Development of 4,4′-substituted-xylBINAP ligands for highly enantioselective hydrogenation of ketones

Article abstract of DOI:10.1021/jo048333s

(Chemical Equation Presented) A family of 4,4′-substituted-xylBINAPs was synthesized in multistep sequences and characterized by NMR spectroscopy and mass spectrometry. Ru(diphosphine)(diamine)Cl₂ complexes based on these 4,4′-substituted-xylBINAPs and chiral diamines (DPEN and DAIPEN) were synthesized by treatment of [(benzene)RuCl₂]₂ with 4,4′-substituted-xylBINAP followed by chiral diamine, and characterized by ¹H and ³¹P NMR spectroscopy and mass spectrometry. These Ru complexes were used for asymmetric hydrogenation of aromatic ketones in a highly enantioselective manner with complete conversion. With 0.1% catalyst loading, complete conversion and enantioselectivity greater than 99% were obtained for most of the aromatic ketones examined. These Ru catalysts thus gave the highest ee for asymmetric hydrogenation of aromatic ketones among all of the catalysts reported in the literature. A single-crystal X-ray diffraction study of Ru[(R)-L₄] [(R,R)-DPEN]Cl₂ indicated that the 4-methyl group of the naphthyl ring and the methyl groups of the two xylyl moieties form a fence on the opposite side of the DPEN ligand of the Ru center. These three methyl groups will have significant repulsive interactions with the bulky aryl ring of the hydrogen-bonded aromatic ketone in the disfavored transition state. These results support our hypothesis of combining dual modes of enantiocontrol (i.e., the substituents on 4,4′-positions of the binaphthyl framework and the methyl groups on the bis(xylyl)phosphino moieties) to achieve higher stereoselectivity in the hydrogenation of aromatic ketones.

Full text of DOI:10.1021/jo048333s

Development of 4,4′-Substituted-XylBINAP Ligands for Highly
Enantioselective Hydrogenation of Ketones
Helen L. Ngo and Wenbin Lin*
Department of Chemistry, CB#3290, University of North Carolina, Chapel Hill, North Carolina 27599
wlin@unc.edu
Received September 20, 2004
A family of 4,4′-substituted-xylBINAPs was synthesized in multistep sequences and characterized
by NMR spectroscopy and mass spectrometry. Ru(diphosphine)(diamine)Cl
these 4,4′-substituted-xylBINAPs and chiral diamines (DPEN and DAIPEN) were synthesized by
treatment of [(benzene)RuCl with 4,4′-substituted-xylBINAP followed by chiral diamine, and
2
complexes based on
2 2
]
1
31
characterized by H and P NMR spectroscopy and mass spectrometry. These Ru complexes were
used for asymmetric hydrogenation of aromatic ketones in a highly enantioselective manner with
complete conversion. With 0.1% catalyst loading, complete conversion and enantioselectivity greater
than 99% were obtained for most of the aromatic ketones examined. These Ru catalysts thus gave
the highest ee for asymmetric hydrogenation of aromatic ketones among all of the catalysts reported
4 2
in the literature. A single-crystal X-ray diffraction study of Ru[(R)-L ][(R,R)-DPEN]Cl indicated
that the 4-methyl group of the naphthyl ring and the methyl groups of the two xylyl moieties form
a fence on the opposite side of the DPEN ligand of the Ru center. These three methyl groups will
have significant repulsive interactions with the bulky aryl ring of the hydrogen-bonded aromatic
ketone in the disfavored transition state. These results support our hypothesis of combining dual
modes of enantiocontrol (i.e., the substituents on 4,4′-positions of the binaphthyl framework and
the methyl groups on the bis(xylyl)phosphino moieties) to achieve higher stereoselectivity in the
hydrogenation of aromatic ketones.
1
. Introduction
cessful industrial processes such as the synthesis of
L-Dopa2a and (S)-Metolachlor. An industrially useful
asymmetric catalyst needs to have both high activity
3
Homogeneous asymmetric catalysis has undergone
1
tremendous growth over the past four decades. Many
highly enantioselective asymmetric catalytic processes
are now available for the synthesis of a wide variety of
chiral compounds for the pharmaceutical, agrochemical,
and other industries. Among these processes, catalytic
asymmetric hydrogenation is undoubtedly the most
(
TON) and high enantioselectivity. A practically useful
asymmetric catalyst thus either needs to have an ex-
tremely high turnover number (TON) or can be readily
recycled and reused.
In 1995, Noyori et al. disclosed one of the most powerful
methods for the production of chiral secondary alcohols
2
mature technology, as exemplified by numerous suc-
(
2) (a) Knowles, W. S. Adv. Synth. Catal. 2003, 345, 3. (b) Noyori,
R. Angew. Chem., Int. Ed. 2002, 41, 2008. (c) Zhou, Y. G.; Tang, W.;
Wang, W. B.; Li, W.; Zhang, X. J. Am. Chem. Soc. 2002, 124, 4952. (d)
Ireland, T.; Tappe, K.; Grossheimann, G.; Knochel, P. Chem. Eur. J.
2002, 8, 843. (e) Ohkuma, T.; Koizumi, M.; Muniz, K.; Hilt, G.; Kabuto,
C.; Noyori, R. J. Am. Chem. Soc. 2002, 124, 6508.
(3) (a) Togni, A.; Breutel, C.; Schnyder, A.; Spindler, F.; Landert,
H.; Tijani, A. J. Am. Chem. Soc. 1994, 116, 4062. (b) Blaser, H.-U.
Adv. Synth. Catal. 2002, 344.
(
1) (a) Hayashi, T.; Tomioka, K.; Yonemitsu, O. Asymmetric Syn-
thesis: Graphical Abstracts and Experimental Methods; Gordon and
Beach Science Publishers: Amsterdam, The Netherlands, 1998. (b)
Ojima, I., Ed. Catalytic Asymmetric Synthesis; VCH: New York, 1993.
(
c) Lin, G.-O.; Li, Y.-M.; Chan, A. S. C. Principles of Applications
Asymmetric Synthesis; Wiley-Interscience: John Wiley & Sons: New
York, 2001.
1
0.1021/jo048333s CCC: $30.25 © 2005 American Chemical Society
Published on Web 01/15/2005
J. Org. Chem. 2005, 70, 1177-1187
1177

Ngo and Lin
SCHEME 1
Our work on heterogeneous asymmetric hydrogenation
of aromatic ketones unexpectedly showed that solid Ru-
precatalyst with 4,4′-substituted BINAP exhibited much
higher ee values than its parent homogeneous BINAP
system.12 Our group has since then examined homoge-
neous asymmetric hydrogenation of aromatic ketones
13
using a family of tunable 4,4′-substituted BINAP ligands.
These Ru(4,4′-substituted BINAP)(diamine)Cl complexes
via the asymmetric reduction of aromatic ketones using
molecular hydrogen (Scheme 1). For example, a combi-
nation of Ru[(S)-BINAP](DMF) Cl , (S,S)-1,2-diphenyl-
n 2
ethylenediamine (DPEN), and KOH in 2-propanol cata-
lyzed the asymmetric hydrogenation of 1-acetonaphthone
to give (R)-1-(1-naphthyl)ethanol in 97% ee and >99%
conversion (Scheme 1). Optimal homochiral Ru(xylBI-
NAP)(DAIPEN)Cl
2
4
exhibited ee values comparable to those of the best
catalysts prepared by Noyori et al. More importantly, an
entirely new approach toward enantiocontrol was achieved
by relying on repulsive interactions between the aryl
group of aromatic ketones and bulky substituents on the
4,4′-positions of BINAP in the disfavored transition state.
In this paper, we would like to report our efforts in the
design of a family of 4,4′-substituted-XylBINAP ligands
and in combining two modes of enantiocontrol (i.e., the
substituents on 4,4′-postions of the binaphthyl framework
and the methyl groups on the bis(xylyl)phosphino moi-
eties) to design highly enantioselective Ru catalysts for
the reduction of aromatic ketones.
4
2
complex (DAIPEN is (2R)-(-)-1,1-bis-
(
4-methoxyphenyl)-3-methyl-1,2-butanediamine) cata-
lyzes the hydrogenation of a variety of simple aromatic
ketones in the presence of strong bases such as KOH,
KO-i-C
alcohols of >95% ee.
3
H
7
, or KO-t-C5
4 9
H in 2-propanol to give secondary
Since Noyori’s original disclosure, much effort has been
devoted to further tuning of the Ru(diphosphine)(diami-
ne)Cl
2
catalyst system as well as understanding the
2. Results and Discussion
6
mechanism of this powerful catalytic system. Seminal
contributions by Noyori and others have established that
this catalyst system follows a nonclassical metal-ligand
bifunctional mechanism, whereby a hydride on the Ru
and a proton of the NH group are simultaneously
2
transferred to the CdO function through a six-membered
2
.1. Synthesis of 4,4′-Substituted-xylBINAP Lig-
ands. A family of 4,4′-substituted-xylBINAP ligands was
obtained in multistep sequences starting from known
enantiopure BINOL derivatives in relatively high yield
for each step. All the intermediates and final ligands were
readily purified by using silica gel chromatography and
7
hydrogen-bonded transition state. Although many other
1
13
1
characterized by H and C{ H} NMR spectroscopy and
chiral diphosphines have also been examined for the
highly asymmetric hydrogenation of aromatic ketones,
there is no consensus on exactly how enantiocontrol
occurs in this interesting catalytic system. As shown in4
Scheme 2, many phosphine systems including BINAP,
mass spectrometry. Phosphorus-containing compounds
31
1
were also characterized by P{ H} NMR spectroscopy.
Enantiopure 4,4′-bis(TMS)-2,2′-bis[bis(xylyl)phosphino]-
1
1
,1′-binaphthyl ligand, L , was synthesized in 7 steps
starting from known 6,6′-dichloro-4,4′-dibromo-2,2′-bis-
8
9
10
11
HexaPHEMP, P-Phos, PhanePhos, and SpiroPhos
14
(
(
TBDMS)-1,1′-binaphthalene in 27.6% overall yield
gave good to excellent enantioselectivity. All these ef-
ficient diphosphines share a common feature of possess-
ing bis(xylyl)phosphino moieties.
Scheme 3). Lithiation of 6,6′-dichloro-4,4′-dibromo-2,2′-
n
bis(TBDMS)-1,1′-binaphthalene by BuLi at -78 °C in
THF followed by the addition of trimethylsilyl bromide
afforded 6,6′-dichloro-4,4′-bis(TMS)-2,2′-bis(TBDMS)-1,1′-
binaphthalene, 1. The TBDMS groups in 1 were depro-
(4) (a) Ohkuma, T.; Ooka, H.; Ikariya, T.; Noyori, R. J. Am. Chem.
Soc. 1995, 117, 10417. (b) 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. (c) Ohkuma, T.; Ishii,
D.; Takeno, H.; Noyori, R. J. Am. Chem. Soc. 2000, 122, 6510.
tected with nBu
4
NF in THF to afford the dihydroxy
intermediate 2, which was hydrodechlorinated in the
presence of Pd/C catalyst to give 4,4′-bis(TMS)-2,2′-
dihydroxy-1,1′-binaphthalene (3). The dihydroxy groups
in 3 were converted to triflate groups by treatment with
(
5) 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.
(6) (a) Genov, D. G.; Ager, D. J. Angew. Chem., Int. Ed. 2004, 43,
triflic anhydride (Tf
bis(triflato)-1,1′-binaphthalene (4) was reacted with bis-
xylyl)phosphine oxide in the presence of Pd(OAc) , 1,4-
bis(di-phenylphosphino)butane (dppb), and H u¨ nig’s base
2
O). The resulting 4,4′-bis(TMS)-2,2′-
2
4
816. (b) Scalone, M.; Waldmeier, P. Org. Process Res. Dev. 2003, 7,
18. (c) Wu, J.; Ji, J.-X.; Guo, R.; Yeung, C.-H.; Chan, A. S. C. Chem
(
2
Eur. J. 2003, 9, 2963. (d) Chaplin, D.; Harrison, P.; Henschke, J. P.;
Lennon, I. C.; Meek, G.; Moran, P.; Pilkington, C. J.; Ramsden, J. A.;
Watkins, S.; Zanotti-Gerosa, A. Org. Process Res. Dev. 2003, 7, 89. (e)
Wu, J.; Chen, H.; Kwok, W.; Guo, R.; Zhou, Z.; Yeung, C.-H.; Chan, A.
