Angewandte
Chemie
DOI: 10.1002/anie.201208305
Rearrangements
Gold-Catalyzed Rearrangement of Allylic Oxonium Ylides: Efficient
Synthesis of Highly Functionalized Dihydrofuran-3-ones**
Junkai Fu, Hai Shang, Zhaofeng Wang, Le Chang, Wenbing Shao, Zhen Yang,* and
Yefeng Tang*
Rearrangements of allylic oxonium ylides have been recog-
nized as powerful tools for the syntheses of oxygenated
carbocycles.[1] This type of transformation typically proceeds
through a cascade carbenoid generation/oxonium ylide for-
mation/[2,3]-sigmatropic rearrangement. The most common
method to generate an oxonium ylide is the decomposition of
an a-carbonyl diazo compound with a metal catalyst to form
the metallocarbenoid, which is then trapped by the oxygen
atom of an allylic ether (A!C, Scheme 1A).[2] Given that
diazo compounds are usually hazardous and explosive, and
their preparation and handling are not trivial, the synthetic
utility of this type of transformation has been somewhat
limited. In this context, the search for a system that is free of
diazo compounds and thus less hazardous to promote the
rearrangement of allylic oxonium ylides is of great value.[3]
Recently, a-oxo gold carbenoids have received consider-
able attentions because they were assumed to be the key
intermediates in a range of intriguing transformations,[4] such
[5]
[6]
ꢀ
ꢀ
as gold-catalyzed C H insertion, O H insertion, cyclo-
propanation,[7] dipolar cycloaddition[8] and others.[9] Readily
generated through intra- or intermolecular oxidation of gold-
activated alkynes, a-oxo gold carbenoids display versatile
reactivity, analogous to that of metallocarbenoids derived
from diazo carbonyl compounds. For instance, Davies and
Albrecht reported a gold-catalyzed [2,3]-sigmatropic rear-
rangement of sulfur ylides through an internal redox-combi-
nation strategy.[10] More recently, Zhang and co-workers
developed a facile synthesis of dihydrofuran-3-one deriva-
tives from the readily available homopropargylic alcohols
[6a]
ꢀ
through a gold-catalyzed intramolecular O H insertion.
Inspired by these seminal contributions, we envisioned that
a similar strategy could be used in the [2,3]-sigmatropic
rearrangement of oxonium ylides, as rationalized by the
transformations from E!D (Scheme 1B). The proposed
strategy would enable the [2,3]-sigmatropic rearrangement of
oxonium ylides to proceed with readily available, diazo-free
precursors under exceptionally mild conditions and with an
operationally simple procedure. Moreover, the resulting
product D features a highly functionalized dihydrofuran-3-
one scaffold, which could be further elaborated into the core
structures of various bioactive natural products, such as that
of griseofulvin.[1c]
Scheme 1. A) [2,3]-Sigmatropic rearrangement promoted by a metallo-
carbenoid that was derived from a diazo carbonyl compound. B) Pro-
posed mechanism for the [2,3]-sigmatropic rearrangement promoted
by an a-oxo gold carbenoid.
[*] J. Fu, Z. Wang, Dr. L. Chang, W. Shao, Prof. Dr. Z. Yang
Laboratory of Chemical Genomics, Peking University
Shenzhen Graduate School
To test the hypothesis, we initiated our studies by treat-
ment of model substrate 1 with the conditions employed by
Zhang and co-workers in their studies (Scheme 2).[6a] The
reaction was completed in three hours and led to the
formation of two major products, one of which was the by-
product resulting from direct deallylation of 1 (product
structure not shown), and the other was the benzofuran
allylic ether 2. Although the expected [2,3]-sigmatropic
rearrangement product 3 was not observed, we were pleased
to find that 2 was converted almost quantitatively into 3 upon
standing for 72 hours in CDCl3. The structure of 3 was
unambiguously confirmed by X-ray crystallography.[11] Sub-
sequently, the conversion of 1 to 3 could be effected in one pot
simply by increasing the reaction temperature to 608C. The
observations indicated that the transformation of 1 to 3, albeit
formally a [2,3]-sigmatropic rearrangement, may indeed
proceed through a mechanism distinctly different from the
Xili, Nanshan District, Shenzhen 518055 (China)
E-mail: zyang@pku.edu.cn
Dr. H. Shang, Prof. Dr. Y. Tang
The Comprehensive AIDS Research Center, Department of
Pharmacology & Pharmaceutical Sciences, School of Medicine
Tsinghua University
Beijing 100084 (China)
E-mail: yefengtang@tsinghua.edu.cn
[**] We acknowledge financial support from the National Science
Foundation of China (21102081, 21272133), New Teachers’ Fund for
Doctor Stations, Ministry of Education (20110002120011), and
opening foundation of Laboratory of Chemical Genomics, Peking
University of Shenzhen Graduate School. We thank Dr. Tuoping Luo
(H3 Biomedicine Inc., MA (USA)) and Prof. Zhigang Wang (Peking
University) for the helpful discussions.
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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