Acylation of Csp2-H bond with acyl sources derived from alkynes: Rh-Cu bimetallic catalyzed CC bond cleavage

Article abstract of DOI:10.1039/c6cc05769a

A Rh-Cu bimetallic catalyzed o-acylation of acyloxacetamide with alkynes has been described. This transformation provides a novel, concise way to synthesize ortho-acylphenols using functionalized alkynes as acylating reagents. Mechanistic studies revealed a Rh-Cu relay process, in which O₂ plays a critical role for the formation of carbonyl compounds.

Full text of DOI:10.1039/c6cc05769a

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EDGE ARTICLE
Acylation of Csp2-H bond with acyl sources derived from alkynes:
Rh-Cu Bimetallic Catalyzed C≡C bond cleavage †
Received 00th January 20xx,
Accepted 00th January 20xx
Ying Xie,*,a
A Rh-Cu bimetallic catalyzed o-acylation of acyloxacetamide with alkynes has been described. This transformation provides
DOI: 10.1039/x0xx00000x
a novel concise way to synthesize ortho-Acylphenols using functionalized alkynes as acylated reagent. Mchanistic study
www.rsc.org/
revealed the Rh-Cu relay process, in which O2 plays
a critical role for formation of the carbonyl compounds.
Previous works demonstrated that transition-metal-catalyzed
cross coupling reactions via directing-group-assisted with
alkyne have been considered as powerful tools for variety
cyclic compounds through (3+2),9 (4+2),10 (5+2) cycloaddition
to products11. until now, the Csp2-H acylation of arenes using
novel acyl sources derived from the transition-metal-catalyzed
Introduction
Aryl ketones are common Skelton in many classes of
biologically active compounds and natural products (figure 1).1
Consequently, how to synthesize these products has drawn
much attention, and various of methods have been developed
for the preparation of aryl ketones. Traditional methods
carried out to access these compounds by using activated
substrates (Friedel-Crafts).2 Recently, transition-metal-
catalyzed C-H functional reaction is considered as a powerful
strategy for the construction of these ketones.3 In this regards,
various directing group assisted Csp2-H bond acylation with
cleavage of C
≡C bonds remains unknown (Scheme 1c). Jiao's
works have been indicated that alkenes can be efficiently
oxidized and further promoted C=C bond cleavage for
carbonylation.12 Therefore, we assume alkynes can be
converted to electron-rich olefins that may be oxidized under
Jiao's catalyst system for the construction of the carbonyl
compounds. Recently multiple function of alkynes have been
achieved by the atom transfer C-H function strategy13, for
example, Lu's group developed a method of transformation
aldehydes,4 alcohols5
，
toluenes 6or -oxocarboxylic acid 7as
α
acyl surrogates for the synthesis of the aryl ketones were
described. Despite these impressive advances, acylation of
phenol within a single step is scarce except Wang group has
been develop perfect work Copper-catalyzed ortho-acylation
of phenols with aryl aldehydes . so how to develop a novel,
more efficiently acyl surrogate for the access to ortho-
14
from amide to multiple alkynes using Rh(III) as catalysts
subsequently Zhao and co-works have been reported that a
several heterocyclic scaffolds was been given by base on the
orthohydroxyphenyl-substituted enamides intermiedate by
cocatalyst regulation 15. Inspired by these transformations, we
described a Rh-Cu catalyzed cascade reaction of alkynes with
N-phenoxyacetamides to give ortho-Acylphenols under mild
conditions.
8
Acylphenols is still in urgent need.
EtO
O
O
OH
O
OMe
O
OMe
OMe
MeO
Me
OH
OMe
Cl
Plant-growth promoter
Griseophenone B
OH
O
OCH3
OMe O
OH
HO
O
O
O
CH2OH
OH
MeO
OH
OMe
Silybin
Tatarinoid A
Figure 1. Natural and drug containing ortho-Acylphenols
a.School of Chemistry and Environmental Engineering, Sichuan University of
Science & Engineering, Zigong 643000, China E-mail: xy_org2016@126.com
b.† Footnotes relaꢀng to the ꢀtle and/or authors should appear here.
Electronic Supplementary Information (ESI) available: CCDC 1443747. For ESI
and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c000000x
Scheme 1 Acylation of Csp2-H bond with acyl sources derived from alkynes: Rh-
Cu Bimetallic Catalyzed C≡C bond cleavage
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phenoxyacetamides (1j) gave the desired product with high
regioselectivity and moderate yields. Whereas the ortho-
substituted N-phenoxyacetamides (1d) gave poorer yield of
product (3d) due to higher steric hindrance. Subsequently,
variety of internal alkynes as acyl sources was also tested. It
was found that not only a broad scope of symmetrical (e.g.
Results and discussion
Optimization studies
In preliminary experiments,
N-phenoxyacetamide (1a) was
treated with [{Cp*RhCl2}2] (2.5 mol%), NHPI (20 mol%)11b, and
alkyne (2a) in MeOH at 30 ˚C for 24 hours under air, however
no desired product was observed (table 1, entry 1). Then a
search for appropriate additives was pursued, previous aromatic heterocyle substituted interalkyne, 2-Butyne) but
investigations by Jiao demonstrated that Cu/O2 catalyst system
could be efficient for the cleavage of C=C, C C bonds of
also unsymmetrically substituted internal alkynes could
efficiently react with 1a to give the corresponding products in
moderate yields.
≡
carbonyl derivatives. So we tried various cooper salts as
additives for the reaction. Among of these salts, Cu(OAc)2
