A new atropisomeric P,N ligand for rhodium-catalyzed asymmetric hydroboration

Article abstract of DOI:10.1021/jo0159542

A new optically active and large dihedral angle atropisomeric P,N ligand, pyphos, which contains a tertiary phosphine and pyridine moiety, was prepared and resolved through diastereomeric complexation with chiral palladium amine complexes. The hexafluorophosphate salt of the diastereomers were found to be separable by fractional recyrstallization, while the corresponding chloride salt did not. [Rh(COD)pyphos] PF₆ complex was synthesized by metalation of pyphos with [Rh(COD)Cl]₂ followed by anion exchange with NH4PF6 in excellent yield, and the target rhodium complex was characterized by single-crystal X-ray crystallography. The chiral cationic rhodium complex was utilized in the enantioselective hydroboration of vinylarenes. Excellent regioselectivity and good enantioselectivity were observed, and the ee values were found to be dependent on the electronic properties of para-substituted styrenes.

Full text of DOI:10.1021/jo0159542

J . Org. Chem. 2002, 67, 2769-2777
2769
A New Atr op isom er ic P ,N Liga n d for Rh od iu m -Ca ta lyzed
Asym m etr ic Hyd r obor a tion
Fuk Yee Kwong,†,‡ Qingchuan Yang,† Thomas C. W. Mak,† Albert S. C. Chan,§ and
Kin Shing Chan*,†
Department of Chemistry, Open Laboratory of Chirotechnology of the Institute of Molecular Technology
for Drug Discovery and Synthesis, The Chinese University of Hong Kong, Shatin, New Territories,
Hong Kong, and Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic
University, Hung Hom, Hong Kong
ksc@cuhk.edu.hk
Received J uly 20, 2001
A new optically active and large dihedral angle atropisomeric P,N ligand, pyphos, which contains
a tertiary phosphine and pyridine moiety, was prepared and resolved through diastereomeric
complexation with chiral palladium amine complexes. The hexafluorophosphate salt of the
diastereomers were found to be separable by fractional recyrstallization, while the corresponding
chloride salt did not. [Rh(COD)pyphos]PF6 complex was synthesized by metalation of pyphos with
[Rh(COD)Cl]2 followed by anion exchange with NH4PF6 in excellent yield, and the target rhodium
complex was characterized by single-crystal X-ray crystallography. The chiral cationic rhodium
complex was utilized in the enantioselective hydroboration of vinylarenes. Excellent regioselectivity
and good enantioselectivity were observed, and the ee values were found to be dependent on the
electronic properties of para-substituted styrenes.
In tr od u ction
selectivity.9 Apart from the regio- and chemoselectivity
of hydroboration, the most interesting application is the
enantioselective version of this reaction which can be
aplied to the natural product and drug synthesis.10 The
first asymmetric hydroboration was reported by Burgess
using norborene and chiral Rh-DIOP catalyst to give 55%
ee at -40 °C.11-13 A highly enantioselective hydroboration
reaction (up to 96% ee, -78 °C) was then reported by
Hayashi’s group, who employed a cationic rhodium-
BINAP catalyst for the reaction of styrenes.14,15 Subse-
quently, other catalysts for asymmetric hydroboration
have been developed; Togni,16,17 Brown,18-21 Chung,22
Fleet,23 and Guiry24 employed Rh complexes of chiral
The discovery of the oxidative addition of Wilkinson’s
catalyst (Rh(PPh3)3Cl) with boron hydrides such as
catecholborane has led to the development of metal-
catalyzed hydroboration.1,2 The hydroboration reaction is
markedly accelerated in the presence of the rhodium
catalyst2 and has a significant effect on the regiochem-
istry of the reaction.3-8 This invention also demonstrated
that the catalyzed and the uncatalyzed reactions can
display complementary functional group and diastereo-
† The Chinese University of Hong Kong.
‡ Current address: Department of Chemistry, Massachusetts In-
stitute of Technology. E-mail: fyk@mit.edu.
The University Grants Committee Area of Excellence Scheme
(Hong Kong).
(9) Sato, M.; Miyaura, M.; Suzuki, A. Chem. Lett. 1989, 1405-1408.
(10) For review, see: Fu, G. C. In Transition Metals for Organic
Synthesis Building Blocks and Fine Chemicals; Beller, M., Bolm, C.,
Eds.; Wiley-VCH: New York, 1998; Vol. 2.
(11) Burgess, K.; Ohlmeyer, M. J . J . Org. Chem. 1988, 53, 5178-
5179.
(12) (a) Burgess, K.; Donk, W. A.; Ohlmeyer, M. J . Tetrahedron:
Asymmetry 1991, 2, 613-621. (b) Burgess, K.; Ohlmeyer, M. J .;
Whitmire, K. H. Organometallics 1992, 11, 3588-3600.
(13) For the most recent reference using chiral diphosphine ligands
in asymmetric hydroboration, see: Demay, S.; Volant, F.; Knochel, P.
Angew. Chem., Int. Ed. 2001, 40, 1235-1238.
§ The Hong Kong Polytechnic University.
(1) (a) Kono, H.; Ito, K.; Nagai, Y. Chem. Lett. 1975, 1095-1096.
For review in hydroboration, see: (b) Brown, H. C. In Hydroboration;
Benjamin, W. A., Ed.; New York, 1962. (c) Burgess, K.; Ohlmeyer, M.
J . Chem. Rev. 1991, 91, 1179-1191. (d) Hoveyda, A. H.; Evans, D. A.;
Fu, G. C. Chem. Rev. 1993, 93, 1307-1370. (e) Brown, J . M. Chem.
Soc. Rev. 1993, 22, 25-41. (f) Fu, G. C.; Evans, D. A.; Muci, A. R. In
Advances in Catalytic Process; Doyle, M. P., Ed.; J AI Press: London,
1995; Vol. 1, pp 95-121. (g) Noyori, R. Asymmetric Catalysis in Organic
Synthesis; J ohn Wiley & Sons: New York, 1994; pp 131-133. (h)
J acobsen, E. N.; Pfaltz, A.; Yamamoto, H. Comprehensive Asymmetric
Catalysis; Springer: Berlin, 1999. (i) Beletskaya, I.; Pelter, A. Tetra-
hedron 1997, 53, 4957. (j) Nishiyama, H.; Itoh, K. In Catalytic
Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley-VCH: New York,
2000; pp 133-138.
(14) BINAP ) 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl. Hayashi,
T.; Matsumoto, Y.; Ito, Y. J . Am. Chem. Soc. 1989, 111, 3426-3428.
(15) Hayashi, T.; Matsumoto, Y.; Ito, Y. Tetrahedron: Asymmetry
1991, 2, 601-612.
(16) For ferrocenyl/aryl P and pyrazole
N moiety with planar
(2) Ma¨nnig D.; No¨th, H. Angew. Chem., Int. Ed. Engl. 1985, 24, 878-
880; Angew Chem. 1985, 97, 979-980.
chirality and chiral center, see: Schnyder, A.; Hintermann, L.; Togni,
A. Angew. Chem., Int. Ed. 1995, 34, 931-933. The pyrazole-containing
ferrocenylphosphine in asymmetric hydroboration of styrenes gave high
ee of products. However, only 66% regioselectivity was observed.
(17) Schnyder, A.; Togni, A.; Wiesli, U. Organometallics 1997, 16,
255-260.
(3) Evans, D. A.; Fu, G. C.; Hoveyda, A. H. J . Am. Chem. Soc. 1988,
110, 6917-6918.
