Synthesis of a novel chiral binaphthyl phospholane and its application in the highly enantioselective hydrogenation of enamides.

Article abstract of DOI:10.1021/ol991074m

[formula: see text] A new chiral phosphine, (R,R)-1,2-bis[(R)-4,5-dihydro-3H-dinaphtho[2,1- c:1',2'-e]phosphepino]benzene [abbreviated as (R,R)-binaphane] was prepared on the basis of a practical route from a readily accessible enantiomerically pure binap

Full text of DOI:10.1021/ol991074m

ORGANIC
LETTERS
1
999
Vol. 1, No. 10
679-1681
Synthesis of a Novel Chiral Binaphthyl
Phospholane and Its Application in the
Highly Enantioselective Hydrogenation
of Enamides
1
Dengming Xiao, Zhaoguo Zhang, and Xumu Zhang*
Department of Chemistry, The PennsylVania State UniVersity,
UniVersity Park, PennsylVania 16802
xumu@chem.psu.edu
Received September 21, 1999
ABSTRACT
A new chiral phosphine, (R,R)-1,2-bis{(R)-4,5-dihydro-3H-dinaphtho[2,1-c:1′,2′-e]phosphepino}benzene {abbreviated as (R,R)-binaphane] was
prepared on the basis of a practical route from a readily accessible enantiomerically pure binaphthanol. This ligand possesses both binaphthyl
chirality and phospholane functionality. Excellent enantioselectivities (95−99.6% ee) have been observed in hydrogenation of an isomeric
mixture of (E)- and (Z)-â-substituted-r-arylenamides by using a Rh−binaphane catalyst. These enantioselectivities are the highest reported to
date for this transformation.
Discovery of new chiral ligands is a major driving force in
developing highly enantioselective transition metal-catalyzed
reactions. New structural motifs play important roles in
determining enantioselectivities and reactivities for a given
transformation. For example, biaryl atropisomeric ligands
have been explored as effective scaffolds for many asym-
possesses both binaphthyl chirality and a phospholane
functionality. The resulting chiral ligand with a rigid 1,2-
bis(phosphino)benzene backbone, (R,R)-1,2-bis{(R)-4,5-di-
hydro-3H-dinaphtho[2,1-c:1′,2′-e]phosphepino}benzene, is
abbreviated as (R,R)-binaphane (1) (Figure 1). Herein we
report the synthesis of this novel chiral phosphine and its
application in Rh-catalyzed highly enantioselective hydro-
genation of enamides.
1
metric transformations. One of the most frequently used
2
chiral chelating phosphines is BINAP. “DuPhos” describes
3
4
5
another family of excellent chiral phosphines, which have
Recently, Gladiali et al. and Stelzer et al. made several
monodentate chiral phospholanes as well as the correspond-
ing racemic chelating derivatives bearing the 1,1′-binaphthyl
framework. However, only limited applications in asym-
a rigid 1,2-bis(phosphino)benzene backbone and electron-
donating phospholane groups. Prompted by these studies, we
choose to make a new chiral chelating phosphine that
4
a
6
metric catalysis were reported. Reetz et al. prepared
chelating chiral phosphites using readily accessible binaph-
thanols as starting materials and demonstrated that they are
excellent ligands for Rh-catalyzed asymmetric hydrogenation
(
1) (a) Whitesell, J. K. Chem. ReV. 1989, 1581. (b) Rosini, C.; Franzini,
L.; Raffaelli, A.; Salvadori, P. Synthesis 1992, 503. (c) Pu, L. Chem. ReV.
998, 98, 2405.
2) (a) Noyori, R.; Takaya, H. Acc. Chem. Res. 1990, 23, 345. (b)
1
(
Ohkuma, T.; Ooka, H.; Hashiguchi, S.; Ikariya, T.; Noyori, R. J. Am. Chem.
Soc. 1995, 117, 2675. (c) Doucet, H.; Ohkuma, T.; Murata, K.; Yokozawa,
T.; Kozawa, M.; Katayama, E.; England, A. F.; Ikariya, T.; Noyori, R.
Angew. Chem., Int. Ed. 1998, 37, 1703. (d) Ohkuma, T.; Koizumi, M.;
Doucet, H.; Pham, T.; Kozawa, M.; Murata, K.; Katayama, E.; Yokozawa,
T.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1998, 120, 13529.
(4) (a) Gladiali, S.; Dore, A.; Fabbri, D.; Lucchi, O. D.; Manassero, M.
Tetrahedron: Asymmetry 1994, 511. (b) Gladiali, S.; Fabbri, D. Chem. Ber.
1997, 130, 543.
(5) Bitterer, F.; Herd, O.; Kuhnel, M.; Stelzer, O.; Weferling, N.;
Sheldrick, W. S.; Hahu, J.; Nagel, S.; Rosch, N. Inorg. Chem. 1998, 37,
6408.
(
3) (a) Burk, M. J. J. Am. Chem. Soc. 1991, 113, 8518. (b) Burk, M. J.;
Feaster, J. E.; Nugent, W. A.; Harlow, R. L. J. Am. Chem. Soc. 1995, 117,
0125.
(6) Reetz, M. T.; Gosberg, A.; Goddard, R.; Kyung, S. J. Chem. Soc.,
Chem. Commun. 1998, 2077.
1
1
0.1021/ol991074m CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/20/1999

