Synthesis of novel BINOL-derived chiral bisphosphorus ligands and their application in catalytic asymmetric hydrogenation

Article abstract of DOI:10.1039/b201976k

Some novel ortho-substituted BINOL-derived bisphosphorus 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 fun

Full text of DOI:10.1039/b201976k

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: xumu@chem.psu.edu
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
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. C2-symmetry chiral bisphosphine ligand L5
(abbreviated as o-NAPHOS) was synthesized from the known
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 (P–M–P) 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 BINAP4
and BINOL,5 which form 7-membered with metals. However,
their simple analogues (Scheme 1), NAPHOS6 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 PPh2 groups and therefore decrease the
influence of the binaphthyl functionality on the orientation of
the phenyl ring of PPh2 groups. (2) The presence of the C–O–P
moiety in BINAPO and the C–CH2–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
compound
(S)-3,3A-diphenyl-2,2-dibromomethyl-1,1A-bina-
phthyl 210 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 210 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 hexane–DCM–
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
their application in Rh(
I
)-catalyzed asymmetric hydrogenation
of functionalized olefins.
Scheme 1
Scheme 2
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CHEM. COMMUN., 2002, 1124–1125
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Table 1 The Rh(
I
)-catalyzed asymmetric hydrogenation of a-dehydroamino
Table 2 The Rh(
I
)-catalyzed asymmetric hydrogenation of a-dehydroamino
acids 4a and enamides 5aa
acids 4 and enamides 5a
Entry
Substrates (R)
Ligands
Eeb
Entry
Substrates (R)
Ligand
Eeb
1
2
3
4
5
6
7
8
9
10
11
12
13
4a
4a
4a
4a
4a
4a
4a
5a
5a
5a
5a
5a
5a
H
H
H
H
H
H
H
Ph
Ph
Ph
Ph
Ph
Ph
BINAPOc
L1
L2
L3
L4
73.2
94.8
99.9
95.4
93.0
98.7
54.0
28.3
67.2
94.3
89.4
90.3
81.8
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
4b
4c
4d
4e
4f
4g
4c
4d
4e
4f
4g
5b
5c
5d
5e
Ph
p-FC6H4
L5
L5
L5
L5
L5
L5
L2
L2
L2
L2
L2
L2
L2
L2
L2
97.8
96.6
95.8
97.8
97.4
97.4
93.4
87.2
92.6
81.5
97.3
95.7
96.3
94.2
94.1
p-MeOC6H4
m-BrC6H4
o-ClC6H4
2-Naphthyl
p-FC6H4
p-MeOC6H4
m-BrC6H4
o-ClC6H4
2-Naphthyl
p-CF3C6H4
m-MeC6H4
p-PhC6H4
2-Naphthyl
L5
NAPHOS
BINAPO
L1
L2
L3
L4
L5
a The reactions were carried out at rt under 45 psi of H2 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)2PF6, toluene; substrate 5: Rh(COD)2SbF6, THF. For
o-NAPHOS ligand L5, optimized reaction conditions of substrate 4:
Rh(COD)2PF6, methanol; substrate 5: Rh(COD)2PF6, 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.
a The reactions were carried out at rt under 45 psi of H2 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)2PF6, toluene; substrate 5: Rh(COD)2SbF6, THF. For
o-NAPHOS ligand L5, optimized reaction conditions of substrate 4:
Rh(COD)2PF6, methanol; substrate 5: Rh(COD)2PF6, 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).
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 literature12 are as follows:
DIPAMP, 94; DIOP, 73; ChiraPhos, 91; BPPM, 98.5; BINAP,
67; BICP, 97.5; Et-DuPhos, 99.4; SpirOP, 99.9.
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.
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 1–6). 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 7–11).
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.
To expand the utility of o-BINAPO ligands system, we have
examined Rh( )-catalyzed enantioselective hydrogenation of
I
simple enamides 5 using L2 as ligand (entries 12–15). High
enantioselectivities (94.1–96.3% 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 P–M–P bite angle. Further
studies of other transition metal complexes of these ligands and
their applications are in progress.
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.
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.
CHEM. COMMUN., 2002, 1124–1125
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