Synthetic studies on cyclobuta[a]indanes: stereocontrolled access to C9-substituted derivatives

We report the preparation of novel ethyl cyclobuta[a]indane derivatives of pharmacological interest. The synthesis of compounds 5 was used as a model to study stereocontrolled access to C9-substituted cyclobutane from the corresponding cyclobutanone 1. Progress was made on two complementary aspects: (1) catalytic hydrogenation from the appropriate cyclobutene precursors; and (2) delivery of the C9 substituent through an intramolecular process. The level of diastereoselectivity obtained through hydrogenation of cyclobutene depends both on the metal used as catalyst and the nature of the functional group proximal to the double bond. The intramolecular delivery approach was diastereospecific, provided that the spiro-intermediate 7 does not ring open during the stereoinduction step. The latter route should allow preparation of quaternary carbon at C9 not available through hydrogenation.