General synthetic route to chiral flexible biphenylphosphine ligands: The use of a chiral additive enables the preparation and observation of metal complexes incorporating the enantiopure form

Article abstract of DOI:10.1021/ol0068896

equation presented The enantio-and diastereomerically pure metal complex of a chirally flexible BIPHEP ligand is obtained through enantiomer-selective coordination of a BIPHEP-Ru complex with enantiopure 3,3′-dimethyldiaminobinaphthyl, DM-DBN, followed by

Full text of DOI:10.1021/ol0068896

ORGANIC
LETTERS
2001
Vol. 3, No. 2
243-245
General Synthetic Route to Chiral
Flexible Biphenylphosphine Ligands:
The Use of a Chiral Additive Enables
the Preparation and Observation of
Metal Complexes Incorporating the
Enantiopure Form†
Koichi Mikami,* Kohsuke Aikawa, and Toshinobu Korenaga
Department of Applied Chemistry, Tokyo Institute of Technology,
Tokyo 152-8552, Japan
kmikami@o.cc.titech.ac.jp
Received November 18, 2000
ABSTRACT
The enantio- and diastereomerically pure metal complex of a chirally flexible BIPHEP ligand is obtained through enantiomer-selective coordination
of a BIPHEP−Ru complex with enantiopure 3,3′-dimethyldiaminobinaphthyl, DM-DBN, followed by epimerization of the remaining BIPHEP−Ru
enantiomer to complex with DM-DABN. Thus, an efficient and general synthetic route to a variety of substituted BIPHEP ligands from biphenol
and observation of the enantiomerically pure BIPHEP ligands in their Ru(II) complexes are described.
In an asymmetric catalysis,1 the choice of a chiral ligand is
a key factor in attaining a certain level of asymmetric
induction and increasing the catalytic activity from the achiral
precatalyst (“ligand accelerated catalysis” 2). However, asym-
metric synthesis or resolution is generally required to obtain
enantiopure forms of chirally rigid ligands. By contrast, we
have reported the use of chirally flexible biphenylphosphine
(BIPHEP) ligands3 (Figure 1) in the Ru-catalyzed asymmetric
hydrogenation, instead of the enantiopure, chirally rigid
BINAP counterparts.4 Inherently, the BIPHEP ligands cannot
be isolated in enantiopure forms without a substituent at the
† Paper by T. Korenaga, M. Terada, and K. Mikami presented at the
45th Symposium on Organometallic Chemistry, Japan, 1998.
(1) (a) Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H. ComprehensiVe
Asymmetric Catalysis, Vol. 1-3; Springer: Berlin, 1999. (b) Transition
Metals for Organic Synthesis; Beller, M., Bolm, C., Ed.; VCH: Weiheim,
1998. (c) Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley:
New York, 1994. (d) Brunner, H.; Zettlmeier, W. Handbook of Enantio-
selectiVe Catalysis; VCH: Weiheim, 1993. (e) Catalytic Asymmetric
Synthesis, Vol. I and II; Ojima, I., Ed.; VCH: New York, 1993; p 2000. (f)
Kagan, H. B. ComprehensiVe Organic Chemistry, Vol. 8; Pergamon:
Oxford, 1992. (g) Asymmetric Catalysis; Bosnich, B., Ed.; Martinus Nijhoff
Publishers: Dordrecht, 1986.
(3) BIPHEP was named after 6,6′-substituted MeO-BIPHEP. (a) Schmid,
R.; Broger, E.; A. Cereghetti, M.; Crameri, Y.; Foricher, J.; Lalonde, M.;
Mu¨ller, R. K.; Scalone, M.; Schoettel, G.; Zutter, U. Pure Appl. Chem.
1996, 68, 131-138. (b) Trabesinger, G.; Albinati, A.; Feiken, N.; Kunz,
R. W.; Pregosin, P. S.; Tschoerner, M. J. Am. Chem. Soc. 1997, 119, 6315-
6323, and references therein.
(4) (a) Mikami, K.; Korenaga, T.; Terada, M.; Ohkuma, T.; Pham, T.;
Noyori, R. Angew. Chem., Int. Ed. 1999, 38, 495-497. (b) Review on
asymmetric activation : Mikami, K.; Terada, M.; Korenaga, T.; Matsumoto,
Y.; Ueki, M.; Angelaud, R. Angew. Chem., Int. Ed. 2000, 39, 3532-3556.
Also see highlights of conformational control of ligand: Mun˜iz, K.; Bolm,
C. Chem. Eur. J. 2000, 6, 2309-2316.
(2) Berrisford, D. J.; Bolm, C.; Sharpless, K. B. Angew. Chem., Int. Ed.
Engl. 1995, 34, 1059.
10.1021/ol0068896 CCC: $20.00 © 2001 American Chemical Society
Published on Web 12/15/2000

