Iridium(I)-catalyzed C-H borylation of α,β-unsaturated esters with bis(pinacolato)diboron

Article abstract of DOI:10.1002/asia.201600078

A new process has been developed for the iridium(I)-catalyzed vinylic C-H borylation of α,β-unsaturated esters with bis(pinacolato)diboron (B₂pin₂). These reactions proceeded in octane at temperatures in the range of 80-120 °C to afford the corresponding alkenylboronic compounds in high yields with excellent regio- and stereoselectivities. The presence of an aryl ester led to significant improvements in the yields of the acyclic alkenylboronates. Crossover experiments involving deuterated substrates as well as a mixture of stereoisomers confirmed that this reaction proceeds via a 1,4-addition/β-hydride elimination mechanism. Notably, this reaction was also used to develop a one-pot borylation/Suzuki-Miyaura cross-coupling procedure. A lucky strike with B₂pin₂: A new method has been developed for the vinylic C-H borylation of α,β-unsaturated esters with bis(pinacolato)diboron (B₂pin₂) using iridium(I) catalysts. These reactions proceeded in octane at 80-120 °C to afford the alkenylboronic compounds in high yields with excellent regio- and stereoselectivities.

Full text of DOI:10.1002/asia.201600078

DOI: 10.1002/asia.201600078
Full Paper
CÀH Borylation
Iridium(I)-catalyzed CÀH Borylation of a,b-Unsaturated Esters with
Bis(pinacolato)diboron
Ikuo Sasaki, Jumpei Taguchi, Hana Doi, Hajime Ito,* and Tatsuo Ishiyama*[a]
Abstract: A new process has been developed for the iridiu-
m(I)-catalyzed vinylic CÀH borylation of a,b-unsaturated
esters with bis(pinacolato)diboron (B2pin2). These reactions
proceeded in octane at temperatures in the range of 80–
1208C to afford the corresponding alkenylboronic com-
pounds in high yields with excellent regio- and stereoselec-
tivities. The presence of an aryl ester led to significant im-
provements in the yields of the acyclic alkenylboronates.
Crossover experiments involving deuterated substrates as
well as a mixture of stereoisomers confirmed that this reac-
tion proceeds via a 1,4-addition/b-hydride elimination mech-
anism. Notably, this reaction was also used to develop
a one-pot borylation/Suzuki–Miyaura cross-coupling proce-
dure.
a palladium pincer complex in 2010.[6c] Although this reaction
proceeded at room temperature to afford the desired alkenyl
boronic esters in good yields, it also afforded the correspond-
ing allyl boronic esters as byproducts. In 2011, Iwasawa and
co-workers reported the dehydrogenative borylation of alkenyl
substrates using (PSiP)PdOTf as a catalyst.[6b] This borylation re-
action proceeded smoothly to give the corresponding alkenyl
boronic esters in high yields, although the products were pro-
duced as a mixture of E- and Z-isomers in some cases. We re-
cently reported the CÀH borylation of alkenes with an iridium
catalyst.[5] Although this particular reaction provided facile
access to a wide range of alkenylboronates in high yield with
good regioselectivity, it was only amenable to cyclic vinyl ether
substrates.
