Rhodium-catalyzed C–H activation/cyclization of enaminones with sulfoxonium ylides toward polysubstituted naphthalenes

Article abstract of DOI:10.1016/j.tetlet.2019.01.051

A rhodium-catalyzed ortho-C–H functionalization and annulation between enaminones and sulfoxonium ylides was developed, affording a series of multi-substituted naphthalenes in good to moderate yields with excellent functional group compatibility. The proc

Full text of DOI:10.1016/j.tetlet.2019.01.051

Accepted Manuscript
Rhodium-Catalyzed C-H Activation/Cyclization of Enaminones with Sulfoxo-
nium Ylides toward Polysubstituted Naphthalenes
Zhenlian Wang, Huang Xu
PII:
S0040-4039(19)30088-7
https://doi.org/10.1016/j.tetlet.2019.01.051
TETL 50584
DOI:
Reference:
Tetrahedron Letters
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7 December 2018
13 January 2019
25 January 2019
Please cite this article as: Wang, Z., Xu, H., Rhodium-Catalyzed C-H Activation/Cyclization of Enaminones with
Sulfoxonium Ylides toward Polysubstituted Naphthalenes, Tetrahedron Letters (2019), doi: https://doi.org/10.1016/
j.tetlet.2019.01.051
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Rhodium-Catalyzed C-H Activation/Cyclization of
Enaminones with Sulfoxonium Ylides
toward Polysubstituted Naphthalenes
Zhenlian Wang*, Huang Xu

1
Tetrahedron Letters
Rhodium-Catalyzed C-H Activation/Cyclization of Enaminones with Sulfoxonium
Ylides toward Polysubstituted Naphthalenes
Zhenlian Wang*, Huang Xu
a School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou, 213164, China
†E-mail: wangzhenlian@cczu.edu.cn
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A rhodium-catalyzed ortho-C–H functionalization and annulation between enaminones
and sulfoxonium ylides was developed, affording a series of multi-substituted naphthalenes
in good to moderate yields with excellent functional group compatibility. The procedure
featured with enaminone acting as both a directing and cyclization bifunctional group, and
the application of sulfoxonium ylide in C–H functionalization.
Available online
Keywords:
.
rhodium catalysis
naphthalenes
annulation
sulfoxonium ylides
Naphthols are not only widely found in natural products
and drug molecules, but also commonly used as raw
materials in pesticides, dyes, and pharmaceutical industries.1
Thus, the construction of these special frameworks has
attracted the continuous attention of organic chemists by
many universal and efficient synthetic routes.2 Compared
with the traditional pathways to access naphthols, C–H
activation strategies are more attractive,3, 4 in terms of
atomic economy, stereoselectivity or efficiency.
Past decades have made considerable strides in transition-
metal-catalyzed ortho-C–H activation reactions leading to the
construction of C–C bonds efficiently and straightforwardly as a
significant measure widely used in the field of organic
chemistry.5 This practical strategy has been successfully applied
to access heterocycles and carbocycles such as naphthols,[4]
through the further cyclization process.
In 2012, Wang6 reported Rh(III)-catalyzed oxidative
synthesis of 1-naphthols through ortho-C–H activation of
ortho-substituted benzoylacetonitrile with alkynes (Scheme
1). Next year, Wang7 and co-workers developed the direct
access to highly substituted 1-naphthols through palladium-
catalyzed oxidative annulation of benzoylacetates and
internal alkynes. In 2016, Zhu8pioneered enaminone as a
directing synthon for Rh(III)-catalyzed C−H coupling with
α-diazo-β-ketoester, alkyne to access 2-formylnaphthol
derivatives under oxidative conditions. As a newly-
developed synthon, sulfoxonium ylide has made remarkable
advances in C–H functionalization in recent years,9 serving
as multiple roles such as C2 carbene synthons and traceless
bifunctional directing groups. Such frameworks were
reported by Li10 and Zhou11 to access 3,4-disubstituted
naphthols and 2,3-disubstituted naphthols, respectively.
Scheme 1. The construction of naphthols frameworks through
ortho-C–H functionalization.