(4) Evans, D. A.; Fu, G. C. J . Am. Chem. Soc. 1991, 113, 4042-
4043.
(5) Evans, D. A.; Fu, G. C. J . Org. Chem. 1990, 55, 2280-2282.
(6) Burgess, K.; Ohlmeyer, M. J . Tetrahedron Lett. 1989, 30, 395-
398.
(7) Burgess, K.; Cassidy, J .; Ohlmeyer, M. J . J . Org. Chem. 1991,
56, 1020-1025.
(8) Zhang, J .; Lou, B.; Guo, G.; Dai, L. J . Org. Chem. 1991, 56, 1670-
1672.
(18) For aryl P and isoquinoline N moiety with chiral axis, see:
Brown, J . M.; Hulmes, D. I.; Layzell, T. P. J . Chem. Soc., Chem.
Commun. 1993, 1673-1674.
(19) Valk, J . M.; Whitlock, G. A.; Layzell, T. P.; Brown, J . M.
Tetrahedron: Asymmetry 1995, 6, 2593-2596.
(20) Doucet, H.; Fernandez, E.; Layzell, T. P.; Brown, J . M. Chem.
Eur. J . 1999, 5, 1320-1330.
10.1021/jo0159542 CCC: $22.00 © 2002 American Chemical Society
Published on Web 03/28/2002

2770 J . Org. Chem., Vol. 67, No. 9, 2002
Kwong et al.
Sch em e 1. Syn th esis of Ch ir a l Atr op isom er ic P ,N
Liga n d
heterotopic P,N ligands to give moderate to high enan-
tioselectivity in the hydroboration of vinylarenes. How-
ever, the reported examples of axially chiral P,N ligands
are limited.25 Recently, Zhang et al. reported that the
dihedral angles of chiral biaryl ligands influenced the
enantioselectivities of the asymmetric hydrogenation
apart from the steric and/or electronic properties of the
ligands.26,27 To access axially tunable advantage in
optimizing the enantioselectivity of a reaction, we envi-
sion that a strategy to incorporate a tert-butyl and a
methyl group in a biaryl ligand for the restriction of sp2-
sp2 biaryl rotation and for the generation of a large
dihedral angle in the chiral ligand. The substitution of
pyridine moiety for one of the aryl rings in the biaryl
ligand would further add an attractive feature for the
phase separation of the ligand from the reaction mixture
by extracting them with hydrochloric acid.28,29 Herein, we
report the preparation of optically active atropisomeric
P,N ligand 4, X-ray characterization of the corresponding
Rh-pyphos complex, and the first application of pyphos
in rhodium-catalyzed asymmetric hydroboration of vinyl-
arenes.
ization studies revealed that the chiral triflate (R)-2
started to racemize at about 100 °C and was configura-
tionally stable at/or below 90 °C even after extensive
reaction. As no phosphination occurred below 110 °C and
other phosphination methods proved to be ineffective,34
the synthesis of chiral P,N ligand 4 from its correspond-
ing optically active triflate precursor is not possible. The
more sterically bulky and reactive triflate analogue,
nonaflate, was then prepared.35 The optically pure non-
aflate (R)-3 was synthesized in 85% yield from optically
pure pyridylphenol (R)-1 using perfluorobutanesulfonic
fluoride in the presence of sodium hydride in dry ether
at room temperature (Scheme 1). Nonaflate (R)-3 was
subjected to palladium-catalyzed phosphination to yield
chiral P,N ligand 4. Though (R)-3 had a higher racem-
ization temperature (105 °C) than that of triflate (R)-2,
it was still not high enough to achieve the phosphination.
Therefore, an alternative synthetic pathway was chosen,
and pyphos 4 was prepared from 1 in racemic form and
its optical resolution was carried out using diastereomeric
complexation with chiral palladium amine complexes
(Scheme 2).
Resu lts a n d Discu ssion
Syn th esis of Atr op isom er ic P ,N Liga n d , p yp h os,
by Usin g Op tica lly Active P yr id ylp h en ol 1. The
synthesis of optically active pyphos 4 was initially
attempted from the optically active pyridylphenol 1.30 The
optically pure 1 was transformed to its triflate derivative
2 in excellent yield31 without racemization, as confirmed
by chiral HPLC analysis (Scheme 1). Triflate (R)-2 was
then subjected to palladium-catalyzed phosphination at
110-115 °C (Scheme 1).32 Nevertheless, the phosphine
ligand 4 was found to be a racemic mixture.33 Racem-
Resolu tion of p yp h os by F r a ction a l Cr ysta lliza -
tion of Dia ster eom er ic P a lla d iu m Com p lexes. The
failure in the preparation of chiral pyphos 4 from opti-
cally pure precursor 1 led to the resolution of pyphos in
later stage. The chiral palladium amine complex was
synthesized from the reaction of (R)-N,N-dimethyl-R-
methylbenzylamine with palladium(II) dichloride in
methanol to form the optically active palladium amine
dimer 5 in 88% yield (Scheme 2).36 This µ-chloro dimer 5
was reacted with pyphos 4 to form the diastereomers
(R,R)-6 and (R,S)-6 (Scheme 2). Initial attempts by
fractional recrystallization of the diastereomers was
unsuccessful using chloroform, dichloromethane, acetone,
toluene, and a mixture of solvents.37
(21) For hydroboration/amination, see: Fernandez, E.; Maeda, K.;
Hooper, M. W.; Brown, J . M. Chem. Eur. J . 2000, 6, 1840-1846. Brown
et al. also reported double asymmetric induction in enantioselective
hydroboration using matched pair of Rh-BINAP complexes with chiral
borane which derived from ephedrine, see: Brown, J . M.; Lloyd-J ones,
G. C. Tetrahedron: Asymmetry 1990, 1, 869-872.
(22) For planar chiral (arene)Cr(CO)3 P and N,N acetal N moiety,
see: Son, S. U.; J ang, H. Y.; Lee, I. S.; Chung, Y. K. Organometallics
1998, 17, 3236-3238.
(23) Martin, A.; Watterson, M. P.; Brown, A. R.; Imtiaz, F.; Win-
chester, B. G.; Watkin, D. J .; Fleet, G. W. J . Tetrahedron: Asymmetry
1999, 10, 355-366.
(24) For aryl P donor, quinazoline N donor with chiral axis, see: (a)
McCarthy, M.; Hooper, M. W.; Guiry, P. J . Chem. Commun. 2000,
1333-1334. For recent review, see: (b) McCarthy, M.; Guiry, P. J .
Tetrahedron 2001, 57, 3809-3844.
(25) The asymmetric catalysis using axially chiral P,N ligands were
only reported by Brown and recently Guiry’s groups, see refs 18-21,
24.
(26) Zhang, Z.; Qian, H.; Longmire, J .; Zhang, X. J . Org. Chem. 2000,
65, 6223-6226.
(27) For other examples concerning the dihedral angle effect, see:
(a) Harada, T.; Takeuchi, M.; Hatsuda, M.; Ueda, S.; Oku, A.
Tetrahedron: Asymmetry 1996, 7, 2479-2484. (b) Lipshutz, B. H.; Shin,
Y.-J . Tetrahedron Lett. 1998, 39, 7017-7020. (c) Chan, A. S. C.; Zhang,
F.-Y.; Yip, C. W. J . Am. Chem. Soc. 1997, 119, 4080-4081.
(28) Chan, A. S. C.; Chen, C. C.; Cao, R.; Lee, M.-R.; Peng, S.-M.;
Lee, G. H. Organometallics 1997, 16, 3469-3473.
