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 beta-lactones are accessible via the intramolecular catalytic, asymmetric nucleophile catalyzed aldollactonization reaction recently developed in our laboratory. These bicyclic beta-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-beta-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. (C) 2002 Elsevier Science Ltd. All rights reserved.