Chiral aminocyclopentene-based cycloaddition strategies to bicyclic [3.3.0] rings

Two cycloaddition methods were applied to chiral protected aminocyclopentenes 2 and 9 and provided novel bicyclic products 3 and 4 in good yields. The explanation for the observed stereochemistry was based on the sterically encumbered β-face forcing the cycloadditions to occur on the α-face of the cyclopentene ring. The stereochemistry of 4 was confirmed by X-ray of the fumarate salt 10 and showed the trans-relationship between the newly formed ring and the chiral –NHBoc group.

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(R)-Methyl 4-(tert-butoxycarbonylamino)cyclopent-1-enecarboxylateC12H19NO4[α]D25=-10.3 (c 1.13, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(2R,3aR,6aR)-Methyl 2-(bis(tert-butoxycarbonyl)amino)-5-methyleneoctahydropentalene-3a-carboxylateC21H33NO6[α]D25=-5.4 (c 1.14, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3aR,6aR)

(2R,3aS,6aS)-Methyl 2-(bis(tert-butoxycarbonyl)amino)-5-oxooctahydropentalene-3a-carboxylateC20H31NO7[α]D25=-31.1 (c 1.55, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3aS,6aS)

(3aR,5R,6aR)-Methyl 2-benzyl-5-(tert-butoxycarbonylamino) octahydrocyclopenta[c]pyrrole-3a-carboxylate fumarateC25H34N2O8[α]D25=+11.3 (c 1, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (3aR,5R,6aR)

(1S,4R)-2-Azabicyclo[2.2.1]hept-5-en-3-oneC6H7NO[α]D25=+551 (c 1, CHCl3)Source of chirality: commercialAbsolute configuration: (1R,4S)

(1R,4S)-Methyl 4-aminocyclopent-2-enecarboxylate hydrochlorideC7H12ClNO2[α]D25=+85.5 (c 1, EtOH)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,4S)

(1R,4S)-Methyl 4-(tert-butoxycarbonylamino)cyclopent-2-enecarboxylateC12H19NO4[α]D25=+59.6 (c 1, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,4S)

(R)-Methyl 4-(tert-butoxycarbonylamino)cyclopent-1-enecarboxylateC12H27NO6[α]D25=-10.3 (c 1.13, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)