Nucleophilic openings of bicyclic β-lactones via acyl C–O and alkyl C–O cleavage: catalytic, asymmetric synthesis of a versatile, carbocyclic nucleoside precursor and protected transpentacin

A variety of carbocycle-fused β-lactones are accessible via the intramolecular catalytic, asymmetric nucleophile catalyzed aldol-lactonization reaction recently developed in our laboratory. These bicyclic β-lactones undergo facile ring cleavage under mild conditions via both acyl C–O and alkyl C–O bond cleavage. Cleavage of the acyl C–O bond with hydroxylamine nucleophiles proceeds at ambient temperature and reductive cleavage is readily accomplished with aluminum and boron reducing agents. Alternatively, alkyl C–O cleavage with various nucleophiles leads to a variety of trans-β-substituted cyclopentane carboxylic acids. The utility of these transformations is demonstrated by the synthesis of protected (1S,2S)-transpentacin and a versatile diol for carbocyclic nucleoside synthesis.