Highly regio- and enantioselective copper-catalyzed hydroboration of styrenes

Full text of DOI:10.1002/anie.200902015

Communications
DOI: 10.1002/anie.200902015
Asymmetric Hydroboration
Highly Regio- and Enantioselective Copper-Catalyzed Hydroboration
of Styrenes**
Dongwan Noh, Heesung Chea, Junghwan Ju, and Jaesook Yun*
3
À
Transition-metal-catalyzed hydroboration reactions of
alkenes[1] have attracted much interest, as they provide
opportunities for unique regio- and enantioselectivity. In
particular, the asymmetric hydroboration of styrene deriva-
tives to afford nonracemic a-borylated products is a useful
example of metathesis between Cu C(sp ) and PinBH exists,
and it is known that a similar metathesis reaction between
Cu C and B B is difficult, we envisioned that a copper(I)
hydride coordinated with an appropriate ligand would
[9]
À
À
undergo regioselective addition to styrene and facilitate an
[11]
efficient transmetalation[10] of the resulting Cu C bond
À
À
reaction, since the resulting C B bond can be transformed
À
À
À
with retention of configuration into a C N, C O, or C C
bond.[1b,2] Although many catalytic systems, including ruth-
enium,[3a] nickel,[3b] samarium,[3c] and lanthanum[3d] catalysts,
have been employed for the transformation, the development
of a highly regio- and enantioselective hydroboration still
remains as a challenge; so far, only combinations of rhodium
complexes and catecholborane (CatBH) at low temperatures
have shown the desirable high regio- and enantioselectiv-
ity.[4,5] Given the instability of catecholborane and the
resulting borylated product, it is necessary to develop efficient
regioselective catalytic systems that are compatible with more
stable (but less reactive) hydroboration reagents, react with
disubstituted olefins, and can readily be rendered enantiose-
lective by the use of nonracemic ligands.
with pinacolborane, rather than b-hydride elimination,[12] to
afford the desired branched boronate ester (Scheme 1).
Scheme 1. Expected catalytic cycle.
Herein, we report that copper(I) complexes coordinated
with chelating phosphine ligands can catalyze the regio- and
enantioselective hydroboration of styrenes with pinacolbor-
ane (PinBH) to afford the corresponding a-borated products.
Reactions proceed with better than 99:1 site selectivity and
with high enantioselectivity in the presence of chiral ligands
for copper between room temperature and 408C. This process
also involves the first stereoselective copper-to-boron trans-
metalation at a benzylic carbon atom.
After exploring a variety of catalytic reaction condi-
tions,[13] we found that styrene reacted slowly with pinacol-
borane (1.2 equiv) in the presence of the catalyst CuCl/
KOtBu/dppbz (5 mol%) in toluene at room temperature to
96% conversion in 48 h. The same reaction at 608C reached
completion within 7 h to give the desired isomer 2 with high
regioselectivity [Eq. (1)]. This reaction is the first highly
regioselective copper-catalyzed hydroboration of styrene.[14]
The observed high regioselectivity could be explained by the
During our studies on the development of new enantio-
selective catalytic processes based on the addition of copper
hydride[6] and copper boryl reagents,[7] we became interested
À
regioselective insertion of styrene into the Cu H bond; the
À
interaction of Cu H s molecular orbital and the p* orbital
À
in how we could make use of the Cu C bond that formed
(LUMO) of the alkene is possibly important in the insertion
step. The phenyl substituent makes the methylene carbon
atom more electrophilic by shifttng p-electron density from
the carbon atom (greater orbital contribution of the methyl-
ene carbon in the LUMO)[15] and directs the addition of HÀ
toward the methylene carbon atom. The copper catalyst is
presumed to allow this insertion mode to form the organo-
copper intermediate without exerting too much steric strain
around the benzylic carbon at which the copper is located.