S. C. J. Org. Chem. 2002, 67, 7908.
i
(
NEt
bis(TMS)-2-triflato-2′-bis(xylyl)phosphinyl-1,1′-binaph-
thyl (5). 5 was then reduced with (EtO) SiH in the
to give 4,4′-bis(TMS)-2-triflato-2′-
2
Pr) in DMSO at 110 °C for 3 days to afford 4,4′-
(7) (a) Sandoval, C. A.; Ohkuma, T.; Muniz, K.; Noyori, R. J. Am.
3
Chem. Soc. 2003, 125, 13490. (b) Abdur-Rashid, K.; Clapham, S. E.;
Hadzovic, A.; Harvey, J. N.; Lough, A. J.; Morris, R. H. J. Am. Chem.
Soc. 2002, 124, 15104-15118‚ (c) Abdur-Rashid, K.; Faatz, M.; Lough,
A. J.; Morris, R. H. J. Am. Chem. Soc. 2001, 123, 7473-7474.
i
presence of Ti(O Pr)
bis(xylyl)phosphino-1,1′-binaphthyl (6). 6 was finally
treated with (xyl) PH in the presence of Ni(dppe)Cl
catalyst and 1,4-diazabicyclo[2.2.2]octane (DABCO) in
DMF to afford the desired ligand L
4-TMS-2,2′-bis[bis(xylyl)phosphino]-1,1′-binaphthyl (L )
2
was synthesized in 9 steps starting from 4-bromo-6,6′-
4
15
2
2
(
8) Henschke, J. P.; Burk, M. J.; Malan, C. G.; Herzberg, D.;
Peterson, J. A.; Wildsmith, A. J.; Cobley, C. J.; Casy, G. Adv. Synth.
Catal. 2003, 345, 300.
1
.
(9) (a) Pai, C.-C.; Lin, C.-W.; Lin, C.-C.; Chen, C.-C.; Chan, A. S. C.
J. Am. Chem. Soc. 2000, 122, 11513. (b) Wu, J.; Chen, H.; Kwok, W.
H.; Lam, K. H.; Zhou, Z. Y.; Yeung, C. H.; Chan, A. S. C. Tetrahedron
Lett. 2002, 43, 1539.
(10) Burk, M. J.; Hems, W.; Herzberg, D.; Malan, C.; Zanotti-Gerosa,
(12) Hu, A.; Ngo, H. L.; Lin, W. J. Am. Chem. Soc. 2003, 125, 11490.
(13) Hu, A.; Ngo, H. L.; Lin, W. Org. Lett. 2004, 6, 2937.
(14) Lee, S. J.; Hu, A.; Lin, W. J. Am. Chem. Soc. 2002, 124, 12948.
(15) Allen, A., Jr.; Ma, L.; Lin, W. Tetrahedron Lett. 2002, 43, 3707.
A. Org. Lett. 2000, 2, 4173.
11) Xie, J.-H.; Wang, L.-X.; Fu, Y.; Zhu, S.-F.; Fan, B.-M.; Duan,
H.-F.; Zhou, Q.-L. J. Am. Chem. Soc. 2003, 125, 4404.
(
1178 J. Org. Chem., Vol. 70, No. 4, 2005

4,4′-Substituted-XylBINAP Ligands
SCHEME 2
SCHEME 3a
a
Reagents and conditions: (i) (a) nBuLi/hexane, -78 °C; (b) (CH3)3SiBr, THF, -78 °C to rt, 12 h; (ii) nBu4NF, THF, rt, 1 h; (iii) H2,
i
Pd/C, Et3N, MeOH, rt, 12 h; (iv) (Tf)2O, pyridine, CH2Cl2, rt, 12 h; (v) HP(O)(Xyl)2, Pd(OAc)2, dppb, Et2N Pr, DMSO, 110 °C, 3 days; (vi)
EtO)3SiH, Ti(O Pr)4, benzene, reflux for 4 h; (vii) HP(Xyl)2, Ni(dppe)Cl2, DABCO, DMF, 110 °C, 3 days.
i
(
dichloro-2,2′-diethoxy-1,1′-binaphthalene16 with an over-
all yield of 31% (Scheme 4). The reaction sequences
leading to 4-TMS-2,2′-bis(triflato)-1,1′-binaphthalene (12)
were the same as for the synthesis of 4,4′-bis(TMS)-2,2′-
bis(triflato)-1,1′-binaphthalene (4). Pd-catalyzed mono-
phosphinylation of 4-TMS-2,2′-bis(triflato)-1,1′-binaph-
2
then converted to triflate groups with use of Tf O. Pd-
catalyzed monophosphinylation of 4,4′-diphenyl-6,6′-
dichloro-2,2′-bis(triflato)-1,1′-binaphthalene (17) with
(xyl) POH, followed by Ti-mediated reduction with (Et O)-
2 3
SiH gave 6,6′-dichloro-4,4′-diphenyl-2-triflato-2′-bis(xyl)-
phosphino-1,1′-binaphthyl (19), which was then treated
thalene with (xyl)
2
POH, however, gave a mixture of two
with (xyl)
2
PH in the presence of Ni catalyst to give the
separable regioisomers, 4-TMS-2-triflato-2′-bis(xylyl)-
phosphinyl-1,1′-binaphthyl (13a) and 4-bis(TMS)-2-bis-
desired ligand L .
3
4
,4′,6,6′-Tetramethyl-2,2′-bis[bis(xylyl)phosphino]-1,1′-
(
xylyl)phosphinyl-2′-triflato-1,1′-binaphthyl (13b), in
roughly 1:1 ratio. Ti-mediated reduction of this mixture
of regioisomers with (EtO) SiH led to a mixture of mono-
phosphino products (14a and 14b), which was directly
treated with (xyl) PH in the presence of Ni(dppe)Cl
catalyst and DABCO in DMF to afford the desired L
,4′-Diphenyl-6,6′-dichloro-2,2′-bis(bis(xylyl)phosphino)-
,1′-binaphthyl ligand (L ) was obtained in 6 steps
binaphthyl (L
4
) was synthesized in 6 steps starting from
17
4
,4′,6,6′-tetrabromo-2,2′-diethoxy-1,1′-binaphthalene with
3
an overall yield of 31.5% (Scheme 6). Pd-catalyzed
coupling of 4,4′,6,6′-tetrabromo-2,2′-diethoxy-1,1′-binaph-
thalene with trimethyboroxine in DME gave 4,4′,6,6′-
tetramethyl-2,2′-diethoxy-1,1′-binaphthalene (20) in very
2
2
2
.
4
high yield. Subsequent steps leading to the desired L
ligand were analogous to those for the synthesis of L1.
.2. Synthesis and Characterization of Ru Pre-
catalysts Based on 4,4′-Substituted-xylBINAP Lig-
4
1
3
starting from 4,4′-dibromo-6,6′-dichloro-2,2′-diethoxy-1,1′-
2
1
3
binaphthalene with an overall yield of 21.4%. Suzuki
coupling of 4,4′-dibromo-6,6′-dichloro-2,2′-diethoxy-1,1′-
2
ands. Ru(diphosphine)(diamine)Cl precatalysts were
binaphthalene with PhB(OH)
PPh
diethoxy-1,1′-binaphthalene (15) in 73% yield. The ethoxy
groups in 15 were deprotected with BBr in CH Cl and
2
in the presence of Pd-
prepared by the following procedure (Scheme 7). First, a
(
3 4
) in DME afforded 4,4′-diphenyl-6,6′-dichloro-2,2′-
mixture of 4,4′-substituted-xylBINAP ligand and 0.5
2 2
equiv of [Ru(benzene)Cl ] was heated in anhydrous DMF
3
2
2
at 100 °C for 1 h and then cooled to room temperature.
(
16) Lee, S. J. Ph.D. Thesis, University of North Carolina at Chapel
Hill, 2003.
(17) Gong, L.-Z.; Hu, Q.-S.; Pu, L. J. Org. Chem. 2001, 66, 2358.
J. Org. Chem, Vol. 70, No. 4, 2005 1179

Ngo and Lin
SCHEME 4a
a
Reagents and conditions: (i) BBr3, CH2Cl2, rt, 12 h; (ii) Bu(CH3)2SiCl, imidazole, DMAP, CH2Cl2, reflux for 12 h; (iii) (a) nBuLi/
t
n
hexane, -78 °C; (b) (CH3)3SiBr, THF, -78 °C to rt, 12 h; (iv) Bu4NF, THF, rt, 1 h; (v) H2(g), Pd/C, Et3N, MeOH, rt, 12 h; (vi) (Tf)2O,
pyridine, CH2Cl2, rt, 12 h; (vii) HP(O)(Xyl)2, Pd(OAc)2, dppb, Et2N Pr, DMSO, 110 °C, 3 days; (viii) (EtO)3SiH, Ti(O Pr)4, benzene, reflux
for 4 h; (ix) HP(Xyl)2, Ni(dppe)Cl2, DABCO, DMF, 110 °C, 3 days.
i
i
SCHEME 5a
a
Reagents and conditions: (i) Pd(PPh3)4, PhB(OH)2, ethanol, 2M Na2CO3/H2O, DME, reflux for 2 days; (ii) BBr3, CH2Cl2, rt, 12 h; (iii)
i
i
Tf2O, pyridine, CH2Cl2, rt, 12 h; (iv) HP(O)(Xyl)2, Pd(OAc)2, dppb, Et2N Pr, DMSO, 110 °C, 3 days; (v) (EtO)3SiH, Ti(O Pr)4, benzene,
reflux for 4 h; (vi) HP(Xyl)2, Ni(dppe)Cl2, DABCO, DMF, 110 °C, 3 days.
1180 J. Org. Chem., Vol. 70, No. 4, 2005

4,4′-Substituted-XylBINAP Ligands
SCHEME 6a
a
Reagents and conditions: (i) trimethylboroxine, Pd(PPh3)4, 2 M Na2CO3/H2O, DME, reflux for 2 days; (ii) BBr3, CH2Cl2, rt, 1 h; (iii)
i
i
Tf2O, pyridine, CH2Cl2, rt, 12 h; (iv) HP(O)(Xyl)2, Pd(OAc)2, dppb, Et2N Pr, DMSO, 110 °C, 3 days; (v) Ti(O Pr)4, (EtO)3SiH, benzene,
reflux for 4 h; (vi) HP(Xyl)2, Ni(dppe)Cl2, DABCO, DMF, 110 °C, 3 days.
1
31
6
FIGURE 1. Tentative assignments of the H{ P} NMR spectrum of (R,RR)-25 in acetone-d .
