Enantiopure 1,2-Bis(tert-butylmethylphosphino)benzene as a highly efficient ligand in rhodium-catalyzed asymmetric hydrogenation

Article abstract of DOI:10.1021/ol101936w

Figure Presented. An electron-rich P-stereogenic bisphosphine ligand named "BenzP" was conveniently prepared from o-dibromobenzene and enantiopure tert-butylmethylphosphine-borane. Its rhodium complex exhibited excellent enantioselectivities of up to 99.9% and high catalytic activity of up to 10000 h^-1 TOF in asymmetric hydrogenations of various functionalized alkenes.

Full text of DOI:10.1021/ol101936w

ORGANIC
LETTERS
2
010
Vol. 12, No. 19
400-4403
Enantiopure
,2-Bis(tert-butylmethylphosphino)benzene
4
1
as a Highly Efficient Ligand in
Rhodium-Catalyzed Asymmetric
Hydrogenation
†
,‡
†
Ken Tamura, Masashi Sugiya, Kazuhiro Yoshida, Akira Yanagisawa, and
‡
‡
,†,‡
Tsuneo Imamoto*
Organic R&D Department, Nippon Chemical Industrial Co., Ltd., Kameido, Koto-ku,
Tokyo 136-8515, Japan, and Department of Chemistry, Graduate School of Science,
Chiba UniVersity, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
imamoto@faculty.chiba-u.jp
Received August 17, 2010
ABSTRACT
An electron-rich P-stereogenic bisphosphine ligand named “BenzP*” was conveniently prepared from o-dibromobenzene and enantiopure
tert-butylmethylphosphine-borane. Its rhodium complex exhibited excellent enantioselectivities of up to 99.9% and high catalytic activity of up
to 10 000 h- TOF in asymmetric hydrogenations of various functionalized alkenes.
1
Chiral phosphine ligands have played an important role in
transition metal-catalyzed asymmetric reactions, and numer-
ous ligands have been designed and synthesized over the
Previously, we synthesized P-stereogenic phosphine ligands
using phosphine-boranes as the key intermediate. Among the
ligands, BisP*, MiniPHOS, QuinoxP*, and AlkynylP* were
found to exhibit very high to almost perfect enantioselec-
tivities in some representative transition metal-catalyzed
1
past four decades. Many of the reported chiral phosphine
ligands exhibit excellent enantioinduction abilities in various
asymmetric transformations. However, the ligands that are
practically useful for the production of chiral compounds
4
asymmetric reactions. One of the features of the ligands is
that they possess a bulky substituent, such as a tert-butyl
group, and a small group, such as a methyl group on the
stereogenic phosphorus atoms. We envisioned that enan-
tiopure 1,2-bis(tert-butylmethylphosphino)benzene (named
BenzP*) (1) would exhibit excellent enantioselectivities and
2
are limited to several outstanding ligands and hence, the
exploration of more efficient and widely applicable chiral
3
phosphine ligands is still a vital research topic.
†
Nippon Chemical Industrial Co., Ltd.
Chiba University.
‡
(2) (a) Zhang, W.; Tongxiang, C.; Zhang, X. Acc. Chem. Res. 2007,
40, 1278–1290. (b) Shimizu, H.; Nagasaki, I.; Matsumura, K.; Sayo, N.;
Saito, T. Acc. Chem. Res. 2007, 40, 1385–1393. (c) de Vries, J. G.; Elsevier,
C. J., Eds. The Handbook of Homogeneous Hydrogenation; Wiley-VCH:
Weinheim, Geramny, 2007; Vol. 1s3. (d) Blaser, H.-U.; Schmidt, E.
Asymmetric Catalysis on Industrial Scale; Wiley-VCH: Weinheim, Ger-
many, 2004. Genet, J.-P. Acc. Chem. Res. 2003, 36, 908–918.
