Synthesis of multisubstituted olefins through regio- and stereoselective silylborylation of an alkynylboronate/chemoselective cross-coupling sequences

Article abstract of DOI:10.1021/ol401333j

A highly regio- and stereoselective silylborylation of an alkynylboronate is disclosed. PhMe₂Si-B_pin undergoes a Pd(OAc) ₂/^tOctNC-catalyzed syn-addition to the alkynylboronate to yield 1-phenyl-1-silyl-2,2-dibor

Full text of DOI:10.1021/ol401333j

ORGANIC
LETTERS
2013
Vol. 15, No. 13
3294–3297
Synthesis of Multisubstituted Olefins
through Regio- and Stereoselective
Silylborylation of an Alkynylboronate/
Chemoselective Cross-Coupling
Sequences
Jiao Jiao,† Kiyohiko Nakajima,§ and Yasushi Nishihara*,†,‡
Division of Earth, Life, and Molecular Sciences, Graduate School of Natural Science and
Technology, Okayama University, 3-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530,
Japan, Japan Science and Technology Agency, ACT-C, 4-1-8 Honcho, Kawaguchi,
Saitama 332-0012, Japan, and Department of Chemistry, Aichi University of Education,
1 Hirosawa, Igaya-cho, Kariya, Aichi 448-8542, Japan
ynishiha@okayama-u.ac.jp
Received May 13, 2013
ABSTRACT
A highly regio- and stereoselective silylborylation of an alkynylboronate is disclosed. PhMe2SiꢀBpin undergoes a Pd(OAc)2/tOctNC-catalyzed syn-
addition to the alkynylboronate to yield 1-phenyl-1-silyl-2,2-diborylethene with high regioselectivity. The product 1-phenyl-1-silyl-2,2-
diborylethene is then chemoselectively arylated by SuzukiꢀMiyaura coupling to afford (Z)-1-silyl-2-borylstilbene derivatives. This approach is
extended to the synthesis of a tetraarylated olefin with four different substituents.
The regio- and stereodefined synthesis of multisubstituted
olefins is one of the most challenging goals in synthetic
organic chemistry. Owing to their interesting photophysical
and redox properties, tetraarylethenes are interesting func-
tional materials and their ring-substituted analogues are
valuable synthetic targets in materials science.1 Moreover,
since the reported procedures are mainly limited to the pre-
paration of symmetrical tetraarylethenes via homocoupling
reactions ofdiaryldiazomethanes,2 diaryldichloromethanes,3
diaryl thioketones,4 and diaryl ketones,5 the development
of a general method for the synthesis of unsymmetrically
substituted tetraarylated olefins, preferably with four dif-
ferent aryl groups, has been a valuable target for organic
chemists.6
We envisaged that a combination of transition-metal-
catalyzed silylborylation7ꢀ9 of unsymmetrical internal
alkynes with cross-coupling reactions could provide a
straightforward synthetic entry for various tetraaryl-
ethenes. However, silylborylation of unsymmetrical inter-
nal alkynes, e.g. 1-phenyl-1-propyne, was reported to
decrease the regioselectivity obviously while the use of
unsymmetrical diarylethynes10 as the substrates is readily
† Okayama University.
§ Aichi University of Education.
‡ Japan Science and Technology Agency.
(1) For example: (a) Schultz, A.; Diele, S.; Laschat, S.; Nimtz, M.
Adv. Funct. Mater. 2001, 11, 441. (b) Verkerk, U.; Fujita, M.; Dzwiniel,
T. L.; McDonald, R.; Stryker, J. M. J. Am. Chem. Soc. 2002, 124, 9988.
(2) Monguchi, K.; Itoh, T.; Hirai, K.; Tomioka, H. J. Am. Chem. Soc.
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€
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Mineno, M.; Muraoka, N.; Yoshida, J. J. Am. Chem. Soc. 2004, 126,
11778. (b) Zhou, C.; Larock, R. C. J. Org. Chem. 2005, 70, 3765. (c)
Tsuji, H.; Ueda, Y.; Ilies, L.; Nakamura, E. J. Am. Chem. Soc. 2010, 132,
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r
10.1021/ol401333j
Published on Web 06/18/2013
2013 American Chemical Society

