A general catalytic synthetic strategy for highly strained methylenecyclobutanes and spiromethylenecyclobutanes
Haotian Zhao, Yu Lin, Mingyu Jiang, Bo Su
Abstract
Highly strained methylenecyclobutanes (MCBs) are intriguing scaffolds in synthetic chemistry and drug discovery, but there is no such strategy that enables the synthesis of structurally diverse MCBs with defined stereochemistry. We report a general synthetic strategy for (boromethylene)cyclobutanes (BMCBs) and spiro-BMCBs by a challenging Cu-catalyzed highly chemo-, stereo-, and regioselective borylative cyclization of aliphatic alkynes. This strategy not only enables the installation of various functionalities at each site on the MCB skeleton with unambiguous stereochemistry but also introduces a versatile boromethylene unit that is readily transformable to a wide range of new functional groups; these features significantly expand the structural diversity of MCBs and are particularly valuable in drug discovery. The concise and divergent total syntheses of four cyclobutane-containing natural products were achieved from one common BMCB obtained by this strategy. The origin of the high regioselectivity in the borylcupration of alkynes and the high efficiency of the strained ring cyclization was also studied.