Abstract
The stereoselective construction of spirocyclic compounds as medicinally relevant scaffolds is of considerable current interest. One underexplored area in this field is the asymmetric synthesis of spirocyclopropanes via transition-metal catalysis, using α-diazo lactones and lactams as carbene precursors. In this study, we report a Rh(2)(S-p-PhTPCP)(4)-catalyzed [2 + 1] cyclopropanation between 3-diazo δ-lactones and lactams and a wide range of alkene substrates, enabling the facile synthesis of 5-oxa and 5-azaspiro[2.5]octanones in yields up to 98%, reasonable levels of diastereoselectivity (up to 11:1 d.r.), and high levels of enantioselectivity (up to 98% ee). The reaction can be run with 0.00005 mol % of catalyst, resulting in 1,740,000 TON, while maintaining stereocontrol. The ring size of the diazo compound, in conjunction with the reaction temperature, has a considerable influence on the reaction. While the reaction with the 5-membered system gave diminished stereoselectivity, the 7-membered counterpart gave enhanced stereocontrol (>30:1 d.r., 99% ee), but the reaction needed to be carried out at low temperatures to avoid a side-reaction caused by a 1,2-hydride shift.