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HFO‐1234yf as a CF 3 ‐Building Block: Synthesis and Chemistry of CF 3 ‐Ynones
Author(s) -
Murray Ben J.,
Marsh Thomas G. F.,
Yufit Dmitri S.,
Fox Mark A.,
Harsanyi Antal,
Boulton Lee T.,
Sandford Graham
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202001071
Subject(s) - chemistry , nucleophile , lithium (medication) , alcohol , stereoselectivity , amine gas treating , organic chemistry , michael reaction , enone , combinatorial chemistry , catalysis , medicine , endocrinology
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.