SCHEME 7
J. Org. Chem, Vol. 70, No. 4, 2005 1181

Ngo and Lin
TABLE 1. Asymmetric Hydrogenation of Aromatic Ketones by Ru(4,4′-Substituted-xylBINAP)-Based Catalysts
L1
DAIPEN
L1
DPEN
L4
DAIPEN
L4
DPEN
L3
DAIPEN
L3
DPEN
L2
DAIPEN
XylBINAP
5
aromatic ketone
DAIPEN
R ) CH3, Ar ) Ph
99.8
99.9
99.3
98.7
99.5
99.2
98.7
99.6
96.2
98.4
99.1
97.7
96.7
97.1
98.2
97.1
99.1
95.9
99.6
99.5
99.5
99.0
99.1
99.4
99.8
99.6
96.5
99.1
95.5
99.8
98.5
99.1
94.1
92.1
96.1
96.1
97.3
98.7
96.5
95.7
98.3
89.9
91.9
65.9
58.1
71.5
61.7
64.9
76.5
29.9
63.3
47.5
87.9
90.1
85.1
85.5
86.3
96.5
86.1
93.5
77.3
98.4
99.1
97.9
94.9
97.1
97.9
96.3
98.9
95.1
99
R ) CH3, Ar ) 1-Np
R ) CH3, Ar ) 2-Np
R ) CH3, Ar ) p-OMe-Ph
R ) CH3, Ar ) p-Cl-Ph
R ) CH3, Ar ) p-Me-Ph
99
98
100
98
98
N/A
99
N/A
N/A
95.9
99
t
R ) CH3, Ar ) p- Bu-Ph
R ) CH2CH3, Ar ) Ph
R ) cyclopropyl, Ar ) Ph
R ) benzyl, Ar ) Ph
R ) NMe2C2H4-, Ar ) Ph
R ) CH3, Ar ) p-NO2-Ph
99.5
One equivalent of chiral diamine was added to the
mixture, which was then heated at 80 °C for 3 h. After
removing the DMF under vacuum at 50 °C, the desired
Ru(diphosphine)(diamine)Cl precatalysts were purified
2
by using silica gel column chromatography in air. Typical
yields for the Ru precatalysts range from 50% to 60%.
All of the Ru(diphosphine)(diamine)Cl
2
precatalysts
1
1
31
31
1
were characterized by H, H{ P}, and P{ H} NMR
spectroscopy and MALDI-TOF mass spectrometry. As
shown in Figure 1 for the representative Ru(diphos-
phine)(diamine)Cl
2
precatalysts (R,RR)-25, a single set
of signals was observed for both 4,4′-substituted-xylBI-
2
NAP and DPEN ligands, consistent with the C sym-
metric nature of these precatalysts. Tentative assign-
ments for the proton signals of (R,RR)-25 were made
1
1
1
31
based on chemical shifts and H- H and H- P coupling
patterns (Figure 1). It is worth noting that two sets of
2
xylyl and NH protons were observed owing to their
diastereotopic nature. In contrast to the C
2
symmetric
1
symmetric
nature of 25-27, precatalysts 28-31 are C
1
31
and its H{ P} NMR spectra are much more complicated.
The proton spectral assignments and purity of the
2
Ru(diphosphine)(diamine)Cl precatalysts are supported
31
1
by their P{ H} NMR spectra. For example, precatalysts
1
2
5-27 show a single 31P{ H} signal at ∼45 ppm, consis-
2
tent with their C symmetric nature. Precatalysts 28, 30,
and 31 on the other hand show two doublets in their
3
1
1
FIGURE 2. Ball-and-stick presentation (top) and space-filling
model (bottom) for one of the two crystallographically inde-
pendent 27 molecules in the single crystal of (R)-(R,R)-27‚2-
isopropanol. Key: red, Ru; green, Cl; blue, N; purple, P;
medium gray, C; light gray, H. The 4-methyl groups of the
naphthyl ring and of the two xylyl moieties are highlighted in
yellow. Key bond distances and angles: Ru1-N2, 2.111(9) Å;
Ru1-N1, 2.16(1) Å; Ru1-P2, 2.226(8) Å; Ru1-P1, 2.227(8) Å;
Ru1-Cl1, 2.39(2) Å; Ru1-Cl3, 2.40(2) Å; N2-Ru1-N1, 78.3-
P{ H} spectrum owing to different chemical environ-
ments of the two bis(xylyl)phosphino moieties.
Dark yellow crystals of (R)-(R,R)-27‚2-propanol were
obtained by recrystallization from a dichloromethane/2-
propanol mixture and crystallized in the R3 space group
with two molecules of 27 and two molecules of disordered
2
-propanol in the asymmetric unit. The Ru centers of 27
adopt an octahedral coordination environment with the
P atoms of ligand L and the N atoms of DPEN in the
(
2)°; N2-Ru1-P2, 172.3(2)°; N1-Ru1-P2, 94.4(2)°; N2-Ru1-
4
P1, 94.3(2)°; N1-Ru1-P1, 172.0(2)°; P2-Ru1-P1, 93.10(9)°;
N2-Ru1-Cl1, 84.2(3)°; N1-Ru1-Cl1, 82.8(2)°; P2-Ru1-Cl1,
equatorial positions and the two chlorine atoms trans to
each other (Figure 2). The bond distances and angles
around the Ru center are within the normal range
expected for a six-coordinate Ru(II) complex. One of the
9
7.7(2)°; P1-Ru1-Cl1, 93.6(2)°; N2-Ru1-Cl3, 83.2(2)°; N1-
Ru1-Cl3, 84.4(3)°; P2-Ru1-Cl3, 93.5(2)°; P1-Ru1-Cl3, 97.8-
(2)°; Cl1-Ru1-Cl3, 163.6(2)°.
L
4
ligands has a dihedral angle of 75.3° between the
naphthyl rings, while the other L ligand adopts a
4
the DPEN ligand of the Ru center. These three methyl
groups will have significant repulsive interactions with
the bulky aryl ring of the hydrogen-bonded aromatic
ketone in the disfavored transition state. We believe that
such a repulsive interaction is responsible for very high
dihedral angle of 76.3° between the naphthyl rings. It is
clear from the space-filling model of 27 that the 4-methyl
group of the naphthyl ring and the methyl groups of the
two xylyl moieties form a fence on the opposite side of
1182 J. Org. Chem., Vol. 70, No. 4, 2005

4,4′-Substituted-XylBINAP Ligands
enantioselectivity in the hydrogenation of aromatic ke-
this concept to the asymmetric hydrogenation of other
more difficult substrates such as alkyl ketones and
imines.
tones by the 27 precatalyst (see below).
2.3. Asymmetric Hydrogenation of Aromatic Ke-
tones with Use of 4,4′-Substituted-xylBINAP-Based
Catalysts. Ru complexes of 4,4′-substituted-xylBINAP
and chiral diamines 25-31 were used in asymmetric
hydrogenation reactions of a variety of unfunctionalized
ketones. As shown in Table 1, a variety of aromatic
ketones with various substituents can be effectively
hydrogenated with the present Ru(diphosphine)(diami-
4. Experimental Section
4
.1. Synthesis of 4,4′-Bis(trimethylsilyl)-2,2′-[bis(bis-
xylyl)phosphino)]-1,1′-binaphthyl (L ). (a) Synthesis of
R)-6,6′-Dichloro-4,4′-bis(trimethylsilyl)-2,2′-bis(tert-bu-
(
(
1
tyldimethylsiloxy)-1,1′-binaphthalene, 1. To a solution of
(
R)-6,6′-dichloro-4,4′-dibromo-2,2′-bis(tert-butyldimethylsiloxy)-
2
ne)Cl precatalysts. With 0.1 mol % catalyst loading, all
1
,1′-binaphthalene (2.0 g, 2.7 mmol) in 60 mL of anhydrous
n
the ketones in Table 1 were completely hydrogenated
under a hydrogen pressure of 700 psi in 20 h. The combi-
nation of (R)-L and (R)-DAIPEN and (R)-L and (R)-
1 4
THF at -78 °C was added 2.4 mL of 2.5 M BuLi in hexane
dropwise. After the addition, the reaction mixture was allowed
to stir at -78 °C for an additional 4 h, then 0.89 mL (5.0 mmol)
3 3
of (CH ) SiBr was added dropwise over a period of half an hour.
DAIPEN gave the best ee values, greater than 99% for
most of the substrates examined. This level of enantio-
selectivity compares favorably with the performance of
The reaction mixture was allowed to slowly warm to room
temperature and stirred for 12 h, and then it was quenched
with water and extracted with EtOAc and washed with water
2
the Ru(xylBINAP)(DAIPEN)Cl system (last column in
3
4
times. The organic layer was dried over MgSO and the
Table 1). To the best of our knowledge, the enantiose-
lectivity seen for (R,RR)-25 and (R,RR)-27 is the highest
ever reported. We have also carried out hydrogenation
reactions with 0.01% catalyst loading, and aromatic
ketones were hydrogenated with complete conversions
and ee values similar to those listed in Table 1.
organic volatiles were removed under reduced pressure. The
crude product was purified by silica gel column chromatogra-
1
phy (hexane) to give 1.4 g (74% yield) of pure 1. H NMR
4
(CDCl
3
) δ 8.17 (d, JH-H ) 4 Hz, 2H), 7.55 (s, 2H), 7.39 (d,
3
3
4
J
H-H ) 8 Hz, 2H), 7.32 (dd, JH-H ) 8 Hz, JH-H ) 4 Hz, 2H),
13
0
.67 (s, 18H), 0.578 (s, 18H), 0.17 (s, 6H), 0.069 (s, 6H). C-
1
{
H} NMR (CDCl
3
) δ 150.4 (s), 139.1 (s), 133.2 (s), 133.1 (s),
2 2
The 6,6′-(Cl) -4,4′-(Ph) -xylBINAP catalyst systems,
1
(
28.8 (s), 128.5 (s), 128.3 (s), 126.7 (s), 126.1 (s), 122.9 (s), 0.993
however, performed very poorly. We believe that the
phenyl groups may form π-edge interactions with the
aromatic groups of the ketones to stabilize the undesired
diastereomeric transition state and thus reduce the ee
values significantly. The 4-TMS-xylBINAP system per-
formed slightly worse than the Ru(xylBINAP)(DAIPEN)-
s), 0.147 (s), -4.24 (s), -4.31 (s). MS m/z 728.9 (calcd m/z 728.1
+
for [M]
).
(b) Synthesis of (R)-6,6′-Dichloro-4,4′-bis(trimethyl-
silyl)-2,2′-dihydroxy-1,1′-binaphthalene, 2. To a solution
of 1 (1.4 g, 1.9 mmol) in 20 mL of anhydrous THF at room
n
temperature was added 4.0 mL (4 mmol) of 1 M Bu
4
NF in
THF via a syringe. The reaction mixture was allowed to stir
at room temperature for another hour and quenched with
water. The mixture was extracted with EtOAc and washed
2
Cl system, probably a result of adoption of an unfavor-
able dihedral angle by the naphthyl rings owing to the
TMS group in the 4-position. In this case, the ketone
substrate will most likely attack from the catalyst side
without the TMS substituent. The TMS group thus will
not have any beneficial effect except for forcing the
adoption of unfavorable dihedral angle between the
naphthyl rings.
with NH
dried over MgSO
under reduced pressure to give pure product of 2 in quantita-
4
Cl twice and then with water. The organic layer was
4
and the organic volatiles were removed
1
tive yield (0.96 g, >99% yield). H NMR (CDCl
3
) δ 8.10 (d,
4
4
3
J
J
H-H ) 2.1 Hz, 2H), 7.60 (s, 2H), 7.25 (dd, JH-H ) 9 Hz and
3
H-H ) 1.2 Hz, 2H), 7.1 (d, JH-H ) 9.6 Hz, 2H), 4.99 (s, 2H),
1
3
1
0
3
.560 (s, 18H). C{ H} NMR (CDCl ) δ 151.7 (s), 142.3 (s),
We have also tested the performance of the mis-
matched catalyst systems. Ru complexes of (R)-4,4′-bis-
1
33.5 (s), 131.9 (s), 129.6 (s), 127.5 (s), 127.4 (s), 126.7 (s), 126.1
+
(
s), 112.3 (s), 0.131 (s). MS m/z 499.7 (calcd m/z 499.6 for [M] ).
c) Synthesis of (R)-4,4′-Bis(trimethylsilyl)-2,2′-bis-
(hydroxyl)-1,1′-binaphthalene, 3. A mixture of anhydrous
MeOH (40 mL) and Et N (0.84 mL, 6 mmol) was added to 2
(0.8 g, 1.6 mmol) and 0.34 g (0.032 mmol) of 10% Pd on
activated carbon. A balloon of H was connected to the reaction
(
TMS)(xylBINAP)/(S,S)-DPEN and (R)-4-TMS-xylBINAP/
(
(
S,S)-DPEN combinations gave 27.7% and 17.9% ee for
the reduction of acetophenone, respectively. These values
are significantly lower than those of the matched pairs.