Scheme 1
Figure 1.
6-position.5 However, the BIPHEP-Ru(II) complexes can
be obtained in diastereomerically enriched forms, after
complexation with a chiral diamine activator (1) to control
the chirality through epimerization of BIPHEPs and (2) to
increase the catalytic activity (“asymmetric activation”) of
the BIPHEP-Ru(II) complexes in the enantioselective
hydrogenation of ketones.4a
The chirality control of BIPHEP-metal complexes can,
in principle, be classified into two extremes. There is a
continuum between the two. One is selective complexation
of the chiral molecule (X-*-X) with one enantiomer of a
racemic BIPHEP-metal complex along with the remaining
BIPHEP-metal enantiomer which eventually epimerizes in
order to complex with the chiral molecule (Figure 2a). The
be synthesized according to this method. Furthermore, the
use of dibromobiphenyl was found to give, after dilithiation
followed by treatment with diphenylphosphine chloride,
5-phenyldibenzophospholane instead of BIPHEP as previ-
ously reported (BPBP (2,2′-bis(diphenylphosphanyl)-1,1′-
biphenyl): originally named)5a (Scheme 1 (3)). Herein, we
wish to report an efficient and general synthetic route to a
variety of substituted BIPHEP ligands from biphenol and
observation of the enantiomerically pure BIPHEP ligands
in their Ru(II) complexes with 3,3′-dimethyldiaminobinaph-
thyl, DM-DABN (named after DABN: diaminobinaphthyl).
The present syntheses of BIPHEPs reflect their flexible
nature in sharp contrast to the chiral rigidity of BINAPs.
The synthesis of BINAP from binaphthyl ditriflate has been
reported using Ni6 and Pd7 catalysts. Particularly, NiCl2(dppe)
is an excellent catalyst for the coupling reaction of Ph2PH
with binaphthyl ditriflate to give BINAP in one step.6
However, the biphenyl ditriflate counterpart (2) with
NiCl2(dppe) and Ph2PH gave a complex mixture of products.
In the BINAP synthesis, Pd(OAc)2 has been used for the
coupling reaction of Ph2P(O)H with binaphthyl ditriflate,
however, to give only binaphthyl monophosphine oxide.6a,7
In sharp contrast, biphenyl ditriflate (2), with Pd(OAc)2 and
Ph2P(O)H in DMSO at 100 °C, was found to afford the
diphosphine oxide, BIPHEPdO (3), presumably due to the
flexibility of the biphenyl dihedral angle as compared to
chirally rigid BINAPs (Scheme 2). The syntheses of substi-
tuted BIPHEPs, namely, the 3,5-dimethyl analogue, DM (i.e.,
Figure 2.
(5) (a) BPBP was also termed for this bisphosphine ligand but synthesized
unsuccessfully to give the monophosphine, 5-phenyldibenzophospholane:
Uehara, A.; Bailar, J. C., Jr. J. Organomet. Chem. 1982, 239, 1-10. See
also: Miyamoto, T. K.; Matsuura, Y.; Okude, K.; Ichida, H.; Sasaki, Y. J.
Organomet. Chem. 1989, 373, C8-C12. (b) Bennett, M. A.; Bhargava, S.
K.; Griffiths, K. D.; Robertson, G. B. Angew. Chem., Int. Ed. Engl. 1987,
26, 260-261. (c) Desponds, O.; Schlosser, M. J. Organomet. Chem. 1996,
507, 257-261. (d) Desponds, O.; Schlosser, M. Tetrahedron Lett. 1996,
37, 47-48.
(6) (a) Cai, D.; Payack, J. F.; Bender, D. R.; Hughes, D. L.; Verhoeven,
T. R.; Reider, P. J. J. Org. Chem. 1994, 59, 7180-7181. (b) Cai, D.; Payack,
J. F.; Bender, D. R.; Hughes, D. L.; Verhoeven, T. R.; Reider, P. J. Org.
Synth. 1998, 6-11.
(7) Synthesis of MOP ligand: Uozumi, Y.; Tanahashi, A.; Lee, S.-Y.;
Hayashi, T. J. Org. Chem. 1993, 58, 1945-1948.
other is nonselective complexation of the chiral molecule
with both enantiomers of racemic BIPHEP-metal complex
followed by epimerization of the less favorable diastereo-
meric BIPHEP-metal complex with the chiral molecule to
the favorable diastereomer (Figure 2b).
Unfortunately, the BIPHEP ligand had been synthesized
starting particularly from triphenylphosphine or its oxide
(Scheme 1 (1) and (2)). Therefore, a variety of BIPHEPs
bearing substituted diarylphosphine (PAr2) groups could not
244
Org. Lett., Vol. 3, No. 2, 2001