Tetrahedron
4
Although chemists strived to open up new synthetic routes
(Table 1, entries 9-12); while acetic acid increased the yield
continuously, methods of synthesizing naphthols through C–
H activation is still finite. In view of present
to a satisfactory level (Table 1, entry 13). The AgSbF6
improved the reaction efficiency, and [RuCl2(p-cymene)]2
was superior to Cp*Rh(OAc)2, [Cp*IrCl2]2 and
CoCp*(CO)I2. To our delight, the 1-hydroxy-3-phenyl-2-
naphthaldehyde (3aa) was isolated in 77% yield in the
presence of 5.0 equivalent of HOAc (Table 1, entry 14).
Meanwhile, high temperature is not beneficial to the
transformation.
methodologies[9-12 on C-H activation with sulfoxonium ylide
as a block for synthesizing cyclic compounds, we propose to
use enaminones13 to access 2,3-disubstituted naphthols with
sulfoxonium ylides through metal-catalyzed C–H
activation/cyclization pathway.
Table 1. Screening the optimized reaction condition.a
Scheme 2. Substrates scope of substituted enaminones.a, b
entry
additive (equiv)
solvent
3aa(%)b
1
--
dioxane
toluene
MeCN
THF
nr
2
--
nr
3
--
23
nr
4
--
5
--
DMF
EtOH
HOAc
DCE
nr
6
--
nr
7
--
trace
49
nr
8
--
9
Cu(OAc)2 (2.0)
NaOAc (2.0)
DCE
10
DCE
nr
11
12
LiOAc (2.0)
H2O (2.0)
DCE
DCE
nr
32
a Reaction conditions: substituted enaminones 1 (0.1 mmol), sulfoxonium
ylide 2a (0.15 mmol), catalyst: [Cp*RhCl2]2 (5 mol %), AgSbF6 (20 mol %),
HOAc (0.5 mmol), DCE (2.0 mL), under air, at 90 oC for 12 h, in a sealed
Schlenk tube, unless otherwise noted. bIsolated yield. cIt is difficult to isolate
the corresponding cross-coupling mixture (3ha and 3ha’), their ratio data was
determined by 1H NMR spectrum.
63, trace [c], 29 [d]
trace [e], nr [f], nr [g]
,
13
14
HOAc (2.0)
HOAc (5.0)
DCE
DCE
77, 56 [h], 70 [i], 76 [j]
a
Reaction conditions: (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one
1a (0.1 mmol), dimethyloxosulfonium benzoylmethylide 2a (0.15 mmol),
catalyst: [Cp*RhCl2]2 (5 mol %), Cp* = 1,2,3,4,5-pentamethylcyclopenta-
1,3-diene, AgSbF6 (20 mol %), solvent (2.0 mL), under air, at 90 oC for
12 h, in a sealed Schlenk tube, unless otherwise noted. b Isolated yield. c
Without AgSbF6. d [RuCl2(p-cymene)]2 (5 mol %), AgSbF6 (20 mol %). e
Cp*Rh(OAc)2 (5 mol %), AgSbF6 (20 mol %). f [Cp*IrCl2]2 (5 mol %),
AgSbF6 (20 mol %). g CoCp*(CO)I2, AgSbF6 (20 mol %). h 80 oC. i100 oC.
j Under N2.
With the optimized reaction conditions in hand, the scope and
limitation of enaminones were studied as shown in Scheme 2.
Generally, the reaction efficiency was not sensitive to the
electron nature of the substituents on the aryl as substrates
bearing both electron-donating (3ba-da, 88-90%) and electron-
withdrawing groups (3ea-ga, 79-87%) all worked well to deliver
the desired products in good to excellent yields. Specially,
substrate with a meta- substituent in phenyl resulted in a mixture
of two regioselective isomers (3ha/3ha’, 69%, 1/1.5). However,
ortho-substituted aryl enaminones failed to work under this
procedure.
We initially chose (E)-3-(dimethylamino)-1-phenylprop-
2-en-1-one (1a), α-benzoyl sulfoxonium ylide (2a) as model
substrates to explore the ortho-C−H
functionalization/cyclization reaction. In the presence of
catalytic amount of [Cp*RhCl2]2 (5 mol %) and AgSbF6 (20
mol %), no reaction took place at all in some solvents such
as dioxane, toluene (Table 1, entries 1-2), THF, DMF,
EtOH, and AcOH (Table 1, entries 4-7). However, in
MeCN, the desired product 1-hydroxy-3-phenyl-2-
naphthaldehyde (3aa) was detected at 90 oC, albeit in a low
yield (23%, Table 1, entry 3). The effect of solvents is
particularly important that the Rh(III)/Ag catalytic system
perform better in DCE, leading to 3aa in a barely acceptable
yield (49%). We also found that neither acetates nor water
had no effect on promoting the conversion of products
Next, the scope of sulfoxonium ylides was investigated
(Scheme 3). Generally, α- aroyl sulfoxonium ylides bearing both
electron-donating (3ab-af, and 3ak 79-88%) or withdrawing
groups (3ag-aj, 70-81%) all worked well to deliver the desired
products in moderate to good yields. The position of substituent
on sulfoxonium ylide has little effect on the reaction process
obviously that ortho-(3ab), meta-(3ac, 3ah, and 3ak), para-
substituted (3ad-3ag, and 3ai-3aj) showed satisfactoryyields.
Besides, this procedure were also applicable for heterocyclic