anticipated to form a mixture of the regioisomers, which
limits a diversity of regio- and stereospecific silylborylated
olefins.7d
Scheme 1. Regio- and Stereoselective Silylborylation of 2
In this communication, we report a novel synthetic
protocol for the preparation of tetrasubstituted olefins,
especially for tetraarylated analogues with four different
aryl groups, using the palladium-catalyzed silylboryla-
tion of alkynylboronates,11 to yield 1-phenyl-1-silyl-2,2-
diborylated olefins with perfect regio- and stereoselectivities,
followed by chemoselective SuzukiꢀMiyaura coupling12
to deliver (Z)-1-silyl-2-borylstilbene motifs. Because the
reagents are readily available and the operations are
simple, this synthetic strategy proves more selective and
tolerant than those previously reported.
According to a report in 1999,7d in the presence of the
in situ generated palladium(0)ꢀisonitrile complex, the
reaction of the silylborane 1 with the alkynylboronate 2
took place in refluxing toluene (Scheme 1; Bpin is pina-
colatoboryl). A catalytic amount of Pd(OAc)2 (2 mol %)
and 1,1,3,3-tetramethylbutyl isonitrile (tOctNC) (30 mol %)
efficiently gave rise to the silylborylation product 3 in 60%
yield as a single isomer. However, the reaction did not
proceed smoothly at lower temperatures with decreased
yields being obtained (17% yield at 50 °C). Pd(OAc)2 in
conjunction with cyclohexyl isonitrile (CyNC) likewise gave
a poor yield (19%). In addition, phosphine and phosphite
ligands could not generate an efficient Pd catalyst for the
reaction.
The stereochemistry of the adduct 3 was confirmed
by X-ray crystallographic analysis.13,14 Thus, silylbor-
ylation was found to take place regio- and stereoselec-
tively with the silyl moiety geminal to the phenyl group.
Although the similar 1,1-diboryl-1-alkenes have been
prepared by gem-diborylation of 1,1-dibromo-1-al-
n
kenes with BuLi/bis(pinacolato)diboron15 or ketone
addition of tris(pinacolato)borylmethyllithium,16 to
the best of our knowledge, there are no known examples
of the silylated 1,1-diboryl-1-alkenes, and they would
be difficult to synthesize under basic conditions due to
desilylation.
A possible catalytic cycle forming 3 is proposed to
explain the observed regioselectivity. This proposed cycle
is presented in Scheme 2. We propose that silylborane 1
oxidatively adds to the Pd(0) catalyst to generate the Pd(II)
species A. Intermediate A then undergoes migratory inser-
tion, wherein alkynylboronate 2 inserts into the PdꢀB
bond (borylpalladation) to form B. Although the boryl-
palladation mechanism has been proposed as the result of
theoretical studies,8c,17 another possibility, silylpallada-
tion, cannot be neglected. This selectivity is opposite to
that observed for the analogous process with organozirco-
nium species.18 Finally, the adduct 3 is produced by
reductive elimination, regenerating the Pd catalyst.
Since functional materials, natural products, and bio-
active pharmaceuticals have all been synthesized with
1,1-diborylated olefins,19,20 to further test the utility of this
building block, compound 3 was successively subjected to
SuzukiꢀMiyaura coupling with an equimolar amount of
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(13) See Supporting Information.
(14) CCDC-643360 (3), -643361 (5a), and -643362 (8) contain the
supplementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
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Org. Lett., Vol. 15, No. 13, 2013
3295