The match/mismatch behaviors exhibited by the Ru-
3
2
mixture after outgassing 3 times to remove oxygen, and the
reaction mixture was allowed to stir at room temperature for
2
(diphosphine)(diamine)Cl catalyst systems based on 4,4′-
substituted-xylBINAP are similar to those reported
earlier, such as Xyl-PhanePhos-Ru-DPEN and Xyl-Spiro-
Phos-Ru-DPEN catalyst systems.1
1
2 h. The mixture was filtered through Celite and the solvent
was removed under reduced pressure. The residue was then
dissolved in EtOAc and washed with water 3 times. The
1,12
4
organic layer was dried over MgSO and the organic volatiles
were removed under reduced pressure to obtain pure product
3. Conclusions
1
3
of 3 in quantitative yield. H NMR (acetone-d
6
) δ 8.15 (d, JH-H
3
)
8.1 Hz, 2H), 7.60 (s, 2H), 7.40 (t, JH-H ) 9 Hz, 2H), 7.30 (t,
H-H ) 8.4 Hz, 2H), 7.22 (dd, JH-H ) 8.7 Hz and JH-H ) 0.9
13 1
We have designed and synthesized a family of 4,4′-
3
3
4
J
substituted-xylBINAPs in multistep sequences. Ru(diphos-
phine)(diamine)Cl complexes based on these 4,4′-sub-
Hz), 0.56 (s, 18H). C{ H} NMR (acetone-d
6
) δ 153.1 (s), 140.4
2
(
s), 135.5 (s), 132.9 (s), 128.8 (s), 126.6 (s), 126.3 (s), 126.2 (s),
stituted-xylBINAPs gave the best enantioselectivity for
the hydrogenation of aromatic ketones among all the
chiral diphosphines that have been reported in the
literature. These results support our hypothesis of com-
bining dual modes of enantiocontrol (i.e., the substituents
on 4,4′-postions of the binaphthyl framework and the
methyl groups on the bis(xylyl)phosphino moieties) to
achieve higher stereoselectivity in the hydrogenation of
aromatic ketones. Future work is directed at extending
1
23.2 (s), 116.4 (s), 0.246 (s). MS m/z 430 (calcd m/z 430.2 for
+
[M] ).
(d) Synthesis of (R)-4,4′-Bis(trimethylsilyl)-2,2′-bis-
triflato)-1,1′-binaphthalene, 4. To a solution of 3 (0.65 g,
.5 mmol) in 1 mL of pyridine and 10 mL of CH Cl at 0 °C
was added 1.1 mL (6.2 mmol) of (Tf) O via a syringe. The
reaction mixture was stirred at room temperature for 12 h,
(
1
2
2
2
2 2
extracted with CH Cl , and washed with water 3 times. The
organic layer was dried over MgSO4 and the filtrate was
removed under reduced pressure to give pure product of 4 in
J. Org. Chem, Vol. 70, No. 4, 2005 1183

Ngo and Lin
7.01 (m, 2H), 5 (m, 2H). 13C{ H} NMR (CDCl
) δ 152.8 (s),
3
1
) δ 8.23 (d, 3JH-H ) 9 Hz,
1
quantitative yield. H NMR (CDCl
3
3
3
2
H), 7.75 (s, 2H), 7.60 (t, JH-H ) 8.4 Hz, 2H), 7.39 (t, JH-H
)
152.5 (s), 132.3 (s), 131.7 (s), 131.5 (s), 130.9 (s), 130.2 (s), 130.1
(s), 129.2 (s), 128.9 (s), 128.6 (s), 127.2 (s), 126.8 (s), 126.3 (s),
125.6 (s), 124.5 (s), 123 (s), 119 (s), 110.9 (s), 110 (s). MS m/z
3
13
1
9
Hz, 2H), 7.31 (d, JH-H ) 7.5 Hz, 2H), 0.58 (s, 18H). C{ H}
) δ 145.1 (s), 144.9 (s), 135.9 (s), 133.3 (s), 128.4
s), 127.9 (s), 127.1 (s), 126.8 (s), 125.7 (s), 124.5 (s), 118.2 (q,
NMR (CDCl
3
+
(
434 (calcd m/z 434.1 for [M] ).
1
J
C-F )+ 318 Hz), -0.0362 (s). MS m/z 694.7 (calcd m/z 694.8
(b) Synthesis of (R)-6,6′-Dichloro-4-bromo-2,2′-bis(tert-
for [M] ).
butyldimethylsiloxy)-1,1′-binaphthalene, 8. 7 (0.38 g, 0.88
t
(
e) Synthesis of (R)-4,4′-Bis(trimethylsilyl)-2-triflato-
mmol), 2.6 mL (2.6 mmol) of 1 M Bu(CH
3
)
2
SiCl in THF, 0.19
2
′-bis(xyl)phosphinyl-1,1′-binaphthyl, 5. A mixture of 4 (0.5
g (2.8 mmol) of imidazole, and 0.09 mg (0.7 µmol) of DMAP
were dissolved in 10 mL of CH Cl . The mixture was heated
to reflux for 12 h, cooled to room temperature, extracted with
CH Cl , and washed with water 3 times. The organic layer
was dried over MgSO and the volatiles were removed under
reduced pressure to give 0.45 g (78% yield) of 7. H NMR
g, 0.72 mmol), HOP(xyl)
2
(0.37 g, 1.4 mmol), Pd(OAc)
2
(0.032
N Pr (0.48 mL,
.9 mmol), and 1 mL of DMSO was prepared in a glovebox.
2
2
i
g, 0.14 mmol), dppb (0.061 g, 0.14 mmol), Et
2
2
2
2
The reaction mixture was then heated at 110 °C for 3 days,
allowed to cool to room temperature, and then extracted with
EtOAc and washed with water 5 times. The organic layer was
4
1
4
4
3
(CDCl ) δ 8.23 (d, JH-H ) 2 Hz, 1H), 7.81 (d, JH-H ) 2 Hz,
3
dried over MgSO
under reduced pressure. The residue was purified by using
silica gel chromatography with CH Cl /acetone (20:1) to give
4
and the organic volatiles were removed
1H), 7.75 (d, JH-H ) 12 Hz, 1H), 7.55 (s, 1H), 7.16 (m, 5H),
0.504 (s, 9H), 0.49 (s, 9H), 0.061 (s, 3H), 0.041 (s, 3H), -0.123
(s, 3H), -0.132 (s, 3H). C{ H} NMR (CDCl ) δ 151.4 (s), 151.1
3
13
1
2
2
1
31
pure product of 5 (0.4 g, 70% yield). H{ P} NMR (CDCl
3
) δ
.4 (m, 1H), 8.35 (m, 1H), 7.89 (m, 1H), 7.54 (m, 1H), 7.42 (m,
H), 7.23 (m, 2H), 7.1 (m, 7H), 6.93 (m, 2H), 2.18 (s, 6H), 2.11
(s), 133.3 (s), 132.5 (s), 130.9 (s), 129.7 (s), 129.2 (s), 128.6 (s),
128.4 (s), 127.9 (s), 127.7 (s), 127.1 (s), 127 (s), 126.5 (s), 126
(s), 125.5 (s), 122.1 (s), 121.4 (s), 121.4 (s), 120.9 (s), 24.94 (m),
24.91 (m,), 17.6 (s), 4.33 (s), -4.43 (s), -4.54 (s). MS m/z 662.6
8
2
(
(
(
(
(
3
1
1
s, 6H), 0.55 (s, 9H), 0.4 (s, 9H). P{ H} NMR (CDCl
s). C{ H} NMR (CDCl
m), 135.8 (m), 135.2 (s), 134.2 (s), 133.8 (s), 133.1 (m), 131.9
s), 129.9 (s), 129.6 (m), 128.8 (m), 128.3 (m), 127.9 (m), 126.2
m), 125,2 (s), 118.2 (q, JC-F ) 330 Hz), 20.2 (m), 0.11 (m).
MS m/z 803.8 (calcd m/z 803.0 for [M] ).
3
) δ +29
13
1
+
3
) δ 145.5 (s), 142.8 (s), 139.2 (m), 137.5
(calcd m/z 662.6 for [M] ).
(c) Synthesis of (R)-6,6′-Dichloro-4-trimethylsilyl-2,2′-
bis(tert-butyldimethylsiloxy)-1,1′-binaphthalene, 9. To a
solution of 0.45 g (0.68 mmol) of 8 in 10 mL of THF at -78 °C
was added 0.46 mL of 2.5 M nBuLi in hexane dropwise. After
the addition, the reaction mixture was allowed to stir at -78
1
+
(
f) Synthesis of (R)-4,4′-Bis(trimethylsilyl)-2-triflato-
′-bis(xyl)phosphino-1,1′-binaphthyl, 6. To a solution of 5
in 20 mL of anhydrous benzene were added 82 µL (0.28 mmol)
2
3 3
°C for an additional 4 h. Then 0.14 mL (1.1 mmol) of (CH ) -
SiBr was then added dropwise over a period of a half hour.
The reaction mixture was allowed to warm to room temper-
ature and stirred for 12 h, and then quenched with water and
extracted with EtOAc and washed with water 3 times. The
i
4 3
of Ti(O Pr) and 0.5 mL (2.7 mmol) of (EtO) SiH via a syringe.
The reaction mixture was heated to reflux for 4 h. The solvent
was removed under reduced pressure and passed through a
short silica gel column with CH
Cl
2 2
. The solvent was removed
4
organic layer was dried over MgSO and the organic volatiles
under reduced pressure to give 0.32 g (82% yield) of pure 6.
were removed under reduced pressure. The crude product was
1
31
H{ P} NMR (CDCl
3
) δ 8.15 (m, 2H), 7.71 (m, 2H), 7.5 (m,
purified by using silica gel column chromatography (hexane)
1
2
6
9
7
H), 7.15 (m, 3H), 7.13 (m, 1H), 7.04 (m, 1H), 6.92 (m, 3H),
to give 0.45 g (>99% yield) of pure 9. H NMR (CDCl
3
) δ 8.05
4
4
3
.78 (s, 1H), 6.62 (s, 1H), 2.25 (s, 6H), 2.1 (s
2
, 6H), 0.58 (s,
(d, JH-H ) 2 Hz, 1H), 7.83 (d, JH-H ) 2 Hz, 1H), 7.75 (d, JH-H
) 8 Hz, 1H), 7.45 (s, 1H), 7.21 (m, 5H), 0.553 (s, 9H), 0.525 (s,
9H), 0.453 (s, 9H), 0.0661 (s, 3H), 0.0446 (s, 3H), -0.0584 (s,
H), 0.39 (s, 9H). 31P{ H} NMR (CDCl
1
) δ -11.8 (s). MS m/z
3
+
87.0 (calcd m/z 787.0 for [M] ).
1
3
1
(
g) Synthesis of (R)-4,4′-Bis(trimethylsilyl)-2,2′-bis(bis-
xylyl)phosphino)-1,1′-binaphthyl, L . A mixture of 6 (170
mg, 0.22 mmol), HP(Xyl) (0.078 mL, 0.32 mmol), Ni(dppe)Cl
12 mg, 0.022 mmol), and DABCO (48 mg, 0.43 mmol) was
prepared in a glovebox. The reaction mixture was then
dissolved in 1 mL of anhydrous DMF and heated at 110 °C
for 2 days. The reaction mixture was allowed to cool to room
temperature, extracted with EtOAc, and washed with water
3
3H), -0.0996 (s, 3H). C{ H} NMR (CDCl ) δ 151.3 (s), 150.5
(
1
(s), 139.1 (s), 133.3 (s), 133.2 (s), 132.7 (s), 129.7 (s), 129.1 (s),
128.8 (s), 128.6 (s), 128.2 (s), 128 (s), 127.5 (s), 126.8 (s), 126.7
(s), 126.4 (s), 126.1 (s), 122.7 (s), 122 (s), 121.5 (s), 25 (s), 24.9
(s), 17.6 (s), 17.5 (s), 0.186 (s), -4.18 (s), -4.27 (s), -4.3 (s),
2
2
(
+
-4.45 (s). MS m/z 640.6 (calcd m/z 640.9 for [M] ).