3
pathway. The intra- and inter- molecular KIEs of deuterium-
(3al) and alkyl (3am) sulfoxonium ylides. In addition, the
structure of 3am was further confirmed by X-ray crystallography
(for details, see Supporting Information). 14
labeled substrates and 2a identified a high value (kH/kD = 3.0 and
4.0, Scheme 4, eqs 2 and 3), suggesting that C−H activation is the
rate-determining step.
Based on the above deuterium-labeling experiments and
previous literatures,8-9, 12-13, 15 a catalytic cycle for the ortho-C−H
functionalization and cyclization of enaminone is proposed
(Scheme 3). Initially, dedimeriation of [Cp*RhCl2]2 and C−H
activation of enaminone (1a) produce a rhodacyclic intermediate
A, which then coordinated with 2a leading to a Rh(III)
Scheme 3. Scope of sulfoxonium ylides.
intermediate B. Then, the key intermediate carbene species C
was produced from B by α- elimination of DMSO. After the
migratory insertion and protonolysis, acylmethylated
intermediate E was generated, and Rh(III) catalyst was released,
completing a catalytic cycle. The intermediate E transformed into
an oxonium salt F under acidic conditions, which went through a
Michael addition-type C−C coupling to furnish a hexatomic ring
G. Then, the intermediate H was formed through the dehydration
process of G. The target product 3aa was obtained by hydrolysis
of imine (intermediate I) to aldehyde.
Scheme 5. Proposed mechanism
a Reaction conditions: (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one 1a
(0.1 mmol), sulfoxonium ylides 2 (0.22 mmol), catalyst: [Cp*RhCl2]2 (5
mol %), AgSbF6 (20 mol %), HOAc (0.5 mmol), DCE (2.0 mL), under air, at
90 oC for 12 h, in a sealed Schlenk tube, unless otherwise noted. b Isolated
yield.
Scheme 4. Mechanism study
In conclusion, we have developed a rhodium-catalyzed ortho-
C−H functionalization and annulation between enaminones and
α- aroyl sulfoxonium ylides toward a series of multi-substituted
naphthalenes in good to moderate yields. Enaminone played a
dual role as a directing group and a cyclization group, and
widened the meaningful application of sulfoxonium ylide in C-H
functionalization.
Acknowledgments
We thank the Jiangsu Key Laboratory of Advanced
Catalytic Materials & Technology (BM2012110) and
Advanced Catalysis and Green Manufacturing Collaborative
Innovation Center for financial supports.
The competition reaction between an electron-rich and an
electron-poor enaminone with 2a shows a higher reactivity for
the electron-rich substrate (Scheme 4, eq 1), which is consistent
with an electrophilic aromatic substitution C−H activation

Tetrahedron
4
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Gao, G. Org. Chem. Front. 2018, 5, 2875.
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5
Highlights
1. The readily available starting material
2. Enaminone acted as a directing and cyclization
bifunctional group.
3. Safe and mild reaction conditions.