Mechanistic Insights on the Selectivity of the Tandem Heck–Ring-Opening of Cyclopropyldiol Derivatives
Anthony Cohen, Alexander Kaushansky, Ilan Marek
Abstract
The preparation of a new class of alkenyl cyclopropyl diols, easily available through a copper-catalyzed carbometalation reaction of cyclopropenes, has enabled the study of key mechanistic aspects of the tandem Heck-cyclopropane ring-opening reaction. Utilizing these substrates containing two distinct hydroxyl groups allowed us to examine parameters affecting the reaction outcome and selectivity. The combination of these experimental results with detailed DFT studies shed light on the mechanism governing the regio- and stereoselectivity of the cyclopropane ring-opening. A thorough investigation displayed the dual roles fulfilled by the hydroxyl group during the reaction, which is key to this remarkable transformation. In addition to its mechanistic implication, the reaction granted access to various lactones possessing up to four stereocenters as a single diastereomer, conveniently prepared in only two catalytic steps from easily accessible achiral cyclopropenes.