Introduction
Alkenyl boronic esters are versatile intermediates in synthetic
organic chemistry,[1] and their utility for the synthesis of CÀC
bonds has been well demonstrated in the synthesis of natural
products, biologically active compounds, and functional mole-
cules.[2] Conventional methods for the preparation of alkenyl
boronic esters include the reaction of B(OR)3 with alkenyl-lithi-
um or -magnesium reagents, and the Pd-catalyzed cross-cou-
pling reaction of alkenyl halides or triflates with (B2pin2) (2) or
pinacolborane (HBpin).[3] However, the application of these
methods has been limited by their lack of functional-group
compatibility, as well as the fact that many alkenyl halides and
triflates are not readily available. Several alternatives to these
reactions have recently been reported that involve the transi-
tion-metal-catalyzed CÀH borylation of alkenyl compounds.[4–6]
Notably, these methods are much more cost effective and en-
vironmentally friendly than the conventional methods de-
scribed above. For example, Olsson and Szabó reported a one-
pot catalytic CÀH borylation/Suzuki–Miyaura coupling se-
quence of a,b-unsaturated esters in 2008.[6h] The reaction pro-
duced the desired products in good yield, however, only termi-
nal alkenes were used as the substrates. Szabó and co-workers
also reported the CÀH borylation of alkenyl compounds with
We also recently reported the direct regioselective ortho CÀ
H borylation of various benzoates and aryl ketones with the
complex [Ir(OMe)(cod)]2/P[3,5-(CF3)2C6H3]3 (cod=1,5-cycloocta-
diene) or AsPh3.[7] Around the same time, several other re-
search groups, including those of Sawamura,[8] Lassaletta,[9] and
Hartwig,[10] also reported similar borylation reactions involving
functionalized arenes. The selectivity of these reactions has
been attributed to the formation of an interaction between
the coordinating heteroatom in the carbonyl group and the iri-
dium metal center.[7–9] Herein, we describe the development of
a new process for the vinylic CÀH borylation of cyclic 1 and
acyclic a,b-unsaturated esters 3 with 2, using an in-situ-gener-
ated iridium complex consisting of readily available [Ir(X)(cod)]2
(X=OMe or Cl) and AsPh3 as a catalyst with octane as a sol-
vent.[11] This reaction proceeded chemoselectively at 80 or
1208C to give the corresponding alkenylboronic compounds 4
or 5 in high yields (Scheme 1). The stereoselective borylation
of acyclic compounds 3 afforded the (E)-alkenylboronates 5.
The mechanism of this reaction involved sequential 1,4-addi-
tion/b-hydride reactions based on the results of crossover ex-
periments involving deuterated substrates and the analysis of
[a] Dr. I. Sasaki, J. Taguchi, H. Doi, Prof. Dr. H. Ito, Dr. T. Ishiyama
Division of Chemical Process Engineering and
Frontier Chemistry Center (FCC)
Graduate School of Engineering
Hokkaido University
Kita 13 Nishi 8 Kita-ku, Sapporo, Hokkaido 060-8628 (Japan)
Fax: (+81)11-706-6562
E-mail: ishiyama@eng.hokudai.ac.jp
hajito@eng.hokudai.ac.jp
Supporting information and the ORCID identification number(s) for the au-
thor(s) of this article can be found under http://dx.doi.org/10.1002/
asia.201600078.
Chem. Asian J. 2016, 11, 1400 – 1405
1400
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Table 1. Optimization of the reaction conditions with 1-cyclohexenecar-
boxylate 1a.[a]
Entry
IrI precursor
Ligand
Solvent
Yield [%][b]
1
2
3
4
5
6
7
8
[Ir(OMe)(cod)]2
[Ir(OMe)(cod)]2
[Ir(OMe)(cod)]2
[Ir(OMe)(cod)]2
[Ir(OMe)(cod)]2
[Ir(OMe)(cod)]2
[Ir(OMe)(cod)]2
[Ir(Cl)(cod)]2
AsPh3
Octane
Octane
Octane
Octane
octane
Mesitylene
DMF
Octane
Octane
Octane
90(84)[c]
P[3,5-(CF3)2C6H3]3
P(C6F5)3
PPh3
P[4-MeOC6H4]3
AsPh3
AsPh3
AsPh3
AsPh3
AsPh3
14
10
20
0
51
0
84
99 (87)
81
9[d]
10[e]
[Ir(OMe)(cod)]2
[Ir(OMe)(cod)]2
Scheme 1. Vinylic CÀH borylation of a,b-unsaturated esters via an iridium C-
[a] Reaction conditions: 1a (0.5 mmol),
2
(0.55 mmol), IrI precursor
enolate intermediate.
