Synthesis of spiro diphosphines and their application in asymmetric hydrogenation of ketones

Article abstract of DOI:10.1021/ja029907i

Synthesis of chiral diphosphine ligands containing a spiro scaffold was described. The ruthenium complexes of these spiro ligands were found to have extremely high activities (S/C up to 100000) and enantioselectivities (ee up to 99.5%) in the asymmetric hydrogenation of aromatic, heteroaromatic, and α,β-unsaturated ketones. Copyright

Full text of DOI:10.1021/ja029907i

Published on Web 03/21/2003
Synthesis of Spiro Diphosphines and Their Application in Asymmetric
Hydrogenation of Ketones
Jian-Hua Xie, Li-Xin Wang, Yu Fu, Shuo-Fei Zhu, Bao-Min Fan, Hai-Feng Duan, and Qi-Lin Zhou*
State Key Laboratory and Institute of Elemento-organic Chemistry, Nankai UniVersity, Tianjin 300071, China
Received December 24, 2002; E-mail: qlzhou@public.tpt.tj.cn
Scheme 1
The design of new chiral ligands is the key in the development
of transition metal catalyzed asymmetric synthesis.1 Many chiral
diphosphine ligands have been prepared and applied in asymmetric
catalytic reactions with excellent enantioselectivities.1,2 Among the
chiral diphosphine ligands that have been reported, the atropisomeric
C2-symmetric phosphines with a biaryl scaffold initiated by Noyori
and co-workers3 with BINAP were found to have the widest
application in the transition metal catalyzed reactions.4 Planar chiral
diphosphines based on ferrocene or paracyclophane backbones have
also been applied to a number of reactions with a remarkable degree
of success.5 However, the spiro diphosphine compounds, another
type of axially chiral ligands, have not been synthesized until now.6
Recently, we designed chiral phosphoramidite ligands (SIPHOS)7
containing a 1,1′-spirobiindane backbone and demonstrated that
these ligands can be highly efficient for the Rh-catalyzed asym-
metric hydrogenation of functionalized olefins. Especially, in the
case of asymmetric hydrogenation of R-arylethenylamines, the spiro
monophosphoramidite ligands provided a significantly higher
level of enantiocontrol compared to that of the monophosphora-
midite ligands derived from BINOL.7b We now describe the
synthesis of spiro diphosphines 6 (SDP) containing 1,1′-spirobi-
indane as a new chiral scaffold and their application in the ruthen-
ium-catalyzed asymmetric hydrogenation of simple ketones with
high activity (S/C up to 100 000) and excellent enantioselectivity
(ee up to 99.5%).
hydrogenation of aromatic, heteroaromatic, and R,â-unsaturated
ketones.
The catalysts 7 (Figure 1) were prepared by reacting ligands 6
with [(C6H6)RuCl2]2 in DMF at 100 °C, followed by the treatment
of the resulting reddish brown solution with 1 equiv of DPEN14 at
room temperature. The complexes, thus obtained, were used directly
in the catalytic reactions. Initial tests with catalyst [((S)-SDP)Ru-
((R,R)-DPEN)Cl2] ((S,RR)-7a) in the asymmetric hydrogenation of
acetophenone in 2-propanol in the presence of t-BuOK (S/B ) 70)
at room temperature provided (S)-1-phenylethanol in quantitative
yield and 90% ee over 1.5 h at S/C ) 5000 (Table 1, entry 1). This
result is slightly better than that obtained with [((R)-BINAP)Ru-
((R,R)-DPEN)Cl2] (87% ee).13a A systematical investigation on the
effect of substituents in the ligands 6 indicated that the introduction
of 3,5-dimethyl groups to P-pheny rings, (S,RR)-7d, dramatically
increased the enantioselectivity to 99% ee (entry 4).18 The enan-
tioselectivity remained to be 98% ee even when the ratio of substrate
to catalyst (S/C) was increased to 100 000 (entry 5).
