Angewandte
Chemie
DOI: 10.1002/anie.201301529
Copper Catalysis
Copper-Catalyzed Arylative Meyer–Schuster Rearrangement of
Propargylic Alcohols to Complex Enones Using Diaryliodonium Salts**
Beatrice S. L. Collins, Marcos G. Suero, and Matthew J. Gaunt*
Propargylic alcohols are among the most useful bifunctional
building blocks available to the synthetic chemist. Generated
through well-established and robust strategic bond-forming
reactions, propargylic alcohols have provided a fertile testing
ground upon which to explore new catalytic activation
pathways. Many previously unknown catalytic transforma-
tions have been discovered starting from these readily
assembled molecules and have greatly expanded the toolbox
of chemical reactions.[1]
Diels–Alder cycloadditions to catalytic hydrogenations.[3]
Notably, there have been two recent developments that are
related to this type of proposed transformation. Firstly, Zhang
et al. reported an oxidative Au-catalyzed reaction of prop-
argylic acetates with arylboronic acids in the presence of
Selectfluor to provide a range of simple trisubstituted enones
in reasonable yields.[4] Secondly, Trost and co-workers
employed a contemporaneous dual catalysis system that
linked Pd-catalyzed p-allylic alkylation with V-catalyzed
rearrangement of proparglic alcohols to form a broad range
of a-allyl enone products.[5]
Of the range of useful reactions available to propargylic
alcohols, the Meyer–Schuster rearrangement to enones is
a transformation of significant synthetic potential that has not
been widely exploited in synthesis.[2] This rearrangement
reaction involves the loss of the hydroxy group from
a propargylic alcohol to form a carbocation intermediate
followed by re-addition of the hydroxy to the remote end of
the carbon–carbon triple bond, forming an allenol. Finally
protonation at the central carbon atom of this species forms
the enone product. A major shortcoming of this classic
reaction is the promotion of the desired rearrangement
amongst many possible (and often more favorable) compet-
ing pathways. One way that the Meyer–Schuster rearrange-
ment can be promoted is through the use of transition metal
catalysts that coordinate the p-system of the alkyne and by
the use of electronically activating substitutents.[2c] As a result,
recent catalytic developments have enabled this process to be
controlled in such a fashion that the enone products can be
formed in good yields and selectivities for the E-isomer. In
order to broaden the utility of this classical process, we
reasoned that if the key protonation step could be replaced by
reaction of the allenol with an electrophile, the Meyer–
Schuster rearrangement could be extended to produce
complex enone products, thereby expanding the repertoire
of synthetically useful transformations available directly from
propargylic alcohol feedstocks. This transformation would
provide facile entry to highly substituted variants of a class of
molecules that are recognized as valuable synthetic building
blocks due to their flexibility in many reactions, ranging from
As part of an ongoing program geared towards the
development of novel catalysis concepts, our laboratory has
developed a series of new carbon–aryl bond forming reactions
exploiting the electrophilic reactivity of high oxidation state
copper(III)–aryl species.[6] Recently, we reported that enol
silanes undergo arylation to give a-aryl carbonyl compounds
through copper-catalyzed reaction with diaryliodonium
salts.[6e] Given that the intermediate in the Meyer–Schuster
reaction is an allenol, we questioned whether a propargylic
alcohol could serve as a source of allenol under our copper-
catalysis conditions and react with a diaryliodonium salt[7]
through the putative copper(III)–aryl species[8] to form
trisubsituted enone products. Herein, we report the realiza-
tion of this ideal through the development of a copper-
catalyzed arylative Meyer–Schuster rearrangement. A range
of substituted propargylic alcohols and a wide selection of
diaryliodonium salts are compatible with this new trans-
formation, delivering complex trisubstituted enone products,
selectively as the E-isomers. These products will find signifi-
cant utility in chemical synthesis.
[*] B. S. L. Collins, Dr. M. G. Suero, Prof. M. J. Gaunt
Department of Chemistry, University of Cambridge
Lensfield Road, Cambridge, CB2 1EW (UK)
E-mail: mjg32@cam.ac.uk
[**] We are grateful to the University of Cambridge (for studentship,
B.S.L.C), the Marie Curie Foundation (M.G.S.), and ERSRC and ERC
(for fellowships to M.J.G). We also thank the EPSRC Mass
Spectrometry Service at the University of Swansea and Dr. Anna
Allen for assistance in the preparation of this manuscript.
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2013, 52, 5799 –5802
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