Table 1. Screening the Optimal Conditions of Chemoselective SuzukiꢀMiyaura Couplinga
reaction. Palladium catalysts with monodentate ligands
were not particularly efficient.
Scheme 2. A Plausible Mechanism of Silylborylation of an
Alkynylboronate 2
Therefore, several representative bidentate ligands were
examined (entries 8ꢀ12). We were delighted to find that
PdCl2(dppf)22 performed significantly better (entry 12).
Although all the examined catalysts gave rise to the
coupling product 5a as a mixture of stereoisomers, the
isomeric mixture was separated by silica gel column chro-
matography. The Z-geometry of the major isomer of
product 5a was confirmed by X-ray crystallographic ana-
lysis.13,14 An authentic product (E)-5a was synthesized
by silylborylation of diphenylethyne to provide com-
parator NMR data,13 and this was indeed distinct from
that of (Z)-5a. This observed chemoselectivity is consistent
with that reported by Shimizu and Hiyama,15a wherein the
CꢀC bond formation at the cis position of the alkyl groups
was observed in the reaction of 1,1-diboryl-1-alkene with aryl
iodides. The CꢀC bond at the cis position of the SiMe2Ph
group was formed with moderate discrimination of two
geminal boryl groups in 3. Considering the conformational
energies (A-values) of the Ph (2.8) and SiMe2Ph (2.5ꢀ2.8)
groups,23 the chemoselectivity cannot be explained simply by
a steric effect. From the viewpoint of electronic demands, the
11B NMR spectrum of 3 showed an overlapped signal at 29.9
ppm, indicating that the two boryl groups are electronically
similar. Thus, at present, the reason why the two boryl groups
in 3 are discriminated remains unclear.
iodobenzene (4a) to ascertain whether the first coupling
would be chemoselective. Various palladium catalysts
and ligands were tested, and the results obtained are
listed in Table 1. A combination of Pd(dba)2 with the
[HPtBuMe2]BF4 salt, which had proven to be the best
catalyst for the SuzukiꢀMiyaura coupling reaction of
alkenylboronates with alkyl bromides,12b was found to
be suboptimal for the present reaction due to desilylation
of 3. Pd(PPh3)4 also exhibited lower reactivity (entries 2
and 3). PEPPSI-IPr21 and Pd2dba3 CHCl3/PtBu3 proved
3
more reactive and afforded a relatively higher yield, albeit
with reduced chemoselectivity (entries 4 and 5). An initial
survey demonstrated that aqueous KOH accelerated the
After optimizing the reaction conditions for the chemo-
selective SuzukiꢀMiyaura coupling of 3, a series of aryl
(20) (a) Coapes, R. B.; Souza, F. E. S.; Thomas, R. L.; Hall, J. J.;
Marder, T. B. Chem. Commun. 2003, 614. (b) Takaya, J.; Kirai, N.;
Iwasawa, N. J. Am. Chem. Soc. 2011, 133, 12980.
(22) Hayashi, T.; Konishi, M.; Kobori, Y.; Kumada, M.; Higuchi, T.;
Hirotsu, K. J. Am. Chem. Soc. 1984, 106, 158.
(21) O’Brien, C. J.; Kantchev, E. A. B.; Valente, C.; Hadei, N.; Chass,
G. A.; Lough, A.; Hopkinson, A. C.; Organ, M. G. Chem.;Eur. J. 2006,
12, 4743.
(23) (a) Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Com-
pounds; John Wiley and Sons: New York, 1993; p 696. (b) Kitching, W.;
Olszowy, H. A.; Drew, G. M.; Adcock, W. J. Org. Chem. 1982, 47, 5153.
3296
Org. Lett., Vol. 15, No. 13, 2013