A variety of aromatic, heteroaromatic, and R,â-unsaturated
ketones can be hydrogenated by catalyst (S,RR)-7d with excellent
enantioselectivities. The results summarized in Table 1 are better
than or comparable to those achieved with Xyl-BINAP-Ru-
DAIPEN,13e Xyl-PhanePhos-Ru-DPEN,15 and Xyl-P-Phos-Ru-
DPEN16 systems. It deserves commendation that the hydrogenation
of acetylferrocene with (S,RR)-7d produced (S)-1-ferrocenylethanol
in 98% ee at S/C ) 5000.19 The enantiomerically enriched 1-ferro-
cenylethanol is a crucial starting material in the synthesis of many
chiral ferrocene compounds such as ferrocenylethylamines and
ferrocenylphosphines.20 Our study provides a practical method to
the synthesis of ferrocenylethanol and related compounds.
In conclusion, we have developed novel chiral diphosphine
ligands with spiro biindane as a new chiral scaffold, which are
highly effective for the asymmetric hydrogenation of ketones. The
extremely high activity and enantioselectivity of their ruthenium
Chiral spiro diphosphines (S)-6 were easily prepared from
enantiomerically pure (S)-1,1-spirobiindane-7,7-diol (1)8 (Scheme
1). The diol (S)-1 was converted into triflate (S)-2 in quantitative
yield. Monophosphinylation of triflate (S)-2 with diarylphosphine
oxide in the presence of Pd catalyst, followed by reduction with
trichlorosilane, generated (S)-7-(diarylphosphino)-7′-trifluoromethane-
sulfonyl)oxy-1,1′-spirobiindanes ((S)-4).9 Phosphinylation and re-
duction of compounds (S)-4 provided desired diphosphines (S)-6
in high yields. Using the same procedure, the diphosphines (R)-6
were also synthesized from (R)-1,1-spirobiindane-7,7-diol.10
The catalytic asymmetric hydrogenation of prochiral ketones
appears to be the most facile route to produce enantiomerically
enriched secondary alcohols. A number of efficient catalysts have
been developed for the asymmetric hydrogenation of functionalized
ketones.4j,11 In contrast, only a few catalysts have been reported in
the asymmetric hydrogenation of simple ketones.12 Recently, a
significant breakthrough was achieved by Noyori and co-workers
by using diphosphine-ruthenium-diamine complexes as catalysts
in the hydrogenation of ketones.13 The most effective catalyst was
trans-[((S)-Xyl-BINAP)Ru((S)-DAIPEN)Cl2]14 which has extremely
high activity and enantioselectivity in the hydrogenation of a wide
range of ketones.13e,f To date, only two other chiral diphosphine
ligands, PhanePhos15 and P-Phos,16 have been reported to approach
the utility of Noyori’s Xyl-BINAP in this important reaction.17 We
are delighted to find that the ruthenium complexes of spiro
diphosphine ligands 6 serve as excellent catalysts for the asymmetric
9
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J. AM. CHEM. SOC. 2003, 125, 4404-4405
10.1021/ja029907i CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
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Figure 1.
Table 1. Asymmetric Hydrogenation of Ketonesa
ketone
c
entry cat.
Ar
R
time (h) convnb (%)
ee (%)
1
2
3
7a C6H5
7b C6H5
7c C6H5
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
C2H5
PhCH2
CH3
CH3
CH3
CH3
1.5
3
100
99
90 (S)
89 (S)
92 (S)
99 (S)
98 (S)
98 (S)
99.2 (S)
99.2 (S)
99 (S)
99.2 (S)
98 (S)
99 (S)
99 (S)
99.5 (S)
98 (S)
99.2 (S)
98 (S)
98 (S)
98 (S)
96 (S)
2.5
1.5
72
100
100
98
4
7d C6H5
7d C6H5
5d
6
7d o-ClC6H4
7d o-BrC6H4
7d m-BrC6H4
7d m-CF3C6H4
7d p-CH3C6H4
7d p-OCH3C6H4
7d p-ClC6H4
7d p-BrC6H4
7d C6H5
3.5
6.5
3
99
100
99
7
8
9
10
11
12
13
14
15
16
2
99
1.5
4.5
1.5
3
100
100
100
100
99
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(10) For experimental details, see the Supporting Information.