The development of an enantioselective copper-catalyzed
hydroboration provided a new challenge, as both the addition
and transmetalation steps affect the formation of the stereo-
genic center.[16] We investigated the asymmetric hydrobora-
tion of styrene with a variety of chiral ligands; representative
results are shown in Table 1. In our first attempt with (R)-p-
Tol-binap, we were pleased to observe moderate enantiose-
lectivity (64% ee), although conversion was low (Table 1,
entry 1). The use of (R,S)-josiphos and the duphos ligand 4
upon the addition of the copper species to electron-deficient
alkenes, instead of destroying the bond by simple protonation
with an alcohol.[6,7] Since the in situ generation of copper
hydride in the presence of pinacolborane has been sug-
gested,[8] we were intrigued by the possibility of forming a new
hydroboration cycle with copper. Although no precedent
[*] D. Noh, H. Chea, J. Ju, 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
[**] This research was supported by a Korea Science and Engineering
Foundation (KOSEF) grant funded by the Korean government
(MEST; No. R01-2008-000-20332-0).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200902015.
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Chemie
Table 2: Copper-catalyzed enantioselective hydroboration of styrene
derivatives with ligand 5.
Entry
1
Substrate
T [8C]
t [h]
Yield [%][a]
91 (100)
ee [%][b]
RT
24
92
2
3
4
RT
RT
40
24
24
24
90 (100)
95 (100)
88 (100)
87
82
90
Table 1: Copper-catalyzed enantioselective hydroboration of styrene with
various ligands.[a]
Entry Ligand
t [h] Conv. [%] Yield [%][b] ee [%][c]
5
6
RT
40
48
24
82 (92)
90 (99)
93
90
1
2
3
4
5
6
(R)-p-Tol-binap
(R)-MeO-biphep
(R,S)-josiphos·EtOH
(S,S)-Me-duphos (4)
(S,S)-Et-duphos
24
24
5
5
24
3
32
34
100
100
26
–
–
89
83
–
64
70
70
83 (R)
8 (R)
92
1 f
7
40
24
90 (100)
91
(S,S,R,R)-tangphos (5)
100
86
[a] Reactions were performed under N2. Compound 2a was formed
exclusively in all cases. [b] Yield of the isolated product. [c] The ee value
was determined by HPLC analysis on a chiral phase of the corresponding
alcohol obtained by oxidation of 2a. Cy=cyclohexyl.
8
40
40
71 (79)
95
9[c]
10
1h
1i
RT
40
RT
RT
48
24
48
5
88 (98)
61 (70)
78 (89)
90 (100)
88
88
87
51
11[c]
12
13
RT
12
90 (100)
60
[a] Yield of the isolated product. Conversion is shown in parentheses.
[b] The ee value was determined by HPLC analysis on a chiral phase.
[c] Ligand 4 was used.
enhanced the reactivity and enantioselectivity of the hydro-
boration to provide 2a in good yield with improved enantio-
selectivity (Table 1, entries 3 and 4). Finally, the best results
were obtained with the P-chiral tangphos ligand 5, which
afforded 2a with 92% ee and greater than 99:1 regioselectiv-
ity (Table 1, entry 6).
Various styrene derivatives, including b-alkyl-substituted
styrenes, were subjected to the hydroboration catalyzed by
the copper(I)–tangphos complex with pinacolborane as the
hydroborating reagent (Table 2). In all cases, the regioselec-
tivity was excellent, and good to high enantioselectivities
were observed. The electronic nature of the substituent
affected conversion; vinyl arenes 1e–g with an electron-
donating substituent on the phenyl group reacted slowly at
room temperature (228C) and required a higher temperature
for reasonable conversion with a slight drop in enantioselec-
tivity (compare entries 5 and 6, Table 2). Whereas styrene
derivatives with a para substituent afforded products 2 with
similar levels of enantioselectivity to that observed with
styrene (92% ee; Table 1, entry 6), meta-chlorostyrene (1d)
was hydroborated with decreased enantioselectivity (82% ee;
Table 2, entry 3). Remarkably, ortho-methoxystyrene (1g)
reacted with the same high enantioselectivity observed for
para-methoxystyrene (Table 2, entry 7). The b-substituted
styrenes[17] 1h and 1i reacted slowly at 408C;[18] however,
good to high enantioselectivities were observed (Table 2,
entries 8 and 10). With these hindered substrates, the duphos
ligand 4 was more efficient in terms of conversion and
afforded the products with 88 and 87% ee, respectively
(Table 2, entries 9 and 11). Vinyl naphthalene derivatives
reacted with moderate enantioselectivity with the copper–
tangphos system (Table 2, entries 12 and 13); better enantio-
selectivity was observed with the (R,S)-josiphos ligand.[19]
In conclusion, we have developed an enantioselective
hydroboration reaction of styrene derivatives under the
catalysis of chiral copper(I)–bisphosphine complexes with
pinacolborane as the hydroborating reagent. This method
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Communications
Takeuchi, T. Shibata, Synlett 2008, 3231 – 3233; e) K. Endo, M.
