A comparative study of the solvolysis reactivity, regioselectivity, and stereochemistry of the duocarmycin a and sa alkylation subunits

The comparative solvolysis reactivity, regioselectivity, and stereochemistry of N-BOC-DSA (4) and N-BOC-DA (5), simple derivatives of the DNA alkylation subunits of duocarmycin SA and A, are detailed. Most important of the observations is the substantially greater reactivity of 5 versus 4 (16x), the modest regioselectivity of both 4 (6.5-4:1) and 5 (1.5:1), and the establishment that the abnormal ring expansion solvolysis proceeds by SN2 addition to the activated cyclopropane with clean inversion of the reacting center stereochemistry.