methyl)-benzenesulfonyl perhydro thiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroleC28H30N2O2S2[α]D29=-10.6 (c 1, CHCl3)Source of chirality: chiral starting materialAbsolute configuration: (2S,3aR,4S,6aR,7aR)

(2S,3aR,4S,6aR,7aR)-cis-2-(p-Methyl)-phenyl-4-benzyl-5-N-(p-methyl)-benzene sulfonyl perhydrothiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroleC29H32N2O2S2[α]D29=-14.8 (c 1, CHCl3)Source of chirality: chiral starting materialAbsolute configuration: (2S,3aR,4S,6aR,7aR)

(2S,3aR,4S,6aR,7aR)-cis-2-(p-Methoxy)-phenyl-4-benzyl-5-N-(p-methyl)-benzenesulfonyl perhydrothiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroleC29H32N2O3S2[α]D29=-15.8 (c 1, CHCl3)Source of chirality: chiral starting materialAbsolute configuration: (2S,3aR,4S,6aR,7aR)

(2S,3aR,4S,6aR,7aR)-cis-2-(p-Chloro)-4-benzyl-5-N-(p-methyl)-benzenesulfonyl perhydro thiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroleC28H29ClN2O2S2[α]D29=-12.8 (c 1, CHCl3)Source of chirality: chiral starting materialAbsolute configuration: (2S,3aR,4S,6aR,7aR)

(2R,3aR,4S,6aR,7aR)-cis-2-(p-Bromo)-phenyl-4-benzyl-5-N-(p-methyl)-benzenesulfonyl perhydrothiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroleC28H29BrN2O2S2[α]D29=-13.8 (c 1, CHCl3)Source of chirality: chiral starting materialAbsolute configuration: (2R,3aR,4S,6aR,7aR)

(2S,3aR,4S,6aR,7aR)-cis-2-(p-Fluoro)phenyl-4-benzyl-5-N-(p-methyl)-benzene sulfonyl perhydro thiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroleC28H29FN2O2S2[α]D29=-15.6 (c 1, CHCl3)Source of chirality: chiral starting materialAbsolute configuration: (2S,3aR,4S,6aR,7aR)