could give a moderated yield of the desired product (54%,
table 1, entry 7) while other Cu additives give poor yields
(table 1, entry 2-6). Subsequently, various parameters were
screened to improve the reaction efficiency (see Supporting
Information (SI)). The results showed that the solvent (Table 1,
entry 7-10) had great influence on the reaction yield and
Methanol was proven to be the most suitable candidate for
this transformation. When we investigated the effect of the
reaction temperature on this transformation, we found that
higher reaction temperatures (50 °C and 80 °C) could lead to
the yield of 3a 86% and 80% respectively (entry 12 and 13).
Table 2. Substrate scope a
entry
1
ketoimine (1)
alkyne
(2)
product (3) (yield)b
Ph
Ph
2a
Table 1.Optimization of Reaction Conditions a
1
3
1a: R= H
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
3a: R= H (85%)
1b: R= p-Me
1c: R= p-Ph
1d: R= o-Me
1e: R= p-Cl
1f: R= p-Br
1g: R= p-F
1h:R=p-CF3
1i: R=p-CO2Me
1j: R= m-Cl
1k: R= 3,5-CH3
3b: R= p-Me (88%)
3c: R= p-Ph (80%)
3d: R= o-Me (44%)
3e: R= p-Cl (78%)
3f: R= p-Br (78%)
3g: R= p-F(59%)
3h:R=p-CF3 (70%)
3i: R= p-CO2Me (67%)
3j: R= m-Cl (65%)
3k: R= 3,5-CH3 (76%)
yield
entry
catalysts
additives
solvent
(%)b
0
1
2
3
4
5
6
7
8
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]l2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
_NHPI
CuCl2
CuBr2
CuO
Cu(CN)2
CuSO4
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
EtOH
i-PrOH
t-AmOH
MeOH
MeOH
MeOH
MeOH
20
32
18
12
8
54
45
12
Trace
86c
80d
0
3l (66%)
2
1a
2b
9
10
12
13
14
15
3
4
5
1a
1a
1a
2c
2d
2e
3m (76%)
3n (74%）
3o (0%)
Cu(OAc)2
0
a Unless otherwise noted, all the reactions were carried out using (1a) (0.10
mmol) and (2a) (0.15 mmol) with metal catalysts (2.5 mol %) in the
presence of co-catalyst (1 equiv) in solvent (2.0 mL)at 30 ˚C for 24 h under
b
air in a sealed reaction tube, followed by flash chromatography on SiO2.
c
d
Isolated yield. The reaction temperature is 50 oC.
The reaction
temperature is 80 oC.
Substrate scope
OH
O
With the optimized conditions in hand, we next
investigated the substrate scope of this reaction with various
internal
alkynes
and
different
substituted
N-
6
7
1a
1a
2f
3p(68%)
3a(56%)
phenoxyacetamides. This transformation could tolerate
various groups at the para-position such as Me, Ph, CF3 and
CO2Me, affording the desired products 3b, 3c, 3h and 3i in
moderate to good yields. Also, the halogen substituents were
well tolerated under the optimized conditions to give products
2g
OH
O
3e-3g. Generally, the electron-donating groups provide
superior yields to electron-withdrawing groups. Furthermore,
it is noteworthy that the meta-Chloro-substituted N-
3p(60%)
8
1a
2h
2 | Chem. Commun., 2016, 00, 1-3
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aAll the reactions were carried out using (1) (0.10 mmol) and alkyne (2)
(0.15 mmol) with [Cp*RhCl2]2 (2.5 mol %) and co-catalyst (1equiv) in MeOH
(2.0 mL) at 50 ˚C for 24 h under air in a sealed reaction tube, followed by
flash chromatography on SiO2. b Isolated yield.
Mechanistic insights
To further investigate the reaction mechanism, several
control experiments were carried out (scheme 4). At first, we
ran the reaction in the presence of argon under our standard
conditions (eq. 1.). No desired products were observed and by-
product enamide
the enaminde
3
was isolated in 68% yield. We then treated
3
in the presence of air and argon under our
standard conditions respectively (eq. 2 and eq.3). Not
surprisingly, no desired products was found when argon was
involved in this transformation. Finally this result suggests that
Scheme 3. Possible Mechanism for the Transformation
enamide
3 might be the intermediate of the reaction and the
oxygen originated from air is crucial to the reaction.
Conclusions
In summary, we have developed a facile and convenient
method for the Rh(
Ⅲ
)-catalyzed acylation of Csp2-H bond of
N-phenoxyacetamide with alkyne under mild conditions using
alkyne as a novelacyl source. The reaction exhibits a good
tolerance for a broad range of functional groups and a variety
of alkynes could be employed as acyl sources to afford ortho-
acylphenols. Detailed mechanism studies on this method and
more transformations using alkynes as acyl sources are being
carried out in our laboratory.
Acknowledgements
The authors has declared that this article does not have any
funding supported.
Scheme 2 Preliminary Mechanism Studies
On the basis of the above result and previous studies,16
a
possible reaction mechanism has been proposed in Scheme 5.
Presumably, the transformation starts with concerted-
metalation-deprotonation step (CMD) to give the five-
Notes and references
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membered rhodacycle intermediate
coordination and insertion to afford the seven-membered
intermediate which undergoes reductive
elimination/oxidative addition to give intermediate . Then
the intermediate was capped by the Cu/O2 and provides the
strained four-membered G, which finally undergoes the
A, followed by alkyne
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D
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4 | Chem. Commun., 2016, 00, 1-3
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EDGE ARTICLE
Ying Xie*
Page No. – Page No.
Acylation of Csp2-H bond
with acyl sources derived
from
alkynes:
Rh-Cu
Bimetallic Catalyzed C≡C
bond cleavage
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