Synthesis of novel BINOL-derived chiral bisphosphorus ligands and their

application in catalytic asymmetric hydrogenation

Yong-Gui Zhou and Xumu Zhang*
Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA.
E-mail: [email protected]
Received (in Cambridge, UK) 19th February 2002, Accepted 1st April 2002
First published as an Advance Article on the web 19th April 2002
Some novel ortho-substituted BINOL-derived bisphos-
phorus ligands (o-BINAPO and o-NAPHOS) were synthesis
from readily available (S)-BINOL; these ligands showed
excellent enantioselectivities (up to 99% ee) in Rh(I)-
catalyzed asymmetric hydrogenation of functionalized ole-
fins.
The design and synthesis of chiral ligands has played an
important role in the development of transition metal-catalysed
asymmetric reactions.
1
In general, metal-complexes of the
effective chiral phosphine ligands are 5, 6 or 7-membered rings.
While a big bite angle (PMP) has a special effect in
asymmetric catalysis.
2
It is difficult to develop effective
catalysts with a 9-membered chelating ring. Biaryl atropiso-
meric ligands have been explored as effective scaffolds for
many asymmetric transformations.
3
Among them, two most
frequently used chiral chelating ligands (Scheme 1) are BINAP
4
and BINOL,
5
which form 7-membered with metals. However,
their simple analogues (Scheme 1), NAPHOS
6
and BINAPO,
7
which form 9-membered ring with metals, are not effective
ligands for asymmetric hydrogenation due to their conforma-
tional flexibility. We believe that there are two possible reasons:
(1) the additional methylene groups in NAPHOS and oxygen
atoms in BINAPO increase the distance between the chiral
binaphthyl moiety and PPh
2
groups and therefore decrease the
influence of the binaphthyl functionality on the orientation of
the phenyl ring of PPh
2
groups. (2) The presence of the COP
moiety in BINAPO and the CCH
2
P moiety in NAPHOS
substantially increases the flexibility of the metal-ligand
complexes and consequently decreases the enantioselectivity.
By the conformational analysis of BINAPO and NAPHOS
metal complexes, we propose that if a group (especially an aryl)
can be introduced to 3,3A-positions of the binaphthyl scaffold,
these groups might improve the conformational rigidity by
controlling the orientation of the phenyl ring adjacent to
phosphine atoms of their metal complexes.
8
Herein we report
the synthesis of these novel chiral bisphosphorus ligands and
their application in Rh(I)-catalyzed asymmetric hydrogenation
of functionalized olefins.
Our synthetic routes are shown in Scheme 2, three 3,3A(or-
tho)-disubstituted BINOL derivatives 1 were synthesized from
commercially available (S)-BINOL according to the known
literature methods.
9
Chiral bisphosphinite ligands L1, L2, L3
and L4 (abbreviated as o-BINAPO) were prepared through
reaction of chlorodiarylphosphine with the corresponding chiral
diols in high yields. C
2
-symmetry chiral bisphosphine ligand L5
(abbreviated as o-NAPHOS) was synthesized from the known
compound (S)-3,3A-diphenyl-2,2-dibromomethyl-1,1A-bina-
phthyl 2
10
in two steps (Scheme 2).
In our previous work on synthesis of a ligand called
binaphane,
11
we found that less reactive 2,2A-dichloromethyl-
1,1A-binaphthyl is more desirable for making chiral phosphines
than 2,2A-dibromomethyl-1,1A-binaphthyl. We tried the known
compound 2
10
for the synthesis of L5, no desired product was
obtained. A simple anion exchange of compound 2 with lithium
chloride in DMF afforded (S)-3,3A-diphenyl-2,2-dichoromethyl-
1,1A-binaphthyl 3 in 95% yield. Nucleophilic attack of com-
pound 3 with lithium diphenylphosphinide in THF produced the
desired bisphosphine ligands L5. The product was further
purified by a short silica gel column eluted with hexaneDCM
EtOAc (80+20+1) in a glove box to give a white solid in 33%
yield.
With these new ligands in hand, catalytic asymmetric
hydrogenation of a-dehydroamino acid derivatives 4 and
enamides 5 have been examined. Methyl (Z)-2-acetamidoacry-
late 4a and N-acetyl-1-phenylethenamide 5a were used as
standard substrates. The optimized results were shown in Table
Scheme 1 Scheme 2
Thi s j our nal i s The Royal Soci et y of Chemi st r y 2002 1124 CHEM. COMMUN. , 2002, 11241125
D
O
I
:

1
0
.