(1.5 mol%), and ligand (6.0 mol%) in solvent (3 mL). [b] Yields were deter-
mined by GC analysis. [c] Isolated yield. [d] Reaction was carried out at
808C. [e] 0.5 mol% [Ir(OMe)(cod)]2 and 2.0 mol% AsPh3 were used.
the products resulting from the reaction of an E/Z isomer mix-
ture. The results also confirmed that an iridium C-enolate is in-
volved as a key intermediate in determining the selectivity of
the borylation reaction. It is noteworthy that this reaction was
also applied to a one-pot borylation/Suzuki–Miyaura cross-cou-
pling procedure to afford the 2-aryl-substituted 1-cycloalkene-
carboxylate in good yield, which showed biological activity as
an antidepressants agent. Some of results in this paper have
been reported in a separate communication.[11]
ing alkenylboronates in high yields (4b: 87%, 4c: 77%, 4d:
85%). Phenyl ester 1e, with five C(sp2)ÀH bonds on its phenyl
moiety, reacted exclusively with 2 at its vinylic position to give
the desired alkenylboronate 4e in 96% yield at 808C.[7,8] This
result highlighted the chemoselectivity of this borylation reac-
tion, with the reaction occurring exclusively at the vinylic CÀH
position despite the presence of aryl CÀH bonds, which nor-
mally react under conventional Ir-catalyzed borylation condi-
tions. The borylation of 3-chloropropyl ester 1 f proceeded ex-
clusively at the vinylic CÀH bond to afford 4 f in high yield
without any side reactions involving the CÀCl bond (86%). The
reaction of the CF3-containing ester 1g afforded 4g in 93%
yield. Furthermore, the 3-methoxy ester 1h reacted completely
to produce 4h in high yield (83%). The reactions of ketone 1i,
ester 1j, and carbamate 1k all proceeded smoothly at 1208C
to afford 4i (65%), 4j (74%), and 4k (72%), respectively. Epox-
ide 1l reacted without any detectable substrate decomposition
under the optimized reaction conditions to give the borylation
product 4l in 79% yield after 0.5 h. Although the borylation re-
actions of various cyclohexene-type substrates produced the
corresponding borylated products in high yields, the reactions
of cycloalkenyl substrates with five-, seven-, and eight-mem-
bered rings resulted in low product yields and required much
harsher reaction conditions (1208C with 2.5 mol% [Ir(OMe)-
(cod)]2 and 10 mol% AsPh3). The reaction of the five-mem-
bered ring-containing substrate 1m with 2 led to the complete
consumption of both starting materials, however, the product
4m was obtained in low yield (20%). The reactions of the
seven- and eight-membered ring containing substrates 1n and
1o also resulted in low yields of the corresponding alkenylbor-
onates 4n and 4o, respectively, even though the substrates
were completely consumed. These results therefore suggested
that substrates 1m–o had decomposed under the reaction
conditions.
Results and Discussion
We initially established the reaction conditions for the vinylic
CÀH borylation with methyl 1-cyclohexenecarboxylate 1a. The
reaction of 1a with 2 (1.1 equiv) in the presence of an IrI pre-
cursor, [Ir(OMe)(cod)]2 (1.5 mol%), and AsPh3 (3 mol%) in
octane at 1208C afforded the desired product 4a in high yield
after 16 h (90% 1H NMR yield, 84% isolated yield, Table 1,
entry 1). A variety of different phosphine ligands, including
P[3,5-(CF)2C6H3]3, P(C6F5)3, PPh3, and P(4-MeOC6H4) were also
evaluated in this reaction, but found to be in effective (4a: 0–
20% after 16 h; Table 1, entries 2–5). The yield of 4a decreased
when mesitylene was employed as a solvent instead of octane
(4a: 51% after 16 h; Table 1, entry 6). Furthermore, no reaction
occurred when N,N-dimethylformamide (DMF) was used as the
solvent (Table 1, entry 7). Using [IrCl(cod)]2 as the iridium pre-
cursor led to a small decrease in the yield of 4a to 84%
(Table 1, entry 8). Notably, the borylation proceeded smoothly
at the lower temperature of 808C (99%, Table 1, entry 9).