Table 2. Chemoselective SuzukiꢀMiyaura Coupling of 3 with
Scheme 3. Sequential SuzukiꢀMiyaura Coupling for Synthesis
of Triarylated Alkenylsilane 6
a
Aryl Iodides 4 or Aryl Bromides 40
entry
arylꢀX
5
yield (Z/E)b
1
Ph-I (4a)
5a
5a
5b
5c
5d
5e
5f
85 (88:12)
78 (87:13)
87 (89:11)
57 (92:8)
2c
3
Ph-Br (4a0)
4-MeOC6H4-I (4b)
2-MeOC6H4-I (4c)
3-MeOC6H4-I (4d)
4-MeC6H4-I (4e)
4-CF3C6H4-I (4f)
4-CF3C6H4-Br (4f0)
4- ClC6H4-I (4g)
4- EtO2CC6H4-I (4h)
4
5
83 (89:11)
92 (88:12)
57 (87:13)
59 (85:15)
92 (88:12)
70 (86:14)
Scheme 4. Synthesis of Tetraarylated Olefin 8
6
7
8c
9
5f
5g
5h
10
a Reaction conditions: 3 (245 mg, 0.5 mmol), 4 or 40 (0.5 mmol),
PdCl2(dppf) (18 mg, 5 mol %), 3 M KOH solution (1.5 mmol, 0.5 mL) in
THF (5 mL). b Isolated yields after silica gel column chromatography;
Z/E ratios were determined by the 1H NMR spectra. c The reaction time
was 18 h.
iodides 4 were subjected to survey the reaction scope.
2-Iodoanisole (4c) afforded the desired product 5c in
moderate yield that we ascribe to a steric effect (entry 4).
As shown in Table 2, it is noteworthy that some aryl
bromides 40 also gave moderate to good yields when the
reaction time was extended to 18 h (entries 2 and 8). It is
also notable that a chloro group in the substrate 4g
remained intact during the reaction with no trace of side
product observed. Synthesis of compounds 5 would be
impracticable via anti-silylborylation7k of unsymmetrical
diarylethynes because the regioselectivity of the addition
would not be controllable.
stereoselective silylborylation of the alkynylboronate and
sequential chemoselective SuzukiꢀMiyaura couplings.
This protocol can be applicable to a variety of functional
groupsonthearylmoieties, includingthosenot compatible
with the organolithium reagents required in previous
approaches. Further studies to clarify the factors for the
selectivity and to expand this synthetic method to a more
general approach to the complicated π-conjugated mole-
cules are in progress.
With a diverse range of reagents 5 in hand, we sequen-
tially introduced an additional aryl group by Suzukiꢀ
Miyaura coupling of the remaining boron moiety. The
triarylated alkenylsilane 6 was synthesized successfully by
Acknowledgment. The authors gratefully thank Prof.
Michinori Suginome (Kyoto University) for valuable dis-
cussions; Ms. Megumi Kosaka and Mr. Motonari
Kobayashi at the Department of Instrumental Analysis,
Advanced Science Research Center, Okayama University
for the measurements of elemental analyses; and the
SC-NMR Laboratory of Okayama University for the
NMR measurements. Y.N. also acknowledges The Sumi-
tomo Foundation.
the reaction of (Z)-5b with 4f in the presence of Pd2dba3
CHCl3/PtBu3 as the catalyst (Scheme 3).
3
Finally, we addressed the synthesis of a tetraarylated
olefin 8 with four different aryl groups through sequential
cross-couplings by utilizing the remaining silyl moiety.
With Br2 and NaOMe in MeOH,24 the silyl group in 6
was successfully transformed to the corresponding bro-
mide 7 along an inversion of stereochemistry. A sequential
SuzukiꢀMiyaura coupling of 7 with 4-cyanophenylboro-
nic acid then afforded the tetraarylated olefin 8 in 88%
yield as a sole product whose structure was unambiguously
confirmed by X-ray diffraction (Scheme 4).13,14
Supporting Information Available. Copies of 1H NMR
and 13C{1H} NMR spectra for all the new compounds, as
well as details on experimental procedures and character-
ization data. This material is available free of charge via
the Internet at http://pubs.acs.org.
In summary, we have successfully developed a synthesis
of tetraarylated olefins featuring a perfectly regio- and
(24) Miller, R. B.; Al-Hassan, M. I. J. Org. Chem. 1985, 50, 2121.
The authors declare no competing financial interest.
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