of dehydroamino acids. Although the synthesis of binaphane
1) is a more demanding task compared with preparation of
2 with methylmagnesium bromide gave (R)-2,2′-dimethyl-
1,1′-binaphthyl (3) in high yield. (R)-2,2′-Dibromomethyl-
1,1′-binaphthyl (4) was prepared by bromination of 3 with
NBS. A simple anion exchange of (R)-2,2′-dibromomethyl-
1,1′-binaphthyl (4) with LiCl afforded (R)-2,2′-dichlorom-
ethyl-1,1′-binaphthyl (5) in high yield. A key element in our
synthesis of chelating phospholane 1 is utilization of a less
reactiVe (R)-2,2′-dichloromethyl-1,1′-binaphthyl (5) to sup-
press the intermolecular reaction with phosphine anions that
attends use of a more reactiVe (R)-2,2′-dibromomethyl-1,1′-
binaphthyl (4). While we failed to prepare the desired
phosphine 1 using (R)-2,2′-dibromomethyl-1,1′-binaphthyl
(
the chiral phosphite ligands reported by Reetz et al., the
arguably greater electron-donating ability of the phospholane
moiety compared with a phosphite makes it an attractive
ligand for many applications.3 A calculated structure of a
Rh complex with 1 (CAChe MM2 program) is shown in
Figure 1. Two naphthyl groups protrude into two opposite
,7
(4) as a starting material, refluxing (R)-2,2′-dichloromethyl-
1,1′-binaphthyl (5) with 1,2-bis(phosphino)benzene and NaH
in THF, followed by recrystallization from ether, gave (R,R)-
binaphane 1 in 55% yield. This efficient synthesis allows us
to make binaphane 1 on a large scale. Using this procedure,
we have also made the corresponding monodentate chiral
binaphthyl phospholane from phenylphosphine in >90%
yield.
Many chiral phosphine ligands have been designed to
achieve high enantioselectivity and reactivity for the asym-
metric hydrogenation of unsaturated substrates such as
Figure 1. (R,R)-Binaphane (1) and its Rh complex.
9
ketones, olefins, and imines. Electron-deficient olefins (e.g.,
dehydroamino acids) are easily reduced with high enanti-
oselectivities using the current suite of catalysts. However,
only a few chiral ligands are effective for the highly
enantioselective hydrogenation of electron-rich olefins such
as simple enamides. In particular, hydrogenation of an
isomeric mixture of (Z)- and (E)-enamides with high enan-
tioselectivity remains a significant challenge.
To test the synthetic utility of (R,R)-binaphane (1), we have
explored the asymmetric hydrogenation of enamides using
a Rh-(R,R)-binaphane (1) complex as the catalyst. Initially,
several experiments were performed to screen optimal
conditions for hydrogenation of N-acetylphenylethenamine
quadrants, and another two naphthyl groups stay back to
leave open the other two quadrants. This steric environment
may be conducive to achieving highly enantioselective
transformations.
To make the desired chiral chelating phospholane 1, we
have developed a practical synthesis route based upon readily
accessible starting materials (Scheme 1). Enanatiomerically
1
0
Scheme 1a
6
a. Rh(COD)
2 6
PF was found to be a more effective catalyst
precursor compared with a neutral Rh species [Rh(COD)-
1
0d,f
Cl]
of enantioselectivity upon hydrogenation of 6a. For example,
5% ee was obtained under 300 psi of H while 90% ee
was achieved under 20 psi of H . Variation of solvents caused
2
.
2
An increase in H pressure resulted in a decrease
8
2
2
dramatic changes in both enantioselectivity and reactivity.
While hydrogenation of N-acetylphenylethenamine was
complete in CH Cl with 90% ee, both the reactivity and
2 2
(7) (a) Zhu, G.; Chen, Z.; Jiang, Q.; Xiao, D.; Cao, P.; Zhang, X. J. Am.
Chem. Soc. 1997, 119, 3836. (b) Jiang, Q.; Jiang, Y.; Xiao, D.; Cao, P.;
Zhang, X. Angew. Chem., Int. Ed. 1998, 37, 1100.
(
8) Cai, D.; Hughes, D. L.; Verhoever, T. R.; Reider, P. J. Tetrahedron
Lett. 1995, 7991.
9) (a) Ojima, I. Ed. Catalytic Asymmetric Synthesis; VCH: New York,
(
a
b
O. c NBS,
2
1993. (b) Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley:
New York, 1994.
Tf
2
O, Py, CH
2
Cl
2
.
4
MeMgBr, NiCl
2
(dppp), Et
. d LiCl, DMF. 1,2-Bisphosphinobenzene,
e
benzoyl peroxide, CCl
NaH, THF.
(
10) (a) Kagan, H. B.; Langlois, N.; Dang, T. P. J. Organomet. Chem.
1
1
1
975, 90, 353. (b) Sinou, D.; Kagan, H. B. J. Organomet. Chem. 1976,
14, 325. (c) Morimoto, T.; Chiba, M.; Archiwa, K. Chem. Pharm. Bull.
992, 40, 2894. (d) Burk, M. J.; Wang, Y. M.; Lee, J. R. J. Am. Chem.
Soc. 1996, 118, 5142. (e) Burk, M. J.; Carsey, G.; Johnson, N. B. J. Org.
Chem. 1998, 63, 6084. (f) Zhu, G.; Zhang, X. J. Org. Chem. 1998, 63,
9590. (g) Zhang, F.-Y.; Pai, C.-C.; Chan, A. S. C. J. Am. Chem. Soc. 1998,
pure binaphthol can be easily obtained using a classic
resolution procedure. (R)-2,2′-Bistriflate-1,1′-binaphthyl (2)
was made from (R)-binaphthol with excess triflic anhydride
2 2
and pyridine in CH Cl . Kumada-type coupling of bistriflate
8
120, 5808. (h) Jiang, Q.; Xiao, D.; Zhang, Z.; Cao, P.; Zhang, X. Angew.
Chem., Int. Ed. 1999, 38, 516. (i) Zhang, Z.; Zhu, G.; Jiang, Q.; Xiao, D.;
Zhang, X. J. Org. Chem. 1999, 64, 1774.
1680
Org. Lett., Vol. 1, No. 10, 1999