Under these conditions, a lower loading of [Ir(OMe)(cod)]2
(0.5 mol%) also gave 4a in reasonable yield (81%; Table 1,
entry 10).
With the optimized conditions in hand, we proceeded to ex-
amine the scope of this CÀH borylation reaction using a variety
of cyclic a,b-unsaturated esters (Table 2). Simple alkyl esters,
such as those bearing ethyl 1b, isopropyl 1c, and tert-butyl 1d
alkyl groups, showed good reactivity to afford the correspond-
Chem. Asian J. 2016, 11, 1400 – 1405
www.chemasianj.org
1401
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Table 2. CÀH borylation of various cyclic a,b-unsaturated esters.[a]
Table 3. CÀH borylation of various acyclic a,b-unsaturated esters.[a]
R=Et (4b): 87% (808C, 6 h)
iPr (4c): 77% (1208C, 3 h)
tBu (4d): 85% (1208C, 2.5 h)
Ph (4e): 96% (808C, 6 h)
X=Cl (4 f): 86% (1208C, 8 h)
CF3 (4g): 93% (1208C, 3 h)
OMe (4h): 83% (1208C, 1 h)
R=Me (4i): 65% (1208C, 2 h)
OMe (4j): 74% (1208C, 16 h)
(4k)
(4l)
72% (1208C, 1 h)
79% (1208C, 0.5 h)
n=0 (4m): 20% (1208C, 16 h)
2 (4n): 43% (1208C, 16 h)
3 (4o): 35% (1208C, 16 h)
[a] Reaction conditions: esters 3a–l (0.5 mmol), 2 (1.0 mmol), [Ir(Cl)(cod)]2
(1.5 mol%), and AsPh3 (6.0 mol%) in octane (3 mL). [b] Yields were deter-
mined by GC analysis. [c] Isolated yield.
[a] Reaction conditions: esters 1b–o (0.5 mmol), 2 (0.55 mmol), [Ir(OMe)(-
cod)]2 (1.5 mol%), AsPh3 (6.0 mol%) in octane (3 mL). [b] Yields were de-
termined by GC analysis. [c] 2.5 mol% [Ir(OMe)(cod)]2 and 10.0 mol%
AsPh3 were used.
showed better reactivity than 3e or 3 f to afford the corre-
sponding (E)-alkenylboronate 5g in 82% yield. However, the
reaction of 2,4,6-trimethoxyphenyl ester 3h afforded only
a moderate yield of the corresponding (E)-alkenylboronate 5g
(64%). The benzodioxole ester 3i, bearing an ortho-dialkoxy-
phenyl moiety, reacted with 2 to afford the boronate 5i in
moderate yield (65%). The borylation of para-dimethylamino-
phenyl ester 3j produced alkenylboronate 5j in 77% yield.
Several sterically congested substrates, including 4-methoxy-
phenyl-(E)-2-methylpent-2-enoates 3k and 4-methoxyphenyl-
(E)-2-methyl-3-phenylacrylate 3l, were also evaluated but
showed low reactivity, with the borylated products being iso-
lated in low yields (5k: 41%, 5l: 19%). In all cases, the stereo-
selectivity of the product was completely retained, whilst the
yield of the borylated compounds varied considerably.
