Rh(III)-Catalyzed Aldehydic C?H Functionalization Reaction between Salicylaldehydes and Sulfoxonium Ylides

Article abstract of DOI:10.1002/adsc.201900276

A novel aldehydic C?H functionalization reaction between salicylaldehydes and sulfoxonium ylides has been developed under rhodium(III) catalysis, affording coupling products in moderate to good yields. A plausible mechanism involving aldehydic C(sp²)?H activation by rhodium(III) and rhodium(III) catalyzed carbene insertion is also proposed. It was also found that the aldehydic C?H functionalization followed by dehydrative cyclization was able to produce flavonoids in one-pot. (Figure presented.).

Full text of DOI:10.1002/adsc.201900276

Title: Rh(III)-Catalyzed Aldehydic C–H Functionalization Reaction
between Salicylaldehydes and Sulfoxonium Ylides
Authors: Guo-Dong Xu, Kenneth Huang, and Zhi-Zhen Huang
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201900276
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10.1002/adsc.201900276
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Rh(III)-Catalyzed Aldehydic C–H Functionalization Reaction
between Salicylaldehydes and Sulfoxonium Ylides
Guo-Dong Xu,a Kenneth L. Huang,b and Zhi-Zhen Huang*,a
a
Department of Chemistry, Zhejiang University, Hangzhou 310058, P.R. China
E-mail: huangzhizhen@zju.edu.cn
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA
b
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
functionalization reaction using a sulfoxonium or
reaction between salicylaldehydes and sulfoxonium ylides sulfonium ylide as a carbene precursor remains
Abstract:
A novel aldehydic C-H functionalization
has been developed under rhodium(III) catalysis, affording
coupling products in moderate to good yields. A plausible
mechanism involving aldehydic C(sp2)-H activation by
rhodium(III) and rhodium(III) catalyzed carbene insertion
is also proposed. It was also found that the aldehydic C-H
functionalization followed by dehydrative cyclization was
able to produce flavonoids in one-pot.
unknown so far. Thus, we carried out the
investigation on aldehydic C-H functionalization
reaction between salicylaldehydes and sulfoxonium
ylides under rhodium(III) catalysis.
Keywords: aldehydic C-H activation; rhodium(III)
catalyzed; salicylaldehydes; sulfoxonium ylides; carbene
insertion
Scheme 1. C-H Functionalization Using Sulfoxonium
Ylides as Carbene Precursors.
Over the past decades, transition-metal-catalyzed C-
H activations following by migration insertions of
metal carbenes resulted from carbene precursors have
been emerged as a powerful strategy for the
formations of carbon-carbon bonds.[1] Among the
employed carbene precursors, diazo compounds are
used most widely. Later sulfoxonium and sulfonium
ylides are found to be good carbene precursors, which
are safer than diazo compounds.[2,3] Recently,
sulfoxonium ylides as carbene precursors were
applied into C-H functionalization under the catalysis
of Rh(III),[3a-p] Ru(II),[3q-r] and Co(III)[3s] (Scheme 1).
For example, in 2017, Aïssa et al. reported that under
rhodium(III) catalysis, a cross-coupling reaction
between α-carbonyl sulfoxonium ylides and aromatic
C-H bonds in 2-arylpyridines performed smoothly to
give corresponding α-arylated ketones.[3a] On the
other hand, among various C-H functionalizations,
aldehydic C-H functionalizations are becoming an
important strategy in constructing carbon-carbon
bonds.[4] However, the study on the aldehydic C-H
functionalizations through insertions of metal
carbenes is rarely disclosed.[5] In 2016, Yao and co-
workers disclosed a Rh(III)-catalyzed annulation
between salicylaldehydes and diazo compounds to
give chromone derivatives (Scheme 2).[5a] To the best
of our knowledge, the report on an aldehydic C-H
Scheme 2. Yao’s Work on Aldehydic C-H Functionali-
zation with Diazo Compounds.
Initially, the exploration and optimization of an
aldehydic C-H functionalization reaction of
salicylaldehyde 1a with sulfoxonium ylide 2a was
carried out. When [RhCp*(MeCN)3](SbF6)2 (2.5
mol %) and NaOAc were employed as a transition-
metal catalyst and a base respectively, we were
pleased to find that the C-H functionalization
reaction occured in DCE at 90 °C, affording the
desired coupling product 3aa in a yield of 67% (entry
1, Table 1). Using [Cp*RhCl2]2 instead of
[RhCp*(MeCN)3](SbF6)2 resulted in the increase of
the yield to 90% (entry 2, Table 1). The other
transition-metal catalysts, such as [Cp*IrCl2]2,
Pd(OAc)2 and [Ru(p-cymene)Cl2]2 were probed as
well. The experimental results indicated that they
1
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10.1002/adsc.201900276
Advanced Synthesis & Catalysis
were less effective than [Cp*RhCl2]2 (compare entry
1 with entries 2-5, Table 1; also see the supporting
information (SI)). When [Cp*RhCl2]2/AgSbF6 was
employed as a catalyst system, 3aa was obtained in a
low yield (entry 6, Table 1). Using NaOEt, CsOAc or
Ag2CO3 as bases led to lower yields as compared to
NaOAc (compare entry 2 with entries 7-9, Table 1;
also see the SI). When other solvents such as ethyl
acetate, MeCN, toluene or dioxane were used instead
of DCE, the yields of 3aa were decreased
remarkabley (entries 12-14, Table 1; also see SI).
