Stereospecific nucleophilic substitution at all-carbon quaternary centers of 3,3-dialkylcyclobutanones with chloride

We investigated stereospecific nucleophilic substitution of optically active 3,3-dialkylcyclobutanones with chloride ion to afford ring-cleaved 3-chloro-3,3-dialkyl ketones in the presence of TiCl4 and Me3SiCl. Optically active substrates were prepared by optical resolution of racemic cyclobutanones through CBS reduction, chromatographic separation, and oxidation. A high degree of stereospecific inversion of configuration at the quaternary carbon center (from er = 98:2 to 91:10) was observed for 2,2-diphenyl-3-(2-phenylethyl)cyclobutanone. Experimental studies varying substituents, combined with DFT calculation, suggest that high stereospecificity is governed by stabilization of nonclassical cyclopropylcarbinyl cations by cation-πconjugation with adjacent aromatics or cation-π interactions with a remote phenyl group.