Rational synthesis of contra-thermodynamic spiroacetals by reductive cyclizations.

ABSTRACT

A synthesis of spiroacetals was developed using a reductive cyclization strategy that leads stereoselectively to spiroacetals with a single anomeric stabilization. The method begins with the synthesis of spiro ortho esters. The ortho ester is converted to a cyano acetal. Reductive lithiation of the cyano acetal generates an axial dialkoxylithium reagent, and intramolecular cyclization produces a new ring with retention of configuration. The strategy is convergent and produces complex spiro acetals in only a few steps. The method will be useful in the synthesis of natural products and will facilitate the synthesis of previously inaccessible contra-thermodynamic acetals.