(
1) For representative reviews, see: (a) B o¨ rner, A., Ed. Phosphorus
Ligands in Asymmetric Catalysis; Wiley-VCH; Weinheim, Germany,
2
008;Vols. 1s3. (b) Guiry, P. J.; Saunders, C. P. AdV. Synth. Catal. 2004,
46, 497. (c) Tang, W.; Zhang, X. Chem. ReV. 2003, 103, 3029–3069. (d)
3
Ohkuma, T.; Kitamura, M.; Noyori, R. Catalytic Asymmetric Synthesis;
Ojima, I., Ed.; Wiley-VCH: Weinheim, Germany, 2000, Chapter 1.
10.1021/ol101936w  2010 American Chemical Society
Published on Web 09/10/2010

high catalytic activities because it has similar structural motif
to t-Bu-BisP* and is expected to form a more rigid five-
membered chelate ring owing to the o-phenylene backbone,
5
as in the case of DuPHOS. This ligand was previously
6
2
synthesized by using a BH -bridged phosphonium salt.
However, the method required considerable skill for the
separation of the enantiomerically enriched intermediates and
the synthetic difficulty hampered even the evaluation of its
enantioinduction ability. Herein, we report an efficient
method for the preparation of this ligand and its high utility
in rhodium-catalyzed asymmetric hydrogenation.
A new synthetic route to chiral diphosphine ligand 1 is
depicted in Scheme 1. The reaction of the lithium derivative
Scheme 1
.
Preparation of Chiral Phosphine Ligand 1 and Its
Rhodium Complex 4
-
Figure 1. ORTEP drawing of complex 4. Hydrogen atoms, SbF
6
anion, and ethyl acetate molecule are omitted for clarity.
(
S,S)-BenzP* can be also prepared by using (R)-tert-
butylmethylphosphine-borane, which is produced in a large
scale from (S ,S)-tert-butyl(methyl)(1-phenylethylcarbam-
oyl)phosphine-borane.
The obtained ligand 1 was converted into rhodium
complex 4 by the reaction with [Rh(cod) ]SbF . Recrystal-
P
1
2
2
6
lization of the complex from ethyl acetate afforded cubic
crystals suitable for single-crystal X-ray analysis. The crystal
structure shown in Figure 1 clearly indicates that the bulky
tert-butyl groups effectively shield two diagonal quadrants
and the methyl groups are positioned in the other quadrants.
This imposed asymmetric environment would lead to excel-
lent enantioselectivity in asymmetric catalysis.
The enantioinduction ability and the catalytic efficiency of
the rhodium complex were examined in the hydrogenation of
various functionalized alkenes. The results are summarized in
Table 1. A typical experiment with methyl 2-acetamidoacrylate
(
3) For recent representative examples, see: (a) Deng, J.; Duan, Z.-C.;
Huang, J.-D.; Hu, X.-P.; Wang, D.-Y.; Yu, S.-B.; Xu, X.-F.; Zheng, Z.
Org. Lett. 2007, 9, 4825–4828. (b) Xie, J.-H.; Zhou, Q.-L. Acc. Chem. Res.
2
2
2
008, 41, 581–593. (c) Stephan, M.; Sterk, D.; Mohar, B. AdV. Synth. Catal.
009, 351, 2779–2786. (d) Schrems, M. G.; Pfaltz, A. Chem. Commun.
009, 6210–6212. (e) Gschwend, B.; Pugin, B.; Bertogg, A.; Pfaltz, A.
