A New Variant of the Kulinkovich Hydroxycyclopropanation. Reductive Coupling of Carboxylic Esters with Terminal Olefins

摘要

Cyclopropanols are valuable synthetic intermediates because of their facile, selective ring-opening reactions to afford intermediates synthetically useful for subsequent structural elaboration. Recently, Kulinkovich reported a diastereoselec-tive hydroxycyclopropanation, which involves treatment of a carboxylic ester with an excess (3 equiv) of Grignard reagent at -78 to 0 °C in the presence of Ti(O-i-Pr)_4 (cat or 1 equiv), affording cis-l,2-dialkylcyclopropan-l-ol in good yield (eq 1). An enantioselective version was achieved by Corey by use of TADDOL. We have successfully implemented the Kulinkovich hydroxycyclopropanation in the stereocontrolled construction of seven- or eight-membered carbocycles by its tandem application with the oxy-Cope rearrangement. The major shortcoming of the original Kulinkovich procedure lies in the requirement of at least 2 equiv of the Grignard reagent, since 1 equiv of the reagent is sacrificed as the corresponding hydrocarbon (R_1CH_2CH_3) during the formation ofthe putative titanacyclopropane intermediate 3. While acceptable for commercially available Grignard reagents, such loss is too inefficient and costly, particularly for synthetically prepared, valuable Grignard reagents. Herein we report an efficient solution by utilizing Ti(O-i-Pr)_4-mediated reductive coupling of carboxylic esters with monosubstituted olefins.