Carboallylation of Electron-Deficient Alkenes with Organoboron Compounds and Allylic Carbonates by Cooperative Palladium/Copper Catalysis

Article abstract of DOI:10.1021/acs.orglett.9b00915

The aryl- and alkylallylation of electron-deficient alkenes was achieved by cooperative palladium/copper catalysis. The reaction affords various carbon skeletons from readily available alkenes, allylic carbonates, and organoboron compounds, whereby a vari

Full text of DOI:10.1021/acs.orglett.9b00915

Letter
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Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Carboallylation of Electron-Deficient Alkenes with Organoboron
Compounds and Allylic Carbonates by Cooperative Palladium/
Copper Catalysis
Kazuhiko Semba,* Naoki Ohta, and Yoshiaki Nakao*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
S
* Supporting Information
ABSTRACT: The aryl- and alkylallylation of electron-
deficient alkenes was achieved by cooperative palladium/
copper catalysis. The reaction affords various carbon skeletons
from readily available alkenes, allylic carbonates, and organo-
boron compounds, whereby a variety of functional groups such
as acetyl, alkoxycarbonyl, bromo, and cyano moieties are
tolerated well.
he dicarbofunctionalization of alkenes is a powerful
approach to construct carbon skeletons, especially
that the allylarylation of 1a produced 4a in 78% yield in the
presence of Pd(OAc)2 (1.0 mol %), P(n-Pr)3 (2.0 mol %),
(IMes)CuCl (10 mol %), and NaOMe (10 mol %) at 80 °C
for 24 h in 1,4-dioxane (entry 1), and the formation of 4-
methyl-1-allylbenzene (5a) was not observed. Other mono-
dentate and bidentate phosphines afforded 4a in low yield
(entries 2−5). Different N-heterocyclic carbenes (NHCs) on
copper(I) chloride also affected the yield of 4a. For example,
the sterically more demanding IPr and the saturated SIMes
decelerated the reaction (entries 6 and 7). To prove the
cooperativity of the catalysis, control experiments were
conducted (entries 8−11), which revealed that all the catalyst
components are indispensable for the present transformation.
Under the optimized conditions, a variety of alkenes, allylic
carbonates, and aryl boronates was screened (Scheme 1).
Electron-rich and -deficient aryl groups were tolerated well
under these conditions. Sterically demanding aryl boronate 2e
afforded the corresponding product in moderate yield, while a
2-naphthyl group (2f) was successfully introduced in 1a. 3-
Thienyl boronate 2g can participate in the optimized
conditions. Regarding the alkenes, electron-donating and
-withdrawing substituents at the para-position on the benzene
ring of 1a did not have an impact on the yield. 1-Cyano-1-
methoxycarbonyl-2-phenylethene (1d) and barbituric acid
derivative 1e are viable alkenes under the optimized
conditions. 2-Methylpropenyl methyl carbonate (3b), cinnam-
yl methyl carbonate (3c), and 1-cyclohex-2-enyl methyl
carbonate (3d) afforded the corresponding product in
moderate and high yield, respectively. It is worth mentioning
that alkyl-9-BBN 2h, 2i, and 2j, which were prepared via the
hydroboration of the corresponding alkenes with H-9-BBN,
T
considering the availability of a broad variety of alkenes.1
The dicarbofunctionalization of α,β-unsaturated alkenes with
organometallic nucleophiles and organic electrophiles is a
particularly well-established and powerful method to construct
complex carbon structures, which has been applied to prepare
biologically active molecules.2 However, typical reaction
protocols require moisture- and/or O2-sensitive organometallic
reagents and multiple steps, which renders the entire process
complicated.3 A method based on bench-stable organo-
metallics would therefore be highly desirable. Following a
seminal report on the diallylation of electron-deficient alkenes
by Pd catalysis,4a−c related Pd-catalyzed dicarbofunctionaliza-
tion reactions of electron-deficient alkenes have been
reported.4d−h Recently, we accomplished the carboallylation
of electron-deficient alkenes by Pd/Cu catalysis using bench-
stable tetraorganosilicon reagents (HOMSi reagents) and
allylic carbonates.5a
Herein, we report the carboallylation of electron-deficient
alkenes with aryl- or alkylboron reagents and allylic carbonates
by synergistic Pd/Cu catalysis.5,6 The advantages of the
present protocol relative to our previous method are (1) in
contrast to the limited amount of aryl HOMSi reagents, a
broader variety of arylboronic acids and their derivatives is
commercially available; and (2) alkyl-9-borabicylo[3,3,1]-
nonane (alkyl-9-BBN) derivatives, which are easily prepared
in situ from the uncatalyzed hydroboration of the correspond-
ing alkenes with H-9-BBN, can be used as an alkylation agent.
Mechanistic studies revealed that the reaction proceeds by
cooperative Pd/Cu catalysis, not by a tandem catalysis as in the
case of our recent example.5a
Initially, we optimized the reaction conditions using
