Highly Enantio- and Diastereoselective Synthesis of 1,2,3-Trisubstituted Cyclopropanes from α,β-Unsaturated Amides and Stabilized Sulfur Ylides Catalyzed by a Chiral Copper(I) Complex
datasetposted on 03.09.2021, 12:37 authored by Santosh K. Pagire, Naoya Kumagai, Masakatsu Shibasaki
The stereoselective preparation of 1,2,3-substituted cyclopropanes from α,β-unsaturated carbonyl compounds in the carboxylic acid oxidation state through Michael addition-initiated ring-closure reactions is a significant challenge in organic synthesis. Herein, the previously elusive catalytic asymmetric cyclopropanation of α,β-unsaturated amides with stabilized sulfur ylides has been efficiently accomplished utilizing a chiral Cu(I) complex. This Lewis acid catalytic system effectively converts a wide range of electron-deficient alkenes into the corresponding 1,2,3-trisubstituted cyclopropanes under mild reaction conditions in good to excellent yields with both high to excellent enantio- and diastereoselectivities. The resulting enantiomerically enriched cyclopropane amides can be readily diversified into promising synthetic intermediates such as β-aminocyclopropanecarboxylic acids with the facile recovery of the 7-azaindoline auxiliary without influencing the optical purity of the cyclopropane unit, which highlights the synthetic efficacy of this catalytic approach.
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stabilized sulfur ylidesmild reaction conditionsefficiently accomplished utilizingunsaturated carbonyl compoundspromising synthetic intermediateschiral cu (unsaturated amidessynthetic efficacychiral copperwide rangetrisubstituted cyclopropanessubstituted cyclopropanesstereoselective preparationsignificant challengereadily diversifiedorganic synthesisoptical puritymichael additioninitiated ringhighly enantiofacile recoveryexcellent yieldsexcellent enantiodiastereoselective synthesisdeficient alkenescyclopropane unitclosure reactionscatalytic approachaminocyclopropanecarboxylic acids