(d) Synthesis of (R)-6,6′-Dichloro-4-trimethylsilyl-2,2′-
dihydroxy-1,1′-binaphthalene, 10. To a solution of 9 (0.45
4
times. The organic layer was dried with MgSO
volatiles were removed under reduced pressure. The residue
was then passed through a short silica gel column with CH
Cl and then with hexane/EtOAc (1:1). The solvents were
removed under reduced pressure to give 120 mg (67% yield)
4
and the
g, 0.69 mmol) in 10 mL of THF at room temperature was added
n
2 mL (2 mmol) of 1 M Bu
4
NF in THF via a syringe. The
2
-
reaction mixture was allowed to stir at room temperature for
another hour and quenched with water. The mixture was
2
extracted with EtOAc and washed with NH
with water. The organic layer was dried over MgSO
organic volatiles were removed under reduced pressure to give
4
Cl twice and then
1
31
of pure L
1
. H{ P} NMR (CDCl
3
) δ 8.11 (m, 2H), 7.78 (s, 2H),
4
and the
7
.40 (m, 2H), 7.02 (m, 4H), 6.75 (m, 12H), 2.16 (s, 12H), 2.10
3
1
1
13
1
(
s, 12H), 0.34 (s, 18H). P{ H} NMR (CDCl
3
) δ -14.6 (s). C-
a pure product of 10 in quantitative yield. H NMR (CDCl
3
) δ
1
4
{
3
H} NMR (CDCl ) δ 138.5 (m), 137.6 (s), 137.3 (s), 137 (m),
8.1 (d, JH-H ) 2 Hz, 1H), 7.82 (m, 1H), 7.6 (s, 1H), 7.34 (m,
1H), 7.15 (m, 5H), 5.27 (s, 2H ), 0.561 (s, 9H). C{ H} NMR
(CDCl ) δ 152.8 (s), 151.8 (s), 142.4 (s), 133.5 (s), 131.9 (s), 131.7
1
3
1
1
36.7 (m), 136.7 (s), 132 (m), 131.9 (s), 131.8 (m), 130.7 (m),
1
29.9 (s), 128.9 (s), 127.8 (s), 125.9 (s), 124.8 (s), 21.2 (s), 0.41
3
+
(
s). MS m/z 879 (calcd m/z 879.2 for [M] ).
(s), 130.4 (s), 129.9 (s), 129.8 (s), 129.4 (s), 128.2 (s), 127.5 (s),
127 (s), 126.6 (s), 126.2 (s), 125.9 (s), 119 (s), 112 (s), 111.3 (s),
4
.2. Synthesis of 4-Trimethylsilyl-2,2′-Bis[bis(xylyl)-
+
phosphino]-1,1′-binaphthal (L
2
). (a) Synthesis of (R)-6,6′-
0.136 (s). MS m/z 428.5 (calcd m/z 428.6 for [M] ).
Dichloro-4-bromo-2,2′-dihydroxy-1,1′-binaphthalene, 7.
To a solution of (R)-6,6′-dichloro-4-bromo-2,2′-diethoxy-1,1′-
(e) Synthesis of (R)-4-Trimethylsilyl-2,2′-dihydroxyl-
1,1′-binaphthalene, 11. A mixture of anhydrous MeOH (5
binaphthalene (0.43 g, 0.88 mmol) in 10 mL of CH
temperature was added 0.25 mL (2.7 mmol) of BBr
Cl
2 2
at room
via a
3
mL) and Et N (0.16 mL, 0.93 mmol) was added to a mixture
3
of 10 (0.16 g, 0.37 mmol) and 10% Pd on activated carbon
(0.079 g, 0.078 mmol). A balloon of H was then attached to
syringe. The reaction mixture was allowed to stir at room
temperature for 1 h. The mixture was quenched with ice water,
2
the reaction mixture and after outgassing 3 times to remove
the oxygen, the reaction mixture was allowed to stir at room
temperature for 12 h. The mixture was filtered through Celite
and the solvents were removed under reduced pressure. The
residue was then extracted with EtOAc and washed with water
extracted with CH
organic layer was dried over MgSO
were removed under reduced pressure to give pure product of
2
Cl
2
, and washed with water 3 times. The
4
and the organic volatiles
1
4
7
in quantitative yield. H NMR (CDCl
Hz, 1H), 7.86 (m, 2H), 7.74 (s, 1H), 7.37 (m, 1H), 7.25 (m, 2H),
3
) δ 8.27 (d, JH-H ) 4
4
3 times. The organic layer was dried over MgSO and the
1184 J. Org. Chem., Vol. 70, No. 4, 2005

4,4′-Substituted-XylBINAP Ligands
organic volatiles were removed under reduced pressure to
(s), 137.6 (m), 137.3 (m), 136.8 (m), 136.4 (m), 135.6 (s), 134.8
(s), 133.5 (s), 132.7 (m), 131.8 (s), 131.6 (s), 131.2 (m), 130.9
(s), 130.7 (s), 130.3 (s), 130.1 (s), 129.9 (s), 129.1 (s), 128.3 (s),
128.1 (s), 127.9 (s), 126.8 (m), 126.4 (s), 126.1 (m), 125.9 (s),
1
obtain pure product of 11 in quantitative yield. H NMR
3
(
(
acetone-d
6
) δ 8.14 (d, JH-H ) 7.5 Hz, 1H), 7.89 (m, 3H), 7.58
3
s, 1H), 7.33 (m, 4H), 7.14 (d, JH-H ) 8.1 Hz, 1H), 7.05 (d,
3
13
1
1
J
H-H ) 8.8 Hz, 1H), 0.546 (s, 9H). C{ H} NMR (acetone-d
δ 154.2 (s), 153.2 (s), 140.4 (s), 135.6 (s), 135.2 (s), 133 (s), 130.3
s), 129.7 (s), 128.8 (s), 128.7 (s), 126.8 (s), 126.6 (s), 126.3 (s),
25.2 (s), 123.5 (s), 123.2 (s), 119.2 (s), 116.3 (s), 114.9 (s), 0.218
6
)
118.2 (q, JC-F ) 318 Hz), 21.2 (s), 21.1 (s), 1.0 (s). MS m/z
+
714.6 (calcd m/z 714.8 for [M] ).
(
(i) Synthesis of (R)-4-Trimethylsilyl-2-bis(xyl)phos-
1
phino-2′-triflato-1,1′-binaphthyl, 14b. To a solution of 13b
+
(
s). MS m/z 358.6 (calcd m/z 358.5 for [M] ).
f) Synthesis of (R)-4-Trimethylsilyl-2,2′-bis(triflato)-
,1′-binaphthalene, 12. To a solution of 11 (0.08 g, 0.31
Cl at 0 °C was
O via a syringe. The reaction
mixture was stirred at room temperature for 12 h, then
extracted with CH Cl and washed with water 3 times. The
organic layer was dried over MgSO and the filtrate was
(0.08 g, 0.11 mmol) in 5 mL of anhydrous benzene were added
i
(
18 µL (0.061 mmol) of Ti(O Pr)
4
and 0.11 mL (0.59 mmol) of
1
3
(EtO) SiH via a syringe. The reaction mixture was heated to
mmol) in 1 mL of pyridine and 10 mL of CH
2
2
reflux for 4 h. The solvents were removed under reduced
pressure and the residue was passed through a short silica
added 0.2 mL (1.1 mmol) of (Tf)
2
gel column with CH
2 2
Cl . The solvent was removed under
1 31
2
2
reduced pressure to give 14b (0.05 g, 64% yield). H{ P} NMR
3
3
4
(CDCl
3
) δ 8.26 (d, JH-H ) 8.4 Hz, 1H), 8.14 (d, JH-H ) 8 Hz,
3 3
removed under reduced pressure to give 0.12 g (92% yield) of
1H), 8.01 (d, JH-H ) 8.4 Hz, 1H), 7.88 (s, 1H), 7.67 (d, JH-H
1
4
3
3
pure 12. H NMR (CDCl
3
) δ 8.27 (d, JH-H ) 7.7 Hz, 1H), 8.15
) 8 Hz, 1H), 7.62 (t, JH-H ) 7.3, 7.4 Hz, 1H), 7.55 (t, JH-H )
3
4
4
(
1
7
(
(
1
-
d, JH-H ) 9.9 Hz, 1H), 8.02 (d, JH-H ) 9 Hz, 1H), 7.79 (s,
7.8, 7.4 Hz, 1H), 7.36 (m, 2H), 7.26 (t, JH-H ) 8.3 Hz, 1H),
4
3
H), 7.65 (d, JH-H ) 9 Hz, 1H), 7.62 (m, 2H), 7.43 (m, 2H),
7.12 (d, JH-H ) 8.4 Hz, 1H), 7.05 (s, 3H), 6.88 (s, 1H), 6.76 (s,
1
3
1
31
1
.32 (m, 2H), -0.609 (s, 9H). C{ H} NMR (CDCl
3
) δ 145.4
1H), 2.37 (s, 6H), 2.21 (s, 6H), 0.51 (s, 9H). P{ H} NMR
13 1
s), 145.1 (s), 145.06 (s), 135.9 (s), 133.3 (s), 133.2 (s), 132.3
s), 131.9 (s), 128.5 (s), 128.3 (s), 127.9 (s), 127.8 (s), 127.3 (s),
3 3
(CDCl ) δ -12.1 (s). C{ H} NMR (CDCl ) δ 145.0 (s), 139 (m),
138.7 (s), 137.5 (m), 137.2 (m), 136.9 (m), 135.8 (m), 133.9 (s),
132.5 (m), 132.1 (s), 131.8 (s), 131.5 (s), 131.1 (s), 130.9 (s),
130.5 (s), 130.2 (m), 129.8 (s), 128.1 (s), 127.8 (m), 127.3 (s),
27.2 (s), 126.9 (s), 125.7 (s), 124.4 (s), 123.6 (s), 119.3 (s),
+
0.0442 (s). MS m/z 622.7 (calcd m/z 622.6 for [M] ).
g) Synthesis of (R)-4-Trimethylsilyl-2-triflato-2′-bis-
xyl)phosphinyl-1,1′-binaphthyl, 13a, and (R)-4-Trimeth-
ylsilyl-2-bis(xyl)phosphinyl-2′-triflato-1,1′-binaphthyl, 13b.
A mixture of 12 (0.07 g, 0.11 mmol), HOP(Xyl) (0.06 g, 0.23
mmol), Pd(OAc) (0.0052 g, 0.023 mmol), dppb (0.007 g, 0.016
N Pr (0.072 mL, 0.44 mmol), and 1 mL of DMSO
1
(
126.8 (s), 126.6 (s), 126.4 (s), 125.7 (s), 119.3 (s), 118 (q, JC-F
(
) 318 Hz), 21.1 (s), 21 (s), 0.99 (s). MS m/z 714.6 (calcd m/z
+
714.8 for [M] ).
2
(j) Synthesis of (R)-4-Trimethylsilyl-2,2′-bis(bis(xylyl)-
2
phosphino)-1,1′-binaphthyl ((R)-L ). A mixture of 14 (0.075
2
i
mmol), Et
2
mg, 0.11 mmol), HP(Xyl) (25 µL, 0.17 mmol), Ni(dppe)Cl
2
2
was prepared in a glovebox. The reaction mixture was heated
at 110 °C for 3 days, allowed to cool to room temperature, and
then extracted with EtOAc and washed with water 5 times.
