Nickel-catalyzed reductive carboxylation of styrenes using CO2

Article abstract of DOI:10.1021/ja8062925

A nickel-catalyzed reductive carboxylation of styrenes using CO₂ has been developed. The reaction proceeds under mild conditions using diethylzinc as the reductant. Preliminary data suggests the mechanism involves two discrete nickel-mediated catalytic cycles, the first involving a catalyzed hydrozincation of the alkene followed by a second, slower nickel-catalyzed carboxylation of the in situ formed organozinc reagent. Importantly, the catalyst system is very robust and will fixate CO₂ in good yield even if exposed to only an equimolar amount introduced into the headspace above the reaction. Copyright

Full text of DOI:10.1021/ja8062925

Published on Web 10/17/2008
Nickel-Catalyzed Reductive Carboxylation of Styrenes Using CO2
Catherine M. Williams, Jeffrey B. Johnson, and Tomislav Rovis*
Department of Chemistry, Colorado State UniVersity, Fort Collins, Colorado 80523
Received August 8, 2008; E-mail: rovis@lamar.colostate.edu
Scheme 1. Envisioned Reactivity
Carbon dioxide is an extremely attractive carbon source that is
readily available, inexpensive, and inherently renewable. Its utiliza-
tion as a C1 feedstock in both large-scale fixation processes and
small-scale synthesis has seen considerable growth in recent years.1
While transition metals promise a mild and efficient alternative for
the incorporation of carbon dioxide into organic molecules, such
methodology remains largely undeveloped.2 Current methods for
catalyzed carbon-carbon bond formation using CO2 have been
largely limited to reactions with extensive π systems (dienes and
diynes)3,4 or in carboxylation of preformed organometallics.5 Herein
we report a nickel-catalyzed reductive carboxylation of styrenes
under an atmosphere of CO2.
The nickel-mediated stoichiometric fixation of carbon dioxide
with alkenes has been known for over 20 years largely due to the
work of Hoberg.6 Inspired by this body of work, we have previously
demonstrated that metalacycles such as 2, generated from cyclic
anhydrides and nickel complexes, could be trapped with Ph2Zn as
a nucleophile.7 We speculated that the use of Et2Zn could lead to
either alkylative (4) or reductive (6) carboxylation of alkenes if
conducted under a CO2 atmosphere (Scheme 1). Although eminently
reasonable on paper, potential problems included balancing desired
reactivity with the potential catalyzed direct addition of the alkylzinc
reagent to CO2, as demonstrated recently by others.5f,g We were
confident, however, that judicious choice of ligand would lead to
a favorable outcome.
Table 1. Initial Ligand Screen for Reductive Carboxylation
entry
R
additive
yield (%)
1
2
3
4
5
6
7
8
CO2Me (a)
CO2Me (a)
CO2Me (a)
CO2Me (a)
CO2Me (a)
H (b)
none
bipy
DBU
pyridine
PPh3
DBU
KHMDS
CS2CO3
<5
NR
88
90
NR
NR
35
H (b)
H (b)
Initial attempts at the reductive carboxylation of activated
styrenes began with electron deficient methyl-4-vinylbenzoate (7a).
Much to our delight a ligand screen (Table 1, entry 3) revealed
thattheuseofNi(COD)2,DBU(1,8-diazabicyclo[5.4.0]undec-7-ene)6,4
and Et2Zn, under CO2 results in the formation of carboxylic acid
8a as a single regioisomer in 85% yield. Perhaps most importantly,
this R-carboxylated product is generated under 1 atm of CO2
supplied by a balloon, avoiding specialized gas manipulation.
56
Furthermore, the reaction is tolerant of a variety of functional
groups, including aryl chlorides, esters, ketones, and nitriles.
While the reaction with activated styrene 7a is quite efficient,
the use of styrene itself under identical conditions results in no
carboxylated product (Table 1, entry 6).
To expand the utility of the reaction, a series of nitrogen and
phosphorus ligands were examined with nearly uniform failure.8
The success of DBU as a ligand was difficult to rationalize but we
speculated that it could be a function of its basicity rather than
simply its donor character. That thought led us to investigate bases
not typically considered ligands on late transition metals. Basic
additives proved moderately successful (Table 1, entry 7), leading
us toward examination of a series of inorganic bases as well. The
use of Cs2CO3 as a ligand/additive affords 8b in 56% yield (entry
8), and with this result we began exploration of the scope.
Hammett σm/p and σp+ values have proven useful in the prediction
