DOI: 10.1002/chem.201502140
Full Paper
&
CÀH Activation
Development of a Rhodium(II)-Catalyzed Chemoselective C(sp3)ÀH
Oxygenation
Yun Lin,[a] Lei Zhu,[b] Yu Lan,*[b] and Yu Rao*[a]
Abstract: We report the first example of RhII-catalyzed
chemoselective double C(sp3)ÀH oxygenation, which can
directly transform various toluene derivatives into highly
valuable aromatic aldehydes with great chemoselectivity
and practicality. The critical combination of catalyst
Rh(OAc)2, oxidant Selectfluor, and solvents of TFA/TFAA
promises the successful delivery of the oxidation with satis-
factory yields. A possible mechanism involving a unique car-
bene–Rh complex is proposed, and has been supported by
both experiments and theoretical calculations.
Introduction
[Rh2(OAc)4] is less coordinating with the carbonyl oxygen atom
of ketone group. In addition, RhII is stronger than RuII and PdII
in terms of the potential oxidizing ability.[10d,11] We envisioned
that certain fine-tuned oxidative conditions with the proper
combination of RhII catalyst and oxidants may direct a sp3 CÀH
oxygenation instead of a sp2 CÀH oxygenation to give aldy-
hyde derivatives. Over the past decade, transition-metal-cata-
lyzed direct functionalization of benzylic C(sp3)ÀH bonds has
gradually emerged as a useful tool for the preparation of val-
uable chemicals.[2f,12] Among those successful discoveries of
benzylic C(sp3)ÀH bond activation, the majority of studies were
focused on palladium- or copper-catalyzed CÀH arylation,[13]
halogenation,[14] acetoxylation,[15] or amidation.[13c,16] In contrast,
other metals, like Ru and Rh, are rarely reported in this type of
benzylic CÀH transformation. To the best of our knowledge,
RhII-catalyzed C(sp3)ÀH oxygenation of benzylic positions has
not been achieved yet. We are particularly interested in the
possible new catalytic activity of rhodium catalysts and the
substrate scope in the C(sp3)ÀH oxygenation reaction. More-
over, expanding the catalyst and reaction scope will provide
more choice and better control for its synthetic applications.
Herein, we report the first example of RhII-catalyzed chemo-
selective double C(sp3)ÀH oxygenation with Selectfluor as the
key oxidant, which can readily transform a broad range of
substrates into valuble aromatic aldehydes (Scheme 1).
Rhodium(II) catalysts, such as [Rh2(OAc)4], have been well
studied in rhodium–carbene[1] and rhodium–nitrene[2] chemis-
try (Scheme 1). The use of [Rh2(OAc)4] has also been reported
in alkylation annulation reaction,[3] Claisen rearragement,[4]
epoxide[5] and aziridine[2n,6] synthesis, and so forth. More
recently, [Rh2(OAc)4] was employed in sp2 CÀH arylation,[7] sp2
CÀH hydroxylation,[8] and sp2 CÀH vinylation.[9]. In comparison
to the above achievements and advances, much less progress
has been made in the field of RhII-catalyzed sp3 CÀH
oxygenation.[10] Compared with RuII and PdII catalysts,
Scheme 1. RhII catalysis for C(sp3)ÀH oxygenation
Results and Disscusion
[a] Y. Lin, Prof. Dr. Y. Rao
To test our hypothesis, a model study was initiated with
di-p-tolylmethanone 1. At the beginning of our investigations,
a variety of oxidants, such as PhI(OAc)2, PhI(TFA)2, K2S2O8 and
Na2S2O8, and so forth, were examined in the presence of
Rh2(OAc)4 in trifluoroacetic acid/trifluoroacetic anhydride (TFA/
TFAA; Table 1). Among them, only the condition using K2S2O8
can provide the corresponding aldehyde 2 in a trace amount
(Table 1, entry 1). We then turned our attention to electrophilic
fluorinating reagents, including N-fluorobenzenesulfonimide
(NFSI), N-fluoropyridinium triflate (NFPy) Selectfluor, and so
MOE Key Laboratory of Protein Sciences
Department of Pharmacology and Pharmaceutical Sciences
School of Medicine and School of Life Sciences
Tsinghua University, Beijing, 100084 (P. R. China)
[b] L. Zhu, Prof. Dr. Y. Lan
School of Chemistry and Chemical Engineering
Chongqing University, Chongqing, 400030 (P. R. China)
Supporting information for this article is available on the WWW under
Chem. Eur. J. 2015, 21, 14937 – 14942
14937
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