(0.0034 g, 0.011 mmol), and DABCO (0.016 g, 0.22 mmol) was
prepared in a glovebox. The reaction mixture was then
dissolved in 1 mL of anhydrous DMF and heated at 110 °C
for 2 days. The reaction mixture was allowed to cool to room
temperature and was extracted with EtOAc and washed with
The organic layer was dried over MgSO
4
and the organic
volatiles were removed under reduced pressure. The residue
was purified by using silica gel chromatography with CH
acetone (20:1) to give a mixture of 13a and 13b in 1:1 ratio
2
Cl
2
:
water 4 times. The organic layer was dried over MgSO and
4
the volatiles were removed under reduced pressure. The
residue was then passed through a short silica gel column with
and 99% total yield.
1
31
3
1
3a: H{ P} NMR (CDCl
3
) δ 8.15 (d, JH-H ) 9.3 Hz, 1H),
2 2
CH Cl and then with hexane:EtOAc (1:1). The solvent was
3
3
8
7
7
6
.09 (d, JH-H ) 9.8 Hz, 1H), 7.99 (d, JH-H ) 9.8 Hz, 1H),
removed under reduced pressure to obtain pure product of L
2
)
3
3
1
31
4
.85 (d, JH-H ) 6.8 Hz, 1H), 7.61 (t, JH-H ) 7.4, 6.8 Hz, 1H),
(0.06 g, 71% yield). H{ P} NMR (CDCl
3
) δ 8.07 (d, JH-H
.53 (m, 2H), 7.2 (m, 9H), 6.97 (s, 1H), 2.27 (s, 6H), 2.23 (s,
7.5 Hz, 1H), 7.84 (m, 2H), 7.77 (s, 1H), 7.52 (m, 1H), 7.32 (m,
2H), 7.0 (m, 5H), 6.8 (m, 2H), 6.7 (m, 8H), 2.34 (s, 12H), 2.17
H), 0.619 (s, 9H). 31P{ H} NMR (CDCl
1
) δ +31.5 (s). C{ H}
13
1
3
3
1
1
5
NMR (CDCl
3
) δ 145.5 (s), 142.8 (s), 137.6 (m), 137.2 (m), 136.2
3
(s, 12H), 0.27 (s, 9H). P{ H} NMR (CDCl ) δ -12.2 (d, JP-P
5 13 1
(
(
(
m), 135.2 (s), 134.4 (m), 133.7 (s), 133.1 (m), 132.8 (m), 131.7
3
) 24 Hz), -13.2 (d, JP-P ) 21 Hz). C{ H} NMR (CDCl ) δ
s), 131.5 (s), 130.5 (s), 129.5 (m), 128.7 (m), 128.1 (m), 127.8
138.5 (m), 137.1 (m), 133.2 (m), 132.1 (m), 131.8 (m), 130.7
(m), 130 (m), 128.9 (m), 127.9 (m), 126.3 (s), 125.9 (s), 125.5
(s), 124.7 (s), 21.2 (m), 0.38 (s). MS m/z 807.6 (calcd m/z 807.1
s), 127.2 (s), 126.9 (s), 126.3 (s), 126.1 (s), 125.1 (s), 21.1 (s),
+
-
0.078 (s). MS m/z 730.1 (calcd m/z 730.8 for [M] ).
+
1
31
3
for [M] ).
1
3b: H{ P} NMR (CDCl
3
) δ 8.15 (d, JH-H ) 7.4 Hz, 1H),
3
7
.9 (s, H
3
, 1H), 7.82 (m, 2H), 7.55 (t, JH-H ) 6.9 Hz, 1H), 7.42
4.3. Synthesis of 4,4′-Diphenyl-6,6′-dichloro-2,2′-bis-
(bis(xyl)phosphino)-1,1′-binaphthyl (L ). (a) Synthesis of
3
(R)-4,4′-Diphenyl-6,6′-dichloro-2,2′-diethoxy-1,1′-binaph-
thalene, 15. A mixture of 4,4′-dibromo-6,6′-dichloro-2,2′-
diethoxy-1,1′-binaphthalene (2.0 g, 3.5 mmol), phenylboronic
3
(
t, JH-H ) 7.9 Hz, 1H), 7.25 (m, 4H), 7.05 (m, 5H), 6.93 (m,
3
1
1
2
H), 2.15 (s, 6H), 2.16 (s, 6H), 0.41 (s, 9H). P{ H} NMR
1
3
1
(
(
(
(
(
(
3 3
CDCl ) δ +28.4 (s). C{ H} NMR (CDCl ) δ 149.7 (s), 142.7
m), 141.5 (m), 141 (m), 139.3 (m), 137.2 (s), 136.7 (s), 136.3
m), 135.8 (m), 135.3 (s), 134.9 (s), 133.9 (s), 133.4 (s), 132.5
m), 131.1 (m), 130.9 (m), 130.6 (m), 130.2 (s), 129.5 (s), 129.4
acid (0.92 g, 6.7 mmol), Pd(PPh
3 4
) (0.2 g, 0.18 mmol), 3 mL of
2 M Na CO , 1 mL of ethanol, and 10 mL of DME was prepared
2
3
1
s), 129.2 (s), 121.1 (s), 120.5 (q, JC-F ) 328 Hz), 17.7 (s), -4.67
in a two-neck flask, degassed for ∼3 min, and then heated to
reflux for 2 days. The reaction mixture was extracted with
EtOAc and washed with water 3 times. The organic layer was
+
s). MS m/z 730.4 (calcd m/z 730.8 for [M] ).
(
h) Synthesis of (R)-4-Trimethylsilyl-2-triflato-2′-bis-
(
xyl)phosphino-1,1′-binaphthyl, 14a. To a solution of 13a
4
dried over MgSO and the organic volatiles were removed
(
0.050 g, 0.11 mmol) in 2 mL of anhydrous benzene were added
µL (0.061 mmol) of Ti(O Pr)
EtO)
under reduced pressure. The residue was purified with silica
i
gel chromatography with hexane:EtOAc (20:1) to give pure 15
8
(
4
and 0.11 mL (0.59 mmol) of
1
SiH via a syringe. The reaction mixture was heated to
(1.4 g, 73% yield). H NMR (CDCl
3
) δ 7.87 (s, 2H), 7.58 (m,
3
3
reflux for 4 h. The solvents were removed under reduced
pressure and the residue was passed through a short silica
10H), 7.39 (s, 2H), 7.19 (s, 4H), 4.11 (m, 4H), 1.14 (t, JH-H
6 Hz, 6H). C{ H} NMR (CDCl
)
1
3
1
3
) δ 153.9 (s), 141 (s), 140.1 (s),
gel column with CH
2
Cl
2
. The solvent was removed under
132.8 (s), 130 (s), 129.6 (s), 128.5 (s), 128.1 (s), 127.7 (s), 127.4
(s), 126.9 (s), 124.9 (s), 119.4 (s), 117.5 (s), 65.1 (s), 14.9 (s).
1
31
reduced pressure to give 14a (0.035 g, 60% yield). H{ P}
3
MS m/z 563.4 (calcd m/z 563.5 for [M] ).
+
NMR (CDCl
3
) δ 8.25 (d, JH-H ) 8.32 Hz, 1H), 7.99 (m, 2H),
7
.79 (s, 1H), 7.59 (m, 4H), 7.37 (m, 1H), 7.27 (m, 1H), 7.20 (t,
(b) Synthesis of (R)-4,4′-Diphenyl-6,6′-dichloro-2,2′-
3
J
H-H ) 8 Hz, 1H), 7.05 (m, 4H), 6.86 (s, 1H), 6.71 (s, 2H),
31 1
dihydroxy-1,1′-binaphthalene, 16. To a solution of 15 (0.70
2.33 (s, 6H), 2.18 (s, 6H), 0.669 (s, 9H). P{ H} NMR (CDCl
3
)
g, 1.2 mmol) in 10 mL of CH
2
Cl
3
2
at room temperature was
via a syringe. The reaction
1
3
1
3
δ -11.2 (s). C{ H} NMR (CDCl ) δ 144.9 (s), 142.9 (s), 137.9
added 0.45 mL (4.8 mmol) of BBr
J. Org. Chem, Vol. 70, No. 4, 2005 1185

Ngo and Lin
mixture was stirred at room temperature for 12 h, quenched
with ice water, extracted with CH Cl , and washed with water
times. The organic layer was dried over MgSO and the
temperature and then extracted with EtOAc and washed with
2
2
4
water 4 times. The organic layer was dried with MgSO and
3
4
the volatiles were removed under reduced pressure. The
residue was then passed through a short silica gel column with
organic volatiles were removed under reduced pressure to give
1
4
pure 16 in quantitative yield. H NMR (CDCl
3
) δ 7.92 (d, JH-H
CH
obtain pure product of R-L
(CDCl ) δ 7.91 (s, 2H), 7.57 (s, 2H), 7.49 (m, 12H), 6.85 (m,
4H), 6.8 (s, 4H), 6.74 (s, 2H), 6.68 (s, 2H), 2.12 (s, 12H), 2.08
2 2
Cl . The solvent was removed under reduced pressure to
3
1 31
)
)
2 Hz, H
5
, 2H), 7.59 (m, 10H), 7.39 (s, H
3
, 2H), 7.29 (dd, JH-H
3
(0.051 g, 57% yield). H{ P} NMR
4
3
8 Hz and JH-H ) 2 Hz, H
7
, 2H), 7.21 (d, JH-H ) 8 Hz, H
) δ 152.3 (s), 143.1
s), 139.1 (s), 132.3 (s), 130.2 (s), 129.8 (s), 128.6 (s), 128 (s),
26.2 (s), 125.6 (s), 126.3 (s), 125.6 (s), 119.8 (s), 110.7 (s). MS
8
,
3
13
1
2
(
H), 5.2 (s, -OH, 2H). C{ H} NMR (CDCl
3
3
1
1
13
1
(s, 12H). P{ H} NMR (CDCl
3
) δ -12.4 (s). C{ H} NMR
1
(CDCl ) δ 140.1 (s), 139.3 (s), 137.4 (m), 137.2 (m), 132.5 (m),
3
+
m/z 507.5 (calcd m/z 507.4 for [M] ).
c) Synthesis of (R)-4,4′-Diphenyl-6,6′-dichloro-2,2′-bis-
triflato)-1,1′-binaphthalene, 17. To a solution of 16 (0.63
g, 1.2 mmol) in 1 mL of pyridine and 10 mL of CH Cl at 0 °C
was added 0.7 mL (3.6 mmol) of (Tf) O via a syringe. The
reaction mixture was stirred at room temperature for 12 h,
extracted with CH Cl , and washed with water 3 times. The
organic layer was dried over MgSO and the organic volatiles
131.9 (m), 130.2 (m), 129.4 (m), 129.3 (s), 128.4 (s), 127.5 (s),
(
126.1 (s), 124.6 (s), 21.2 (s), 21.1 (s). MS m/z 956 (calcd m/z
+
(
956 for [M] ).
2
2
4.4. Synthesis of 4,4′,6,6′-Tetramethyl-2,2′-bis(bis(xyl)-
phosphino)-1,1′-binaphthyl (L ). (a) Synthesis of (R)-
4
2
4,4′,6,6′-Tetramethyl-2,2′-diethoxy-1,1′-binaphthalene, 20.
A mixture of 4,4′,6,6′-tetrabromo-2,2′-diethoxy-1,1′-binaphtha-
lene (1.5 g, 2.4 mmol), trimethylboroxine in 50 wt % THF (4
2
2
4
were removed under reduced pressure to give pure product of
3 4 2 3
mL), Pd(PPh ) (0.14 g, 0.012 mmol), and 2 M Na CO (4.5
1
4
1
7 in quantitative yield. H NMR (CDCl
3
) δ 8.02 (d, JH-H ) 4
mL) was dissolved in 20 mL of DME. The reaction mixture
was degassed for ∼3 min, heated to reflux for 2 days, extracted
with EtOAc, and washed with water 3 times. The organic layer
3
4
Hz, 2H), 7.73 (m, 12H), 7.55 (dd, JH-H ) 8 Hz and JH-H ) 4
3
13
1
Hz, 2H), 7.48 (d, JH-H ) 8 Hz, 2H). C{ H} NMR (CDCl
3
) δ
1
44.9 (s), 144.4 (s), 137.9 (s), 134 (s), 132 (s), 131.8 (s), 129.9
4
was dried over MgSO and the volatiles were removed under
(
1
7
s), 129.0 (s), 128.9 (s), 128.8 (s), 128.7 (s), 125.8 (s), 122.4 (s),
reduced pressure. The crude product was purified by using
1
21.3 (s), 118.2 (q, JC-F ) 318 Hz). MS m/z 771.4 (calcd m/z
silica gel column with toluene to give 1.2 g (88% yield) of 20.
