Regioselective copper-catalyzed carboxylation of allylboronates with carbon dioxide

Article abstract of DOI:10.1021/ol4019375

In the presence of a Cu(I)/NHC catalyst, the reactions of allylboronic pinacol esters with CO₂ (1 atm) are highly regioselective, giving exclusively the more substituted β,γ-unsaturated carboxylic acids in most cases. A diverse array of substituted carboxylic acids can be prepared via this method, including compounds featuring all-carbon quaternary centers.

Full text of DOI:10.1021/ol4019375

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Regioselective Copper-Catalyzed
Carboxylation of Allylboronates
with Carbon Dioxide
Hung A. Duong,* Paul B. Huleatt, Qian-Wen Tan, and Eileen Lau Shuying
Organic Chemistry, Institute of Chemical and Engineering Sciences (ICES),
Agency for Science, Technology and Research (A*STAR), 8 Biomedical Grove,
Neuros #07-01, Singapore 138665
duong_hung@ices.a-star.edu.sg
Received July 10, 2013
ABSTRACT
In the presence of a Cu(I)/NHC catalyst, the reactions of allylboronic pinacol esters with CO2 (1 atm) are highly regioselective, giving exclusively
the more substituted β,γ-unsaturated carboxylic acids in most cases. A diverse array of substituted carboxylic acids can be prepared via this
method, including compounds featuring all-carbon quaternary centers.
Considering the increasing scarcity and cost of fossil
resources, the use of CO2 as a nontoxic, inexpensive, and
abundant reagent in synthetic applications is of consider-
able interest.1 In this regard, CꢀC bond forming reactions
represent a highly useful process. For example, direct
carboxylation of strongly nucleophilic allylmetals such as
organolithiums and Grignard reagents with CO2 provides
a straightforward method to prepare β,γ-unsaturated
carboxylic acids, highly versatile building blocks incorpor-
ating two modifiable functional groups (Scheme 1a).2ꢀ4
A
major drawback of these reactions, however, is the high
reactivity of the metalꢀcarbon bond, which is incompa-
tible with a number of sensitive functional groups.
In a seminal report, Shi and Nicholas showed that
activation of CO2 by the less polar allylstannanes is
possible under palladium catalysis, albeit at high pressures
(33 atm) of CO2 (Scheme 1b).5 Later, Wendt et al. were
able to carboxylate allylstannanes with CO2 at ambient
pressure using a pincer-type palladium complex.6 More
recently, Hazari et al. employed (η3-allyl)Pd(L)(carboxylate)
(L = PR3 or NHC) and allyl-bridged Pd(I) dimers for the
carboxylation of allylstannanes and allylborons with CO2
(1 atm) with high activities.7 Despite these novel developments,
(1) For reviews on CO2 transformations, see: (a) Dell’Amico, D. B.;
Calderazzo, F.; Labella, L.; Marchetti, F.; Pampaloni, G. Chem. Rev.
2003, 103, 3857. (b) Louie, J. Curr. Org. Chem. 2005, 9, 605. (c)
Sakakura, T.; Choi, J.-C.; Yasuda, H. Chem. Rev. 2007, 107, 2365. (d)
Federsel, C.; Jackstell, R.; Beller, M. Angew. Chem., Int. Ed. 2010, 49,
6254. (e) Riduan, S. N.; Zhang, Y. Dalton Trans. 2010, 39, 3347. (f)
Cokoja, M.; Bruckmeier, C.; Rieger, B.; Herrmann, W. A.; Kuhn, F. E.
Angew. Chem., Int. Ed. 2011, 50, 8510.
(2) (a) Friedrich, L. E.; Cormier, R. J. Org. Chem. 1971, 36, 3011. (b)
Courtois, G.; Miginiac, L. J. Organomet. Chem. 1974, 69, 1 and
references therein. (c) O’Connor, P. D.; Kim, U. B.; Brimble, M. A.
Eur. J. Org. Chem. 2009, 4405.
(3) For examples on applications of β,γ-unsaturated carboxylic acids
in synthesis, see: (a) Andreana, P. R.; McLellan, J. S.; Chen, Y.; Wang,
P. G. Org. Lett. 2002, 4, 3875. (b) Fekner, T.; Muller-Bunz, H.; Guiry,
P. J. Org. Lett. 2006, 8, 5109. (c) Yang, S.-H.; Caprio, V. Synlett 2007, 8,
1219. (d) O’Connor, P. D.; Kim, U. B.; Brimble, M. A. Eur. J. Org.
