Corey‐Сhaykovsky cyclopropanation of dehydroalanine in the Ni(II) coordination environment: Electrochemical vs. chemical activation

Abstract

The Corey-Chaykovsky method was used for α,α-cyclopropanation of dehydroalanine in the form of chiral Ni(II) Schiff-base complexes. For generation of the Corey ylide, electrochemical and chemical deprotonation were tested. For sulphonium salts more easily reduced than the Michael acceptor, the direct electrochemical reduction of the salt in the presence of the dehydroalanine complex gives almost quantitative yield of the cyclopropanated amino acid derivative. For the salts reduced at more cathodic potentials than the Ni-Schiff-base complex and are not prone to rearrangements, electrochemical deprotonation followed by the addition of the complex gives significantly higher yield of the cyclopropanated complex then deprotonation with common bases. Notably, insertion of the substituent either in the sulphonium salt or at the double bond of the dehydroalanine complex yields formation of the cyclopropane derivatives with the opposite configurations of the β-stereocenter. The (R;R,cis)-isomer dominates in the former case whereas the (S;R,trans)-diastereomer is formed in the latter case. To shed light on the stereoselectivity observed, the activation free energies for four alternative ring-closure steps leading to four possible diastereomers were calculated using the DFT approach.