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Rapid Access to β‐Trifluoromethyl‐Substituted Ketones: Harnessing Inductive Effects in Wacker‐Type Oxidations of Internal Alkenes
Author(s) -
Lerch Michael M.,
Morandi Bill,
Wickens Zachary K.,
Grubbs Robert H.
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201404712
Subject(s) - trifluoromethyl , regioselectivity , chemistry , allylic rearrangement , methylene , trifluoromethylation , wacker process , yield (engineering) , fluorine , organic chemistry , catalysis , palladium , alkyl , materials science , metallurgy
We present a practical trifluoromethyl‐directed Wacker‐type oxidation of internal alkenes that enables rapid access to β‐trifluoromethyl‐substituted ketones. Allylic trifluoromethyl‐substituted alkenes bearing a wide range of functional groups can be oxidized in high yield and regioselectivity. The distance dependence of the regioselectivity was established by systematic variation of the number of methylene units between the double bond and the trifluoromethyl group. The regioselectivity enforced by traditional directing groups could even be reversed by introduction of a competing trifluoromethyl group. Besides being a new powerful synthetic method to prepare fluorinated molecules, this work directly probes the role of inductive effects on nucleopalladation events.