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Copper‐Catalyzed 1,5‐Addition of Grignard reagents to Enantioenriched Donor–Acceptor Cyclopropanes with Inversion
Author(s) -
Takada Seijiro,
Saito Taichi,
Iwata Kiitsu,
Nishii Yoshinori
Publication year - 2016
Publication title -
asian journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.846
H-Index - 44
eISSN - 2193-5815
pISSN - 2193-5807
DOI - 10.1002/ajoc.201600313
Subject(s) - chemistry , stereoselectivity , bicyclic molecule , isomerization , aryl , reagent , regioselectivity , alkylation , protonation , catalysis , medicinal chemistry , enantioselective synthesis , enol , alkyl , organic chemistry , stereochemistry , ion
A highly regioselective and stereoselective 1,5‐addition of alkyl groups to enantioenriched donor–acceptor cyclopropanes 1 and bicyclic cyclopropanes such as 6‐aryl‐1‐methoxycarbonyl‐3‐oxabicyclo[3.1.0]hexan‐2‐ones 4 using a Grignard reagent with a catalytic amount of Cu(OTf) 2 (0.1 equivalent) afforded optically active diesters 2 or trans ‐α,β‐disubstituted γ‐butyrolactones 5 with an excellent level of stereoinduction. An excess of the Grignard reagent is necessary to perform the 1,5‐alkylation with high yields. In the reaction of the enantioenriched bicyclic lactone 4 , a highly stereoselective 1,5‐addition and subsequent highly trans ‐selective protonation of the magnesium enolate via keto‐enol isomerization furnished the trans ‐α,β‐disubstituted‐γ‐lactones with three contiguous chiral centers with excellent enantioselectivity. Based on the results, we also proposed the mechanism through cluster ion pairs or a simple ion pair to rationalize the high stereoselectivity of the reaction.