Thus, it can be concluded that the optimized reaction
should be performed under the catalysis of
[Cp*RhCl2]2 (2.5 mol %) in the presence of NaOAc
(2.0 equiv.) at 90 °C in DCE.
benzene salicylaldehydes 1g-j or at the 4-position of
benzene rings in salicylaldehydes 1k-n, no matter
they are electron-withdrawing groups or electron-
donating groups, the reaction proceeded smoothly to
afford the corresponding coupling products 3ga-ja or
3ka-na in satisfactory yields. However, 4-nitro
substituted salicylaldehyde led to a poor yield (20%)
of corresponding product. Salicylaldehydes 1p-r
bearing two electron-withdrawing groups also
performed the coupling reaction well with
sulfoxonium ylide 2a to give the desired products
3pa-ra in satisfactory yields. 1-Hydroxy-2-
naphthaldehyde 1t as an expansion of aromatic
counterparts from salicylaldehydes also undergo the
reaction expediently to afford 3ta in a 79% yield.
Table 1. Optimization of the Aldehydic C-H
Functionalization Reaction between Salicylaldehyde 1a
and Sulfoxonium Ylide 2a.[a]
Table 2. The Scope of Salicylaldehydes 1 in the Aldehydic
C-H Functionalization Reaction with Sulfoxonium Ylide
2a.[a]
Entry
1
[M]
Base
Solvent Yield(%)[b]
[Cp*Rh(MeCN)3]
(SbF6)2
NaOAc
DCE
67
2
3
[Cp*RhCl2]2
[Cp*IrCl2]2
[Ru(p-
NaOAc
NaOAc
DCE
DCE
90
0
4
5
6
NaOAc
NaOAc
NaOAc
DCE
DCE
DCE
0
0
cymene)Cl2]2
[c]
Pd(OAc)2
[Cp*RhCl2]2/
40
[d]
AgSbF6
7
8
9
10
11
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
--
NaOEt
CsOAc
Ag2CO3
--
DCE
DCE
DCE
DCE
DCE
ethyl
acetate
0
80
61
0
NaOAc
0
12
[Cp*RhCl2]2
NaOAc
68
13
14
[Cp*RhCl2]2
[Cp*RhCl2]2
NaOAc MeCN
NaOAc dioxane
28
0
[a]
Reaction conditions: 1a (0.10 mmol), 2a (0.12 mmol),
[M] (2.5 mol %), base (2.0 equiv.), solvent (2.0 mL), 90 °C,
for 24 h in a sealed tube. [b] Isolated yields. [c] Pd(OAc)2 (10
mol %). [d] AgSbF6 (10 mol %).
[a]
Reaction conditions: 1a (0.10 mmol), 2 (0.12 mmol),
[Cp*RhCl2]2 (2.5 mmol %), NaOAc (2.0 equiv.), DCE
(2.0 mL), 90 °C, for 24 h. Isolated yields.
With the optimized conditions in the hand, the
scope of salicylaldehydes 1 in the aldehydic C-H
functionalization reaction was investigated. We found
that a series of salicylaldehydes 1a-s were able to
undergo the reaction with sulfoxonium ylide 2a to
give the corresponding coupling products 3aa-sa in
moderate to good yields (Table 2). In view of the
yields of 3ba-fa, the salicylaldehydes 1b-d bearing
electron-withdrawing groups at the 5-position of
benzene rings seem to be more beneficial to the
reaction as compared to those 1e-f bearing electron-
donating groups at the 5-position of benzene rings.
No matter substituents are at the 3-position of
After various salicylaldehydes 1a-s were examined
in the C-H functionalization reaction, the scope of
sulfoxonium ylides 2 was also studied (Table 3). It
was found that under rhodium(III) catalysis, diverse
sulfoxonium ylides 2b-j were able to undergo the
aldehydic C-H functionalization reaction expediently
with salicylaldehyde 1a in the presence of sodium
acetate under the optimized conditions. The
sulfoxonium ylides 2b-g bearing either electron-
donating groups or electron-withdrawing groups on
benzene rings resulted in the desired coupling
2
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10.1002/adsc.201900276
Advanced Synthesis & Catalysis
proposed as shown in Scheme 4. First, under the
direction of hydroxyl group, [Cp*RhX2] activates the
C(sp2)-H bond of aldehydic group in salicylaldehyde
1a to form a five-membered rhodacyclic intermediate
A. Next, sulfoxonium ylide 2a reacts with the
rhodacycle intermidiate A to form a betaine
intermediate B. DMSO breaking away from the
intermidiate B leads to rhodium(III) carbene species
C. Then, a migratory insertion of carbene group into
the C(sp2)-Rh bond in the intermidiate C affords a
six-membered rhodacycle intermediate D. Finally,
protonolysis of the intermediate D results in the
coupling product 3aa with regenerating active
[Cp*RhX2].
products 3ab-ag with up to 90% yield. When the
phenyl group in sulfoxonium ylide 2a were switched
to thienyl or alkyl group, the reaction still performed
smoothly to give the corresponding product 3ah or
3ai-aj respectively.