(29) (a) Hu, W.; Pai, C. C.; Chen, C. C.; Xue, G.; Chan, A. S. C.
Tetrahedron: Asymmetry 1998, 9, 3241-3245. (b) Hu, W.; Chen, C.
C.; Xue, G.; Chan, A. S. C. Tetrahedron: Asymmetry 1998, 9, 4183-
4187. (c) Pai, C. C.; Lin, C.-W.; Lin, C.-C.; Chen, C.-C.; Chan, A. S. C.;
Wong, W. T. J . Am. Chem. Soc. 2000, 122, 11513-11514.
(30) Zhang, H. C.; Kwong, F. Y.; Tian, Y.; Chan, K. S. J . Org. Chem.
1998, 63, 6886-6890.
(31) Triflate ) trifluoromethanesulfonate. For review in trifluo-
romethanesulfonation, see: Stang, P. J .; Hanack, M.; Subramanian,
L. R. Synthesis 1982, 85-126.
(32) (a) Kwong, F. Y.; Chan, K. S. Organometallics 2000, 19, 2058-
2060. (b) Kwong, F. Y.; Chan, K. S. Organometallics 2001, 20, 2570-
2578.
The alternative (R)-N,N-dimethyl-R-methylnaphthyl-
amine resolving agent was recently found to be more
effective than its phenyl derivative, (R)-N,N-dimethyl-
(33) The ee (%) determination of pyphos ligand was accomplished
by its pyphos oxide derivative 2-(2′-diphenylphosphinyl-4′,6′-di-tert-
butyl-1′-phenyl)-3-methylpyridine 9 using chiral HPLC (chiralpak AD
column, hexane:2-propanol ) 975:25, flow rate ) 1.0 mL/min, UV )
254 nm).
(34) Kwong, F. Y.; Chan, A. S. C.; Chan, K. S. Tetrahedron 2000,
56, 8893-8899 and references therein.
(35) Nonaflate ) nnonafluorobutanesulfonate. (a) Niederpru¨m, H.;
Voss, P.; Beyl, V. Liebigs. Ann. Chem. 1973, 20-32. (b) Knochel et al.
reported that nonaflate reacted 1.4 times faster than triflate in Zn-
mediated coupling reactions; see: Rottla¨nder, M.; Knochel, P. J . Org.
Chem. 1998, 63, 203-208.
(36) (a) Kerr, P. G.; Leung, P. H.; Wild, S. B. J . Am. Chem. Soc.
1987, 109, 4321. (b) Roberts, N. K.; Wild, S. B. J . Chem. Soc., Dalton.
Trans. 1979, 2015-2021.
(37) Chloroform (13% de), dichloromethane (10% de), acetone (2%
de), toluene (2% de), chloroform/butanol (8% de). The diastereomeric
excesses were estimated by 1H NMR integration.

P,N Ligand for Rh-Catalyzed Asymmetric Hydroboration
J . Org. Chem., Vol. 67, No. 9, 2002 2771
Sch em e 2. Resolu tion of P yp h os by Dia ster eom er ic Com p lexa tion
Ta ble 1. Resu lts of Dia ster eom er ic Cr ysta lliza tion of
Sch em e 3. Decom p lexa tion of Ch ir a l Com p lex
p yp h os-Am in e-P a lla d iu m Com p lex
entry
X-
solvent
dea (%)
1
2
3
4
5
Cl
Cl
PF6
PF6
PF6
CHCl3
CH2Cl2
CHCl3
CHCl3/ether
CH2Cl2
2
5
>99
>99
13
a
Determined by 1H NMR integration.
R-methylbenzylamine.38 The µ-chloro bridge palladium
dimer 7 was then prepared in 89% yield (Scheme 2),
which subsequently reacted with pyphos 4 to yield the
diastereomers (R,R)-8 and (R,S)-8 as the chloride salt or
hexafluorophosphate salt after anion exchange with NH4-
PF6 in dichloromethane (Scheme 2). The diastereomers
of 8 were then fractionally crystallized using different
solvents (Table 1). Interestingly, the chloride salts of 8
were inseparable using chloroform, but the PF6 salts were
found to have excellent diastereomeric crystallization
upon using the same solvent (Table 1, entries 1 and 3).
However, dichloromethane proved to be inferior for
diastereomeric crystallization in either Cl or PF6 salts
of 8 (Table 1, entries 2 and 5). The addition of diethyl
ether to chloroform only enhanced the rate of crystal-
lization of (R,R)-8 but had no deleterious effect on the
diastereomeric excess (Table 1, entry 4). The optically
active pyphos (R)-4 was obtained by the decomplexation
of (R,R)-8 by using dppe (1,2-bis(diphenylphosphino)-
ethane) in dichloromethane in quantitative yield (Scheme
3).
Resolu tion of Bia r yl P ,N Liga n d by Ch ir a l HP LC.
The alternative resolution method was accomplished by
chiral HPLC. The direct resolution of pyphos 4 using a
Daicel OD, OD-H, OJ , or AD chiral column was unsuc-
cessful. To our delight, the corresponding more polar
pyphos oxide 9, which was prepared by oxidation of
pyphos 4 in excellent yield (Scheme 4), could be resolved
using a Daicel AD column to afford the optically active
pyphos oxide (R)-9 and (S)-9.39 The chiral P,N ligand 4
was then obtained by reduction of the corresponding
Sch em e 4. Resolu tion of P yp h os by Ch ir a l HP LC
phosphine oxide using trichlorosilane40 in toluene at 90
°C for 2 days in 70% yield without racemization (Scheme
4). The racemization temperature of pyphos 4 was found
to be 130 °C in dodecane.
Syn th esis a n d Str u ctu r a l Ch a r a cter iza tion of
Rh -P ,N Com p lex. The Rh complex of 4 was prepared
by mixing [Rh(COD)Cl]2 with 4 in dichoromethane at
room temperature for 5 min, followed by anion exchange
with NH4PF6 in 82% yield after crystallization in dichlo-
romethane (Scheme 5). A single crystal of rhodium
complex 10 was obtained after recrystallization in layered
mixtures of dichloromethane/diethyl ether. Table 2 lists
the crystal and data collection parameters. The structure
of the rhodium-pyphos complex is shown in Figure 1.
(38) Alcock, N. W.; Brown, J . M.; Hulmes, D. I. Tetrahedron:
Asymmetry 1993, 4, 743-756.
(39) HPLC conditions: Hex/iPrOH ) 9/1, flow rate ) 0.6 mL/min,
TR ) 14.66 min, tS ) 21.99 min.
(40) For reduction of phosphine oxide, see: Naumann, K.; Zon, G.;
Mislow, K. J . Am. Chem. Soc. 1969, 91, 7012-7023.

2772 J . Org. Chem., Vol. 67, No. 9, 2002
Kwong et al.