Chem. 2009, 4405. (e) Hartog, T. D.; Macia, B.; Minnaard, A, J.;
Feringa, B. L. Adv. Synth. Catal. 2010, 352, 999. (f) Gu, Z.; Zakarian,
A. Org. Lett. 2011, 13, 1080.
(4) For other CO2 transformations leading to β,γ-unsaturated car-
boxylic acids, see: (a) Tokuda, M.; Kabuki, T.; Katoh, Y.; Suginome, H.
Tetrahedron Lett. 1995, 36, 3345. (b) Takimoto, M.; Mori, M. J. Am.
Chem. Soc. 2001, 123, 2895. (c) Takimoto, M.; Mori, M. J. Am. Chem.
Soc. 2002, 124, 10008. (d) Takaya, J.; Iwasawa, N. J. Am. Chem. Soc.
2008, 130, 15254. (e) Takaya, J.; Sasano, K.; Iwasawa, N. Org. Lett.
2011, 13, 1698.
(5) Shi, M.; Nicholas, K. M. J. Am. Chem. Soc. 1997, 119, 5057.
(6) (a) Johansson, R.; Wendt, O. F. Dalton Trans. 2007, 488. (b)
Johnson, M. T.; Johansson, R.; Kondrashov, M. V.; Steyl, G.; Ahlquist,
M. S. G.; Roodt, A.; Wendt, O. F. Organometallics 2010, 29, 3521.
(7) (a) Wu, J.; Green, J. C.; Hazari, N.; Hruszkewycz, D. P.;
Incarvito, C. D.; Schmeier, T. J. Organometallics 2010, 29, 6369. (b)
Hruszkewycz, D. P.; Wu, J.; Hazari, N.; Incarvito, C. D. J. Am. Chem.
Soc. 2011, 133, 3280. (c) Wu, J.; Hazari, N. Chem. Commun. 2011, 47,
1069. (d) Hazari, N.; Hruszkewycz, D. P.; Wu, J. Synlett 2011, 13, 1793–
1797. (e) Hruszkewycz, D. P.; Wu, J.; Green, J. C.; Hazari, N.; Schmeier,
T. J. Organometallics 2012, 31, 470–485.
r
10.1021/ol4019375
XXXX American Chemical Society

carboxylation of allylborons and allylstannanes possessing
substituent(s) at positions other than the β-carbon remains
elusive under palladium catalysis.5,6b,7c
speculated that an allylcopper(I) species resulting from
the transmetalation of an allylboronate with a Cu(I)
catalyst could readily react with CO2.9 Encouraged by
many important advances in the synthesis of allylboronic
esters,10 we explored the reaction of these environmentally
friendly organoborons with CO2 under copper catalysis.
We set out to investigate the reaction of allylboronic
pinacol ester 1a with CO2 (1 atm) where several products
could be formed, including 2a (branched), 2a0 (linear), and
the isomerized compounds (Table 1).11 Pleasingly, a com-
bination of [Cu(IPr)Cl] (10 mol %) and KOtBu (1.1 equiv)
Scheme 1. Direct Carboxylation of Allylmetals with CO2
1
gave 2a in 75% yield as determined by H NMR of the
crude mixture (Table 1, entry 1), with only a trace of 2a0
being formed. Under these conditions, isomerized pro-
ducts 2a-i or 2a0-i were not observed. Further screening
revealed that in situ generation of the catalyst from CuCl/
IPrCl resulted in a lower yield of 2a (entry 2). The less
bulky ligand IMes or a different base KOMe12 was also
active for this reaction, giving 2a in 60% and 71% yields,
respectively (entries 3 and 4). The reaction could be run
with as low as 5 mol % of Cu(IPr)Cl without affecting the
yield of 2a to any significant extent (entries 5 and 6).
Phosphine ligands such as BINAP and CyJohnphos could
alsoleadtomoderateyields of2a(entries 7 and 8). Boththe
Cu(I) catalyst and base were critical to the formation of 2a,
as no product was formed in the absence of either one
(entries 9 and 10).
Under the optimized conditions, a variety of β,γ-unsa-
turated carboxylic acids were synthesized via carboxyla-
tion of allylboronates (Table 2). In most cases (except
entries 7 and 8), we could only observe traces of other
byproducts by 1H NMR in the crude mixture after work-
up. Allylboronic esters with a primary alkyl substituent at
the γ-carbon reacted with CO2 under copper catalysis to
give the corresponding branched carboxylic acids in
54ꢀ79% yield (entries 1ꢀ6). The reaction yield and selec-
tivity were greatly hampered when a sterically demanding
substituent was introduced at the γ-carbon (entries 7 and 8).
