Synthesis and conformational studies of 9-benzyloxy-18-substituted [3.3]metacyclophanes

A series of syn-[3.3]metacyclophanes (MCPs) containing internal substituted benzyloxy group have been synthesized by the modified TosMIC coupling reaction followed by acid treatment and Wolff-Kishner reduction. anti-Mono-and di-benzyloxy[3.3]MCPs are synthesized by O-benzylation of the corresponding hydroxy[3.3]MCPs, which are obtained by demethylation of methoxy[3.3]MCPs with BBr₃ at room temperature. An interesting and intriguing result was obtained when syn-6,15-di-tert-butyl-9-methoxy-18-methyl[3.3]MCP-2,11-dione was treated with TMSI to afford the formation of a dihydrobenzofuran ring by a nucleophilic intramolecular cyclization reaction. The ¹H NMR and X-ray analysis of 6a confirms that it adopts a syn (chair-chair) conformation in both solution and solid state.