Sch em e 5. P r ep a r a tion of Rh od iu m -P ,N
Com p lex 10
Ta ble 2. Cr ysta l Da ta a n d Str u ctu r e Refin em en t Deta ils
of 10
empirical formula
formula weight
T (K)
C41H50Cl2F6NP2Rh
906.57
293(2)
wavelength (Å)
crystal system
space group
0.71073
orthorhombic
P212121
F igu r e 1. X-ray crystal structure of Rh-pyphos 10.
unit cell dimensions
a ) 10.5493(6) Å
b ) 14.9952(8) Å
c ) 25.9098(1) Å
R ) 90.0°
â ) 90.0°
γ ) 90.0°
4098.5(4)
4
Ta ble 3. Selected Bon d Dista n ces (Å) a n d An gles (d eg)
for Com p lex 10
Bond Distances
Rh(1)-N(1)
Rh(1)-C(38)
Rh(1)-C(34)
P(1)-C(21)
P(1)-C(27)
N(1)-C(5)
2.130(4) Rh(1)-C(37)
2.154(5) Rh(1)-C(33)
2.242(5) Rh(1)-P(1)
1.817(5) P(1)-C(8)
1.835(5) N(1)-C(1)
1.370(6)
2.135(4)
2.211(4)
2.2995(12)
1.834(4)
1.354(6)
volume (Å3)
Z
density (calcd) (Mg/m3)
absorption coefficient
1.469
0.683
(mm-1
F(000)
)
Bond Angles
1864
N(1)-Rh(1)-P(1)
81.77(9)
C(21)-P(1)-C(27) 105.2(2)
C(21)-P(1)-C(8) 107.0(2)
crystal size (mm)
θ range for data collection
(deg)
0.41 × 0.38 × 0.34
1.57-26.00
Ta ble 4. Resu lts of Asym m etr ic Hyd r obor a tion of
Styr en e
limiting indices
-11 e h e 13
-18 e k e 16
-31 e l e 20
reflections collected
24 697
independent reflections
absorption correction
max transmission
8014 (Rint ) 0.0343)
empirical
1.000
min transmission
refinement method
data/restraints/parameters
goodness-of-fit on F2
final R Indices [I > 2σ(I)]
R indices (all data)
0.8776
full-matrix least-squares on F2
8014/49/474
T
timea
solvent (°C) (h) yieldb eec
%
%
0.997
entry
1
catalyst, mol %
R1 ) 0.0437, wR2 ) 0.1114
R1 ) 0.0554, wR2 ) 0.1195
-0.03 (3)
0.00000 (5)
0.495 and -0.537
1 mol % Rh(COD)2BF4, THF
pyphos
1 mol % Rh(COD)2BF4, THF
pyphos
1 mol % Rh(COD)2BF4, THF
pyphos
1 mol % [Rh(COD)Cl]2, THF
pyphos
1 mol % Rh(COD)2BF4, DME
pyphos
1 mol % Rh(COD)2BF4, CH2Cl2
pyphos
rt
rt
0
12
12
18
48
24
24
70
69
70
90
absolute structure parameter
extinction coefficient
largest diff peak and hole
2
3
4
5
6
72
(e Å-3
)
72
The X-ray crystal structure of 10 showed both the
tertiary phosphine P and pyridine N atom are well
coordinated to the rhodium center. The Rh(1)-N(1) bond
distance is 2.130 Å, which is similar to that in Togni’s
ferrocenyl phosphine/pyrazole ligand-Rh complex (Table
3).41 However, the Rh(1)-P(1) bond distance (2.2995(12)
Å) of pyphos showed a shorter distance than the rhodium
complex of ferrocenyl phosphine/pyrazole ligand (2.311-
(4) Å),41 which demonstrated that the P moiety in pyphos
ligand coordinated closer to rhodium. This may have
better chiral induction in asymmetric catalysis. The
dihedral angle between the C(7)-C(8)-C(9)-C(10)-
C(11)-C(12) aryl and pyridyl ring was 72° [for free
pyphos ligand, the dihedral angle is 87° and 89° from
ChemDraw 3D calculations and the X-ray single-crystal
structure (the quality of crystal was poor), respectively].
Some distortion of the chiral axis C(5)-C(7) was ob-
served, which may be due to the steric hindrance of the
adjacent tert-butyl group (Figure 1).
0
trace
55
0
89
85
0
65
a
b
Monitored by GC. Isolated yield. c Determined by HPLC
using a Daicel OD-H column. Average at least two runs for entries
1 and 3.
Ca ta lytic Asym m etr ic Hyd r obor a tion . The chiral
atropisomeric P,N ligand 4 was applied in asymmetric
hydroboration (Table 4). In the presence of a catalytic
amount (1 mol %) of Rh(COD)2BF4 and (R)-pyphos 4,
styrene reacted completely with catecholborane in THF
at room temperature for 12 h. The corresponding 1-phe-
nylethanol was obtained in 70% yield with 69% ee (Table
4, entry 1). Excellent regioselectivity was observed as the
formation of side product, benzyl alcohol, was less than
1% as determined by GC-MS. When the catalyst loading
was increased to 2 mol %, identical rates, yield, and
enantioselectivity were obtained (Table 4, entry 2).
(41) (a) Schnyder, A.; Togni, A. Wiesli, U. Organometallics 1997,
16, 255-260; (b) Angew. Chem., Int. Ed. Engl. 1995, 34, 931-933.

P,N Ligand for Rh-Catalyzed Asymmetric Hydroboration
J . Org. Chem., Vol. 67, No. 9, 2002 2773
Ta ble 5. Resu lts of Asym m etr ic Hyd r obor a tion of
P a r a -Su bstitu ted Styr en es
entry
X
eec (%)
confign
log (R/S)
σp
1
2
3
4
OMe
Me
H
94a
93b
90b
79b
R
R
R
R
1.51
1.44
1.27
0.93
-0.26
-0.17
0.00
Cl
+0.23
a
b
Determined by GCD. Determined by HPLC using a Daicel
OD-H column. c % ee were reported in average over at least two
runs (entries 1, 3, and 4).
F igu r e 2. Hammett plot of the ee value of hydroboration
Lowering the temperature to 0 °C increased the enan-
tiomeric excess of the sec-alcohol 11 up to 90% ee without
affecting the regioselectivity (Table 4, entry 3). The
neutral complex, [Rh(COD)Cl]2/(R)-pyphos system, did
not catalyze the hydroboration reaction (Table 4, entry
4). The stereoselectivity was relatively insensitive to
solvent change; however, a lower product yield was
obtained when DME or CH2Cl2 solvent was used (Table
4, entries 5 and 6). The enantioselectivity of the sec-
alcohol versus time was also investigated.42 The enana-
tiomeric excess of 11 was found to be 82% at the
beginning of the first 2 h and the ee value remained
constant at 90% ee until the end of the reaction.
The optimized Rh-catalyzed asymmetric hydroboration
conditions were applied to para-substituted styrenes with
different electronic properties. The regioselectivity form-
ing 1-arylethylborane was excellent (>98:2 to 99:1) for
all the styrenes examined, irrespective of the electron-
releasing or electron-withdrawing nature of the substi-
tutent group on the phenyl ring. The p-methoxystyrene
showed the highest enantioselectivity with 94% ee of the
1-(4-methoxyphenyl)ethanol 12 formed (Table 5, entry 1).
The less electron-donating p-methylstyrene with refer-
ence to p-methoxystyrene gave slightly lower enantio-
meric excess of the alcohol 13 compared with 12 (Table
5, entries 1 and 2). However, much lower enantiomeric
excess of p-chlorophenylethanol 14 was observed in the
electron-deficient p-chlorostyrene (Table 5, entry 4).
The enantioselectivity in this catalyzed hydroboration
of para-substituted styrenes depends on the electronic
effect of styrene.43 The results showed that the ee ranged
from 79% ee for the p-chloro substituent to 94% ee for
p-methoxy substituent. A plot of log(R/S) of the hydro-
boration product versus Hammett constant σp gave a
modestly straight line with R2 equal to 0.984 (Figure 2).44
A linear free energy relationship was obeyed.
products with Hammett constants.
