HFO‐1234yf as a CF<sub>3</sub>‐Building Block: Synthesis and Chemistry of CF<sub>3</sub>‐Ynones
Ben J. Murray, Thomas G. F. Marsh, Dmitri S. Yufit, Mark A. Fox, Antal Harsányi, Lee T. Boulton, Graham Sandford
Abstract
Reaction of low cost, readily available 4 th generation refrigerant gas 2,3,3,3‐tetrafluoropropene (HFO‐1234yf) with lithium di iso propylamide (LDA) leads to formation of lithium 3,3,3‐trifluoropropynide, addition of which to a range of aldehydes formed CF 3 ‐alkynyl alcohol derivatives on multigram scale, which were oxidised using Dess–Martin periodinane (DMP) to give substituted CF 3 ‐ynones with minimal purification required. Michael‐type additions of alcohol and amine nucleophiles to CF 3 ‐ynones are rapid and selective, affording a range of CF 3 ‐enone ethers and enaminones in excellent yields with high stereoselectivity for the Z ‐isomer. By analogous reactions with difunctional nucleophiles, a wide range of CF 3 ‐substituted pharmaceutically relevant heterocyclic structures can be accessed, exemplified in the simple synthesis of the anti‐arthritis drug celecoxib from HFO‐1234yf in just three steps.