of reactivity.9 With few exceptions, electron deficient styrenes with
positive σ values undergo reductive carboxylation very efficiently
regardless of substitution pattern (Table 2, 7h, 7k, 7l), while those
with negative σ values generally fail to produce the desired product.
Although our screens involve 10 mol % nickel, we have shown
that 1 mol % Ni(acac)2 works equally well.10 Typical reaction
conditions utilize a balloon containing approximately 1 L of CO2
(45 mmol). To test consumption efficiency, a reaction was run in
a 15 mL flask with only a headspace of CO2: roughly 1 equiv of
carbon dioxide relative to styrene 7k (eq 1). Complete consumption
of styrene was observed and 92% of 8k was isolated indicating
that the hydrocarboxylation reaction proceeds under CO2 pressure
well below 1 atm.
Although Hoberg’s work involving metalacycles provided the
intellectual impetus for this research, initial investigations suggest
a different mechanism may be operative, one proceeding through
a nickel-hydride active catalyst (B, Scheme 2). Insertion of styrene
into the nickel-hydride bond provides benzyl nickel species C; a
transmetalation generates the benzylic zinc species D, the product
9
14936 J. AM. CHEM. SOC. 2008, 130, 14936–14937
10.1021/ja8062925 CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Reductive Carboxylation Substrate Scope
a Standard conditions: Ni(acac)2 (10 mol %), Cs2CO3 (20 mol %), Et2Zn (250 mol %). b See reference 9. c Isolated yield.
Scheme 2. Proposed Reductive Carboxylation Mechanism
References
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(8) See Supporting Information.
(9) Hansch, C; Leo, A.; Taft, R. W. Chem. ReV. 1991, 91, 165.
(10) Reaction of 7k (0.6 mmol) provides 8k in 89% yield. This also demonstrates
Cs2CO3 does not provide appreciable amounts of CO2.
(11) (a) Vettel, S.; Vaupel, A.; Knochel, P. Tetrahedron Lett. 1995, 36, 1023.
(b) Klement, I.; Lu¨tjens, H.; Knochel, P. Tetrahedron Lett. 1995, 36, 3161.
(12) The use of other reductants (i-PrOH, Ph3SiH, H2) provides <10% yield.
Me2Zn does not provide alkylated product; Ph2Zn affords benzoic acid.
(13) Substrate 7c provides >50% ethylnaphthalene with ∼10% 8c when
quenched after 1 h.
(14) Heterogeneous catalysis remains a consideration, although a preliminary
mercury drop experiment does not support it. See:Widegren, J. A.; Finke,
R. G. J. Mol. Catal. A 2003, 198, 317.
(15) A preformed naphthyl methylzinc reagent does not undergo carboxylation
in the absence of nickel (18 h, THF, 23 °C, 1 atm CO2).
of net hydrozincation of the alkene,11 while also regenerating Et-
Ni complex A. ꢀ-Hydride elimination and release of ethylene from
A generates the presumed active catalyst B.12 A separate catalytic
cycle involving transmetalation back to nickel (D to C) generates
another benzylic nickel species which undergoes insertion of CO2
prior to transmetalation with Et2Zn, producing the hydrocarboxy-
lation product F and regenerating precatalyst A. In support of this
mechanism, we note that a D2O quench after 1 h provides significant
amounts of the reduced alkene bearing a deuterium in the benzylic
position, suggestive of the presence of D.13,14 Importantly, the direct
5f,g
addition of dialkylzinc reagent to CO2
is extremely slow.15
A catalyzed hydrocarboxylation has been developed for a variety
of electron deficient and neutral ortho, meta, and para styrene
analogues.16 This reaction represents the foundation of a methodol-
ogy to incorporate carbon dioxide in the preparation of more
complex synthetic intermediates. Of additional interest is the
efficient uptake of CO2, which occurs under only 1 atm of CO2.
Studies to extend the reaction scope17 are in progress.
Acknowledgment. J.B.J. thanks the NIH for a postdoctoral
fellowship. TR thanks Lilly, Boehringer-Ingelheim and Johnson and
Johnson for support, and the Monfort Family Foundation for a
Monfort Professorship. We thank Professor Rick Finke for helpful
discussions.
(16) For hydroacylation of styrenes using anhydrides and H2, see:Hong, Y.-T.;
Barchuk, A.; Krische, M. J. Angew. Chem., Int. Ed. 2006, 45, 6885.
(17) Under these conditions, cyclohexadiene, decene, and ꢀ-methylstyrene give
<10% yield of expected product.
Supporting Information Available: Experimental procedures,
ligand screen, and spectral data for all new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
JA8062925
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