Rh(I)-catalyzed cross-coupling of α-diazoesters with arylsiloxanes

Article abstract of DOI:10.1021/acs.orglett.5b00052

An Rh(I)-catalyzed cross-coupling of diazoesters with arylsiloxanes has been successfully achieved. This transformation is a new method for the construction of the C(sp³)-C(sp²) bond, thus providing an alternative synthesis of α-aryl esters. Rh(I)-carbene migratory insertion has been proposed to be involved in this coupling reaction. The reaction represents the first example of utilizing arylsiloxane as the coupling partner in the carbene-involved cross-coupling reactions.

Full text of DOI:10.1021/acs.orglett.5b00052

Letter
pubs.acs.org/OrgLett
Rh(I)-Catalyzed Cross-Coupling of α‑Diazoesters with Arylsiloxanes
Ying Xia, Zhen Liu, Sheng Feng, Fei Ye, Yan Zhang, and Jianbo Wang*
Beijing National Laboratory of Molecular Sciences (BNLMS) and Key Laboratory of Bioorganic Chemistry and Molecular
Engineering of Ministry of Education, College of Chemistry, Peking University, Beijing 100871, China
S
* Supporting Information
ABSTRACT: An Rh(I)-catalyzed cross-coupling of diazoest-
ers with arylsiloxanes has been successfully achieved. This
transformation is a new method for the construction of the
C(sp3)−C(sp2) bond, thus providing an alternative synthesis
of α-aryl esters. Rh(I)−carbene migratory insertion has been
proposed to be involved in this coupling reaction. The reaction
represents the first example of utilizing arylsiloxane as the coupling partner in the carbene-involved cross-coupling reactions.
Scheme 1. Cross-Coupling Reactions with Diazo Compounds
ransition-metal-catalyzed cross-coupling reactions have
Tbeen established as indispensible tools for carbon−carbon
bond formation in modern organic synthesis. In this area,
organosilicon reagents (Hiyama reaction and Hiyama−Denmark
reaction) represent attractive coupling partners due to their facile
availability, low toxicity, relative stability, and good functional-
group compatibility when compared to other organometallic
reagents.1,2 Apart from the classical and/or modified coupling
reactions with aryl halides3 as the electrophiles, organosilicon
reagents can also couple with alkynyl halides4 and alkyl halides,5
including the more challenging unactivated alkyl halides.5a−c In
addition, organosilicon reagents also have been applied to C−H6
and C−C7 bond couplings under suitable catalytic reaction
systems.
On the other hand, diazo compounds, including those
generated in situ from the corresponding N-tosylhydrazones
under basic conditions, have recently emerged as a new type of
cross-coupling partners in transition-metal-catalyzed reactions.8
The cross-coupling of diazo compounds with organometallic and
related reagents represents a unique method for the construction
of C−C bonds.9,10 For example, in 2004, Fu and co-workers
reported a Cu(I)-catalyzed Sonogashira-type coupling of diazo
compounds with terminal alkynes in which the 3-alkynoate
products are difficult to synthesize using the traditional
Sonogashira reaction.9a This type of coupling reaction was
further developed by the groups of Wang9b and Ma,9c who
employed different types of diazo precursors to obtain the
Sonogashira-type products by forming C(sp3)−C(sp) bonds.
Moreover, the Pd(II)-catalyzed Sonogashira-type coupling of
diazo compounds or N-tosylhydrazones was reported to afford
conjugated enynes (Scheme 1, a).9d The Suzuki-type coupling of
diazo compounds was first realized with the catalysis of Pd
complexes under oxidative conditions.10a Subsequently, this
coupling reaction was expanded by employing Rh(I) catalysts
(Scheme 1, b).10d,11
some challenges exist for the development of this type of
coupling reaction: (1) the low polarizability of the C−Si bond in
organosilicons requires special bases for transmetalation, which
may decompose the labile diazo substrates; (2) the oxidant
required for the regeneration of the Pd catalysts may not be
compatible with the diazo compounds that are labile to oxidation.
