ORGANIC
LETTERS
2011
Vol. 13, No. 13
3470–3473
Trifluoromethanesulfonic Acid Catalyzed
Isomerization of Kinetic Enol Derivatives
to the Thermodynamically Favored
Isomers
Phil Ho Lee,*,† Dongjin Kang,† Subin Choi,† and Sunggak Kim*,‡
Department of Chemistry, Kangwon National University, Chuncheon 200-701,
Republic of Korea, and Division of Chemistry and Biological Chemistry,
School of Physical and Mathematical Sciences,
Nanyang Technological University, Singapore 637371, Singapore
phlee@kangwon.ac.kr; sgkim@ntu.edu.sg
Received May 6, 2011
ABSTRACT
Trifluoromethanesulfonic acid catalyzed isomerization of kinetic enol derivatives to the thermodynamically favored isomers was developed.
Under the present conditions, kinetic enol phosphates, enol acetates and benzoates, and enol sulfonates were smoothly isomerized to produce
the corresponding thermodynamically favored isomers in good to excellent yields.
Considerable attention has been focused on the selective
synthesis of enol derivatives due to their usefulness in
various synthetic transformations.1 An early, and still
frequently used, route to enol derivatives is the trapping
of ketone or aldehyde enolates generated in situ under
either kinetic- or equilibrium-controlled conditions.2 The
major issue in these transformations is selectivity (kinetic
vs. thermodynamic). In particular, the more substituted
thermodynamic enol derivatives from unsymmetrical ke-
tones normally predominate under thermodynamic con-
ditions but do not form exclusively, which is a serious
problem in the regioselective alkylation of unsymmetrical
ketones.3 Moreover, hydrolysis of labile enol derivatives to
carbonyl compounds provokes another problem. Thus,
† Kangwon National University.
‡ Nanyang Technological University.
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10.1021/ol2012132
Published on Web 06/09/2011
2011 American Chemical Society