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Site-Selective and Stereoselective C-H Functionalization of N-Cyclopropylamides via a Directed Remote Metalation
Yuri Ermolovich1,2, Maryia V Barysevich1,3, Jasper Adamson4
1Department of Chemistry and Biotechnology, School of Science , Tallinn University of Technology , Tallinn 12618 , Estonia.
Abstract:
A new methodology for site-selective and stereoselective C-H functionalization of aminocyclopropanes via directed remote lithiation has been developed. Treatment of N-directing group (DG = pivaloyl, tetramethylsuccinimidoyl) arylcyclopropanes with t-BuLi results in a clean β-lithiation and, following quench with electrophiles, leads to a range of cyclopropane derivatives. Sequential double lithiation-methylation to give a dimethylated cyclopropane has been achieved. X-ray, NMR, and computational studies allow rationalization of syn-DG β-deprotonation selectivity via a DG-lithium base coordinated complex.
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