Chem.sEur. J. 2009, 15, 12993–13007. (f) Korenaga, T.; Osaki, K.;
Maenishi, R.; Sakai, T. Org. Lett. 2009, 11, 2325–2328. (g) Oki, H.; Oura,
I.; Nakamura, T.; Ogata, K.; Fukuzawa, S. Tetrahedron: Asymmetry 2009,
of (S)-tert-butylmethylphosphine-borane (2) with o-dibro-
mobenzene afforded (R)-(2-bromophenyl)(tert-butyl)meth-
ylphosphine-borane (3) as a crystalline compound with
complete retention of configuration at the phosphorus atom
2
0, 2185–2191. (h) Tang, W.; Qu, B.; Capacci, A. G.; Rodriguez, S.; Wei,
X.; Haddad, N.; Narayanan, B.; Ma, S.; Grinberg, N.; Yee, N. K.;
Krishnamurthy, D.; Senanayake, C. H. Org. Lett. 2010, 12, 176–179. (i)
Fandrick, D. R.; Fandrick, K. R.; Reeves, J. T.; Tan, Z.; Tang, W.; Capacci,
A. G.; Rodriguez, S.; Song, J. J.; Lee, H.; Yee, N. K.; Senanayake, C. H.
J. Am. Chem. Soc. 2010, 132, 7600–7601. (j) Tang, W.; Capacci, A. G.;
White, A.; Ma, S.; Rodriguez, S.; Qu, B.; Savoie, J.; Patel, N. D.; Wei, X.;
Haddad, N.; Grinberg, N.; Yee, N. K.; Krishnamurthy, D.; Senanayake,
C. H. Org. Lett. 2010, 12, 1104–1107. (k) Zhang, X.; Cao, B.; Yan, Y.;
Yu, S.; Ji, B.; Zhang, X. Chem.sEur. J. 2010, 16, 871–877. (l) Zupancic,
B.; Mohar, B.; Stephan, M. Org. Lett. 2010, 12, 1296–1299. (m) Zupancic,
B.; Mohar, B.; Stephan, M. Org. Lett. 2010, 12, 3022–3025. (n) Xie, J.-B.;
Xie, J.-H.; Liu, X.-Y.; Kong, W.-L.; Li, S.; Zhou, Q.-L. J. Am. Chem. Soc.
7
-9
in 65% yield.
This compound was reacted successively
with 1,4-diazabicyclo[2.2.2]octane (DABCO), sec-butyl-
lithium, tert-butyldichlorophosphine, and methylmagnesium
1
1
bromide to give desired ligand 1 in 38% yield. It should
be noted that these four reaction steps were carried out in
one pot without isolation of the intermediates and ligand 1
was readily separated as a crystalline solid without chro-
matographic separation from other byproduct, such as a
meso-diphosphine isomer. The counter enantiomer ligand
2
010, 132, 4538–4539. (o) Shi, S.-L.; Xu, L.-W.; Oisaki, K.; Kanai, M.;
Shibasaki, M. J. Am. Chem. Soc. 2010, 132, 6638–6639. (p) Zhang, X.;
Huang, K.; Hou, G.; Cao, B.; Zhang, X. Angew. Chem., Int. Ed. 2010, 49,
6421–6424.
Org. Lett., Vol. 12, No. 19, 2010
4401

Table 1. Asymmetric Hydrogenation of Prochiral Substrates Catalyzed by Rhodium Complex 4
a
All reactions were carried out in methanol at room temperature.
(
(
0
5a) shows that the hydrogenation with a 1000 substrate/catalyst
s/c) ratio under 3 atm hydrogen pressure was completed within
.3 h to give the product with 99.9% ee (entry 1). The reaction
methods for the production of chiral ꢀ-amino acids, and
considerable effort has been made in this area. In most
1
3
with a 10 000 s/c ratio under 5 atm hydrogen pressure was also
completed within a short time (1 h) to give the product without
any decrease of the enantioselectivity (entry 2). Other R-dehy-
droamino acid derivatives (5b-g) were also subjected to
hydrogenation under similar reaction conditions. All reactions
except that of 2-pyrrolyl derivative (5g) afforded excellent ee
values of the corresponding products (entries 3-9). The high
enantioinduction ability of this catalyst was proved also in the
hydrogenation of 1-acetamido-1-(p-nitrophenyl)ethene (6) and
dimethyl R-benzoyloxyethenephosphonate (7) (entries 10 and
(
5) (a) Burk, M. J.; Feaster, J. E.; Nugent, W. A.; Harlow, R. L. J. Am.