benzalmalononitrile (1a), p-tolyl boronic acid neopentylglycol
ester (2a), and allyl methyl carbonate (3a) as model substrates
(Table 1). After screening a variety of parameters, we found
Received: March 14, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b00915
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Table 1. Allylarylation of Benzalmalononitrile (1a) with p-
Tolyl Boronic Acid Neopentylglycol Ester (2a) and Allyl
Methyl Carbonate (3a)
Scheme 2. Proposed Mechanism for the Carboallylation of
Electron-Deficient Alkenes by Cooperative Pd/Cu Catalysis
yield of 4a
yield of 5a
a
b
entry deviation from standard conditions
(%)
(%)
1
2
3
4
5
6
7
none
78
17
24
<5
34
23
<5
<5
17
<5
<5
13
16
<5
PPh3 instead of P(n-Pr)3
PCy3 instead of P(n-Pr)3
P(t-Bu)3 instead of P(n-Pr)3
dppe instead of P(n-Pr)3
(IPr)CuCl instead of (IMes)CuCl
(SIMes)CuCl instead of (IMes)
CuCl
8
9
10
11
w/o Pd(OAc)2
w/o Pd(OAc)2/P(n-Pr)3
w/o (IMes)CuCl
<5
<5
<5
<5
<5
<5
<5
<5
w/o (IMes)CuCl/NaOMe
could be directly used as an alkylation reagent without
a
Yield determined by 1H NMR spectroscopy (internal standard:
purification under the optimized conditions (eq 1).
b
1,3,5-trimethoxybenzene). Yield determined by GC (internal
standard: n-C11H24).
Scheme 1. Substrate Scope under Optimized Conditions
To gain insights into the reaction mechanism, the time-
course of the allylarylation of 1a with 2a and 3a was
monitored. During the course of the reaction, the allylarylation
product was the sole detectable product by GC analysis, in
sharp contrast to the observation of hydroarylation product of
1a in the allylarylation with phenyl HOMSi by Pd/Cu
catalysis.7 The cross-coupling reaction of an alkylcopper
species 6a, which was prepared via the arylcupration8 of 1a,
and 3a was carried out (eq 2).9 The reaction afforded 4a in
60% yield in the presence of Pd(OAc)2/P(n-Pr)3, whereas the
yield decreased to 14% in the absence of Pd(OAc)2. These
results and the control experiments in Table 1 (entries 8−11)
should support that the present reaction proceeds in a Pd/Cu
cooperative manner, as shown in Scheme 2.
B
DOI: 10.1021/acs.orglett.9b00915
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
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On the basis of the results of this mechanistic study, a
plausible mechanism is proposed in Scheme 2. It seems feasible
that organocopper 8 is generated from copper methoxide 7
and organoboron reagent 2. Subsequently, 8 could add across
the double bond of electron-deficient alkenes 1 to afford
alkylcopper 6. A reaction between alkylcopper 6 and π-
allylpalladium 10, which could be generated by the oxidative
addition of allylic carbonate 3 to Pd(0) (9), would afford
carboallylation product 4, 9, and copper methoxide 7.
In conclusion, we developed a method for the carboallyla-
tion of electron-deficient alkenes by cooperative Pd/Cu
catalysis, which affords a variety of carbon skeletons in a
single operation. The present protocol is more convenient than
previous methods based on organosilicon reagents given the
commercial availability of a broader range of organoboron
compounds.
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ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b00915.
Detailed experimental procedures, including spectro-
scopic and analytical data (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: semba.kazuhiko.5n@kyoto-u.ac.jp.
*E-mail: nakao.yoshiaki.8n@kyoto-u.ac.jp.
ORCID
Kazuhiko Semba: 0000-0001-7903-4091
Yoshiaki Nakao: 0000-0003-4864-3761
Notes
The authors declare no competing financial interest.
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16, 4467. (b) Liebeskind, L. S.; Fengl, R. W. J. Org. Chem. 1990, 55,
5359. (c) Huang, J.; Chan, J.; Chen, Y.; Borths, C. J.; Baucom, K. D.;
Larsen, R. D.; Faul, M. M. J. Am. Chem. Soc. 2010, 132, 3674.
ACKNOWLEDGMENTS
■
This research was supported by a Grant-in-Aid for Young
Scientists (B) (JP26810058) from MEXT, the CREST
program “Establishment of Molecular Technology towards
the Creation of New Functions” (JPMJCR14L3) from the JST,
and The Asahi Glass Foundation.
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2013, 52, 3208. (e) Vercruysse, S.; Cornelissen, L.; Nahra, F.; Collard,
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L.; Riant, O. Chem. - Eur. J. 2014, 20, 1834. (f) Nahra, F.; Mace, Y.;
Boreux, A.; Billard, F.; Riant, O. Chem. - Eur. J. 2014, 20, 10970.
(g) Smith, K. B.; Logan, K. M.; You, W.; Brown, M. K. Chem. - Eur. J.
2014, 20, 12032. (h) Logan, K. M.; Smith, K. B.; Brown, M. K. Angew.
Chem., Int. Ed. 2015, 54, 5228. (i) Friis, S. D.; Pirnot, M. T.;
Buchwald, S. L. J. Am. Chem. Soc. 2016, 138, 8372. (j) Friis, S. D.;
Pirnot, M. T.; Dupuis, L. N.; Buchwald, S. L. Angew. Chem., Int. Ed.
REFERENCES
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Organic Letters
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D
DOI: 10.1021/acs.orglett.9b00915
Org. Lett. XXXX, XXX, XXX−XXX