Diastereoselective Synthesis of Spiro[2,n]alkanes via Intramolecular Carbolithiation

Abstract

Spirocycles are appealing motifs for drug design owing to their inherently rigid three-dimensional structure, but synthetic strategies to construct highly substituted spiroalkanes remain scarce. We report a highly diastereoselective protocol for the synthesis of spiro[2.n]alkanes via intramolecular carbolithiation of cyclopropenes. The methodology provides straightforward access to spiro[2.n]alkanes sizes as single diastereomers, with up to three contiguous quaternary centres. The trapping of a generated intermediate with an electrophile provides access to functionalized spirocycles bearing halo, silyl, alcohol or carbonyl functionalities