To further expand the utility of our newly developed vinylic
CÀH borylation, we investigated its application to acyclic a,b-
unsaturated esters (Table 3). The reaction of methyl (E)-2-meth-
ylbut-2-enoate 3a with 2.0 equivalents of 2 proceeded at
1208C in the presence of [Ir(Cl)(cod)]2 (1.5 mol%) as the cata-
lyst precursor and AsPh3 (3 mol%) as the ligand to afford the
(E)-alkenylboronate 5a in moderate yield with excellent stereo-
selectivity. Several other alkyl (E)-2-methylbut-2-enoates, in-
cluding the methoxy 3b and ethyl thioether 3c substrates
showed moderate-to-low reactivity, with both reactions provid-
ing the E-isomer exclusively (5b: 48%, 5c: 21%). When phenyl
ester 3d was used as the substrate, the yield of the corre-
sponding alkenylboronate 5d increased (5d: 62%). Based on
the higher yield of this reaction, we proceeded to examine the
borylation of various aryl esters. The reactions of the para- and
ortho-methoxyphenyl esters 3e and 3 f proceeded smoothly to
give the desired alkenylboronates 5e and 5 f in 76 and 74%
yields, respectively. Notably, 2,4-dimethoxyphenyl ester 3g
We then investigated the one-pot synthesis of a bioactive
compound through a sequential vinylic CÀH borylation/cross-
coupling reaction (Scheme 2).[13] Compound 6 has been report-
ed to be an inhibitor of monoamine transporters.[14] The alke-
Chem. Asian J. 2016, 11, 1400 – 1405
www.chemasianj.org
1402
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
reductive elimination of the Ir-hydride complex D would lead
to the formation of the desired products 4 or 5. Finally, the oxi-
dative addition of B2pin2 to D, followed by the reductive elimi-
nation of HBpin, would regenerate A. According to pathway 2,
complex B would undergo a 1,4-insertion reaction as opposed
to an oxidative insertion reaction to the iridium enolate E.[16]
The subsequent isomerization of E would afford the Ir complex
F, which would have an IrÀC bond with a syn configuration be-
tween the Ir center and the b-H atom. Finally, the b-hydride
elimination of complex F would result in the formation of de-
sired products 4 or 5 and D.
To elucidate the mechanism of this CÀH borylation reaction,
we investigated the effect of varying the number of equiva-
lents of 1a added to 2 under the optimized conditions
[Eq. (1)]. The results revealed that the addition of 0.5 equiva-
lents was optimal, with larger charges (i.e., 1.0 or 3.0 equiv),
leading to a 5-fold decrease in the yield. This indicates that the
coordination step might not be the rate determining step. We
also conducted a competition experiment with 1a (X=H or D)
and 1b at 1208C, which revealed that the reaction proceeded
without any discernible isotope effect [Scheme 4, Eq. (2)]. This
result indicates that pathway 1 is less plausible because the ox-
idation step proposed in pathway 1 would cause a large iso-
tope effect if it is the rate limiting step. Although the above
two mechanistic experiments could not give a decisive result,
we currently suppose pathway 2 is more plausible. This mecha-
nism can explain the following stereo-divergent results by con-
sidering the enolate intermediate in pathway 2.
Scheme 2. One-pot borylation/Suzuki–Miyaura cross-coupling procedure.
[a] GC yield based on 2-bromonaphthalene.
nylboronate 4a was prepared from 1a under the optimized
conditions shown in Table 1. Distilled water was added to the
reaction mixture in this case to hydrolyze the HBpin byproduct
generated during the course of the Ir-catalyzed borylation, be-
cause this material inhibited the subsequent cross-coupling re-
action. Finally, the cross-coupling reaction was conducted by
adding 2-bromonaphthalene (2.5 mmol), K3PO4 (3.0 equiv), and
PdCl2(dppf) (5 mol%) (dppf=diphenylphosphinoferrocene) to
the reaction mixture without evaporating the solvent or the
prior purification of the product. The cross-coupling product 6
was obtained in 47% yield (78%, GC yield) from this two-step
reaction.
The two catalytic cycles proposed for the current transfor-
mation are shown in Scheme 3. Both of these cycles would in-
volve the initial formation of the mono- (n=1) or tris- (n=3)
boryliridium complex A by the reaction of the corresponding
IrI complex with B2pin2.[15] According to pathway 1, the elec-
tron-donating oxygen atom of the ester group would coordi-
nate to the Ir metal center of complex A to give complex B,
which would undergo an oxidative addition to the vinylic CÀH
bond to produce the pseudo metallacycle C. The subsequent
It is noteworthy that the borylation of acyclic compounds
under these conditions afforded the (E)-products selectively.