+
1
71.5 for [M] ).
3
H NMR (CDCl ) δ 7.78 (s, 2H), 7.28 (s, 2H), 7.07 (s, 4H), 4.2
13 1
(
d) Synthesis of (R)-4,4′-Diphenyl-6,6′dichloro-2-tri-
(m, 4H), 2.80 (s, 6H), 2.49 (s, 6H), 1.8 (m, 6H). C{ H} NMR
flato-2′-bis(xyl)phosphinyl-1,1′-binaphthyl, 18. A mixture
3
(CDCl ) δ 153.3 (s), 134.5 (s), 132.6 (s), 132.5 (s), 128.6 (s), 127.9
of 17 (0.15 g, 0.19 mmol), HOP(xyl)
2
(0.065 g, 0.25 mmol), Pd-
(0.004 g, 0.019 mmol), dppb (0.008 g, 0.019 mmol),
N Pr (0.48 mL, 0.57 mmol), and 1 mL of DMSO was
(s), 126.2 (s), 123.1 (s), 119.2 (s), 117.4 (s), 65.3 (s), 21.7 (s),
+
(
Et
OAc)
2
2
19.9 (s), 15.1 (s). MS m/z 370 (calcd m/z 370.5 for [M] ).
i
(b) Synthesis of (R)-4,4′,6,6′-Tetramethyl-2,2′-dihydroxy-
prepared in a glovebox. The reaction mixture was then heated
at 110 °C for 3 days. The mixture was then extracted with
EtOAc and washed with water 5 times. The organic layer was
1,1′-binaphthalene, 21. To a solution of 20 (1.2 g, 3.2 mmol)
in 10 mL of CH
mmol) of BBr
to stir at room temperature for 12 h, quenched with ice water,
then extracted with CH Cl , and washed with water 3 times.
The organic layer was dried over MgSO and the volatiles were
removed under reduced pressure to give pure product of 21 in
2
Cl
2
at room temperature was added 2 mL (13
3
via a syringe. The reaction mixture was allowed
dried over MgSO
under reduced pressure. The residue was purified by using
silica gel chromatography with CH Cl :acetone (20:1) to give
.09 g (53% yield) of pure 18. H{ P} NMR (CDCl ) δ 7.95 (d,
H-H ) 2 Hz, 1H), 7.88 (d, JH-H ) 2 Hz, 1H), 7.73 (s, H
H), 7.5 (m, 10H), 7.25 (m, 2H), 7.15 (m, 2H), 7.0 (m, 7H), 2.2
4
and the organic volatiles were removed
2
2
2
2
4
1
31
0
3
4
4
1
J
3
,
3
quantitative yield. H NMR (CDCl ) δ 7.8 (s, 2H), 7.22 (s, 2H),
3 4 3
1
7.15 (dd, JH-H ) 9 Hz and JH-H ) 3 Hz, 2H), 7.08 (d, JH-H
13 1
3
1
1
13
1
(
s, 6H), 2.1 (s, 6H). P{ H} NMR (CDCl
) δ 145.3 (s), 142.5 (s), 141.8 (s), 140.4 (s), 140.3
s), 139.3 (s), 139.2 (s), 138.9 (s), 138.5 (s), 138.4 (s), 138.2 (s),
3
) δ +29.2 (s). C{ H}
3
) 9 Hz, 2H), 2.77 (s, 6H), 2.50 (s, 6H). C{ H} NMR (CDCl )
NMR (CDCl
3
δ 151.6 (s), 137.4 (s), 133.2 (s), 131.8 (s), 129.1 (s), 128.9 (s),
(
1
124.8 (s), 123.8 (s), 118.3 (s), 109.0 (s), 21.6 (s), 19.5 (s). MS
+
37.9 (s), 137.8 (s), 137.7 (s), 137.6 (s), 137.3 (s), 137.2 (s), 135.3
m/z 342.4 (calcd m/z 342.4 for [M] ).
(
(
(
(
m), 134.8 (s), 134.4 (m), 133.8 (m), 133.4 (m), 133 (s), 132.8
s), 132.3 (s), 131.6 (s), 131.5 (s), 131.3 (s), 130.9 (m), 130.8
m), 130 (s), 129.5 (m), 129.1 (m), 128.5 (m), 128.8 (m), 127
m), 125.9 (s), 125.3 (m), 125 (m), 124.4 (m), 120.6 (s), 118 (q,
(c) Synthesis of (R)-4,4′,6,6′-Tetramethyl-2,2′-bis(tri-
flato)-1,1′-binaphthalene, 22. To a solution of 21 (0.46 g, 1.3
mmol) in 1 mL of pyridine and 10 mL of CH Cl at 0 °C was
2
2
added 1 mL of (Tf) O via a syringe. The reaction mixture was
2
1
J
C-F ) 320 Hz), 22.2 (s). MS m/z 879.7 (calcd m/z 879.7 for
stirred for an additional 12 h. The reaction mixture was then
extracted with CH Cl and washed with water 3 times. The
+
[
M] ).
2
2
(
e) Synthesis of (R)-4,4′-Diphenyl-6,6′dichloro-2-tri-
4
organic layer was dried over MgSO and the volatiles were
flato-2′-bis(xyl)phosphino-1,1′-binaphthyl, 19. To a solu-
removed under reduced pressure to give 0.5 g (61% yield) of
1
3
tion of 18 (0.09 g, 0.1 mmol) in 5 mL of anhydrous benzene
22. H NMR (CDCl
3
) δ 7.88 (s, 2H), 7.40 (s, 2H), 7.22 (d, JH-H
i
4
3
were added 16 µL (0.054 mmol) of Ti(O Pr)
4
and 99 µL (0.53
) 9.9 Hz and JH-H ) 1.5 Hz, 2H), 7.15 (d, JH-H ) 9.0 Hz,
1
3
1
mmol) of (EtO)
3
SiH via a syringe. The reaction mixture was
3
2H), 2.84 (s, 6H), 2.54 (s, 6H). C{ H} NMR (CDCl ) δ 144.4
heated to reflux for 4 h. The solvent was removed under
reduced pressure and the residue was then passed through a
(s), 138.5 (s), 136.9 (s), 131.9 (s), 131.5 (s), 129.7 (s), 127.4 (s),
123.7 (s), 121.5 (s), 119.7 (s), 21.9 (s), 19.7 (s). MS m/z 606.8
+
short silica gel column with CH
2
Cl
2
. CH
2
Cl
2
was removed
(calcd m/z 606.6 for [M] ).
under reduced pressure to give 0.08 g (>99% yield) of pure
(d) Synthesis of (R)-4,4′,6,6′-Tetramethyl-2-triflato-2′-
bis(xylyl)phosphinyl-1,1′-binaphthyl, 23. A mixture of 22
(0.3 g, 0.49 mmol), HOP(xyl) (0.26 g, 0.9 mmol), Pd(OAc)
1
31
1
9. H{ P} NMR (CDCl
3
) δ 8.0 (m, 2H), 7.6 (m, 13H), 7.31
(
m, 2H), 7.1 (m, 1H), 6.95 (m, 4H), 6.85 (s, 1H), 6.65 (m, 1H),
2
2
3
1
1
i
2
.25 (s, 6H), 2.15 (s, 6H). P{ H} NMR (CDCl
3
) δ -10.4 (s).
(0.022 g, 0.097 mmol), dppb (0.042 g, 0.099 mmol), Et N Pr
2
(0.33 mL, 2.0 mmol), and 1 mL of DMSO was prepared in a
glovebox. The reaction mixture was then heated at 110 °C for
3 days, extracted with EtOAc, and washed with water 5 times.
1
3
1
C{ H} NMR (CDCl
3
) δ 144.4 (s), 142.8 (s), 140.5 (s), 139.7
(
(
(
s), 138.3 (m), 136.6 (m), 133.5 (s), 133.4 (m), 132.2 (m), 131.8
m), 130.8 (m), 130.2 (m), 129.4 (m), 127.9 (m), 127.4 (s), 125.3
m), 121.4 (s), 21.5 (s). MS m/z 863.6 (calcd m/z 863.8 for [M] ).
+
The organic layer was dried over MgSO and the volatiles were
4
(
f) Synthesis of (R)-4,4′-Diphenyl-6,6′dichloro-2,2′-bis-
bis(xyl)phosphino)-1,1′-binaphthyl ((R)-L ). A mixture of
9 (80 mg, 0.093 mmol), HP(Xyl) (34 µL, 0.14 mmol), Ni(dppe)-
(12 mg, 9.3 µmol), and DABCO (24 mg, 0.19 mmol) was
removed under reduced pressure. The residue was purified by
(
3
using silica gel chromatography with CH
Cl
2 2
:acetone (20:1) to
) δ 7.85 (s,
, 1H), 7.62 (s, 1H), 7.10 (m, 4H), 6.10 (m, 5H),
6.82 (m, 2H), 2.74 (s), 2.63 (s), 2.52 (s), 2.49 (s), 2.20 (s, 6H),
1
31
1
2
give 0.31 g (88% yield) of 23. H{ P} NMR (CDCl
1H), 7.76 (s, H
3
Cl
2
3
prepared in a glovebox. The reaction mixture was then
dissolved in 1 mL of anhydrous DMF and heated at 110 °C
for 2 days. The reaction mixture was allowed to cool to room
3
1
1
13
1
2.04 (s, 6H). P{ H} NMR (CDCl
(CDCl ) δ 144.7 (s), 137.9 (s), 137.6 (s), 137.4 (s), 136.9 (s), 136.8
3
) δ +30.8 (s). C{ H} NMR
3
1186 J. Org. Chem., Vol. 70, No. 4, 2005

4,4′-Substituted-XylBINAP Ligands
1
31
(
(
(
(
s), 136.7 (s), 136.1 (s), 134.6 (s), 134.4 (s), 133.9 (m), 132.9
m), 132.4 (s), 132.2 (m), 131.2 (s), 129.5 (m), 128.9 (s), 128.6
s), 127.8 (s), 123.3 (s), 123 (s), 118.9 (s), 21.9 (s), 21.7 (s), 21
4 2 3
Ru[(R)-L )][(R,R)-DPEN]Cl , 27: H{ P} NMR (CDCl ) δ
8.15 (s, 2H), 7.68 (s, 8H), 7.55 (s, 2H), 7.04 (m, 5H), 6.81 (m,
3
3
5H), 6.51 (d, JH-H ) 8.8 Hz, 2H), 6.03 (d, JH-H ) 9.7 Hz,
s), 20.9 (s), 19.7 (s), 19.5 (s). MS m/z 715.2 (calcd m/z 714.8
2H), 5.83 (s, 4H), 4.18 (m, 2H), 3.16 (m, 2H), 3.0 (m, 2H), 2.77
+
31
1
for [M] ).
(s, 6H), 2.37 (s, 6H), 2.26 (s, 12H), 1.78 (s, 12H). P{ H} NMR
(
3
CDCl ) δ +44.1 (s). MS m/z 1139.9 (calcd m/z 1139.4 for [M -
(
e) Synthesis of (R)-4,4′,6,6′-Tetramethyl-2-triflato-2′-
+
Cl] ).
