Organic Letters
Letter
2c was obtained in 85% yield when a mixture of alkenyl
alcohols 1c, 1c′, and 1c′′ were subjected to the standard
reaction conditions. In addition, the racemic ketone 2ae was
isolated in 65% yield when the chiral alcohol 1ae was used
(Scheme 3b). Moreover, a deuterated reaction was carried out,
and the deuteration was found along the alkyl chain (Scheme
3c). These results suggested that this reaction involves a
dissociative chain-walking process.2f,10b Surprisingly, although
full conversion was observed when the reaction was quenched
after 10 min under the standard conditions, the byproduct 3a
was obtained in almost quantitative yield, which could be
further converted into the ketone 2a (Scheme 3d). Addition-
ally, ketone 2ag was isolated in 29% yield along with 56% of 3a
when the reaction was treated with 20 mol % of [RhCl(cod)]2
and quenched after 10 min (Scheme 3e), indicating that the
alkenyl alcohol first underwent β-H elimination to generate the
unsaturated ketone and then the chain-walking process. To
establish what the true catalyst is, we synthesized RhCl-
(Xantphos) and used it to catalyze the isomerization of 1a.13
Pleasingly, the catalysts RhCl(Xantphos) and [RhCl(cod)]2/
Xantphos gave identical results (Scheme 3f). Furthermore, in
the absence of CsOAc, [Rh(OAc)(cod)]2/Xantphos afforded
the same results as the standard conditions provided. On the
basis of the results, we believe that Rh(OAc)(Xantphos)
should be the true catalyst.
On the basis of the observed results, we proposed a plausible
mechanism for this isomerization (Scheme 4). Initially, the
reaction of [RhCl(cod)]2 with CsOAc produces Rh−OAc,
which then reacts with 1 to afford intermediate A. Subsequent
β-H elimination results in the formation of Rh−H, which
undergoes migratory insertion with 1 to give intermediate B.
The following β-H elimination provides intermediate C and
Rh−H. The intermediate C then goes through dissociative
migration insertions/β-hydride elimination (chain-walking) to
give intermediate D, followed by the Rh-catalyzed isomer-
ization of allylic alcohol5 to deliver the desired ketone 2 and
regenerate the Rh−H species.
Wanxiang Zhao − State Key Laboratory of Chemo/Biosensing
and Chemometrics, College of Chemistry and Chemical
Engineering, Hunan University, Changsha 410082, P. R.
Authors
Wenke Dong − State Key Laboratory of Chemo/Biosensing and
Chemometrics, College of Chemistry and Chemical Engineering,
Hunan University, Changsha 410082, P. R. China
Hongxuan Yang − State Key Laboratory of Chemo/Biosensing
and Chemometrics, College of Chemistry and Chemical
Engineering, Hunan University, Changsha 410082, P. R. China
Complete contact information is available at:
Author Contributions
†W.D. and H.Y. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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Financial support from the National Natural Science
Foundation of China (grant nos. 21702056, 21971059,
21702055), the National Program for Thousand Young
Talents of China, and Fundamental Research Funds for the
Central Universities is greatly appreciated.
REFERENCES
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(1) (a) Fu, G. C. In Modern Rhodium-Catalyzed Organic Reactions;
Evan, P. A., Ed.; Wiley-VCH: New York, 2005; pp 79−91.
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12, 233. (c) Vilches-Herrera, M.; Domke, L.; Borner, A. Isomer-
(2) For selected examples, see: (a) Grotjahn, D. B.; Larsen, C. R.;
Chem. Soc. 2007, 129, 9592. (b) Wakamatsu, H.; Nishida, M.; Adachi,
(PPh3)3. J. Org. Chem. 2000, 65, 3966. (c) Kochi, T.; Hamasaki, T.;
Chem. Soc. 2012, 134, 16544. (d) Masarwa, A.; Didier, D.; Zabrodski,
2014, 505, 199. (e) Werner, E. W.; Mei, T.-S.; Burckle, A. J.; Sigman,
Soc. 2015, 137, 3462.
In summary, we have developed an efficient rhodium-
catalyzed remote olefin isomerization reaction in which a
variety of aromatic and alkyl alkenyl alcohols were transformed
to ketones in good to excellent yield. This catalytic redox-
neutral process employed a commercially available catalyst and
ligand ([RhCl(cod)]2 and Xantphos), and no additive was
required. Moreover, this protocol features high efficiency, good
functional group tolerance, a broad substrate scope, and
excellent compatibility with complex molecules. Noticeably,
the catalyst loading can be reduced to 0.2 mol % without any
detrimental effect on the yield. Preliminary mechanistic studies
provide support for the dissociative chain-walking mechanism.
ASSOCIATED CONTENT
* Supporting Information
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sı
The Supporting Information is available free of charge at
Experimental procedures, characterization, and NMR
spectra for obtained compounds (PDF)
(3) For selected reviews, see: (a) van der Drift, R. C.; Bouwman, E.;
AUTHOR INFORMATION
Corresponding Authors
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Chem. Rev. 2003, 103, 27. (c) Ahlsten, N.; Bartoszewicz, A.; Martín-
Wen Yang − State Key Laboratory of Chemo/Biosensing and
Chemometrics, College of Chemistry and Chemical Engineering,
Hunan University, Changsha 410082, P. R. China;
D
Org. Lett. XXXX, XXX, XXX−XXX