When a 50:50 (mol/mol) mixture of the (E)- and (Z)-isomers of
3e was used as the substrate, both of the isomers
were consumed at the same rate. However, this reac-
tion afforded the (E)-isomer 5e as the major product
(98:2) in 44% yield (Scheme 5a). To develop a better
understanding of this reaction, we investigated the
borylation of a mixture of (Z)-3e and (E)-para-ethoxy-
phenyl ester 3m (Scheme 5b). The mixture of (Z)-3e
and (E)-3m reacted with 2 to afford (E)-5e and (E)-
5m in 15 and 71% yields, respectively. Notably, the
reaction of (Z)-3e alone under the optimized condi-
tions also gave (E)-5e in 13% yield. These results
therefore suggested that the (E)- and (Z)-isomers
were both reacting under these conditions to give
a single isomer. The selectivity observed in this case
therefore most likely occurred as a consequence of
steric repulsion between the b-methyl group and the
carbonyl group of the ester moiety (Scheme 5c)
Conclusions
In summary, the iridium complexes prepared by the
reaction of [Ir(OMe)(cod)]2 and [Ir(Cl)(cod)]2 with
AsPh3 have been shown to be efficient catalysts for
the vinylic CÀH borylation of a,b-unsaturated esters
with 2. These borylation reactions proceeded at the
vinylic position with good chemo- and stereoselectiv-
Scheme 3. Proposed mechanism.
Chem. Asian J. 2016, 11, 1400 – 1405
www.chemasianj.org
1403
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
ity, even for substrates bearing an aryl group, which would
normally react though their own CÀH bonds under conven-
tional Ir-catalyzed borylation conditions. Furthermore, this reac-
tion showed good functional group tolerance towards a wide
range of functional groups, including halogen, acyl, alkoxycar-
bonyl, carbamoyl, and epoxy groups. The results of crossover
reactions involving a deuterated substrate and a mixture of E/
Z-isomers suggested that this transformation proceeded via se-
quential 1,4-addition/b-hydride elimination reactions. We also
achieved a one-pot borylation/cross-coupling procedure for
the rapid synthesis of a drug candidate; further highlighting
the synthetic utility of this reaction.
Experimental Section
A Representative Procedure for the Iridium(I)-Catalyzed Vinylic CÀH
Borylation of 1a (Table 1).
[Ir(OMe)(cod)]2 (4.97 mg, 0.0075 mmol), bis(pinacolato)diboron (2)
(140 mg, 0.55 mmol), and AsPh3 (9.19 mg, 0.030 mmol) were
placed in an oven-dried two neck flask. The flask was subsequently
connected to a vacuum/nitrogen manifold through a rubber tube
and vacuum purged with nitrogen three times. Octane (3 mL) was
added to the flask through a rubber septum, and the resulting
mixture was stirred at room temperature for 10 min. Compound
1a (70.1 mg, 0.5 mmol) was then added to the reaction mixture,
and the resulting mixture was stirred at 80 or 1208C. Upon com-
pletion of the reaction, the mixture was concentrated to give a resi-
due, which was purified by flash column chromatography over
silica gel (EtOAc/hexane, 1:99–5:95) to give the corresponding alke-
nylboronate 4a as a colorless oil.
Scheme 4. Investigation of the reaction mechanism.
Acknowledgements
This work was financially supported by a Grant-in-Aid for Sci-
entific Research (B) (No. 21350049) from the Ministry of Educa-
tion, Culture, Sports, Science, and Technology, Japan and the
MEXT (Japan) program “Strategic Molecular and Materials
Chemistry through Innovative Coupling Reactions” of Hokkaido
University.
Keywords: alkenyl boronates · borylation · diboron · iridium ·
a,b-unsaturated esters
[1] N. Miyaura, Y. Yamamoto in Comprehensive Organometallic Chemistry III
(Eds.: R. H. Crabtree, D. M. P. Mingos, P. Knochel), Elsevier, Oxford, 2007,
9, pp. 145.
[2] a) M. M. Heravi, E. Hashemi, Tetrahedron 2012, 68, 9145–9178; b) S.
Papst, A. F. M. Noisier, M. A. Brimble, Y. Yang, G. W. Krissansen, Bioorg.