1
0
3
9
/
b
2
0
1
9
7
6
k
1. We found that 3,3-disubstituted bisphosphinite ligands o-
BINAPO are better than nonsubstituted BINAPO. For substrate
4a, ee increased from 73.2 to 99.9%. For substrate 5a, ee
changed from 28.3 to 94.3%. A 3,3-disubtituted bisphosphine
ligand L5 (o-NAPHOS) is also more effective for asymmetric
hydrogenation than the corresponding NAPHOS ligand, en-
antioselectivity increased from 54.0 to 98.7% for hydrogenation
of 4a by changing ligand NAPHOS to L5. These results
supported our hypothesis of the importance of conformational
rigidity in asymmetric catalysis. With o-BINAPO ligands, our
hydrogenation results are comparable with those obtained with
other chiral phosphorus-rhodium catalysts. For example, the ee
values (%) of 6a reported in the literature
12
are as follows:
DIPAMP, 94; DIOP, 73; ChiraPhos, 91; BPPM, 98.5; BINAP,
67; BICP, 97.5; Et-DuPhos, 99.4; SpirOP, 99.9.
A variety of a-dehydroamino acid derivatives 4 were
employed as substrates for the Rh-catalyzed hydrogenation
reaction using L5 as ligand, the result was shown in Table 2
(entries 16). High enantiomeric excesses have been achieved.
There is no major electronic effect on the substitution pattern of
4. However, for an o-BINAPO ligand L2, the ees were
substrate-dependent (entries 711).
To expand the utility of o-BINAPO ligands system, we have
examined Rh(I)-catalyzed enantioselective hydrogenation of
simple enamides 5 using L2 as ligand (entries 1215). High
enantioselectivities (94.196.3% ee) have also been achieved.
In conclusion, we have developed some novel, highly
effective chiral bisphosphorus ligands based on a chiral
binaphthyl backbone for catalytic asymmetric hydrogenation of
enamides and a-dehydroamino acids. The 9-membered ring
chelation with transition metals is still effective for asymmetric
catalysis, and these ligands are likely to be effective for other
catalytic reactions due to the big PMP bite angle. Further
studies of other transition metal complexes of these ligands and
their applications are in progress.
This work was supported by grants from National Institutes
of Health. We acknowledge a generous loan of precious metals
from Johnson Matthey Inc. XZ thanks Supelco for a gift of
chiral GC column.
Notes and references
1 For reviews: (a) Comprehensive Asymmetric Catalysis, ed. E. N.
Jacobsen, A. Pfaltz and H. Yamamoto, Springer, New York, 1999; (b)
Catalytic Asymmetric Synthesis, ed. I. Ojima, VCH, New York, 1993,
and 1999; (c) R. Noyori, Asymmetric Catalysis in Organic Synthesis,
John Wiley & Sons, New York, 1994; (d) W. A. Nugent, T. V.
Rajanbabu and M. J. Burk, Science, 1993, 259, 479; (e) R. A. Sheldon,
Chirotechnology, Marcel Dekker, New York, 1993.
2 P. W. N. M. van Leeuwen, P. C. J. Kamar, J. N. H. Reek and P. Dierkes,
Chem. Rev., 2000, 100, 2741.
3 (a) J. K. Whitesell, Chem. Rev., 1989, 89, 1581; (b) C. Rosini, L.
Franzini, A. Raffaelli and P. Salvadori, Synthesis, 1992, 503; (c) L. Pu,
Chem. Rev., 1998, 98, 2405.
4 (a) R. Noyori and H. Takaya, Acc. Chem. Res., 1990, 23, 345; (b) T.
Ohkuma, H. Ooka, S. Hashguchi, T. Ikariya and R. Noyori, J. Am.
Chem. Soc., 1995, 117, 2675; (c) T. Ohkuma, M. Koizumi, H. Doucet,
T. Pham, M. Kozawa, K. Murata, E. Katayama, T. Yokozawa, T. Ikariya
and R. Noyori, J. Am. Chem. Soc., 1998, 120, 13529.
5 (a) A. L. Costa, M. G. Piazza, E. Tagaliavini, C. Trombini and A.
Umani-Ronchi, J. Am. Chem. Soc., 1993, 115, 7001; (b) K. Mikami and
S. Matsukawa, Nature, 1997, 385, 613.
6 K. Tamao, H. Yamamoto, H. Matsumoto, N. Miyaki, T. Hayashi and M.
Kumada, Tetrahedron Lett., 1977, 1389.
7 R. Grubbs and R. A. DeVries, Tetrahedron Lett., 1977, 1879.
8 Previous successful examples by using this strategy see: (a) K. Ishihara
and H. Yamamoto, J. Am. Chem. Soc., 1994, 116, 1561; (b) D. P. Heller,
D. R. Goldberg and W. D. Wulff, J. Am. Chem. Soc., 1997, 119, 10551
and references cited therein.