Chem. Soc. 1993, 115, 10125–10138. (b) Burk, M. J. In Handbook of Chiral
Chemicals; Ager, D. J., Ed.; Marcel Dekker: New York, 1999; pp 339-359.
c) Burk, M. J. Acc. Chem. Res. 2000, 33, 363–372. (d) Burk, M. J. In
Handbook of Chiral Chemicals, 2nd ed.; CRC Press: Boca Raton, FL, 2006;
pp 249-268 and references cited therein.
(
Imamoto, T.; Yamaguchi, K. Org. Lett. 2006, 8, 6103–6106.
(7) Bayardon, J.; Laureano, H.; Chaux, F.; Leroux, F.; Henry, J. C.;
Jug e´ , S. 2010, patent pending. Professor Sylvain Jug e´ of the University of
Bourgogne informed T. Imamoto before their publication that the reaction
of o-dibromobenzene with (o-methoxyphenyl)phenylphosphine-borane in
the presence of n-butyllithium afforded (o-bromophenyl)(o-methoxyphe-
nyl)phenylphosphine-borane. We deeply thank Professor Jug e´ for his
personal communication.
(8) It is noted that the use of o-dichlorobenzene in place of o-
dibromobenzene provided no trace of the desired compound but the borane
adduct of (R,R)-1,3-bis(tert-butylmethylphosphino)benzene as the major
product.
(
6) Yamamoto, Y.; Koizumi, T.; Katagiri, K.; Furuya, Y.; Danjo, H.;
1
1).
The asymmetric hydrogenation of ꢀ-dehydroamino acid
derivatives and related substrates is one of the most efficient
(
4) (a) Imamoto, T.; Watanabe, J.; Wada, Y.; Masuda, H.; Yamada, H.;
(9) To determine the enantiomeric excess of compound 3 by HPLC
analysis using a chiral column, (()-2-(boranato-tert-butylmethylphosphi-
no)bromobenzene was prepared by the successive reactions of o-dibro-
Tsuruta, H.; Matsukawa, S.; Yamaguchi, K. J. Am. Chem. Soc. 1998, 120,
1
2
635–1636. (b) Yamanoi, Y.; Imamoto, T. J. Org. Chem. 1999, 64, 2988–
10
989. (c) Gridnev, I. D.; Yamanoi, Y.; Higashi, N.; Tsuruta, H.; Yasutake,
mobenzene with i-PrMgCl·LiCl, tert-butyldichlrophosphine, methylmag-
M.; Imamoto, T. AdV. Synth. Catal. 2001, 343, 118–136. (d) Imamoto, T.;
Sugita, K.; Yoshida, K. J. Am. Chem. Soc. 2005, 127, 11934–11935. (e)
Imamoto, T.; Saitoh, Y.; Koide, A.; Ogura, T.; Yoshida, K. Angew. Chem.,
Int. Ed. 2007, 46, 8636–8639.
nesium bromide, and BH
tion.
3
·THF. See details in the Supporting Informa-
(10) Krasovskiy, A.; Knochel, P. Angew. Chem., Int. Ed 2004, 43, 3333–
3336.
4402
Org. Lett., Vol. 12, No. 19, 2010

cases, the hydrogenation of (E)-derivatives gives rise to high
enantioselectivity compared with that of (Z)-derivatives; the
reactions of the latter require high hydrogen pressure and/or
a long reaction time, and the enantioselectivity is consider-
derivatives (9-12) (entries 16-20). In regard to enantiose-
lectivity and turnover frequency (TOF), these results are
3
h,15
comparable to the highest values reported so far.
In conclusion, we have developed a convenient method
for the preparation of enantiopure 1,2-bis(tert-butylmeth-
ylphosphino)benzene (BenzP*) from tert-butylmethylphos-
phine-borane and o-dibromobenzene. Its rhodium complex
exhibited excellent enantioselectivities of up to 99.9% and
3
l,14
ably low.