Med. Chem. 2012, 20, 5139–5149; c) V. P. Ghidu, J. Q. Wang, B. Wu, Q. S.
Liu, A. Jacobs, L. J. Marnett, G. A. Sulikowski, J. Org. Chem. 2008, 73,
4949–4955; d) E. P. Gillis, M. D. Burke, J. Am. Chem. Soc. 2007, 129,
6716–6717; e) S. Harper, S. Avolio, B. Pacini, M. Di Filippo, S. Altamura,
L. Tomei, G. Paonessa, S. Di Marco, A. Carfi, C. Giuliano, J. Padron, F.
Bonelli, G. Migliaccio, R. De Francesco, R. Laufer, M. Rowley, F. Narjes, J.
Med. Chem. 2005, 48, 4547–4557.
[3] a) N. Miyaura, K. Maruoka in Synthesis of Organometallic Compounds
(Ed.: S. Komiya), Wiley, Chichester, 1997, p. 345; b) K. L. Billingsley, S. L.
Buchwald, J. Org. Chem. 2008, 73, 5589–5591; c) K. L. Billingsley, T. E.
Barder, S. L. Buchwald, Angew. Chem. Int. Ed. 2007, 46, 5359–5363;
Angew. Chem. 2007, 119, 5455–5459; d) T. Ishiyama, J. Takagi, A.
Kamon, N. Miyaura, J. Organomet. Chem. 2003, 687, 284–290; e) J.
Scheme 5. Selectivity of the borylation of acyclic esters.
Chem. Asian J. 2016, 11, 1400 – 1405 www.chemasianj.org
1404
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Takagi, K. Takahashi, T. Ishiyama, N. Miyaura, J. Am. Chem. Soc. 2002,
124, 8001–8006; f) T. Ishiyama, N. Miyaura, J. Organomet. Chem. 2000,
611, 392–402; g) K. Takahashi, J. Takagi, T. Ishiyama, N. Miyaura, Chem.
Lett. 2000, 126–127; h) P. R. Eastwood, Tetrahedron Lett. 2000, 41,
3705–3708.
R. B. Coapes, S. N. Edes, D. N. Coventry, F. E. S. Souza, R. L. Thomas, J. J.
Hall, S. W. Bi, Z. Y. Lin, T. B. Marder, Dalton Trans. 2008, 1055–1064; j) A.
Caballero, S. Sabo-Etienne, Organometallics 2007, 26, 1191–1195; k) V. J.
Olsson, K. J. Szabó, Angew. Chem. Int. Ed. 2007, 46, 6891–6893; Angew.
Chem. 2007, 119, 7015–7017; l) R. B. Coapes, F. E. S. Souza, R. L. Thomas,
J. J. Hall, T. B. Marder, Chem. Commun. 2003, 614–615.
[4] For aromatic CÀH borylation, see: a) T. Ishiyama, N. Miyaura, Pure Appl.
Chem. 2006, 78, 1369—1375; b) T. Ishiyama, J. Takagi, Y. Yonekawa, J. F.
Hartwig, N. Miyaura, Adv. Synth. Catal. 2003, 345, 1103–1106; c) T. Ish-
iyama, Y. Nobuta, J. F. Hartwig, N. Miyaura, Chem. Commun. 2003,
2924–2925; d) T. Ishiyama, N. Miyaura, J. Organomet. Chem. 2003, 680,
3–11; e) J. Takagi, K. Sato, J. F. Hartwig, T. Ishiyama, N. Miyaura, Tetrahe-
dron Lett. 2002, 43, 5649–5651; f) T. Ishiyama, J. Takagi, K. Ishida, N.
Miyaura, N. R. Anastasi, J. F. Hartwig, J. Am. Chem. Soc. 2002, 124, 390–
391; g) T. Ishiyama, J. Takagi, J. F. Hartwig, N. Miyaura, Angew. Chem. Int.
Ed. 2002, 41, 3056–3058; Angew. Chem. 2002, 114, 3182–3184; h) J. Y.