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3.5
7d C6H5
7d 2-naphthyl
46
100
98
100
99
98
100
4
5
5
5
3
17e 7d ferrocenyl
18
19
20f
7d 2-furyl
7d 2-thienyl
7d trans-PhCHdCH CH3
a Reactions were conducted at 20-25 °C under 50 atm of H2 pressure
using a 2.0-2.5 M solution in 2-propanol containing (S,RR)-7d (S/C )
5000) and t-BuOK (S/B ) 70). b Determined by GC or 1H NMR. c The ee
were determined by chiral GC or HPLC. The absolute configuration was
determined by comparison of the sign of optical rotation or retention time
with 1iterature data. d S/C ) 100 000, at 40 °C. e Using a 1.0 M solution
in 2-propanol, S/B ) 50. f S/B ) 50.
complexes for the hydrogenation of a variety of prochiral ketones
indicated a good potential for wide application of these spiro
diphosphine ligands. Studies of these spiro ligands in other transition
metal catalyzed asymmetric reactions are in progress.
(14) Xyl-BINAP ) 2.2′-bis(di-3,5-xylylphosphino)-1,1′-binaphthyl. Tol-BINAP
) 2,2′-bis(di-4-tolylphosphino)-1,1′-binaphthyl. DAIPEN ) 1,1-dianisyl-
2-isopropyl-1,2-ethylenediamine. DPEN ) 1,2-diphenylethylenediamine.
(15) PhanePhos
) 4,12-bis(diphenylphospino)-[2,2]paracyclophane. Xyl-
PhanePhos ) 4,12-bis(di-3,5-xylylphospino)-[2,2]paracyclophane. See:
Burk, M. J.; Hems, W.; Herzberg, D.; Malan, C.; Zanotti-Gerosa, A. Org.
Lett. 2000, 2, 4173.
Acknowledgment. We thank the National Natural Science
Foundation of China, the Major Basic Research Development
Program (Grant G2000077506), and the Ministry of Education of
China for financial support.
(16) P-Phos ) 2,2′,6,6′-tetramethoxy-4,4′-bis(diphenylphosphino)-3,3′-bipy-
ridine. See: Wu, J.; Chen, H.; Kwok, W.-H.; Guo, R.-W.; Zhou, Z.-Y.;
Yeung, C.-H.; Chan, A. S. C. J. Org. Chem. 2002, 67, 7908.
(17) (2R,2′R)-Bis(diphenylphosphino)-(1R,1′R)-dicyclopentane (BICP) was also
tested in this reaction, providing the enantioselctivities which are lower
by 10-20% ee than those obtained with Noyori’s BINAP-Ru-diamine
system, see: Cao, P.; Zhang, X. J. Org. Chem. 1999, 64, 2127.
(18) With the catalyst (S,SS)-7d, which represents a mismatch in chirality
between SDP and DPEN, (S)-1-phenylethanol was produced in 28% ee.
(19) [((S)-Tol-BINAP)Ru((S)-DAIPEN)Cl2] (87% ee) and [((S)-Xyl-Phane-
Phos)Ru((R,R)-DPEN)Cl2] (92% ee) were also used in the hydrogenation
of acetylferrocene, see refs 13f and 15.
Supporting Information Available: Preparations and properties
of compounds 2-6 and 7, procedures for asymmetric hydrogenation
of ketones, GC behavior of chiral alcohols (PDF). This material is
available free of charge via the Internet at http://pubs.acs.org.
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