Carboallylation of electron-deficient alkenes by palladium/copper catalysis

Article abstract of DOI:10.1039/c8cc06023a

A method for the carboallylation of electron-deficient alkenes with tetraorganosilicon reagents and allylic carbonates based on Pd/Cu catalysis has been developed. This method affords a wide range of structurally diverse carbon skeletons from readily available starting materials, and tolerates various functional groups.

Full text of DOI:10.1039/c8cc06023a

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Carboallylation of Electron-Deficient Alkenes by
Palladium/Copper Catalysis
Received 00th January 20xx,
Accepted 00th January 20xx
Kazuhiko Semba,* Naoki Ohta, Yuko Yano, and Yoshiaki Nakao*
DOI: 10.1039/x0xx00000x
www.rsc.org/
A method for the carboallylation of electron-deficient alkenes organocupration of electron-deficient alkenes7 followed by Pd-
with tetraorganosilicon reagents and allylic carbonates based on catalyzed allylation8 could achieve higher compatibility of such
Pd/Cu catalysis has been developed. This method affords a wide dicarbofunctionalizations. In this scenario, the scope of carbon
range of structurally diverse carbon skeletons from readily functionalities should be expanded compared to the known Pd
available starting materials, and tolerates various functional systems, as the nucleophiles and electrophiles are activated
groups.
independently by the Cu and Pd catalysts. Herein, we report
the allylarylations, alkenylallylations, and alkylallylations of
electron-deficient alkenes with air- and moisture-stable
HOMSi® reagents9 by Pd/Cu catalysis (eq 3). Moreover, we
report preliminary results on the asymmetric allylarylations of
alkenes.
The conjugate addition of organometallics across electron-
deficient alkenes followed by reactions of the resulting
alkylmetals with carbon-electrophiles is useful for the
construction of carbon skeletons and has been applied to the
preparation of bioactive molecules (eq 1).1 However, such
reactions typically consist of multi-step operations, and require
moisture- and/or air-sensitive organometallic reagents such as
organozinc, -aluminium, -copper, -titanium, or triorganoboron
reagents.1,2 In contrast, methods based on catalytically
generated alkyl complexes of transition-metals are more
useful, as they require merely a single operation to construct
two C–C bonds and they can use air- and moisture-stable
organometallics such as organoboronic acid derivatives or
organostannanes via the transmetallation of these stable
organometallics and transition-metal catalysts. Yamamoto and
co-workers have reported pioneering work on the Pd-
catalyzed diallylation of electron-deficient alkenes using
allylstannanes (eq 2).3a–c Related transformations including
allylbenzylations,3d allylpropargylations,3e,f allylcyanations,3g
and acetonation-allylations3h have also been developed.
However, the accessible combinations of carbon
functionalities remain limited. Although an alternative method
based on radical reactions have been developed, the reaction
was limited to alkylallylation.4
The allylarylation of benzalmalononitrile (1a) with phenyl
HOMSi®
(2a), which exhibits good stability toward air and
moisture, and allyl methyl carbonate (3a) was carried out using
various phosphine ligands and CuCl complexes of N-
heterocyclic carbenes (NHCs). After screening various reaction
parameters, the allylarylation of 1a (0.30 mmol) with 2a (0.30
mmol) and 3a (0.30 mmol) proceeded efficiently in the
During the course of our studies on synergistic cooperative
catalysis,5,6
metal
we
anticipated
that
catalytic
presence
of
Pd(OAc)2
(1.0
mol%),
1,3-
bis(diphenylphosphino)propane (dppp, 1.0 mol%), (IMes)CuCl
(5.0 mol%), and LiOt-Bu (20 mol%) to furnish 4a in 96% yield
without formation of allylbenzene (5a) (entry 1). The effects of
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the phosphine ligands are summarized in entries 2–7. PPh3, position of the aryl group of the aryl silicon reagents 2a–d
P(n-Pr)3, and PCy3 afforded the corresponding allylarylation were tolerated. Acetyl group, which would be difficult to be
product 4a in moderate to good yield, whereas P(t-Bu)3 tolerated under the conditions based on the moisture-
resulted in poor yield (entries 2–5). Bidentate phosphines such sensitive organometallics, was intact, although the yield was
as 1,2-bis(diphenylphosphino)ethane (dppe) and 1,1’- moderate due to the undesired cross-coupling between 2d and
bis(diphenylphosphino)ferrocene (dppf) were also effective 3a to afford p-allylacetophenone. Moreover, it should be
(entries 6 and 7). The effects of the (NHC)CuCl complexes are noted that alkenyl and alkyl silicon reagents were also viable
shown in entries 8–10. (SIMes)CuCl, i.e., a complex similar to substrates under the standard conditions. Alkenyl HOMSi®
(IMes)CuCl showed good reactivity (entry 8). Bulkier NHC- reagents afforded the alkenylallylation products in good yields
ligated copper complexes afforded 4a in lower yields and 5a in under retention of the stereochemistry of the double bond
moderate yields (entries 9 and 10). The effects of varying the
(2f–i). Methyl, n-alkyl, and cyclopropyl groups could thus be
base are shown in entries 11–13. The yields of 4a decreased introduced (2j
–l).