The electronic effect of asymmetric hydroboration could
probably be explained by a series of metal-alkene
complexes where electron-rich styrenes coordinate more
strongly trans to the pyridine than the electron-poor
analogues (Figure 3).45-49 Hence, we suggest that in the
transition state the more electron-rich styrene may
coordinate closer to the rhodium center, resulting in
improved stereochemical communication and thus gives
rise to a higher enantioselectivity (Figure 3, model A).
However, for the electron-poor styrene, it has a greater
possibility to coordinate to the rhodium center in two
modes as it is far from the chiral environment in the
transition state (Figure 3, model B).46 Therefore, a lower
ee of the product is observed.
A comparison of dihedral angle and steric effect with
other atropisomeric ligands is shown in Table 6. The
pyphos ligand probably lies into the optimal board range
of dihedral angle (see QUINAP, 67°; pyphos 87°) in
catalytic asymmetric hydroboration as the ee values are
similar. In contrast with asymmetric hydrogenation, the
optimal range is rather sharp and the ee values versus
dihedral angles changed dramatically.26 The steric effects
of the ligands also play an important role in determining
the stereoselectivity of the reaction. A six-membered ring
metal-ligand (Rh-pyphos) coordination was found to be
better than a seven-member ring (Rh-BINAP) coordina-
(44) For the values of Hammett constants, see: Gordon, A. J .; Ford,
R. A. The Chemist’s Companion; J ohn Wiley: New York, 1972.
(45) Kurosawa, H.; Ikeda, I. J . Organomet. Chem. 1992, 428, 289-
301.
(46) For evidences for the role of dπ-pπ bonding in rhodium-
mediated hydroboration, see: (a) Burgess, K.; van der Donk, W. A.;
J arstfer, M. B.; Ohlmeyer, M. J . J . Am. Chem. Soc. 1991, 113, 6139-
6144. For a review in metal-alkene binding, see: (b) Gladysz, J . A.;
Boone, B. J . Angew. Chem., Int. Ed. Engl. 1997, 36, 551-583.
(47) Burgess has proposed a transition structure model for the
catalyzed hydroboration of 1,1-disubstituted allylic alcohol deriva-
tives: (a) Burgess, K.; Ohlmeyer, M. J . Tetrahedron Lett. 1989, 30,
5861-5864. (b) Moser, W. R., Slocum, D. W., Eds. Homogeneous
Transition Metal Catalyzed Reactions; Advances in Chemistry Series
230; American Chemical Society: Washington, DC, 1992; pp 163-177.
This model assumes that complexation of the olefin to the metal is
the rate stereochemical-determining step of the reaction.
(48) For selected reference in hydroboration mechanistic studies,
see: (a) Evans, D. A.; Fu, G. C. J . Org. Chem. 1990, 55, 2280-2282.
(b) Evans, D. A.; Fu, G. C.; Anderson, B. A. J . Am. Chem. Soc. 1992,
114, 6679-6685. (c) Burgess, K.; Van der Donk, W. A.; Westcott, S.
A.; Marder, T. B.; Baker, R. T. Calabrese, J . C. J . Am. Chem. Soc. 1992,
114, 9350-9393. (d) Westcott, S. A.; Blom, H. P.; Marder, T. B.; Baker,
R. T. J . Am. Chem. Soc. 1992, 114, 8863-8869.
(49) For other mechanistic studies of steric and electronic effects in
insertion of olefin, see: Burger, B. J .; Santarsiero, B. D.; Trimmer, M.
S.; Bercaw, J . E. J . Am. Chem. Soc. 1988, 110, 3134-3146.
(42) Table 4, entry 3 conditions were used without modification.
Samples were taken from the reaction mixture in intervals of 30 min,
1 h, 2 h, 4, 16, and 18 h. After oxidation of the product by alkaline
hydrogen peroxide, the organic extract was diluted, filtered over Celite
and analyzed by chiral HPLC using OD-H column.
(43) For recent selected references concerning electronic effects in
asymmetric catalysis, see: (a) Zhang, H. C.; Xue, F.; Mak, T. C. W.;
Chan, K. S. J . Org. Chem. 1996, 61, 8002-8003. (b) J acobsen, E. N.;
Zhang, W.; Gu¨ler, M. L. J . Am. Chem. Soc. 1991, 113, 6703-6704. (c)
Lo, M. M. C.; Fu, G. C. J . Am. Chem. Soc. 1998, 120, 10270-10271.
(d) Lo, W. C.; Che, C. M.; Cheng, K. F.; Mak, T. C. W. Chem. Commun.
1997, 1205-1206. (e) Doucet, H.; Fernandez, E.; Layzell, T. P.; Brown,
J . M. Chem. Eur. J . 1999, 5, 1320-1330. (f) Palucki, M.; Finney, N.
S.; Pospisil, P. J .; Guler, M. L.; Ishida, T.; J acobsen, E. N. J . Am. Chem.
Soc. 1998, 120, 948-954. (g) Wong, H. L.; Tian, Y.; Chan, K. S.
Tetrahedron Lett. 2000, 41, 7723-7726. (h) Bachmann, S.; Mezzetti,
A. Helv. Chim. Acta. 2001, 84, 3063-3074.

2774 J . Org. Chem., Vol. 67, No. 9, 2002
Ta ble 6. Com p a r ison of Dih ed r a l An gles a n d Ster ic Effects of Atr op isom er ic Liga n d s
Kwong et al.
a
The dihedral angles were estimated by ChemDraw 3D calculation of the free ligands.
Con clu sion
A new optically active atropisomeric P,N ligand, py-
phos, with a large dihedral angle containing a tertiary
phosphine and pyridine moiety was prepared and re-
solved through diastereomeric complexation with chiral
palladium naphthylamine complexes in a hexafluoro-
phosphate salt other than chloride salt. The [Rh(COD)-
pyphos]PF6 complex was synthesized in excellent yield,
and the single crystal of rhodium-PN complex was
characterized by X-ray crystallography. The cationic
chiral rhodium complex was applied to enantioselective
hydroboration of vinylarenes. Excellent regioselectivities
and good enantioselectivities were observed, and the ee
values were found to be obeyed a linear free energy
relationship with the Hammett constants.
Exp er im en ta l Section
Gen er a l Con sid er a tion s. Unless otherwise noted, all
materials were obtained from commercial suppliers and used
without further purification. Tetrahydrofuran (THF) was
distilled from sodium benzophenone ketyl under nitrogen
immediately prior to use. Dichloromethane, pyridine, styrene
and triethylamine were distilled from calcium hydride under
nitrogen atmosphere before use. N,N-Dimethylformamide was
distilled from magnesium sulfate under reduced pressure.
Rh(COD)2BF4 and [Rh(COD)Cl]2 were prepared according to
literature method without modification.50 Thin-layer chroma-
tography was performed on precoated silica gel 60 F254 plates.
Silica gel (70-230 and 230-400 mesh) was used for column
chromatography. 1H NMR spectra were recorded on a 300 MHz
spectrometer. Spectra were referenced internally to the re-
sidual proton resonance in CDCl3 (δ 7.26 ppm) or with
tetramethylsilane (TMS, δ 0.00 ppm) as the internal standard.
Chemical shifts (δ) were reported as part per million (ppm)
on a δ scale downfield from TMS. 13C NMR spectra were
recorded on a 75 MHz spectrometer and referenced to CDCl3
(δ 77.00 ppm). 31P NMR spectra were recorded on a 162 MHz
and referenced to 85% H3PO4 externally. Coupling constants
(J ) are reported in hertz (Hz). HPLC analyses were conducted
on a Waters 486 system with a UV detector at 254 nm, using
a Daicel OD column (0.46 × 25 cm), Daicel OD-H column (0.46
× 15 cm) and Daicel AD column (0.46 × 25 cm). GC-MS
analysis was conducted on a HP G1800C GCD system using
a HP5MS column (30 m × 0.25 mm) or Alltech â-cyclodextrin
chiral column (50 m × 0.25 mm). The Hammett plot was
generated using MacCurve Fit version 1.1, Kevin Raner
Software 1994.
