Synthesis of B-protected β-styrylboronic acids via iridium-catalyzed hydroboration of alkynes with 1,8-naphthalenediaminatoborane leading to iterative synthesis of oligo(phenylenevinylene)s

Article abstract of DOI:10.1021/ol9003096

Hydroboration of aromatic and aliphatic alkynes with 1,8- naphthalenediaminatoborane ((dan)BH) proceeded in the presence of [IrCl(cod)]₂ complex with a DPPM or DPEphos ligand, affording alkenylboronic acids whose boronyl groups are masked by th

Full text of DOI:10.1021/ol9003096

ORGANIC
LETTERS
2009
Vol. 11, No. 9
1899-1902
Synthesis of B-Protected
ꢀ-Styrylboronic Acids via
Iridium-Catalyzed Hydroboration of
Alkynes with
1,8-Naphthalenediaminatoborane
Leading to Iterative Synthesis of
Oligo(phenylenevinylene)s
Noriyuki Iwadate and Michinori Suginome*
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of
Engineering, Kyoto UniVersity, Katsura, Kyoto 615-8510, Japan
suginome@sbchem.kyoto-u.ac.jp
Received February 12, 2009
ABSTRACT
Hydroboration of aromatic and aliphatic alkynes with 1,8-naphthalenediaminatoborane ((dan)BH) proceeded in the presence of [IrCl(cod)]2
complex with a DPPM or DPEphos ligand, affording alkenylboronic acids whose boronyl groups are masked by the diaminonaphthalene
group. The masked alkenylboronic acids thus obtained from alkynes bearing halo-substituted aryl groups served as new coupling modules
in an iterative Suzuki-Miyaura cross-coupling reaction for the synthesis of oligo(phenylenevinylene)s.
Suzuki-Miyaura coupling is currently recognized as the most
reliable, selective, and widely applicable cross-coupling
reaction for the synthesis of conjugated organic molecules
such as oligoarenes and arene-vinylene conjugates.1,2 One
of the major attractive features of the Suzuki-Miyaura
coupling reaction over other cross-coupling reactions is the
stability and availability of the organoboronic acid deriva-
tives. In addition, recent progress in reactivity control by
introduction of “protecting”3-5 or “activating”6 groups to
the boron atoms of organoboronic acids allows new cross-
coupling systems, which have rarely been achieved on the
basis of other cross-coupling reactions.
(1) (a) Miyaura, N. Top. Curr. Chem. 2002, 219, 11. (b) Suzuki, A.;
Brown, H. C. In Organic Synthesis Via Boranes; Aldrich: Milwaukee, 2003;
Vol. 3. (c) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457
.
(2) (a) Tour, J. M. Chem. ReV. 1996, 96, 537. (b) Berresheim, A. J.;
Mu¨ller, M.; Mu¨llen, K. Chem. ReV. 1999, 99, 1747. (c) Segura, J. L.; Martin,
N. J. Mater. Chem. 2000, 10, 1747. (d) Kraft, A.; Grimsdale, A. C.; Holmes,
A. B. Angew. Chem., Int. Ed. 1998, 37, 402. (e) Schlu¨ter, A. D. J. Polym.
We have been involved in the development of new
protective groups for the boronyl groups (B(OH)2) in the
Suzuki-Miyaura coupling reaction.4 We have established
Sci., Part A: Polym. Chem. 2001, 39, 1533
.
10.1021/ol9003096 CCC: $40.75
Published on Web 03/30/2009
 2009 American Chemical Society

that 1,8-diaminonaphthalene serves as a highly efficient
protective agent for the boronyl groups in the Suzuki-Miyaura
coupling, leading to the development of an iterative coupling
system for oligoarene derivatives.4,5,7 In our studies on the
application of the boron-masking strategy to the iterative
synthesis of oligo(phenylenevinylene)s, which are receiving
increasing attention because of their light-emitting and NLO
properties, it was desirable to establish a convenient and
straightforward synthesis of the masked coupling modules.
Although the masked modules may be prepared from the
corresponding boronic acids via condensation with 1,8-
diaminonaphthalene,8 we decided to seek methods for direct
introduction of the masked boronyl group into the organic
molecules. Herein, we describe the synthesis of masked
ꢀ-styrylboronic acids by hydroboration of alkynes with 1,8-
naphthalenediaminatoborane ((dan)BH), whose reactivity has
been established recently in Ir-catalyzed C-H borylation of
arenes.9 We also demonstrate the use of the masked
ꢀ-styrylboronic acids in the synthesis of oligo(phenylenevi-
nylene)s via iterative Suzuki-Miyaura coupling.
colborane, showed only low catalytic activities (entries 1 and
2).10 A cationic rhodium complex also failed to promote the
hydroboration efficiently (entry 3). Our examination of
iridium complexes showed that neutral iridium complexes
had higher activities than the rhodium complexes (entries
5-11).11,12 We observed a significant influence of the
phosphine ligands on the catalytic activity and found that
DPPM and DPEphos showed high catalytic activities (entries
6 and 11). The reaction in the presence of the iridium-
DPEphos catalyst afforded trans-ꢀ-borylstyrene 2a in 83%
yield along with the corresponding Z stereoisomer and
regioisomer in less than 5% yield each (90:5:5). The major
isomer was easily separated from the other isomers by silica
gel column chromatography. Although there observed no
strong influence of the solvent on the reaction yields,
hydroboration in CH2Cl2 was significantly faster than reac-
tions in toluene, THF, dioxane, and acetonitrile (entries
12-15).
The optimized reaction conditions were applicable to the
hydroboration of other alkynes (Table 2).13
Arylacetylenes
Hydroboration of phenylacetylene (1a) with (dan)BH was
initially examined in the presence of rhodium and iridium
catalysts (Table 1). Wilkinson’s catalyst and the correspond-
1b-1g bearing methyl, methoxy, dimethylamino, ethoxy-
carbonyl, and acetyl groups afforded the corresponding trans-
products in good yields (entries 1-6). Note that electron-
donating groups increased the reactivity of the triple bonds,
allowing the reaction to proceed at room temperature,
whereas arylacetylenes bearing an electron-withdrawing
group needed 50 °C for the reaction to proceed (entries 5
and 6). Unsymmetrical, 1-phenylpropyne (1h) underwent the
hydroboration in a regioselective manner, giving the ꢀ-styrylb-
orane-type product 2h with high regio- and stereoselectivity
(entry 7). It should be noted that aliphatic alkynes 1i-1k
underwent hydroboration with 1 under the identical reaction
conditions (entries 8-10). Cross-coupling modules 2l-2n,
which have bromine atoms at the ortho, meta, and para
positions on the aromatic rings, could be synthesized by this
reaction (entries 11-13). Substituted p-bromostyrene mod-
ules 2o and 2p could be prepared in good yields by
hydroboration of the corresponding p-bromophenylacetylenes
(entries 14 and 15). 2,5-Thiophenylethenyl module 2q was
also synthesized, albeit in moderate yield. Note that iso-
merically pure products were readily isolated by silica gel
column chromatography in most cases, although stereo- and/
Table 1. Optimization of Hydroboration of Phenylacetylene
with (dan)BHa
ent
catalyst
solvent
ligand
% yield of 4b
1
2
3
4
5
6
7
8
RhCl(PPh3)3
[RhCl(cod)]2
[Rh(cod)2]BF4
[Ir(cod)2]BF4
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
toluene
THF
5
3
20
34
50
81
76
60
26
61
83
76 (84)
68 (85)
59 (77)
52 (73)
PPh3
PPh3
PPh3
PPh3
DPPM
DPPE
DPPP
DPPB
DPPF
DPEphos
DPEphos
DPEphos
DPEphos
DPEphos
9
10
11
12
13
14
15
(3) (a) Molander, G. A.; Ellis, N. Acc. Chem. Res. 2007, 40, 275. (b)
Molander, G. A.; Sandrock, D. L. J. Am. Chem. Soc. 2008, 130, 15792.
(4) (a) Noguchi, H.; Hojo, K.; Suginome, M. J. Am. Chem. Soc. 2007,
129, 758. (b) Noguchi, H.; Shioda, T.; Chou, C.-M.; Suginome, M. Org.
Lett. 2008, 10, 377.
dioxane
CH3CN
(5) (a) Gillis, E. P.; Burke, M. D. J. Am. Chem. Soc. 2007, 129, 6716.
(b) Lee, S. J.; Gray, K. C.; Peak, J. S.; Burke, M. D. J. Am. Chem. Soc.
2008, 130, 466.
a A mixture of 1, alkyne (1.5 equiv), transition metal complex (5 mol %
Rh or Ir), and ligand (6.0 mol %) in CH2Cl2 was stirred at room temperature
for 2 h under a nitrogen atmosphere. b GC yield. Yields after 24 h are
shown in the parentheses.
(6) Cyclic triolborates: (a) Yamamoto, Y.; Takizawa, M.; Yu, X.-Q.;
Miyaura, N. Angew. Chem., Int. Ed. 2008, 47, 928. Trifluoroborates: (b)
Molander, G. A.; Ellis, N. Acc. Chem. Res. 2007, 40, 275.
(7) (a) Ishikawa, S.; Manabe, K. Chem. Lett. 2006, 35, 164. (b) Ishikawa,
S.; Manabe, K. Chem. Commun. 2006, 2589.
(8) For the syntheses and properties of PhB(dan), see: Kaupp, G.; Naimi-
Jamal, M. R.; Stepanenko, V. Chem.-Eur. J. 2003, 9, 4156, and references
therein.
(9) Iwadate, N.; Suginome, M. J. Organomet. Chem. 2009, in press;
DOI:, 10.1016/j.jorganchem.2008.11.068. For precedents of the preparation
and reaction of (dan)BH, see: (b) Caserio, F. F., Jr.; Cavallo, J. J.; Wagner,
R. I. J. Org. Chem. 1961, 26, 2157. (c) Smith, M. R., III. PCT WO 03/
006158 A2.
ing neutral rhodium/PPh3 catalyst, which are known to be
effective catalysts for hydroboration of alkynes with pina-
(10) Mannig, D.; Noth, H. Angew. Chem., Int. Ed. Engl. 1985, 24, 878.
1900
Org. Lett., Vol. 11, No. 9, 2009

Table 2. Iridium-Catalyzed Hydroboration of Alkynes with
Table 3. Suzuki-Miyaura Coupling of Masked ꢀ-Styrylboronic
(dan)BHa
Acidsa
a See ref 13 for experimental details. b Isolated yield.
yields (entries 4 and 5). Thiophene module 2q similarly
afforded the corresponding aryl/thiophene/CdC ternary
system 4f in good yield (entry 6).
Using the divalent coupling modules 2n and 2o repeatedly,
iterative synthesis of oligo(phenylenevinylene) (OPV here-
after) was demonstrated (Scheme 1). The dan group of the
biaryl-vinyleneborane 4c was unmasked by treatment with
hydrochloric acid.15 The unmasked alkeneboronic acid 4c′
was reacted with coupling module 2o, which has alkyl chains
on the aromatic core, in the presence of palladium/SPhos
catalyst.16,17 OPV 5 was isolated in 87% yield with perfect
recovery of the protective group on the boronyl group. To
obtain reproducible and good yields in the cross-coupling
a A mixture of 1, alkyne (1.5 equiv), [IrCl(cod)]2 (5.0 mol % Ir), and
ligand (6.0 mol %) in CH2Cl2 was stirred at 25 or 50 °C under a nitrogen
atmosphere. b Isolated yield for isomerically pure material unless otherwise
noted. c Trans:cis.
(11) Ir-catalyzed hydroborations: (a) Evans, D. A.; Fu, G. C.; Hoveyda,
A. H. J. Am. Chem. Soc. 1992, 114, 6671. (b) Yamamoto, Y.; Fujiwara,
R.; Umemoto, T.; Miyaura, N. Tetrahedron 2004, 60, 10695.
(12) Reviews for catalytic hydroboration, see: (a) Beletskaya, I.; Pelter,
A. Tetrahedron 1997, 53, 4957. (b) Burgess, K.; Ohlmeyer, M. J. Chem.
ReV. 1991, 91, 1179. (c) Crudden, C. M.; Edwards, D. Eur. J. Org. Chem.
2003, 24, 4695. Asymmetric variants: (d) Hayashi, T. In ComprehensiVe
Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.;
Springer: Berlin, 1999; Vol. 1, p 351.
or regioisomers were formed in all the reactions (see
Supporting Information).
The coupling modules 2l-2q were used in Suzuki-
Miyaura cross-coupling reactions (Table 3). Masked ꢀ-styryl-
boronic acids 2l-2n having an o-, m-, or p-Br group
underwent cross-coupling with p-tolylboronic acid in the
presence of a Pd[P(t-Bu)3]2 catalyst to give the corresponding
(ꢀ-borylalkenyl)biaryls 4a-4c in good yields (entries 1-3).14
The modules having alkyl and alkoxy side chains on the
aromatic ring also underwent the coupling reaction in high
(13) Typical procedure for the hydroboration of alkynes with (dan)BH.
Synthesis of 2o. A mixture of [IrCl(cod)]2 (15.8 mg, 24 µmol) and DPPM
(21.7 mg, 56 µmol) in CH2Cl2 (4 mL) was stirred at rt for 10 min under a
nitrogen atmosphere. (dan)BH (149 mg, 0.89 mmol) and 4-bromo-2,5-
dihexylphenylacetylene (494 mg, 1.41 mmol) in CH2Cl2 (10 mL) was added
to the solution. The mixture was stirred at 50 °C for 8 h. The resultant
solution was evaporated under vacuum and purified by silica gel column
chromatography (SiO2 pretreated with 1% Et3N in hexane, AcOEt/hexane
1:30), affording 2o (368 mg, 80%).
Org. Lett., Vol. 11, No. 9, 2009
1901

After deprotection of the dan masking group, the third
coupling was carried out with 2n. The OPV 6 having three
repeating phenylenevinylene units was obtained in high yield.
In summary, hydroboration of alkynes with 1,8-naphtha-
lenediaminatoborane ((dan)BH) has been optimized and
applied to the synthesis of oligo(phenylenevinylene)s via
iterative Suzuki-Miyaura coupling. Among the transition
metal catalysts, a neutral iridium(I) complex having bispho-
sphine ligands showed higher catalytic activities than rhod-
ium catalysts, which are often used in the hydroboration with
pinacolborane and catecholborane. Aryl alkynes having
halogen groups on their aromatic rings were successfully
hydroborated under the optimized reaction conditions, lead-
ing to the formation of masked coupling modules for the
iterative cross-coupling reaction. The masked modules were
unmasked with aqueous acids and coupled with organobo-
ronic acids. Highly selective Suzuki-Miyaura cross-coupling
took place with the protected boronyl group left intact.
Synthesis of new coupling modules and their application to
the synthesis of functionalized oligo(phenylenevinylene)s is
now being undertaken in this laboratory.
Scheme 1. Iterative Synthesis of Oligo(phenylenevinylene) 6
Acknowledgment. This work was supported by Grant-
in-Aid for Scientific Research from Ministry of Education,
Culture, Sports, Science and Technology, Japan.
reaction using SPhos, it is important to add water (3.0 equiv)
to the reaction system. When dry K3PO4 was used without
adding water, the reaction proceeded only sluggishly.
Supporting Information Available: Experimental pro-
cedures and spectral data for new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
(14) Typical procedure for the cross-coupling reaction of 2. Synthesis
of 4c. To a mixture of 2n (49.2 mg, 0.141 mmol), p-tolylboronic acid (3)
(19.2 mg, 0.141 mmol), and CsF (42.8 mg, 0.282 mmol) in THF (0.7 mL)
was added Pd(PtBu3)2 (1.44 mg, 0.00282 mmol) under a nitrogen atmo-
sphere. The mixture was stirred at 60 °C for 4 h. After extraction with
CH2Cl2, the organic phase was washed with brine and dried over Na2SO4.
Filtration, evaporation, and purification by silica gel column chromatography
(CH2Cl2/hexane 1:1 (5% NEt3)) gave 4c (42.0 mg, 87%).
(15) Typical procedure for the unmasking step. Synthesis of 4c′. To a
solution of 4c (43 mg, 0.068 mmol) in THF (0.54 mL) was added
hydrochloric acid (5 N, 54 µL, 0.27 mmol). The solution was stirred at
room temperature for 4 h, resulting in precipitation of protonated 1,8-
diaminonaphthalene. The suspension was filtered through a pad of Celite,
and the solution was dried over K2CO3. Filtration and evaporation of the
solvent in vacuo gave the corresponding boronic acid (35.3 mg, 99% yield)
as a colorless solid. The boronic acid was used in the subsequent cross-
coupling reaction without further purification.
OL9003096
(16) SPhos: 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl. Bard-
er, T. E.; Walker, S. D.; Martinelli, J. R.; Buchwald, S. L. J. Am. Chem.
Soc. 2005, 127, 4685.
(17) Typical procedure for the cross-coupling using SPhos as a ligand.
Synthesis of 5. To a mixture of Pd(OAc)2 (0.40 mg, 1.78 µmol), SPhos
(1.46 mg, 3.56 µmol), 2o (46.0 mg, 0.0899 mmol), 4c′ (21.2 mg, 0.0890
mmol), and K3PO4 (dried, 56.7 mg, 0.267 mmol) in THF (0.750 mL) was
added H2O (4.80 mg, 0.267 mmol) under a nitrogen atmosphere. The
mixture was stirred at 50 °C for 24 h. After extraction with CH2Cl2, the
organic phase was washed with brine and dried over Na2SO4. Filtration,
evaporation, and purification by silica gel column chromatography (pre-
treated with 1% NEt3 in hexane, CH2Cl2/hexane 1:5) gave coupling product
5 (48.8 mg, 87%).
1902
Org. Lett., Vol. 11, No. 9, 2009