Cp*Rh(III)-catalyzed enantioselective C(sp³)–H amidation of cyclobutanes Xing Xu 1 , Ken Yamazaki 1,2 , Darren J. Dixon 1 1 Department of Chemistry, University of Oxford, Oxford, UK, 2 Division of Applied Chemistry, Okayama University, Japan. Cyclobutanes and N-containing heteroaromatics are core units found in many natural products and are important motifs embedded in a variety of biologically active molecules. However, the synthesis of cyclobutane scaffolds with precisely-controlled selectivity has proven difficult according to the previous methods. Most cyclobutane skeletons obtained through [2+2] photocycloaddition processes tend to be 1,3-disubstituted, or multi-substituted isomers, and suffer from poor stereoselectivity; meanwhile, the direct C(sp 3 )–H functionalization of saturated cyclobutanes has received limited attention from the synthetic community. 1 This work describes the first expedient access to affording the enantioenriched amidated cyclobutanes through the direct asymmetric C(sp 3 )–H amidation of cyclobutanes with useful pyrimidine as a strong coordinating directing group in combination with an electron-deficient Cp*Rh(III) catalyst. 2 A newly designed axially chiral carboxylic acid (CCA) was found to be the key to obtaining high levels of enantiocontrol. We envision this methodology will broaden access towards enantioenriched cyclobutane building blocks and stimulate new developments in the merger of enantioselective desymmetrization with Rh-catalyzed C–H activation.
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