F igu r e 3. Suggested transition-state models for electronically
controlled asymmetric hydroboration.
tion mode (Table 6). This trend was probably caused by
the closer ligand to rhodium distance.
Recover y of P ,N Liga n d Usin g a n Aqu eou s Ex-
tr a ction P r ocess. Pyphos 4 is configurationally stable
in acidic medium. The pyridine moiety of the P,N ligand
allows the facile acid/aqueous extraction of ligand for
recycling of the catalyst. The partition coefficient of
pyphos ligand in layered diethyl ether and 12 N hydro-
chloric acid was found to be 9:91, respectively. Thus, the
acid layer was separated and neutralized by sodium
hydroxide solution to pH 8 and extracted with dichlo-
romethane to afford 91% of recovery of P,N ligand 4. The
% ee of the aqueous extracted ligand was >99% as
verified by chiral HPLC. This characteristic serves as
another basis for the development of a new generation
of chiral ligands and the application of other catalyst-
recyclable asymmetric reactions.
(50) Fryzuk, M. D.; Bosnich, B. J . Am. Chem. Soc. 1977, 99, 6262-
6267.

P,N Ligand for Rh-Catalyzed Asymmetric Hydroboration
J . Org. Chem., Vol. 67, No. 9, 2002 2775
(R)-3,5-Di-ter t-bu tyl-2-(3′-m eth yl-2′-p yr id yl)p h en yl Tr i-
flu or om et h a n esu lfon a t e (2). (R)-3,5-Di-tert-butyl-2-(3′-
methyl-2′-pyridyl)phenol30,43a (R)-(1) (297 mg, 1.0 mmol) was
dissolved in dry dichloromethane (5 mL) under nitrogen at
rate, 0.3 mL/min) tR ) 9.82 min, tS )11.20 min. F or (R)-3:
HPLC (column: analytical Daicel OD-H, solvent, hexane/2-
propanol ) 99:1; UV lamp, 254 nm; flow rate, 0.4 mL/min) tR
) 6.41 min, tS ) 7.28 min.
room temperature in
a
three-necked round-bottom flask.
2-(2′-Dip h en ylp h osp h in o-4′,6′-d i-ter t-bu tyl-1′-p h en yl)-
3-m eth ylp yr id in e32 (p yp h os) (4). Racemic 3,5-di-tert-butyl-
2-(3′-methyl-2′-pyridyl)phenyl trifluoromethanesulfonate (1)
(1.07 g, 2.5 mmol), palladium(II) acetate (56 mg, 0.25 mmol),
and triphenylphosphine (1.51 g, 5.8 mmol) were dissolved in
dry DMF (10 mL) under nitrogen. The solution was heated to
110-115 °C for 4.5 days, and the color of the solution was
changed from yellow to red. The reaction was cooled, and DMF
was removed under reduced pressure. The residue was purified
by column chromatography on silica gel using a solvent
mixture of (hexane/ethyl acetate ) 6:1, Rf ) 0.6) as eluent to
obtain the crude product. This crude product was then purified
by column chromatography on silica gel with eluent (toluene/
ethyl acetate ) 20:1) to afford the pure 2-(2′-diphenylphos-
phino-4′,6′-di-tert-butyl-1′-phenyl)-3-methylpyridine (pyphos)
(4) (790 mg, 68%) as a white solid: mp 135-136 °C; Rf ) 0.6
Pyridine (0.26 mL, 3.0 mmol) and trifluoromethanesulfonic
anhydride (triflic anhydride) (0.18 mL, 1.1 mmol) in dry
dichloromethane (3 mL) were then added slowly to the reaction
mixture. White fumes evolved, and the color of the solution
was changed from yellow to orange. The reaction mixture was
stirred at room temperature for 2 h. Water (5 mL) was added,
and the aqueous phase was extracted with dichloromethane
(20 mL × 3). The combined organic extract was washed with
water and brine, dried over MgSO4, and rotary-evaporated.
The resultant brown residue was purified by column chroma-
tography on silica gel using a solvent mixture (hexane/ethyl
acetate ) 5:1) as the eluent to afford (R)-3,5-di-tert-butyl-2-
(3′-methyl-2′-pyridyl)phenyl trifluoromethanesulfonate (R)-(2)
(408 mg, 95%) as white solids: Rf ) 0.6 (hexane/ethyl acetate
) 4:1); mp 96-98 °C; HPLC (column: analytical Daicel OD-
H, solvent, hexane/2-propanol ) 995:5; UV lamp, 254 nm; flow
1
(toluene/ethyl acetate ) 15:1); H NMR (300 MHz, CDCl3) δ
rate, 0.3 mL/min) tR ) 11.20 min; [R]20 ) +2.3 (c ) 0.6,
1.13 (s, 9 H), 1.17 (s, 9 H), 1.94 (s, 3 H), 7.04-7.30 (m, 13 H),
7.60 (d, 1 H, J ) 2.0 Hz), 8.34 (d, 1 H, J ) 4.3 Hz); 13C NMR
(75 MHz, CDCl3) δ 19.9, 31.1, 32.4, 34.8, 37.2, 125.8, 127.9,
128 (d, J CP ) 8.0 Hz), 128.2 (d, J CP ) 4.6 Hz), 130.1, 131.2 (d,
J CP ) 7.6 Hz), 131.1 (d, J CP ) 7.5 Hz), 133.4 (d, J CP ) 19.3
Hz), 134.0 (d, J CP ) 20.0 Hz), 137.1 (d, J CP ) 8.7 Hz), 138.0
(d, J CP ) 9.3 Hz), 138.2, 145.1, 147.1 (d, J CP ) 5.6 Hz), 149.7;
31P NMR (162 MHz, CDCl3) δ -11.60; MS (EI) m/z (relative
intensity) 465 (M+, 80), 450 (88), 408 (100), 388 (82), 374 (22),
358 (35), 342 (23); HRMS (ESIMS) calcd for C32H36NPH+
466.2658, found 466.2622.
D
1
CHCl3); H NMR (300 MHz, CDCl3) δ 1.16 (s, 9 H), 1.36 (s, 9
H), 2.12 (s, 3 H), 7.20 (s, 1 H), 7.23 (dd, 1 H, J ) 7.8 Hz, 4.8
Hz), 7.57 (d, 1 H, J ) 8.0 Hz), 7.63 (d, 1 H, J ) 0.8 Hz), 8.53
(d, 1 H, J ) 4.0 Hz); 13C NMR (75 MHz, CDCl3) δ 19.1, 29.7,
31.1, 35.1, 37.5, 115.4, 118.2 (q, J CF ) 317.6 Hz), 124.4, 132.7,
133.1, 138.3, 146.4, 148.2, 150.5, 152.1, 152.5; MS (EI) m/z
(relative intensity) 430 (M+ + 1, 74), 414 (52), 296 (19), 281
(100), 266 (22); HRMS (ESIMS) calcd for C21H26F3NO3SH+
430.1658, found 430.1647.