using NaOt-Bu or KOt-Bu (entries 11 and 12). When K2CO3 was
Table 2. Scope of organosilicon reagents 2.
used, 4a was obtained in 44% yield (entry 13). Under the
optimized reaction conditions, the reaction did not proceed in
the absence of Pd(OAc)2 or (IMes)CuCl (entries 14 and 15).
These results clearly demonstrate that both Pd and Cu
catalysts are indispensable for the present transformation.
Table 1. Allylarylation of benzalmalononitrile (1a) with phenyl HOMSi® (2a) and allyl
methyl carbonate (3a)
Entry
Deviation from
the standard conditions
none
Yield of
4a (%)a
96
Yield of
5a (%)a
<5
1
2
PPh3 instead of dppp
53
26
The scope of alkenes
1 and allylic carbonates 3 was
3
4
P(n-Pr)3 instead of dppp
PCy3 instead of dppp
84
82
14
77
59
74
23
18
70
50
44
<5
<5
<5
<5
<5
<5
<5
<5
50
34
<5
<5
<5
<5
9
demonstrated
in
Table
3.
1,1-Dicyano-2-(4-
1,1-dicyano-2-(4-
methoxyphenyl)ethene
(1b),
5
P(t-Bu)3 instead of dppp
dppe instead of dppp
fluorophenyl)ethene (1c), and 1,1-dicyano-2-cyclohexylethene
1d) afforded the corresponding products in moderate to good
6
(
yields. 1-Cyano-1-alkoxycarbonyl alkene 1e afforded the
7
dppf instead of dppp
corresponding allylarylation product, which represents useful
8
(SIMes)CuCl instead of (IMes)CuCl
(IPr)CuCl instead of (IMes)CuCl
(SIPr)CuCl instead of (IMes)CuCl
NaOt-Bu instead of LiOt-Bu
KOt-Bu instead of LiOt-Bu
K2CO3 instead of LiOt-Bu
w/o Pd(OAc)2
intermediates en route to β-amino acid derivatives, in good
9
yield, while barbituric acid derivative 1f afforded the
allylarylation product in moderate yield. Chalcone (1g) was not
a viable substrate under the standard conditions probably due
to low efficiency of the arylcupration across chalcone. A
variety of allylic carbonates including acyclic and cyclic ones
were examined. When branched allylic carbonate 3b was
employed, the corresponding linear product was obtained in
good yield with high stereoselectivity. Under the applied
reaction conditions, various functionalities including OTBS,
amide, alkoxycarbonyl, and CN substituents remained intact.
To gain insight into the underlying reaction mechanism,
time-course of the allylarylation of 1a with 2a and 3a was
monitored (Figure S2). At the initial stage, hydroarylation
10
11
12
13
14
15
w/o (IMes)CuCl
a Yield determined by GC (internal standard: n-C13H28).
With optimized conditions in hand, the scope of
organosilicon reagents was examined with 1a and 3a (Table 2).
Electron-donating or -withdrawing substituents at the para-
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product 6a was observed. This observation would support that
the present allylarylation proceeds through Cu-catalyzed
hydroarylation of 1a followed by Pd-catalyzed allylation of
6a 6k,l
In fact, allylarylation of 1b in the presence of
.
hydroarylation product 6a preferentially afforded allylation
product 4a rather than allylarylation product 4b (eq 4).
Table 3. Scope of alkenes 1 and allylic carbonates 3.
Scheme 1. A plausible mechanism.
To further demonstrate the synthetic utility of the present
method, asymmetric allylarylations were explored. When
chiral bidentate phosphine L110 was employed, the
allylarylation of 1a afforded 4b in 19% yield (e.r. = 86:14) (eq
5). Moreover, an asymmetric allylarylation of 1e was achieved
by using a chiral palladium catalyst containing L2 11
afforded 4o in 81% yield (e.r. = 76:24) (eq 6).
,
which
According to the mechanistic studies, a plausible reaction
mechanism is depicted in Scheme 1. An organocopper complex
11 should be generated from copper alkoxide 10 and
organosilicon reagent
2 (step d in the Cu cycle). An
organocupration across electron-deficient alkenes followed by
protonation with MeOH should afford hydroarylation product
6
and copper alkoxide 10 (steps e and f in the Cu cycle). The
nucleophilic substitution of -allylpalladium complex , which
should be generated from low-valent palladium complex and
allylic carbonates , with carbon-nucleophiles generated from
should afford the allylarylation product under concomitant
π
8
7
3
6
4
regeneration of the low-valent palladium species
and c in the Pd cycle).
7 (steps a, b
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6
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Conclusions
In conclusion, we have developed carboallylations of
electron-deficient alkenes by Pd/Cu catalysis, in which two
different organic functionalities such as aryl, alkenyl, alkyl, and
allyl moieties are introduced simultaneously across the C=C
bond of alkenes. Though preliminary, asymmetric
allylarylations were accomplished using chiral-phosphine-
ligated Pd and Cu catalysts. The present transformations
should thus be powerful tools to construct complex carbon
skeletons from readily available alkenes in high step-efficiency.
Conflicts of interest
There are no conflicts to declare.
Acknowledgement
This research was supported by a Grant-in-Aid for Young
Scientists (B) (26810058) from MEXT, the CREST program
“Establishment of Molecular Technology towards the Creation
of New Functions” (JPMJCR14L3) from the JST, and The Asahi
Glass Foundation.
7
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The carboallylation of electron-deficient alkenes with tetraorganosilicon reagents and allylic
carbonates has been developed by palladium/copper catalysis.