Cho, M. K. Tse, D. Holmes, R. E. Maleczka, M. R. Smith III, Science, 2002,
295, 305–308.
[7] a) T. Ishiyama, H. Isou, T. Kikuchi, N. Miyaura, Chem. Commun. 2010, 46,
159–161; b) H. Itoh, T. Kikuchi, T. Ishiyama, N. Miyaura, Chem. Lett. 2011,
40, 1007–1008.
[8] K. Yamazaki, S. Kawamorita, H. Ohmiya, M. Sawamura, Org. Lett. 2010,
12, 3978–3981.
[9] A. Ros, R. López-Rodríguez, B. Estepa, E. lvarez, R. Fernµndez, J. M. Las-
saletta, J. Am. Chem. Soc. 2012, 134, 4573–4576.
[10] T. A. Boebel, J. F. Hartwig, J. Am. Chem. Soc. 2008, 130, 7534–7535.
[11] I. Sasaki, H. Doi, T. Hashimoto, T. Kikuchi, H. Ito, T. Ishiyama, Chem.
Commun. 2013, 49, 7546–7548.
[12] V. Farina, B. Krishnan, J. Am. Chem. Soc. 1991, 113, 9585–9595.
[13] We previously reported a one-pot borylation/Suzuki–Miyaura cross-
coupling sequence, see: T. Kikuchi, Y. Nobuta, J. Umeda, Y. Yamamoto, T.
Ishiyama, N. Miyaura, Tetrahedron 2008, 64, 4967–4971.
[14] M. D. Petersen, S. V. Boye, E. H. Nielsen, J. Willumsen, S. Sinning, O.
Wiborg, M. Bols, Bioorg. Med. Chem. 2007, 15, 4159–4174.
[15] a) J. F. Hartwig, Acc. Chem. Res. 2012, 45, 864–873; b) T. M. Boller, J. M.
Murphy, M. Hapke, T. Ishiyama, N. Miyaura, J. F. Hartwig, J. Am. Chem.
Soc. 2005, 127, 14263–14278.
[5] For our reports on alkenyl CÀH borylation, see: a) T. Kikuchi, J. Takagi,
H. Isou, T. Ishiyama, N. Miyaura, Chem. Asian J. 2008, 3, 2082–2090;
b) T. Kikuchi, J. Takagi, T. Ishiyama, N. Miyaura, Chem. Lett. 2008, 37,
664–665.
[6] a) I. A. I. Mkhalid, J. H. Barnard, T. B. Marder, J. M. Murphy, J. F. Hartwig,
Chem. Rev. 2010, 110, 890–931; b) J. Takaya, N. Kirai, N. Iwasawa, J. Am.
Chem. Soc. 2011, 133, 12980–12983; c) N. Selander, B. Willy, K. J. Szabó,
Angew. Chem. Int. Ed. 2010, 49, 4051–4053; Angew. Chem. 2010, 122,
4145–4147; d) A. Kondoh, T. F. Jamison, Chem. Commun. 2010, 46, 907–
909; e) T. Ohmura, Y. Takasaki, H. Furukawa, M. Suginome, Angew. Chem.
Int. Ed. 2009, 48, 2372–2375; Angew. Chem. 2009, 121, 2408–2411;
f) V. J. Olsson, K. J. Szabó, J. Org. Chem. 2009, 74, 7715–7723; g) C. N.
Garon, D. I. McIsaac, C. M. Vogels, A. Decken, I. D. Williams, C. Kleeberg,
T. B. Marder, S. A. Westcott, Dalton Trans. 2009, 1624–1631; h) V. J.
Olsson, K. J. Szabó, Org. Lett. 2008, 10, 3129–3131; i) I. A. I. Mkhalid,
[16] F. DØn›s, A. PØrez-Luna, F. Chemla, Chem. Rev. 2010, 110, 2366–2447.
Manuscript received: January 20, 2016
Accepted Article published: March 1, 2016
Final Article published: April 5, 2016
Chem. Asian J. 2016, 11, 1400 – 1405
www.chemasianj.org
1405
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim