Over the past decades, considerable attention has been devoted to the development of asymmetric methodologies for the synthesis of cyclopropane derivatives. However, the examples of enantioselective cyclopropanation reactions via Michael-Initiated Ring Closure (MIRC) between α,β-unsaturated aldehyde and diazo compounds are uncommon. Recently, we developed chiral oxazaborolidinium ion (COBI) catalyzed enantioselective cyclopropanation of α- or α,β-substituted acroleins with various α-alkyl diazo compounds providing highly functionalized cyclopropane compounds with excellent trans/cis ratio (>20:1) and stereoselectivity (up to >99% ee). The synthetic utility of this methodology was demonstrated in the first total synthesis and absolute structure determination of Hamavellone B exhibiting antimalarial activity.
We envisaged that this approach could be extended to enantioselective synthesis of 2,5-dihydrooxepine. While 2,5-dihydrooxepine has been synthesized by retro-Claisen rearrangement of the corresponding vinylcyclopropylcarboxaldehyde, examples of asymmetric synthesis of 2,5-dihydrooxepines using this approach are rare due to the multiple steps required for the preparation of the chiral vinylcyclopropylcarboxaldehyde. Here, we report COBI-catalyzed enantioselective synthesis of 2,5-dihydrooxepine through tandem-cyclopropanation-retro-Claisen rearrangement with α-vinyl diazo compounds. A wild range of 2,5-dihydrooxepines with aliphatic and aromatic group were obtained in high yield (up to 86%) and excellent enantioselectivity (up to >99% ee).