We
report a one-step, Ru(II)-catalyzed cyclopropanation reaction that is
conceptually different from the previously reported protocols that include
Corey-Chaykovsky, Simmons-Smith, and metal catalyzed carbene attack on olefins.
Under the current protocol, various alcohols are transformed into sulfone
substituted cyclopropanes with excellent isolated yields and diastereoselectivities.
This new reaction forms highly congested cyclopropane products with three new
C–C bonds, three or two new chiral centers and one new quaternary carbon
center. 22 examples of isolated substrates are given. Previously reported
synthetic routes for similar substrates are all multi-step, linear routes that
proceed with overall low yields and poor control of stereochemistry.
Experimental mechanistic investigations suggest initial metal-catalyzed
dehydrogenation of the alcohol substrate and catalyst independent stepwise
attack of two equivalents of sulfone on the aldehyde under basic conditions.
While the Ru(II) is only responsible for the initial dehydrogenation step, the
rate of aldehyde formation is crucial to maintaining the right balance of
intermediates needed to afford the cyclopropane product.
Highly Diastereo- and Enantioselective Synthesis of Nitrile-Substituted Cyclopropanes by Myoglobin-Mediated Carbene Transfer Catalysis