(Figure 2).4a Complexation of BIPHEP ligand with [RuCl2-
(C6H6)]2 in DMF gave the racemic RuCl2(biphep)(dmf)n (8a)
(BIPHEP-Ru). A mixture of BIPHEP-Ru (8a) and (R)-
DM-DABN (9) was found to provide only RuCl2[(R)-biphep]-
[(R)-dmdabn] ((R)-8a/(R)-9) in dichloromethane as observed
Scheme 2
1
by H NMR analysis10 (Figure 2a). The remaining (S)-
BIPHEP-Ru (8a) complexed, only after epimerization to
(R)-8a, with (R)-DM-DABN (9) in 2-propanol at 50 °C as
detected in 1H NMR spectra.10 Indeed, the (R)/(R)-configu-
ration of the BIPHEP-RuCl2/DM-DABN diastereomer was
determined by X-ray analysis of the single-crystal obtained
from dichloromethane-ether-hexane (Figure 3).11 Thus, (R)-
Xyl)-BIPHEPdO (3b) and 3,5-di-tert-butyl analogue 3c were
also achieved in 60% and 87% yields, respectively, using
the corresponding Ar2P(O)Hs which were prepared from
ArMgBr and (EtO)2P(O)H. These BIPHEPdOs (3a-c) were
easily converted to BIPHEPs (4a-c) by reduction with
trichlorosilane in 91%, 82%, and 95% yields, respectively.
When 1 equiv of Ar2P(O)Hs were used for biphenyl
ditriflate 2, the monophosphine oxides (5a and 5b) could be
obtained in 70% and 90% yields, respectively. Furthermore,
the biphenyl monophosphine oxide monotriflate (5) thus
obtained could be utilized for the synthesis of other biphenyl
phosphine ligands (6 and 7). The triflate group in 5a was
converted to a carbomethoxy group by treatment of CO/
MeOH with Pd catalyst.8 Reduction of phosphine oxide gave
carbomethoxy phosphine 6a in 57% yield (two steps). The
carbomethoxy group in 6a was easily converted to oxazoline.
The carbomethoxy group in 6a reacted with amino alcohol
in the presence of Na.9 Cyclization9 gave phosphino oxazo-
line 7a in 62% yield (two steps).
Figure 3.
8a/(R)-9 was eventually obtained from the initial BIPHEP-
Ru racemic complex (8a) quantitatively.
In summary, we have disclosed herein that the enantio-
and diastereomerically pure metal complex of the BIPHEP
ligand can be obtained quantitatively through enantiomer-
selective coordination of BIPHEP-Ru complex with enan-
tiopure DM-DABN, followed by epimerization of the
remaining BIPHEP enantiomer in order to complex with
DM-DABN. We have also reported an efficient and general
synthetic route to a variety of substituted BIPHEP ligands
from biphenol.
The BIPHEP ligands can be transformed to several metal
complexes in racemic forms. However, the chirality control
of the BIPHEP ligands in their metal complexes is feasible
in two manners by the aid of a chiral molecule (X-*-X)
Acknowledgment. We are grateful to Drs. H. Kumoba-
yashi and N. Sayo of Takasago International Corp. We also
thank to Dr. Kenji Yoza in Nippon Brucker Co. for X-ray
analysis of RuCl2(biphep)(dmdabn) complex. This work was
financially supported by the Ministry of Education, Science,
Sports and Culture of Japan (Nos. 09238209 and 10208204)
and the Research Fellowships of the Japan Society for the
Promotion of Science for Dr. Toshinobu Korenaga.
(8) Ogasawara, M.; Yoshida, K.; Kamei, H.; Kato, K.; Uozumi, Y.;
Hayashi, T. Tetrahedron: Asymmetry 1998, 9, 1779-1787.
(9) Zhang, W.; Yoneda, Y.; Kida, T.; Nakatsuji, Y.; Ikeda, I. Tetrahe-
dron: Asymmetry 1998, 9, 3371-3380.
1
(10) Only one diastereomer was observed in H NMR spectra. (R)-8a/
(R)-9: δ 4.04 (d, 9.3 Hz, 2H, amino proton), 4.78 (d, 9.3 Hz, 2H, amino
proton).
(11) X-ray analysis of RuCl2[(R)-binap][(R)-dmdabn]: Mikami, K.;
Korenaga, T.; Ohkuma, T.; Noyori, R. Angew. Chem., Int. Ed. 2000, 39,
3707-3710.
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