Stereospecific Cross‐Coupling Reactions Provide Conformationally‐Biased Arylalkanes with Anti‐Leukemia Activity

Abstract

A focused small library of carbamates and alcohols was prepared employing stereospecific Kumada-ring opening reactions of tetrahydropyrans. The core framework of the library members is acyclic and incorporates 1,3-substituents, to provide a conformational bias in avoiding syn-pentane interactions. A new compound with micromolar activity against MOLT-4, CCRF-CEM, and HL-60(TB) leukemia cell lines was identified from this series. Scheme 1. a) Stereospecific ring-opening Kumada reaction. b) Library synthesis. Scheme 2. Alcohols synthesized via Kumada ring-opening crosscoupling reaction. Syn-(�)-5 used rac-BINAP as the ligand. Scheme 3. Dimethyl and morpholine carbamate derivatives. CommunicationIsr. J. Chem. 2020, 60, 402 -405