(S)-3,5-Di-ter t-bu tyl-2-(3′-m eth yl-2′-p yr id yl)p h en yl Tr i-
flu or om eth a n esu lfon a te (S)-(2). (S)-3,5-Di-tert-butyl-2-(3′-
methyl-2′-pyridyl)phenol30,43a (S)-(1) (65 mg, 0.22 mmol) was
used to yield the (S)-3,5-di-tert-butyl-2-(3′-methyl-2′-pyridyl)-
phenyl trifluoromethanesulfonate (S)-(2) (85 mg, 90%, 100%ee)
according to the above procedure. HPLC (column: analytical
Daicel OD-H, solvent, hexane/2-propanol ) 995:5; UV lamp,
Di-µ-ch lor ob is[(R)-d im et h yl(1-p h en ylet h yl)a m in a t o-
C2,N]d ip a lla d iu m (II) (5).36 Palladium(II) dichloride (618 mg,
3.5 mmol) and lithium chloride (348 mg, 7.0 mmol) were
dissolved in methanol (15 mL) at 60 °C. The solution was then
stirred for 1 h until a deep red solution was obtained. The
solution was filtered and treated with (R)-N,N-dimethylphen-
ylethylamine (1.2 g, 8.1 mmol). The yellow precipitate formed
was filtered at room temperature, washed with methanol, and
dried under reduced pressure to obtain di-µ-chlorobis[(R)-
dimethyl(1-phenylethyl)aminato-C2,N]dipalladium(II) (885 mg,
88%) as yellow solid: MS (FAB) m/z (relative intensity) 581
254 nm; flow rate, 0.3 mL/min) tR ) 9.82 min; [R]20 ) -2.2 (c
D
) 0.6, CHCl3).
(R)-(3,5-Di-ter t-bu tyl-2-(3′-m eth yl-2′-pyr idyl)ph en yl Non -
a flu or obu ta n esu lfon a te (R)-(3). (R)-3,5-Di-tert-butyl-2-(3′-
methyl-2′-pyridyl)phenol30,43a (R)-(1) (594 mg, 2.0 mmol) in
anhydrous ether (3 mL) was added to NaH (120 mg, 2.7 mmol)
in anhydrous ether (7 mL) at 0 °C. Nonafluorobutanesulfonyl
fluoride (1.2 g, 4.0 mmol) was then added under nitrogen at 0
°C. After complete addition, the reaction mixture was heated
to reflux for 2 h. The reaction mixture was then cooled and
added with water (20 mL). The aqueous phase was extracted
by diethyl ether (50 mL × 2). The combined organic phase was
washed with water and brine and dried over MgSO4. The
solvent was removed by rotary evaporation, and the residue
was purified by column chromatography on silica gel using a
solvent mixture (hexane/ethyl acetate ) 5:1) as the eluent to
yield the (R)-3,5-di-tert-butyl-2-(3′-methyl-2′-pyridyl)phenyl
nonafluorobutanesulfonate (R)-(3) (984 mg, 85%) as light
yellow solids: Rf ) 0.6 (hexane/ethyl acetate ) 5:1); mp 48-
50 °C; HPLC (column: analytical Daicel OD-H, solvent,
hexane/2-propanol ) 99:1; UV lamp, 254 nm; flow rate, 0.4
mL/min) tR ) 6.67 min; [R]20D ) +2.2 (c ) 0.7, CHCl3); 1H NMR
(300 MHz, CDCl3) δ 1.16 (s, 9 H), 1.36 (s, 9 H), 2.11 (s, 3 H),
7.22 (d, 1 H, J ) 0.9 Hz), 7.24 (dd, 1 H, J ) 3.8 Hz, 7.4 Hz),
7.55 (d, 1 H, J ) 7.5 Hz), 7.63 (d, 1 H, J ) 1.6 Hz), 8.52 (d, 1
H, J ) 3.9 Hz); 13C NMR (75 MHz, CDCl3) δ 19.2, 31.1, 32.3,
35.1, 37.1, 109.2-118.9 (m), 115.1, 123.1, 124.5, 129.3, 133.9,
137.6, 146.0, 148.0, 150.4, 152.7, 155.2; MS (FAB) m/z (relative
intensity) 580 (M+ + 1, 60), 564 (10), 297 (30), 282 (100), 266
(33); HRMS (ESIMS) calcd for C24H26F9NO3SH+ 580.1562,
found 580.1536.
(M+, 20), 544 (22), 391 (70), 307 (100); [R]20 ) -53.2 (c ) 0.5,
D
CH2Cl2).
(R,R)- a n d (R,S)-[Dim et h yl(1-p h en ylet h yl)a m in a t o-
C2,N]-[2-(2′-d ip h en ylph osp h in o-4′,6′-d i-ter t-bu tyl-1′-p h en -
yl)-3-m eth ylpyr idin e]palladiu m (II) Hexaflu or oph osph ate
((R,R)-6 a n d (R,S)-6). Di-µ-chlorobis[(R)-dimethyl(1-phenyl-
ethyl)aminato-C2,N]dipalladium(II) (5) (290 mg, 0.5 mmol) and
2-(2′-diphenylphosphino-4′,6′-di-tert-butyl-1′-phenyl)-3-meth-
ylpyridine (4) (465 mg, 1.0 mmol) were dissolved in degassed
methanol (20 mL) under nitrogen and stirred until a clear
solution was obtained. Ammonium hexafluorophosphate (163
mg, 1.0 mmol) in degassed water (15 mL) was then added.
After a half portion of NH4PF6 was added, white precipitate
formed. The suspension was stirred vigorously at room tem-
perature for 1 h. The precipitate was filtered, washed with
water and methanol, and dried under reduced pressure to yield
the (R,S)- and (R,R)-[dimethyl(1-phenylethyl)aminato-C2,N]-
[2-(2′-diphenylphosphino-4′,6′-di-tert-butyl-1′-phenyl)-3-meth-
ylpyridine]palladium(II) hexafluorophosphate (800 mg, 92%)
as white solid: mp 230 °C dec; [R]20D ) +100.5 (c ) 0.5, CHCl3);
1H NMR (300 MHz, CDCl3) δ 1.10 (s, 18 H), 1.22 (s, 18 H),
1.41 (d, 3 H, J ) 6.6 Hz), 1.58 (s, 3 H), 1.62 (s, 3 H), 1.75 (d,
3 H, J ) 6.6 Hz), 2.61 (d, 3 H, J ) 2.4 Hz), 2.79 (d, 3 H, J )
3.3 Hz), 2.86 (d, 3 H, J ) 2.1 Hz), 3.02 (d, 3 H, J ) 3.3 Hz),
3.57 (q, 1 H, J ) 6.6 Hz), 4.87 (q, 1 H, J ) 6.6 Hz), 6.07-6.13
(m, 2 H), 6.38-6.42 (m, 2 H), 6.81-6.99 (m, 10 H), 7.13 (s, 1
H), 7.16 (s, 1 H), 7.25-7.65 (m, 18 H), 7.75 (s, 2 H), 8.68 (dd,
2 H, J ) 9.7, 4.5 Hz); 13C NMR (75 MHz, CDCl3) δ 9.19, 19.8,
19.9, 25.1, 30.8, 32.8, 32.9, 34.9, 38.1, 38.2, 42.0, 47.9, 48.7,
51.6, 72.1, 76.1, 122.0, 123.2, 123.8 (d, J CP ) 11.0 Hz), 124.3
(d, J CP ) 11.1 Hz), 124.6 (d, J CP ) 10.9 Hz), 125.2, 125.7 (d,
Gen er a l P r oced u r es for Ra cem iza tion Exp er im en t:
F or (R)-2. A 5 mL Telfon stopcock flask was charged with
(R)-2 (5 mg, 11 µmol) and dodecane (2 mL) under nitrogen.