We were attracted to the Cu(I)-catalyzed reactions of
carbon nucleophiles with CO2 that have captured the
attention of several groups over the past few years.8 In
particular, the Hou group,8d,f the Iwasawa group8e and the
Sawamura group8g independently showed that carboxyla-
tions of aryl-, alkenyl-, and alkylborons with CO2 (1 atm)
can be facilitated in the presence of a Cu(I) catalyst. We
questioned whether a direct carboxylation strategy with
CO2 (1 atm) could be developed to enable the synthesis of a
diverse array of β,γ-unsaturated carboxylic acids. We
(9) For reports on Cu(I)-catalyzed allylations of carbonyls, see: (a)
Kanai, M.; Wada, R.; Shibuguchi, T.; Shibasaki, M. Pure Appl. Chem.
2008, 5, 1055 and references therein. (b) Vieira, E. M.; Snapper, M. L.;
Hoveyda, A. H. J. Am. Chem . Soc. 2011, 133, 3332.
(10) For prepration of allylboronic esters from allyl halides via a
Grignard reagent, see: (a) Gerbino, D. C.; Mandolesi, S. D.; Schmalz,
ꢀ
H.-G.; Podesta, J. C. Eur. J. Org. Chem. 2009, 3964. (b) Clary, J. W.;
Rettenmaier, T. J.; Snelling, R.; Bryks, W.; Banwell, J.; Wipke, W. T.;
(8) For reviews, see: (a) Correa, A.; Martin, R. Angew. Chem., Int.
Ed. 2009, 48, 6201. (b) Ackermann, L. Angew. Chem., Int. Ed. 2011, 50,
3482. (c) Wenzhen, Z.; Xiaobing, L. Chin. J. Catal. 2012, 33, 745. For
Cu-catalyzed carboxylation of organoborons, see: (d) Ohishi, T.;
Nishiura, M.; Hou, Z. Angew. Chem., Int. Ed. 2008, 47, 5792. (e) Takya,
J.; Tadami, S.; Ukai, K.; Iwasawa, N. Org. Lett. 2008, 10, 2697. (f)
Ohishi, T.; Zhang, L.; Nishiura, M.; Hou, Z. Angew. Chem., Int. Ed.
2011, 50, 8114. (g) Ohmiya, H.; Tanabe, M.; Sawamura, M. Org. Lett.
2011, 13, 1086. For related Cu-catalyzed carboxylation of other carbon
nucleophiles, see: (h) Zhang, L.; Cheng, J.; Ohishi, T.; Hou, Z. Angew.
Chem., Int. Ed. 2010, 49, 8670. (i) Goossen, L.; Rodriguez, N.; Manjolinho,
F.; Lange, P. P. Adv. Synth. Catal. 2010, 352, 2913. (j) Zhang,
W.-Z.; Li, W.-J.; Zhang, X.; Zhou, H.; Lu, Z.-B. Org. Lett. 2010, 12,
4748. (k) Yu, D.; Zhang, Y. Proc. Natl. Acad. Sci. U.S.A. 2010, 23,
20184. (l) Fujihara, T.; Xu, T.; Semba, K.; Terao, J.; Tsuji, Y. Angew.
Chem., Int. Ed. 2011, 50, 523. (m) Inamoto, K.; Asano, N.; Kobayashi,
K.; Yonemoto, M.; Kondo, Y. Org. Biomol. Chem. 2012, 10, 1514. (n)
Motokura, K.; Kashiwame, D.; Miyaji, A.; Bab, T. Org. Lett. 2012, 14,
2642. (o) Zhang, L.; Cheng, J.; Carry, B.; Hou, Z. J. Am. Chem. Soc.
2012, 134, 14314. (p) Inomata, H.; Ogata, K.; Fukuzawa, S.-I.; Hou, Z.
Org. Lett. 2012, 14, 3986.