To our knowledge, the coupling reactions between organo-
silicons and diazo compounds for C−C bond formation are not
known in the literature. Herein, we report the first Hiyama-type
coupling of diazo compounds under the catalysis of Rh(I)
complex (Scheme 1, c).
Initially, the reaction of phenylsiloxane 1 and diazoester 2a
were carried out with Pd(PPh3)4 as the catalyst under oxidative
conditions. However, the expected coupling product 3 was either
not observed or only formed in very low yield with benzoquinone
(BQ) or CuCl2 as the oxidant (Scheme 2, a). Further
optimization under palladium catalysis failed to improve the
yield, which indicates that the diazoester, the oxidant, and TBAF
are incompatible in one reaction system. We then turned our
attention to rhodium catalysis, in which the oxidant is not needed
because the terminating step of the catalytic cycle is the
protonation instead of β-H elimination. Gratifyingly, the
As a continuation of our interest in cross-coupling reactions of
diazo compound, we turned our attention to a Hiyama-type
coupling of organosilicon reagents with diazo compounds.
However, compared to the corresponding Suzuki-type coupling,
Received: January 7, 2015
© XXXX American Chemical Society
A
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Letter
a
Scheme 2. Cross-Coupling of Phenylsiloxane with Diazoester:
(a) Initial Attempt with Pd Catalysis; (b) Initial Attempt with
Rh Catalysis; (c) Optimized Reaction Conditions with Rh
Catalysis
Scheme 3. Reaction Scope of Aryl Diazoesters
coupling of phenylsiloxane 1 with donor−acceptor diazoester 4a
under rhodium catalysis could afford the expected product 5a in
18% isolated yield (Scheme 2, b).
With this initial result, further optimization of the reaction
conditions was carried out. Through screening the reaction
parameters, we concluded that the product 5a could be isolated
in 78% yield under the optimized conditions as shown in Scheme
2, c.12 Since α-aryl esters are a class of important molecules in
various fields,13 we then proceeded to explore the scope of this
Rh(I)-catalyzed Hiyama-type coupling. A series of aryl
diazoesters (4a−w) were initially tested with phenylsiloxane 1
under the optimized reaction conditions (Scheme 3). The ester
group on the diazo compound showed a negligible effect on this
transformation, and the corresponding products were obtained
in 72−81% yields (5a−d). The reactions with para- (4e−n),
meta- (4o−q), and ortho-substituted (4r−t) aryl diazoesters as
well as the multisubstituted diazo compounds (4u−w) all
proceeded well, giving the corresponding coupling products in
good yields.
a
Reaction conditions: [Rh(cod)OH]2 (2 mol %), PCy3·HBF4 (10 mol
%), TBAF (0.2 mmol), 4a−w (0.2 mmol), 1 (0.3 mmol), H2O (200
b
μL), THF (4.0 mL), 80 °C under N2 for 5 h, isolated yields. Yield in
parentheses was for the reaction on a 5 mmol scale. The reaction was
carried out in dioxane at 100 °C with 2 equiv of 1.
c
a
Scheme 4. Reaction Scope of Arylsiloxanes
For the more stable diazo compounds that bear electron-
withdrawing substituents (4i−n,q,s,t,v,w), it was noted that
higher reaction temperature was necessary. The reactions with
these diazoesters were carried out at 100 °C in dioxane. Under
such conditions, the diazo compounds could be fully converted
with satisfactory yields. Notably, the chloro and bromo
substituents are tolerated in this reaction, providing the
opportunity for further transformations through transition-
metal-catalyzed coupling reactions. In addition, the enolizable
ketone moiety is also tolerated (5n), while such a moiety is not
compatible with the Pd-catalyzed α-arylation of esters due to the
strong basic conditions.
a
The reaction conditions are the same as described in Scheme 3.