the enantioselectivity were lower in methanol (14% ee and
substrates with an electron-donating group showed higher
enantioselectivity (entry 2, 89% ee; entry 5, 90% ee).
Although very good enantioselectivities have been obtained
for hydrogenation of R-arylenamides without substitituents
in the â-position, the highlight of the Rh-binaphane (1)
catalyst is its ability to reduce â-substituted-R-arylenamides
with excellent enantioselectivities. Several â-substituted-R-
arylenamides, as a mixture of (E)/(Z) isomers, were reduced
with high enantioselectivities (entries 7-13, 95-99.6% ee).
A small electronic effect was observed. For example,
hydrogenation of 6h bearing an electron-donating 4-methoxy
substituent in the aryl group proceeded with the higher
enantioselectivity (entry 8, 99.6% ee) compared with the
86% conversion). The reaction did not proceed in toluene.
Next, a variety of enamides were prepared according to
literature procedures10a-f and employed as substrates for this
asymmetric hydrogenation reaction (Table 1). These experi-
Table 1. Highly Enantioselective Hydrogenation of Enamides
Catalyzed by a Rh-(R,R)-Binaphane Complexa
result obtained with 6i with an electron-withdrawing 4-CF
3
substituent (entry 9, 97% ee). Although there are several
chiral phosphine systems such as DuPhos, BPE, and BICP
that are effective for hydrogenation of an isomeric mixture
10d-f
of (E)- and (Z)-enamides,
the enantioselectiVities achieVed
with the Rh-(R,R)-binaphane (1) catalyst are the highest
reported to date. Since the product 7 can be easily converted
to the corresponding arylalkylamine through hydrolysis under
acidic conditions, hydrogenation with the Rh-binaphane (1)
complex provides a practical method for preparing a variety
of chiral arylalkylamines.
In conclusion, a new axially chiral ligand (R,R)-binaphane
(1) has been developed. This ligand afforded excellent
enantioselectivities when utilized in Rh-catalyzed asymmetric
hydrogenation of trisubstituted electron-rich enamides. The
detailed mechanism is under investigation, and other ap-
plications of this new ligand for asymmetric catalysis will
be disclosed in due course.
a
The reaction was carried out at room temperature under an initial
hydrogen pressure of 20 psi for 24 h. The catalyst was made in situ by
stirring a solution of Rh(COD)2PF6 and (R,R)-binaphane (1) in CH2Cl2.
[
Substrate (0.04 M)]:[Rh]:(R,R)-binaphane (1) )100:1:1.5. The reaction
Acknowledgment. We gratefully acknowledge the sup-
port by the National Institutes of Health, a Camille and Henry
Dreyfus Teacher-Scholar Award, an ONR Young Investiga-
tor Award, and a DuPont Young Faculty Award for this
work. We also thank Johnson Metthey Inc. for a generous
loan of precious metals and Supelco for a gift of chiral GC
columns.
b
proceeded in quantitative yield. The configuration of the product was
determined by comparison of optical rotation with reported data. Enamides
6
were determined by chiral GC with a Supelco chiral select 1000 column or
by chiral HPLC with a Regis (S,S)-Whelk-01 column.
c
were made according to the literature methods. d Enantiomeric excesses
1
0f
ments were performed under the optimal conditions for
hydrogenation of N-acetylphenylethenamine (6a). The elec-
tronic character of attached aryl groups in R-arylenamides
had only a small effect on the enantioselectivity. Introducing
an electron-withdrawing group into the R-arylenamides
resulted in lower enantioselectivity (entry 3, 82% ee) while
Supporting Information Available: Experimental details
and spectroscopic data. This material is available free of
charge via the Internet at http://pubs.acs.org.
OL991074M
Org. Lett., Vol. 1, No. 10, 1999
1681