9 (a) P. J. Cox, W. Wang and V. Snieckus, Tetrahedron Lett., 1992, 33,
2253; (b) K. B. Simonsen, K. V. Gothelf and K. A. Jorgenson, J. Org.
Chem., 1998, 63, 7536; (c) W. S. Huang, Q. S. Hu and L. Pu, J. Org.
Chem., 1999, 64, 7940.
10 T. Ooi, M. Kameda and K. Maruoka, J. Am. Chem. Soc., 1999, 121,
6519.
11 D. Xiao, Z. Zhang and X. Zhang, Org.Lett., 1999, 1, 1679.
12 (a) K. E. Koenig, in Asymmetric Synthesis, ed. J. D. Morrison,
Academic Press, New York, 1985, Vol. 5, p. 71; (b) G. Zhu, P. Cao, Q.
Jiang and X. Zhang, J. Am. Chem. Soc., 1997, 119, 1799; (c) M. J. Burk,
J. E. Feaster, W. A. Nugent and R. L. Harlow, J. Am. Chem. Soc., 1993,
115, 10125; (d) A. S. C. Chan, W. Hu, C. C. Pai, C. P. Lau, Y. Jiang, A.
Mi, M. Yan, J. Sun, R. Lou and J. Deng, J. Am. Chem. Soc., 1997, 119,
9570.
Table 1 The Rh(I)-catalyzed asymmetric hydrogenation of a-dehydroamino
acids 4a and enamides 5a
a
Entry Substrates (R) Ligands Ee
b
1 4a H BINAPO
c
73.2
2 4a H L1 94.8
3 4a H L2 99.9
4 4a H L3 95.4
5 4a H L4 93.0
6 4a H L5 98.7
7 4a H NAPHOS 54.0
8 5a Ph BINAPO 28.3
9 5a Ph L1 67.2
10 5a Ph L2 94.3
11 5a Ph L3 89.4
12 5a Ph L4 90.3
13 5a Ph L5 81.8
a
The reactions were carried out at rt under 45 psi of H
2
for 12 h in 3 mL
solvent with 100% conversion [substrate (0.5 mmol scale):Rh: Ligand = 1:
0.01: 0.011]. For o-BINAPO ligands, optimized reaction conditions of
substrate 4: Rh(COD)
2
PF
6
, toluene; substrate 5: Rh(COD)
2
SbF
6
, THF. For
o-NAPHOS ligand L5, optimized reaction conditions of substrate 4:
Rh(COD)
2
PF
6
, methanol; substrate 5: Rh(COD)
2
PF
6
, methanol. The S
absolute configurations were assigned by comparison of optical rotations
with the known reported data.
b
The ees were measured by GC chiral
columns (Chiralsil VAL III and Chiralselect 1000).
c
The result was
reported in Tetrahedron Lett., 1977, 1879.
Table 2 The Rh(I)-catalyzed asymmetric hydrogenation of a-dehydroamino
acids 4 and enamides 5
a
Entry Substrates (R) Ligand Ee
b
1 4b Ph L5 97.8
2 4c p-FC
6
H
4
L5 96.6
3 4d p-MeOC
6
H
4
L5 95.8
4 4e m-BrC
6
H
4
L5 97.8
5 4f o-ClC
6
H
4
L5 97.4
6 4g 2-Naphthyl L5 97.4
7 4c p-FC
6
H
4
L2 93.4
8 4d p-MeOC
6
H
4
L2 87.2
9 4e m-BrC
6
H
4
L2 92.6
10 4f o-ClC
6
H
4
L2 81.5
11 4g 2-Naphthyl L2 97.3
12 5b p-CF
3
C
6
H
4
L2 95.7
13 5c m-MeC
6
H
4
L2 96.3
14 5d p-PhC
6
H
4
L2 94.2
15 5e 2-Naphthyl L2 94.1
a
The reactions were carried out at rt under 45 psi of H
2
for 12 h in 3 mL
solvent with 100% conversion [substrate (0.5 mmol scale):Rh: ligand = 1:
0.01: 0.011]. For o-BINAPO ligands, optimized reaction conditions of
substrate 4: Rh(COD)
2
PF
6
, toluene; substrate 5: Rh(COD)
2
SbF
6
, THF. For
o-NAPHOS ligand L5, optimized reaction conditions of substrate 4:
Rh(COD)
2
PF
6
, methanol; substrate 5: Rh(COD)
2
PF
6
, methanol. The S
absolute configurations were assigned by comparison of optical rotations
with the known reported data.
b
The ees were measured by GC (Chiral VAL
III and Chiral select 1000) or HPLC using chiral columns (Chiralcel OJ).
1125 CHEM. COMMUN. , 2002, 11241125