Hirokami, T. Shibata, Organometallics 2008, 27, 5390 – 5393; see
also Ref. [5b].
shows that a stereoselective transmetalation of a benzylic
carbon–copper bond is possible with pinacolborane; further
studies are needed to elucidate details of the mechanism. The
desired stable a-borated product can be obtained with high
regio- and enantioselectivity under mild conditions. Further
studies on the mechanism of catalysis and the application of
the catalytic system to other classes of olefins are in progress.
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Angew. Chem. Int. Ed. 2006, 45, 2785 – 2787; b) D. Lee, Y. Yang,
J. Yun, Org. Lett. 2007, 9, 2749 – 2751.
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Experimental Section
À
[8] For the in situ generation of Cu H from CuOAc with
General procedure:
A mixture of CuCl (0.015 mmol, 1.5 mg),
pinacolborane in reductive aldol reactions, see: a) D. Zhao, K.
Oisaki, M. Kanai, M. Shibasaki, J. Am. Chem. Soc. 2006, 128,
14440 – 14441; b) Y. Du, L.-W. Xu, Y. Shimizu, K. Oisaki, M.
Kanai, M. Shibasaki, J. Am. Chem. Soc. 2008, 130, 16146 – 16147.
[9] L. Dang, Z. Lin, T. B. Marder, Organometallics 2008, 27, 4443 –
NaOtBu (0.03 mmol, 3.0 mg), and (S,S,R,R)-tangphos (5;
0.0165 mmol, 4.7 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, 89.8 mL) was added to the reaction mixture,
and stirring was continued for 10 min at room temperature. Styrene or
a styrene derivative (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 with further toluene (0.2 mL) and sealed. The
reaction was monitored by TLC and GC. Upon completion of the
reaction, the reaction mixture was filtered through a pad of Celite and
concentrated. The product was purified by chromatography on silica
gel.
4454.
2
À
[10] For the transmetalation of C(sp ) Cu with Sn, see: a) L. T.
Leung, K. S. Leung, P. Chiu, Org. Lett. 2005, 7, 5249 – 5252; for
the transmetalation of C(sp ) Cu with boron, see: b) B. H.
Lipshutz, Z. V. Boskovic, D. H. Aue, Angew. Chem. 2008, 120,
10337 – 10340; Angew. Chem. Int. Ed. 2008, 47, 10183 – 10186;
for transmetalation from a copper enolate to a boron enolate
with pinacolborane, see Ref. [8a,b].
2
À
ˇ
ˇ
ˇ
[11] For examples of isolated benzylic organocopper complexes, see:
a) V. W.-W. Yam, W.-K. Lee, K. K. Cheung, H.-K. Lee, W.-P.
Leung, J. Chem. Soc. Dalton Trans. 1996, 2889 – 2891; b) D. S.
Laitar, E. Y. Tsui, J. P. Sadighi, Organometallics 2006, 25, 2405 –
2408.
[12] For the thermal stability of alkyl copper(I) complexes coordi-
nated with tertiary phosphines and the decomposition of these
complexes through b-elimination, see: A. Miyashita, T. Yama-
moto, A. Yamamoto, Bull. Chem. Soc. Jpn. 1977, 50, 1109 – 1117;
see also Refs. [11b,14].
Received: April 15, 2009
Published online: July 9, 2009
Keywords: asymmetric catalysis · copper · hydroboration ·
.
pinacolborane · styrene
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À
[16] In most cases of the enantioselective catalysis of Cu H addition
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[17] We found that Z alkenes, such as (Z)-b-methylstyrene and
indene, were not reactive.
[18] We observed 63% conversion of 1h in 24 h at 408C.
[19] Compounds 2j and 2k were obtained with 66 and 78% ee,
respectively.
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