Table 3. The Scope of Sulfoxonium Ylides 2 in the
Aldehydic C-H Functionalization Reaction with
Salicylaldehyde 1a. [a]
[a]
Reaction conditions: 1a (0.10 mmol), 2 (0.12 mmol),
[Cp*RhCl2]2 (2.5 mmol %), NaOAc (2.0 equiv.), DCE (2.0
mL), 90 °C, for 24 h. Isolated yields.
Scheme 4. Plausible Mechanism for the Aldehydic C-H
Functionalization Reaction.
To gain insight into the mechanistic pathway of the
aldehydic C-H functionalization reaction, a kinetic
isotopic experiment was conducted under the
standard conditions. Two parallel reactions using
equimolar amounts of salicylaldehyde 1a and
deuterated salicylaldehyde 1a-D5 were performed
respectively (Scheme 3). The value of the kinetic
isotope effect (KIE) is 2.33, and the KIE result
suggests that the aldehydic C(sp2)-H functionalization
may be a rate-determining step in the coupling
reaction.
To demonstrate the scalability and practicality of
the aldehydic C-H functionalization reaction, a gram-
scale reaction was performed under rhodium(III)
catalysis. The exprimental result shew that the
reaction of salicylaldehyde
1a (1.22 g) with
sulfoxonium ylide 2a (2.35 g) proceeded readily to
give the desired coupling product 3aa (0.96 g) under
the optimized conditions (Scheme 5).
Scheme 5. The Aldehydic C-H Functionalization Reaction
on a Gram-Scale
The coupling products 3 in this work are important
building blocks for the synthesis of flavonoids. So we
performed the aldehydic C-H functionalization
reaction followed by intramolecular cyclization in
one-pot. After the reaction of salicylaldehydes 1a, 1e,
Scheme 3. Kinetic Isotope Effect Study
On the basis of precedent literatures,[3e,5a]
a
plausible mechanism for the reaction between
salicylaldehyde 1a and sulfoxonium ylide 2a is
3
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10.1002/adsc.201900276
Advanced Synthesis & Catalysis
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temperature by adding aqueous sulfuric acid,
affording corresponding flavonoids 4a-e in
satisfactory yields respectively (Scheme 6).
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Scheme 6. Aldehydic C–H Functionalization Followed by
Dehydrative Cyclization for the Synthesis of Flavonoids in
One-pot.
In conclusion, we have developed an aldehydic C-
H functionalization reaction of salicylaldehydes 1
with sulfoxonium ylides 2 by rhodium(III) catalysis
and in the presence of sodium acetate. It was found
that various functional groups in salicylaldehydes 1
and sulfoxonium ylides 2 are compatible with the
reaction, affording corresponding coupling products 3
in moderate to good yields. A plausible mechanism
involving aldehydic C(sp2)-H activation by
rhodium(III) and rhodium(III)-catalyzed carbene
insertion
is
also
proposed.
Moreover,
salicylaldehydes 1 and sulfoxonium ylides 2 were
able to undergo the C-H functionalization followed
by dehydrative cyclization in one-pot to produce
corresponding flavonoids 4.
Experimental Section
General procedure for the aldehydic C-H functionalization
reaction: The reaction mixture of salicylaldehyde 1 (0.10
mmol), sulfoxonium ylide 2 (0.12 mmol), [Cp*RhCl2]2
(1.5 mg, 0.0025 mmol, 2.5 mol %) and NaOAc (16.4 mg,
0.20 mmol) in DCE (2.0 mL) was stirred at 90 °C for 24 h.
Then, the mixture was evaporated under reduced pressure,
and the residue was purified by column chromatography
(silica gel, ethyl acetate/ petroleum ether = 1/20 as eluent)
to give desired coupling product 3.
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Acknowledgements
[5] a) P. S. Sun, S. Gao, C. Yang, S. Guo, A. Lin, H. Yao,
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The financial support from National Natural Science Foundation
of China (No. 21372195) is gratefully acknowledged.
References
[1] Some reviews on C-H functionalizations by metal
carbene insertions: a) H. M. L. Davies, R. E. J.
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4
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10.1002/adsc.201900276
Advanced Synthesis & Catalysis
COMMUNICATION
Rh(III)-Catalyzed
Functionalization
Aldehydic
Reaction
C-H
between
Salicylaldehydes and Sulfoxonium Ylides
Adv. Synth. Catal. Year, Volume, Page – Page
Guo-Dong Xu, Kenneth L. Huang, and Zhi-Zhen
Huang*
5
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