Ru[(R)-L
) δ 8.80 (s, 1H), 8.68 (s, 1H), 8.02 (m, 2H), 7.77 (s, 2H), 7.59
bis(xyl)phosphino-1,1′-binaphthyl, 24. To a solution of 23
1
31
(
0.31 g, 0.43 mmol) in 5 mL of anhydrous benzene were added
1 2
)][(R)-DAIPEN]Cl , 28: H{ P} NMR (acetone-
i
7
2 µL (0.24 mmol) of Ti(O Pr)
4
and 0.5 mL (2.7 mmol) of
d
6
(EtO) SiH via a syringe. The reaction mixture was then heated
3
(s, 2H), 7.44 (m, 5H), 7.24 (m, 2H), 7.12 (s, 1H), 6.92 (m, 4H),
6.79 (m, 2H), 6.6 (m, 2H), 6.06 (m, 4H), 5.68 (s, 2H), 4.64 (m,
1H), 4.16 (m, 1H), 3.93 (s, 3H), 3.82 (s, 3H), 3.3 (m, 1H), 2.83
(m, 3H), 2.67 (m, 1H), 2.52 (m, 1H), 2.35 (m, 3H), 2.0 (s, 12H),
to reflux for 4 h. The organic solvents were removed under
reduced pressure and the crude product was passed through
a short silica gel column with CH
2 2
Cl . The solvent was then
3
1
1
removed under reduced pressure to give 0.30 g (>99% yield)
1.82 (s, 12H), 0.66 (s, 9H), 0.57 (s, 9H). P{ H} NMR (acetone-
1
31
5
5
of 24. H{ P} NMR (CDCl
3
) δ 7.80 (m, 2H), 7.31 (m, 2H), 7.1
6
d ) δ +47.8 (d, JP-P ) 40 Hz) and +45.3 (d, JP-P ) 40 Hz).
+
(
2
s, 2H), 6.91 (m, 6H), 6.63 (s, 2H), 2.80 (s, 3H), 2.65 (s, 3H),
.49 (s, 3H), 2.48 (s, 3H), 2.23 (s, 12H), 2.10 (s, 12H). P{ H}
MS m/z 1294.1 (calcd m/z 1294.5 for [M - 2Cl] ).
3
1
1
1
31
Ru[(R)-L )][(R)-DAIPEN]Cl , 29: H{ P} NMR (acetone-
2
2
1
3
1
1 31
NMR (CDCl
3
) δ -11.0 (s). C{ H} NMR (CDCl
3
) δ 144.2 (m),
d ) H{ P} NMR spectrum indicated that there are two
6
1
1
1
37.5 (m), 137(m), 136.3 (m), 135.3 (m), 134.5 (s), 133.1 (s),
diastereometers. Phosphorus proton decoupled spectrum showed
3
1
1
32.5 (s), 131.3 (m), 130 (m), 129.9 (m), 129.7 (m), 127.5 (s),
four sets of phosphorus peaks. P{ H} NMR (acetone-d ) δ
6
5
5
23.3 (m), 119.7 (s), 21.9 (s), 21.8 (s), 21.2 (s), 21.1 (s), 19.7
+48.1 (d, J
) 38 Hz), +46.8 (d, J
P-P
) 37 Hz), +45.8 (d,
P-P
+
5
5
(
m). MS m/z 699 (calcd m/z 698.8 for [M] ).
J
) 38 Hz), and +44.4 (d, J
P-P
) 38 Hz). MS m/z 1292.1
P-P
+
(
f) Synthesis of (R)-4,4′,6,6′-Tetramethyl-2,2′-bis(bis-
xyl)phosphino)-1,1′-binaphthyl ((R)-L ). A mixture of 24
(0.18 mL, 0.6 mmol), Ni(dppe)Cl
0.06 g, 0.04 mmol), and DABCO (0.12 g, 0.8 mmol) was
(calcd m/z 1292.4 for [M] ).
2 3
Ru[(R)-L )][(R)-DAIPEN]Cl , 30: H{ P} NMR (CDCl )
1
31
(
4
3
(
(
0.3 g, 0.4 mmol), HP(Xyl)
2
2
δ 8.50 (s, 1H), 8.37 (s, 1H), 7.82 (m, 4H), 7.75 (m, 2H), 7.7 (s,
2H), 7.53 (m, 10H), 7.35 (m, 4H), 6.92 (s, 1H), 6.78 (m, 7H),
6.65 (m, 2H), 6.13 (m, 2H), 6.05 (s, 1H), 5.99 (s, 1H), 4.25 (m,
1H), 4.58 (m, 2H), 4.08 (m, 2H), 3.85 (s, 3H), 3.75 (s, 3H), 3.27
(m, 2H), 2.5 (m, 3H), 2.26 (s, 6H), 2.23 (m, 3H), 1.99 (s, 6H),
prepared in a glovebox. One milliliter of anhydrous DMF was
added to the reaction mixture and the resulting mixture was
heated at 110 °C for 2 days. The reaction mixture was allowed
to cool to room temperature and then extracted with EtOAc
and washed with water 4 times. The organic layer was dried
31
1
5
1.77 (s, 6H), 1.72 (s, 6H). P{ H} NMR (CDCl
) 37 Hz) and +43.8 (d, JP-P ) 38 Hz). MS m/z 1442.7 (calcd
3
) δ +46 (d, JP-P
5
+
over MgSO
pressure. The residue was then passed through a short silica
gel column with CH Cl , and the solvent was then removed
under reduced pressure to give 0.23 g (68% yield) of L
{
4
and the volatiles were removed under reduced
m/z 1442.3 for [M] ).
1
H{31P} NMR (CDCl3)
Ru[(R)-L )][(R)-DAIPEN]Cl , 31:
4
2
2
2
δ 8.21 (s, 1H), 8.05 (s, 1H), 7.70 (s, 2H), 7.63 (s, 1H), 7.59 (s,
1H), 7.56 (s, 2H), 7.35 (m, 5H), 7.04 (s, 1H), 6.84 (m, 5H), 6.71
(m, 2H), 6.54 (m, 2H), 5.98 (m, 4H), 4.52 (m, 1H), 4.04 (m,
1H), 3.84 (s, 3H), 3.74 (s, 3H), 3.32 (m, 1H), 2.74 (m, 6H), 2.65
(m, 1H), 2.34 (m, 1H), 2.35 (s, 6H), 2.28 (s, 6H), 1.74 (m, 24H).
1
4
. H-
) δ 7.78 (s, 2H), 7.35 (s, 2H), 6.97 (m, 4H),
.82 (m, 12H), 2.72 (s, 6H), 2.56 (s, 6H), 2.23 (s, 12H), 2.10 (s,
31
P} NMR (CDCl
3
6
31
1
13
1
1
3 3
2H). P{ H} NMR (CDCl ) δ -10.3 (s). C{ H} NMR (CDCl )
δ 144.7 (m), 144.3 (m), 138.4 (m), 137.9 (m), 137 (m), 136.8
31P{
1
H} NMR (CDCl ) δ +47.4 (d,
P-P
).
5
JP-P ) 39 Hz) and +45.2
) 36 Hz). MS m/z 1206.1 (calcd m/z 1206.5 for [M -
3
(
(
(
m), 135.9 (s), 134.2 (m), 133.2 (s), 132.9 (s), 132 (m), 131.5
s), 131.3 (s), 130.6 (m), 129.9 (s), 128.7 (s), 127.2 (s), 123.3
(d,
5
J
+
2Cl]
s), 21.9 (s), 21.2 (s), 21.1 (s), 19.7 (s). MS m/z 791.1 (calcd m/z
4
.6. A Typical Procedure for Asymmetric Hydrogena-
tion of Aromatic Ketones. Ru(disphosphine)(diamine)Cl
precatalyst (3.3 mg, 3.3 µmol) and 2 mol % of KO Bu were
transferred into a 1-dram vial in a glovebox. After the addition
of 1-acetonaphthone (0.5 mL, 3.3 mmol), the reaction mixture
was quickly transferred into a stainless steel autoclave and
sealed. After purging with H six times, the final H pressure
was adjusted to 700 psi. After 24 h, the autoclave was
depressurized and the reaction mixture was washed with
diethyl ether and water twice. The diethyl ether layer was then
passed through a mini silica gel column. An aliquot was
analyzed on GC to give conversion and ee values. The absolute
configurations of enantioenriched products from the present
experiments were assigned based on GC to be same as those
samples obtained from Ru-BINAP catalyzed reactions.
+
7
91 for [M] ). [R]
D
+210.6 (CH
2
Cl
2
, c 0.05).
2
t
4
.5. A Typical Procedure for the Synthesis of Ru-4,4′-
Substituted-xylBINAP-Diamine Precatalysts. A mixture
of [Ru(benzene)Cl
1
8
2
]
2
1
(7.1 mg, 0.014 mmol) and L (37.4 mg,
0
.029 mmol) in anhydrous DMF (2 mL) was heated at 100 °C
under nitrogen for 1 h and was then cooled to room temper-
ature. (R,R)-DPEN (6.3 mg, 0.025 mmol) was added to the
mixture. With stirring, DPEN slowly dissolved in the solution
in approximately 15 min and the color of the solution changed
from orange-red to yellow. After the mixture was stirred at
2
2
8
0 °C for 3 h and at room temperature for 12 h, DMF was
removed under vacuum at room temperature and then at 50
C. The residue was purified with silica gel column chroma-
°
tography in air with a mixture of hexane:EtAOc (4:1) to give
2
3 mg (61% yield) of pure (R,RR)-25 precatalyst.
1
31
Ru[(R)-L
1 2
)][(R,R)-DPEN]Cl , 25: H{ P} NMR (acetone-
3
Acknowledgment. We thank NSF (CHE-0208930)
for financial support. We thank Dr. Aiguo Hu for helpful
discussions and Dr. Chuande Wu for help with X-ray
structural analyses. W.L. is an A.P. Sloan Fellow, a
Beckman Young Investigator, a Cottrell Scholar of
Research Corp, and a Camille Dreyfus Teacher-Scholar.
d
6
) δ 8.54 (s, 2H), 7.90 (d, JH-H ) 8.8 Hz, 2H), 7.38 (m, 5H),
3
7
8
.20 (t, JH-H ) 7.3 and 7.8 Hz, 2H), 7.15 (m, 5H), 6.87 (m,
3
3
H), 6.73 (t, JH-H ) 7.4 and 7.9 Hz, 2H), 6.14 (d, JH-H ) 8.3
Hz, 2H), 6.05 (s, 4H), 4.26 (m, 2H), 3.56 (m, 2H), 3.03 (m, 2H),
31
1
2
3
.26 (s, 12H), 1.78 (s, 12H), 0.51 (s, 18H). P{ H} NMR (CDCl )
+
δ +46.5 (s). MS m/z 1226.7 (calcd m/z 1226.9 for [M - Cl] ).
1
31
3 2 3
Ru[(R)-L )][(R,R)-DPEN]Cl , 26: H{ P} NMR (CDCl ) δ
8
4
(
2
.40 (s, 2H), 7.88 (s, 2H), 7.84 (m, 2H), 7.66 (s, 4H), 7.61 (m,
Supporting Information Available: Detailed chiral GC
conditions, H{ P} NMR spectra of (R)-L1-4
spectra of (R,RR)-25, -27, and -28, representative chiral GC
traces for the secondary alcohol products with (R,R)-28, and
crystallographic data (CIF file). This material is available free
of charge via the Internet at http://pubs.acs.org.
1
31
31
1
H), 7.5 (m, 6H), 7.07 (m, 6H), 6.78 (m, 6H), 6.72 (m, 2H), 6.28
,
P{ H} NMR
3
d, JH-H ) 9.2 Hz, 2H), 6.05 (s, 4H), 4.22 (m, 2H), 3.27 (m,
3
1
1
H), 3.04 (m, 2H), 2.20 (s, 12H), 1.77 (s, 12H). P{ H} NMR
+
(CDCl
3
) δ +43.9 (s). MS m/z 1340.8 (calcd m/z 1340.2 for [M] ).
(18) Zelonka, R. A.; Baird, M. C. Can. J. Chem. 1972, 50, 3063.
JO048333S
J. Org. Chem, Vol. 70, No. 4, 2005 1187