The operability and the efficiency of this Rh(I)-catalyzed
carbene coupling was demonstrated by scale-up experiments.
Under the same reaction conditions, the electron-neutral and
electron-deficient aryl diazoesters were both scaled up to gram
synthesis, and the corresponding diaryl acetates 5c and 5w could
be obtained in 90% (1.21 g) and 87% (1.28 g) yields,
respectively.12 Notably, the yields of the gram-scale synthesis
were 10−15% higher than that of the small-scale reactions.
Next, the scope of arylsiloxanes 6a−o was investigated by
reacting with aryl diazoester 4c under the optimized reaction
conditions (Scheme 4). The coupling reaction with para- (6a−g)
and meta-substituted (6h−j) arylsiloxanes worked well in this
transformation, while the reaction with ortho-substituted
arylsiloxanes (6k−l) only gave diminished yields. This is
presumably attributed to the steric hindrance of the ortho
substituents. In addition, the electron-rich substituents on the
para- or ortho-position of the aryl ring were found to have
negative effects on this transformation, as shown by the
diminished yields in the cases of 7b and 7l. On the contrary,
arylsiloxanes bearing electron-withdrawing substituents gener-
ally afforded the corresponding products in good to excellent
yields (7c−g,j). Again, arylsiloxanes containing chloro or bromo
groups worked well in this reaction (7f−g,j). Finally,
B
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Letter
naphthylsiloxane proved to be a suitable coupling partner,
affording the corresponding product 7n in 50% yield.
substrate in this Rh(I)-catalyzed reaction, providing diaryl
phosphonate 10i in moderate yield.
Finally, the Rh(I)-catalyzed Hiyama-type coupling was applied
to the synthesis of α-heteroaryl esters, which are difficult to
access through other methods. As illustrated in Scheme 7, a range
Apart from aryl diazoesters, the alkyl-substituted diazoesters
were also explored. The alkyl diazoesters were found to be
suitable substrates for this transformation at lower reaction
temperature, giving products 8a−h in moderate to good yields
(Scheme 5). A series of alkyl diazoesters 2a−d were reacted
a
Scheme 7. Synthesis of α-Heteroaryl Esters
a
Scheme 5. Reaction Scope of Alkyl Diazoesters
a
Unless otherwise noted, the reaction conditions are the same as
a
b
The reaction conditions are the same as described in Scheme 3,
described in Scheme 3. The reaction was carried out in dioxane at
100 °C with 2 equiv (0.4 mmol) of arylsiloxane. The reaction was
carried out with 2.5 equiv (0.5 mmol) of 3-thienylsiloxane. The
c
except 2 equiv (0.4 mmol) of arylsiloxane was used and the reaction
was carried out at 70 °C.
d
reaction was carried out at 70 °C.
smoothly with phenylsiloxane (8a−d). It is noted that the
terminal C−C double bond remains intact in this transformation,
indicating that the high chemo-selectivity for the reaction
between arylsiloxane and diazo moiety in the Rh(I)-catalyzed
reaction (8d). Substituted arylsiloxanes also show good reactivity
to alkyl diazoester 2a, providing the corresponding aryl
propanoates 8e−h in good yields.
Then more stable diazo compounds, which bear two electron-
withdrawing groups, were investigated. It was noted that such
diazo compounds require elevated temperature for the reaction
to complete, similar to that of the electron-deficient aryl
diazoesters (Scheme 6). Under such conditions, a series of
symmetric (9a−d) and unsymmetric (9e−f) diazomalonates
were smoothly converted to the corresponding α-aryl malonates
in 40−72% yields. Both electron-deficient and electron-rich
arylsiloxanes participate in this transformation (10g,h). In
addition, the α-aryl diazophosphonate was also a suitable
of α-heteroaryl esters could be obtained with the present
method. Heteroaryl diazo compounds, such as 3-pyridinyl (12a)
and 3-thienyl (12b) diazoesters, could smoothly undergo the
coupling reaction with a series of arylsiloxanes. Furthermore,
heteroarylsiloxane could also react with different types of diazo
compounds to afford the corresponding products 13g−j.