Singaram, B. J. Org. Chem. 2011, 76, 9602. For Pd-catalyzed borylation
ꢀ
of allyl alcohols, see: (c) Olsson, V. J.; Sebelius, S.; Selander, N.; Szabo,
K. J. J. Am. Chem. Soc. 2006, 128, 4588. (d) Dutheuil, G.; Selander, N.;
ꢀ
Szabo, K. J.; Aggarwal, V. K. Synthesis 2008, 14, 2293. (e) Selander, N.;
ꢀ
Paasch, J. R.; Szabo, K. J. Am. Chem. Soc. 2011, 133, 409. For Pd- and
Ni-catalyzed borylation of allyl halides, see: (f) Ishiyama, T.; Ahiko, T.;
Miyaura, N. Tetrahedron Lett. 1996, 37, 6889. (g) Zhang, P.; Roundtree,
I. A.; Morken, J. A. Org. Lett. 2012, 14, 1416. For Cu-catalyzed
borylation of allylic alcohol derivatives, see: (h) Ito, H.; Kawakami,
C.; Sawamura, M. J. Am. Chem. Soc. 2005, 127, 16034. (i) Ito, H.; Ito, S.;
Sasaki, Y.; Sawamura, M. J. Am. Chem. Soc. 2007, 129, 14856. (j)
Guzman-Martinez, A.; Hoveyda, A. H. J. Am. Chem. Soc. 2010, 132,
10634. (k) Ito, H.; Kunii, S.; Sawamura, M. Nat. Chem. 2010, 2, 972. (l)
Park, J. K.; Lackey, H. H.; Ondrusek, B. A.; McQuade, D. T. J. Am.
Chem. Soc. 2011, 133, 2410. (m) Ito, H.; Miya, T.; Sawamura, M.
Tetrahedron 2012, 68, 3423.
(11) Isomerized products were observed in the Pd(0)-catalyzed reac-
tions (ref 5).
(12) KOMe was previously shown to be superior to KOtBu in the
Cu-catalyzed carboxylation of alkylboranes (ref 8f).
B
Org. Lett., Vol. XX, No. XX, XXXX

Table 1. Screening Conditions for Cu(I)-Catalyzed
Carboxylation of 1a with CO2
Table 2. Cu-Catalyzed Carboxylation of Substituted
Allylboronic Pinacol Estersa
a
2a
(%)b
2a0
(%)b
entry
Cu(I)
L
base
1
2
Cu(IPr)Cl
CuCl
ꢀ
KOtBu
KOtBu
KOtBu
KOMe
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
ꢀ
75
62
60
71
77
28
40
61
0
trace
trace
trace
trace
trace
trace
8
IPrCl
3
CuCl
IMesCl
4
Cu(IPr)Cl
Cu(IPr)Clc
Cu(IPr)Cld
CuClc
ꢀ
5
ꢀ
6
ꢀ
7
BINAP
8
CuClc
CyJohnPhose
trace
0
9
ꢀ
ꢀ
10
Cu(IPr)Cl
ꢀ
0
0
a 10mol% Cu(I)/L, 1.1equivofbase, CO2 (1 atm), 1 mL of THF, 70 °C,
16 h. b Determined by 1H NMR of the crude mixture after workup using an
internal standard. c 5 mol % was used. d 3 mol % was used. e 10 mol % of
ligand was used.
While 1g led to only a trace amount of the carboxylic acid
product as determined by 1H NMR (entry 7), the reaction of
cinnamylboronate 1h afforded 2h in 30% isolated yield
together with the regiomeric product 2h0 being formed in a
significant amount (entry 8). Nonsubstituted allylboronate
1i could be carboxylated in 68% isolated yield (entry 9).
Reactions of allylboronates with a methyl substituent at
either the R- or β-carbon led to the corresponding carboxylic
acids in 62% and 65% yields, respectively (entries 10 and 11).
Since the branched carboxylic acid was favored over
the linear regioisomer, we became interested in the con-
struction of all-carbon quaternary centers,13 a highly
valuable structural motif present in a wide range of bio-
logically active compounds, employing the current CO2
transformation. 1l indeed reacted with CO2 to give 2l in
69% yield, albeit at a higher catalyst loading (15 mol %)
(entry 12). At lower catalyst loadings (5ꢀ10 mol %), a
significant amount of unreacted starting material could be
observed in the crude mixture. Other γ,γ-disubstituted
allylboronates also underwent the reactions with CO2 to
afford R,R-disubstituted β,γ-unsaturated carboxylic acids
in 41ꢀ64% yields (entries 14ꢀ17).
a 1 equiv of allylboronate, 5 mol % Cu(IPr)Cl, 1.1 equiv of base,
c
THF, 70 °C, 16 h. b Isolated yields. The linear isomer 2h0 was also
isolated in 13%. d 15 mol % Cu(IPr)Cl was employed. e A mixture of
(13) For some recent examples on the synthesis of all-carbon qua-
ternary centers, see: (a) Smejkal, T.; Han, H.; Breit, B.; Krische, M. J.
J. Am. Chem. Soc. 2009, 131, 10366. (b) Minko, Y.; Pasco, M.; Lercher,
L.; Botoshansky, M.; Marek, I. Nature 2012, 490, 522. (c) Evans, P. A.;
Oliver, S.; Chae, J. J. Am. Chem. Soc. 2012, 134, 19314.