We employed the rhodium catalyst with the
BenzP* ligand in the hydrogenation of several ꢀ-dehy-
droamino acid derivatives, and the results are added in Table
1. The hydrogenation of methyl (E)-3-acetamido-2-butenoate
-
1
(
(E)-8) in the presence of 0.1 mol % catalyst under 3 atm of
activities of up to 10 000 h TOF in the asymmetric
hydrogenation of various functionalized alkenes, including
ꢀ-dehydroamino acid esters. In addition to the catalytic
efficiency, the handling ease in air indicates the versatile
utility of the ligand in a wide variety of transition metal-
catalyzed asymmetric reactions.
hydrogen pressure was completed within 0.8 h to give a
product with 99.6% ee (entry 12). We are pleased to find
that the (Z)-isomer ((Z)-8) reacted under the same conditions
to afford a product with a slightly lower ee (97.6%) (entry
1
3). A 1:1 mixture of (E)-8 and (Z)-8 was also subjected to
hydrogenation and excellent enantioselectivity (98.7%) was
achieved (entry 14). The reaction with a 5000 s/c ratio
furnished a product with 97.9% ee (entry 15). Similarly high
to excellent enantioselectivities were observed in the hydro-
genation of propyl, isopropyl, phenyl, and p-methoxyphenyl
Further study on the preparation of related ligands and
their application to the production of useful enantiopure
compounds is in progress in our laboratory and the results
will be published in due course.
Acknowledgment. The authors thank Professor Sylvain
Jug e´ , University of Bourgogne, and Professor Hiroshi Danjo,
Konan University, for valuable discussion.
(
11) While the chiral ligand BenzP* is an electron-rich diphosphine, its
crystalline solid was robust in air; it was not readily oxidized on exposure
to air for one week.
(
12) Imamoto, T.; Tamura, K.; Ogura, T.; Ikematsu, Y.; Mayama, D.;
Sugiya, M. Tetrahedron: Asymmetry 2010, 21, 1522–1528.
13) (a) Juaristi, E.; Soloshonok, V. A. EnantioselectiVe Synthesis of
-Amino Acids, 2nd ed.; Wiley Interscience: Hoboken, NJ, 2005. (b) Guo.,
Supporting Information Available: Detailed descriptions
of experimental procedures and X-ray crystallographic data
(CIF). This material is available free of charge via the Internet
at http://pubs.acs.org.
(
ꢀ
Y.; Shao, G.; Li, L.; Wu, W.; Li, R.; Li, J.; Song, J.; Qiu, L.; Prashad, M.;
Kwong, F. Y. AdV. Synth. Catal 2010, 352, 1539–1553. (c) Weiner, B.;
Szymanski, W.; Janssen, D. B.; Minnaard, A. J.; Feringa, B. L. Chem. Soc.
ReV 2010, 39, 1656–1691, and references cited therein.
OL101936W
(
14) (a) Zhu, G.; Chen, Z.; Zhang, X. J. Org. Chem. 1999, 64, 6907–
6
910. (b) Yasutake, M.; Gridnev, I. D.; Higashi, N.; Imamoto, T. Org. Lett.
2
001, 3, 1701–1704. (c) Holz, J.; Monsees, A.; Jiao, H.; You, J.; Komarov,
(15) (a) Tang, W.; Zhang, X. Org. Lett. 2002, 4, 4159–4161. (b) Lee,
S.-G.; Zhang, Y. J. Org. Lett. 2002, 4, 2429–2431. (c) Tang, W.; Wang,
W.; Chi, Y.; Zhang, X. Angew. Chem., Int. Ed. 2003, 42, 3509–3511.
I. V.; Fischer, C.; Drauz, K.; B o¨ rner, A. J. Org. Chem. 2003, 68, 1701–
1
707
.
Org. Lett., Vol. 12, No. 19, 2010
4403