Notably, the unsymmetric (13h) and symmetric (13i)
diheteroaryl acetates could be readily accessed via this method.
A tentative mechanism was proposed in Scheme 8.12 Initially,
[Rh(cod)(OH)]2 dedimerizes and then undergoes ligand
Scheme 8. Proposed Reaction Mechanism
a
Scheme 6. Reaction Scope of Diazomalonates
exchange with PCy3 to generate an active catalyst species A,
which undergoes transmetalation with arylsiloxane to form aryl
Rh(I) intermediate B with the aid of TBAF.14 Subsequently, the
coordination of the aryl diazoacetate to rhodium center generates
an η1-C diazo complex C. For this step, the electron-donating
substituents on the aryl diazoacetate substrates should facilitate
the coordination. Dinitrogen extrusion then occurs from
intermediate C to generate a Rh(I)−carbene complex D,15
a
The reaction conditions are the same as described in Scheme 3,
except 2 equiv (0.4 mmol) of arylsiloxane was used and the reaction
was carried out at 100 °C in dioxane.
C
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Letter
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which then undergoes migratory insertion to afford oxa-π-allyl
Rh(I) intermediate E.16 Finally, E is protonated with H2O to
deliver the coupling product with the regeneration of the catalyst
A.
In conclusion, we have reported the first Rh(I)-catalyzed
Hiyama-type cross-coupling reaction between arylsiloxanes and
diazoesters. A series of diazo compounds, including aryl, alkyl,
and heteroaryl diazoesters as well as diazomalonates, participate
in this reaction.17 This transformation shows good functional
group compatibility and can be scaled up, thus constituting an
alternative method to the previously established Ni- and Pd-
catalyzed synthesis. Finally, this reaction is an excellent example
to demonstrate the fact that the merging of carbene chemistry
with cross-coupling is generally applicable to various coupling
partners.8c
́
(9) (a) Suarez, A.; Fu, G. C. Angew. Chem., Int. Ed. 2004, 43, 3580.
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(11) Organoborons also react with diazo compounds under transition-
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3090 and references therein.
ASSOCIATED CONTENT
■
S
* Supporting Information
(12) For details, see the Supporting Information.
Experimental details, spectral data, and 1H and 13C NMR spectra
for products. These materials are available free of charge via the
Internet at http://pubs.acs.org.
(13) For selected reviews, see: (a) Johansson, C. C. C.; Colacot, T. J.
Angew. Chem., Int. Ed. 2010, 49, 676. (b) Bellina, F.; Rossi, R. Chem. Rev.
2010, 110, 1082.
(14) For a review on Rh(I)-catalyzed coupling with organometallic
compounds, see: Fagnou, K.; Lautens, M. Chem. Rev. 2003, 103, 169.
(15) Cohen, R.; Rybtchinski, B.; Gandelman, M.; Rozenberg, H.;
Martin, J. M. L.; Milstein, D. J. Am. Chem. Soc. 2003, 125, 6532.
(16) For the reports on catalytic Rh(I)−carbene migratory insertions,
see ref 10d and: (a) Xia, Y.; Liu, Z.; Liu, Z.; Ge, R.; Ye, F.; Hossain, M.;
Zhang, Y.; Wang, J. J. Am. Chem. Soc. 2014, 136, 3013. (b) Yada, A.;
Fujita, S.; Murakami, M. J. Am. Chem. Soc. 2014, 136, 7217.
(17) We have also attempted the cross-coupling with N-tosylhy-
drazone and aryldimethylsilanol as the substrates, but the reactions
failed to afford the expected coupling products. For details, see the
Supporting Information.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: wangjb@pku.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This project was supported by the 973 program
(2012CB821600) and NSFC (Grant Nos. 21272010 and
21332002).
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