E- and Z-isomers were employed. f 10 mol % Cu(IPr)Cl was employed.
Reactions of cyclic allylboronates proceeded with ex-
cellent regioselectivity (entries 16ꢀ18). Compounds featur-
ing an exocyclic olefin can be prepared by the reaction of
cyclohexenyl 1r with CO2 under copper catalysis (entry 18).
A range of functionalized allylboronates could react with
CO2 under the Cu-catalyzed conditions (entries 3ꢀ6 and 17),
(14) It should be noted that potassium O-alkylcarbonate, which can
be formed by the reaction of CO2 with a potassium alkoxide, may play a
role in the carboxylation. In fact, a reaction of 1a with KO2COMe,
prepared from CO2 and KOMe, in the presence of 5% Cu(IPr)Cl at
70 °C resulted in a 64% yield of 2a.
(15) For a discussion on 1,3-metal transposition in allylic metals, see:
Sklute, G.; Marek, I. J. Am. Chem. Soc. 2006, 128, 4642.
Org. Lett., Vol. XX, No. XX, XXXX
C

of CO2 with an allylcopper, which exists in a metallotropic
equilibrium between two σ-complexes (Scheme 2).14 Allyl-
metals with ionic characteristics (such as allyllithium, mag-
nesium, and zinc reagents) are known to undergo a rapid 1,3-
metal transposition.15 Allylcopper is in this category.9a The
branched carboxylic acid could be formed via carboxylation
Scheme 2. A Possible Explanation for the Observed
Regioselectivity
0
of the more sterically accessible 3a at the γ-carbon (SE
mechanism, pathway A).2b,16 However, a mechanism invol-
ving carboxylation of the branched allylcopper(I) 3b at the
R-carbon (SE2 mechanism) is also possible.
0
Delivery of CO2 to the γ-carbon of 3a (SE mechanism,
pathway A) becomes challenging when a sterically demand-
ing group is introduced, resulting in low yields of the reac-
tions (Table 2, entries 7 and 8). For 1h, the linear carboxylic
demonstrating the advantage of the current method over
reactions employing strongly nucleophilic organolithi-
ums and Grignard reagents. Substrates incorporating
an ester (OPiv 1c and OBz 1d), silyl ether 1e, benzyl ether
1f, and N-Boc protecting group 1q were successfully
converted to the corresponding β,γ-unsaturated carbo-
nyls. In addition, the allylboronate 1f incorporating an
aryl bromide moiety could undergo the carboxylation in
64% yield (entry 6).
Interestingly, the reactions of regioisomeric allylboronic
esters led to the same product under these conditions (e.g.,
1b vs 1k and 1l vs 1m), suggesting that the carboxylations
of these isomers likely proceed via a common intermediate
(vide infra). In these cases, reactions starting with the
primary allylboronates (1b or 1l) were more efficient
comparedto the secondary and tertiary isomers(1kor 1m).
Hou et al. previously showed that the carboxylation of
aryl- or alkylborons with CO2 in the presence of catalytic
Cu(IPr)Cl and an alkoxide (KOtBu or MeOLi) proceeds via
a reaction of an organocopper intermediate with CO2.8d,f The
regioconvergence observed in the current reaction (Table 2,
entries 2 vs 11, and 12 vs 13) could be explained by a reaction
0
acid 2h0 (R = Ph) could be formed via SE -carboxylation of
3b (pathway A0), which is also problematic due to the steric
interactions between R and the metal center. Overall, car-
boxylation of these substrates is not efficient via either path-
way Aor A0. For1g (R=Et2CH), both pathways are largely
inhibited.
In conclusion, we have shown that allylboronates react
with CO2 (1 atm) under copper catalysis to afford a diverse
range of cyclic and acyclic β,γ-unsaturated carboxylic
acids. In most cases studied, excellent regioselectivity
was observed, favoring the more substituted carboxylic
acids.
Acknowledgment. Financial support for this work was
provided by A*STAR, Singapore. We thank Dr. Charles
William Johannes (ICES) for helpful discussions and
support. We are grateful to Ms. Doris Tan (ICES) for
high resolution mass spectrometric (HRMS) assistance.
Supporting Information Available. Full experimental
procedures and compound characterization (PDF). This
material is available free of charge via the Internet at
http://pubs.acs.org.
(16) For discussions on reactions of allylpalladium with CO2, see refs
6b and 7a. For a discussion on reactions of allylmetals with electrophiles,
see ref 2b.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX