An efficient copper(I)-catalyst system for the asymmetric hydroboration of β-substituted vinylarenes with pinacolborane

Article abstract of DOI:10.1002/asia.201100146

The pinacol of ligands: The (R)-DTBM-Segphos coordinated copper(I) complex was found to be very effective for the asymmetric hydroboration of β-substituted styrene derivatives with pinacolborane (see scheme; DTBM=3,5-di-tert-butyl-4-methoxyphenyl). This new method affords benzylic pinacol boronate esters with excellent levels of regio- and enantioselectivity (>99 %).

Full text of DOI:10.1002/asia.201100146

DOI: 10.1002/asia.201100146
An Efficient Copper(I)-Catalyst System for the Asymmetric Hydroboration
of b-Substituted Vinylarenes with Pinacolborane
Dongwan Noh, Sue Kyoung Yoon, Jiyeon Won, Jin Yong Lee,* and Jaesook Yun*[a]
Dedicated to Professor Eun Lee on the occasion of his retirement and 65th birthday
Hydroboration of unsaturated carbon–carbon bonds is a
valuable synthetic method for the preparation of organobor-
ane intermediates, which can serve as synthons for various
functional groups.[1] Using pinacolborane instead of cate-
cholborane as the borane source in metal-catalyzed hydro-
borations has recently attracted interest owing to its stability
and the ease of handling the resulting boronate ester prod-
ucts.[2] While rhodium-catalyzed hydroborations have re-
ceived major attention,[2b,3] we have recently shown that
phosphine-ligated copper complexes are efficient catalysts
for the highly regioselective hydroboration of styrenes with
pinacolborane, and regioselective and enantioselective hy-
droboration is possible with chiral bisphosphine ligands such
as tangphos and Me-duphos.[4] In this study, we present a
new, more efficient copper-catalytic system by using the
DTBM-Segphos ligand and pinacolborane as the borane
source. This catalyst is remarkably effective for reactions
with challenging vinylarene substrates possessing a substitu-
ent at the b-position or an electron-donating group on the
phenyl ring, which displayed limited reactivity with our pre-
vious catalytic systems. Currently, asymmetric rhodium-cata-
lyzed hydroboration with P,N-chelates, such as quinap
(quinap=1-(2-diphenylphosphino-1-naphthyl)isoquinoline
and its structural derivatives, is the only catalytic solution
for reactions of b-substituted styrenes with catecholborane
as the borane source.[5] However, as reported herein, a new
copper-based system exclusively affords the corresponding
benzylic pinacolboronate esters with high enantioselectivi-
ties up to >99% ee.
As a result of previous ligand screening for the catalytic
hydroboration of styrene, we found that axially chiral biaryl-
based ligands such as Tol-binap[6] and biphep[7] were inferior
to the short-tethered bisphosphine ligands, tangphos and
duphos, in terms of reactivity.[4] Furthermore, from theoreti-
cal calculations, bidentate ligands were found to be more ef-
ficient than monodentate ligands owing to decreased stabili-
zation of the reactant–catalyst complexes (RC) as a result of
steric congestion.[8] Two other bulky bisphosphine ligands
such as QuinoxP and (R)-DTBM-Segphos with similar
tether lengths to duphos and binap, respectively, were
chosen for the copper-catalyzed hydroboration of (E)-1-
phenyl-1-propene (Scheme 1). Surprisingly, (R)-DTBM-Seg-
phos was especially reactive, thus providing the product
with complete conversion and excellent enantioselectivity
(>99% ee) at room temperature within 12 hours, whereas
tangphos, Me-duphos, and QuinoxP ligands displayed limit-
ed activity.
[a] D. Noh, S. K. Yoon, J. Won, Prof. J. Y. Lee, Prof. J. Yun
Department of Chemistry and Institute of Basic Science
Sungkyunkwan University
Suwon 440-746 (Korea)
Fax : (+82)31-290-7075
E-mail: jaesook@skku.edu
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.201100146.
Scheme 1. Hydroboration of (E)-1-phenyl-1-propene.
Chem. Asian J. 2011, 6, 1967 – 1969
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1967

COMMUNICATION
Encouraged by the high reactivity and excellent enantio-
selectivity of the DTBM–Segphos–copper catalyst, asym-
metric hydroborations of various vinylarenes, including b-
substituted vinylarenes, were examined. Excellent enantiose-
lectivities were obtained in all cases regardless of the b-sub-
stituent size (Table 1, entries 1–6). When the substituent was
a tert-butyl group (1e), a longer reaction time was required,
but the enantioselectivity was not compromised (entry 5).
The reaction with the (Z)-isomer was less efficient, and the
hydroboration of indene proceeded with a low conversion
(entry 6). para-Methoxystyrene (1g) and 2-vinylnaphthalene
(1h), which had low reactivity or enantioselectivity with the
Scheme 2. Copper-catalyzed hydroboration of dienes.
Table 1. Enantioselective hydroboration with (R)-DTBM-Segphos–copper catalyst and pinacolborane.
For further insight into the
high activity of the Segphos
ligand system, the energy pro-
file of the catalytic reaction
along the reaction coordinate
was obtained using a suite of
Gaussian 03 programs.[13] The
geometries of the reactant com-
plex, transition state, intermedi-
ate, and product were opti-
mized by density functional
theory (DFT) calculations with
6-311G* basis sets using
Beckeꢁs three parameterized
Lee–Yang–Parr (B3LYP) ex-
Entry
Substrates (1)
t [h]
Conversion [%][a]
Yield [%][b]
ee [%][c]
Ar
R
1
2
3
4
1a; Ph
1b; Ph
1c; Ph
1d; Ph
n-pentyl
CH2OCOCH3
Ph
iPr
tBu
24
12
24
24
48
24
24
12
100
100
100
100
100
62
87
84
93
89
90
50
91
88
>99
99
99
>99
98
98
5
1e; Ph
6[d]
7
1 f; indene
1g; p-MeOC6H4
1h; 2-naphthyl
H
H
100
100
98
85
8
[a] Determined by GC analysis with an internal standard based on consumed starting material. [b] Isolated
yields. [c] Determined by chiral HPLC analysis. [d] Conducted at 408C.
copper–tangphos catalyst, gave complete conversion and
much higher enantioselectivity with the current catalytic
system.
Next, interesting diene substrates possessing a phenyl
group were subjected to the hydroboration conditions. Bis-
ACHTUNGTRENNUNG(vinyl)arene (1i) produced diborated products in a ratio of
95:5, thus giving the major product (2i) in over 99% ee.
Conjugated butadiene-substituted benzene (1j) was also re-
active, and afforded the allylic boronate product[9] instead of
benzylic boronate through reaction with the less hindered
alkene moiety due to steric considerations (Scheme 2).
Although addition of copper hydride to styrene and trans-
metalation of the resulting copper intermediate with pina-
colborane has been examined by theoretical calculations,[8]
the unprecedented complete enantioselectivity of the
copper–DTBM–Segphos complex with b-substituted styr-
enes afforded a favorable opportunity to probe the reaction
mechanism. Deuterated 1-phenyl-1-propene was prepared[10]
and subjected to hydroboration, and the stereochemistry of
the resulting boronate product was analyzed by further oxi-
dation to the alcohol product (Scheme 3).[11] The deuterated
boron addition product was found to have an anti-relation-
ship between the boronate moiety and the deuterium. Cis-
addition of the catalyst and stereoretentive transmetala-
tion[12] through s-bond metathesis provide a rationalization
for formation of the observed product.
Scheme 3. Hydroboration of 2-deuterio-1-phenyl-1-propene.
change functional. As shown in Figure 1, the activation bar-
rier for the addition of copper hydride to the b-methyl-sub-
stituted styrene (first step), which was considered the rate-
limiting step, was calculated to be 6.07 kcalmolÀ1. This barri-
er is much lower than the activation barriers obtained previ-
ously for styrene with other ligand systems.[8,14] This lower
barrier could lead to the high activity; the steric bulkiness of
Segphos might be responsible for the decreased stabilization
of the RC complex, which leads to a reduction in the energy
barrier in the rate-limiting step, and hence the high activity.
In addition, the second step was exothermic with Segphos,
which also helps to explain the high activity under the reac-
tion conditions.
1968
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ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2011, 6, 1967 – 1969

Asymmetric Hydroboration of b-Substituted Vinylarenes
Acknowledgements
This work was supported by National Research Foundation (NRF) grants
funded by the Korean government (No. 20090085824, and 20100001630).
Keywords: asymmetric catalysis · copper · hydroboration ·
pinacolborane · vinylarenes
[1] For reviews, see: a) K. Burgess, M. J. Ohlmeyer, Chem. Rev. 1991,
91, 1179–1191; b) C. M. Crudden, D. Edwards, Eur. J. Org. Chem.
2003, 4695–4712; c) A.-M. Carroll, T. P. OꢁSullivan, P. J. Guiry, Adv.
Synth. Catal. 2005, 347, 609–631; d) S. P. Thomas, V. K. Aggarwal,
Angew. Chem. 2009, 121, 1928–1930; Angew. Chem. Int. Ed. 2009,
48, 1896–1898.
[2] a) S. Pereira, M. Srebnik, Tetrahedron Lett. 1996, 37, 3283–3286;
b) C. M. Crudden, Y. B. Hleba, A. C. Chen, J. Am. Chem. Soc. 2004,
126, 9200–9201; c) Y. Yamamoto, R. Fujikawa, T. Umemoto, N.
Miyaura, Tetrahedron 2004, 60, 10695–10700; d) A. Caballero, S.
Sabo-Etienne, Organometallics 2007, 26, 1191–1195; e) A. G. Karat-
jas, E. Vedejs, J. Org. Chem. 2008, 73, 9508–9510.
Figure 1. Energy profile for the catalytic hydroboration (copper hydride
addition to 1-phenyl-1-propene and subsequent transmetalation with pi-
nacolborane) with the Segphos ligand. See the Supporting Information
(Figure S1) for the calculated structures of RC, TS1, I, TS2, and P.
Although designed as a bidentate ligand, it is noteworthy
that the Segphos ligand acts as a monodentate ligand due to
steric hindrance around the phosphines (Figure S1 in the
Supporting Information).[15] While the Segphos ligand is
bulky, it seems to allow some space around the copper cata-
lyst by coordinating as a monodentate ligand and also pro-
vides an appropriate geometry for high enantioselectivity;
this ligand–copper system can accommodate the steric
demand of substituents around the alkene double bond.
In summary, the Segphos–copper complex proved to be
an extremely efficient catalyst for the hydroboration of b-
substituted styrenes with pinacolborane, thus affording ben-
zylic boronate ester products with excellent enantioselectivi-
ty at room temperature. Further studies into applications of
this catalyst system are in progress.
[3] a) T. Hayashi, Y. Matsumoto, Y. Ito, Tetrahedron: Asymmetry 1991,
2, 601–612; b) S. A. Moteki, D. Wu, K. L. Chandra, D. S. Reddy,
J. M. Takacs, Org. Lett. 2006, 8, 3097–3100; c) K. Endo, M. Hiroka-
mi, T. Shibata, Organometallics 2008, 27, 5390–5393; d) M. Rubina,
M. Rubin, V. Gevorgyan, J. Am. Chem. Soc. 2003, 125, 7198–7199.
[4] D. Noh, H. Chea, J. Ju, J. Yun, Angew. Chem. 2009, 121, 6178–6180;
Angew. Chem. Int. Ed. 2009, 48, 6062–6064; (S,S,R,R)-tangphos=
(1S,1S’,2R,2R’)-1,1’-di-tert-butyl-(2,2’)-diphospholane and (S,S)-Me-
duphos=(+)-1,2-bisACTHNUTRGNE[UNG (2S,5S)-2,5-dimethylphospholano]benzene
[5] a) H. Doucet, E. Fernandez, T. P. Layzell, J. M. Brown, Chem. Eur.
J. 1999, 5, 1320–1330; b) J. M. Valk, G. A. Whitlock, T. P. Layzell,
J. M. Brown, Tetrahedron: Asymmetry 1995, 6, 2593–2596; c) D. J.
Connolly, P. M. Lacey, M. McCarthy, C. P. Saunders, A.-M. Carroll,
R. Goddard, P. J. Guiry, J. Org. Chem. 2004, 69, 6572–6589.
[6] 2,2ꢁ-bis(di-p-tolylphosphino)-1,1ꢁ-binaphthyl.
[7] 2,2ꢁ-bis(diphenylphosphino)-6,6ꢁ-dimethoxy-1,1ꢁ-biphenyl.
[8] J. Won, D. Noh, J. Yun, J. Y. Lee, J. Phys. Chem. A 2010, 114,
12112–12115.
[9] The allylic boronate product decomposed upon chromatography and
thus, was directly oxidized to the corresponding allylic alcohol (3j)
for characterization.
[10] a) T. Takahashi, N. Suzuki, M. Kageyama, D. Y. Kondakov, R. Hara,
Tetrahedron Lett. 1993, 34, 4811–4814; b) E. I. Negishi, J. P. Maye,
D. Choueiry, Tetrahedron 1995, 51, 4447–4462.
Experimental Section
General Procedure
A mixture of CuCl (0.015 mmol, 1.5 mg), NaOtBu (0.03 mmol, 3.0 mg),
and (R)-DTBM-segphos (0.015 mmol, 17.7 mg) in anhydrous toluene
(0.2 mL) was stirred for 10 min in a Schlenk tube under an atmosphere
of nitrogen. Pinacolborane (0.6 mmol, 90 mL) was added to the reaction
mixture and stirred for 10 min at room temperature. Vinylarenes
(0.5 mmol) and tetradecane (0.25 mmol) as an internal standard were
added in toluene (0.1 mL), and the reaction tube was washed further
with toluene (0.2 mL) and sealed. The reaction was monitored by TLC
and GC. The reaction mixture was filtered through a pad of Celite and
concentrated. The product was purified by chromatography on silica gel
(hexanes/ethyl acetate=10:1).
[11] For details, see the Supporting Information; G. Fronza, C. Fuganti,
P. Grasselli, A. Mele, J. Org. Chem. 1991, 56, 6019–6023.
[12] For DFT calculations and experiments on transmetalation of CACHTUNGTRENNUNG
(sp3)-
bound copper species with diboron reagents (e.g. bis(catecholato)di-
boron), see; a) V. Lillo, M. R. Fructos, J. Ramꢂrez, A. A. C. Braga, F.
Maseras, M. M. Dꢂaz-Requejo, P. J. Pꢃrez, E. Fernꢄndez, Chem. Eur.
J. 2007, 13, 2614–2621; b) L. Dang, H. Zhao, Z. Lin, T. B. Marder,
Organometallics 2008, 27, 1178–1186.
[13] Gaussian 03, M. J. Frisch et al., Gaussian, Inc., Wallingford, CT,
2004.
[14] 15.19 and 13.69 kcalmolÀ1 for representative monodentate ligands
(PMe3, PPh3) and 10.43 and 7.73 kcalmolÀ1 for bidentate ligands
(1,2-bis(diphenylphosphino)benzene (dppbz), Me-duphos).
[15] See the Supporting Information.
Received: February 14, 2011
Published online: April 27, 2011
Chem. Asian J. 2011, 6, 1967 – 1969
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
1969