The solution was heated to a specific temperature and moni-
tored by HPLC: HPLC (column: analytical Daicel OD-H,
solvent, hexane/2-propanol ) 995:5; UV lamp, 254 nm; flow
J CP ) 5.4 Hz), 126.4, 127.2 (d, J CP ) 5.4 Hz), 127.5 (d, J CP
)

2776 J . Org. Chem., Vol. 67, No. 9, 2002
Kwong et al.
5.5 Hz), 128.0-129.1 (m), 131.8, 132.3, 135.3 (d, J CP ) 7.9 Hz),
136.5 (d, J CP ) 10.0 Hz), 139.0 (d, J CP ) 24.7 Hz), 139.1, 139.7,
146.3 (d, J CP ) 10.5 Hz), 149.4, 149.6 (d, J CP ) 8.2 Hz), 150.9,
151.9 (d, J CP ) 22.4 Hz), 152.0, 152.6, 154.8, 157.2; 31P (162
MHz, CDCl3) δ -40.45, 40.19, -143.23 (heptet, J PF ) 712.8
Hz); MS (FAB) m/z (relative intensity) 705 (M+ - PF6, 22),
465 (100); HRMS (ESIMS) calcd for C43H45NPPd+ 706.2374,
found 706.2377.
(d, J CP ) 12.2 Hz), 129.2, 129.5 (d, J CP ) 13.4 Hz), 130.5, 131.2
(d, J CP ) 9.9 Hz), 132.1 (d, J CP ) 9.0 Hz), 133.1, 133.6, 134.4,
135.0, 135.8, 136.3, 144.3, 148.2 (d, J CP ) 9.6 Hz), 149.0 (d,
J CP ) 12.3 Hz), 157.3; 31P NMR (162 MHz, CDCl3) δ 30.40;
MS (FAB) m/z (relative intensity) 482 (M+ + 1, 10), 465 (100),
451 (12), 425 (81), 407 (13), 389 (18), 280 (8), 201 (43);
HRMS (ESIMS) calcd for
482.2605.
C
32H36NOPH+ 482.2607, found
(R,R)-[Dim et h yl(1-p h en ylet h yl)a m in a t o-C2,N]-[2-(2′-
d ip h en ylp h osp h in o-4′,6′-d i-ter t-bu tyl-1′-p h en yl)-3-m eth -
ylp yr id in e]p a lla d iu m (II) Hexa flu or op h osp h a te ((R,R)-
(R)-2-(2′-Diph en ylph osph in yl-4′,6′-di-ter t-bu tyl-1′-ph en -
yl)-3-m eth ylp yr id in e ((R)-9). (R)-9 was obtained from pre-
parative chiral HPLC with a Daicel AD column using a solvent
mixture (hexane/2-propanol ) 975:25; UV lamp, 254 nm) as
8).
Di-µ-chlorobis[(R)-dimethyl(1-naphthylethyl)aminato-
C2,N]dipalladium(II) (7) (340 mg, 0.5 mmol) and 2-(2′-
diphenylphosphino-4′,6′-di-tert-butyl-1′-phenyl)-3-methylpyri-
dine (pyphos) (4) (465 mg, 1.0 mmol) were dissolved in
degassed methanol (20 mL) under nitrogen and stirred until
clear solution was obtained. Ammonium hexafluorophosphate
(163 mg, 1.0 mmol) in degassed water (15 mL) was then added.
The suspension was stirred vigorously at room temperature
for 1 h. The precipitate was filtered, washed with water and
methanol, and dried under reduced pressure to yield a mixture
of diastereomers. The (R,R)-[dimethyl(1-phenylethyl)aminato-
C2,N]-[2-(2′-diphenylphosphino-4′,6′-di-tert-butyl-1′-phenyl)-3-
methylpyridine]palladium(II) hexafluorophosphate (R,R)-8 was
obtained from fractional crystallization using layering chlo-
roform/diethyl ether mixture as white solids (830 mg, 92%):
mp 250 °C dec; [R]20D ) +120.5 (c ) 0.5, CHCl3); 1H NMR (300
MHz, CDCl3) δ 1.11 (s, 9 H), 1.16 (s, 9 H), 1.63 (s, 3 H), 1.88
(d, 2 H, J ) 6.3 Hz), 2.88 (s, 6 H), 4.39 (m, 1 H), 6.32 (dd, 1 H,
J ) 5.8 Hz, 2.7 Hz), 6.85-6.93 (m, 4 H), 7.14 (d, 2 H, J ) 9.2
Hz), 7.33-7.49 (m, 8 H), 7.66 (dd, 2 H, J ) 5.9 Hz, 2.8 Hz),
7.75 (d, 1 H, J ) 1.1 Hz), 8.74 (d, 1 H, J ) 4.8 Hz); 13C NMR
(300 MHz, CDCl3) δ 19.9, 23.8, 30.9, 32.7, 32.9, 35.0, 38.3, 48.3,
51.9, 73.1, 123.0, 123.7, 124.6, 125.3 (d, J PC ) 10.2 Hz), 126.1,
128.4-128.9 (m), 131.4, 131.9, 132.4, 135.0-135.2 (m), 136.5
(d, J PC ) 11.1 Hz), 136.7 (d, J PC ) 10.9 Hz), 139.8, 147.0, 148.9,
149.3, 149.7 (d, J PC ) 10.2 Hz), 152.1 (d, J PC ) 10.3 Hz); 31P
(162 MHz, CDCl3) δ 38.90, -143.23 (heptet, J PF ) 712.8 Hz);
MS (FAB) m/z (relative intensity) 756 (M+ - PF6, 20), 465 (90);
the eluent with a flow rate 1.0 mL/min: tR ) 18.12 min; [R]20
) +34.5 (c ) 0.5, CHCl3).
D
(S)-2-(2′-Diph en ylph osph in yl-4′,6′-di-ter t-bu tyl-1′-ph en -
yl)-3-m eth ylp yr id in e ((S)-9). (S)-9 was obtained from pre-
parative chiral HPLC with a Daicel AD column using a solvent
mixture (hexane/2-propanol ) 975:25; UV lamp, 254 nm) as
the eluent with a flow rate 1.0 mL/min: tS ) 39.42 min; [R]20
) -35.2 (c ) 0.5, CHCl3).
D
HP LC Meth od Resolu tion Meth od for (R)-4 a n d (S)-4:
(R)-2-(2′-Dip h en ylp h osp h in o-4′,6′-d i-ter t-bu tyl-1′-p h en yl)-
3-m eth ylp yr id in e ((R)-4). (R)-2-(2′-Diphenylphosphinyl-4′,6′-
di-tert-butyl-1′-phenyl)-3-methylpyridine (R)-9 (30 mg, 0.06
mmol) was dissolved in dry toluene (3 mL) under nitrogen at
room temperature. Trichlorosilane (0.45 mL, 0.6 mmol) and
triethylamine (0.88 mL, 0.66 mmol) were then added, and
white fumes evolved. After the solution was heated to 95 °C
for 2 days, it was cooled to room temperature, and sodium
hydroxide solution (2 M, 10 mL) was added. The aqueous phase
was extracted by dichloromethane (10 mL × 3), and the
combined organic phase was washed with water and brine and
dried over magnesium sulfate. The solvent was rotary evapo-
rated off, and the residue was purified by flash column
chromatography on silica gel using a solvent mixture (hexane/
ethyl acetate ) 5:1) as the eluent to afford the (R)-2-(2′-
diphenylphosphino-4′,6′-di-tert-butyl-1′-phenyl)-3-methylpyri-
dine (pyphos) (R)-4 (20 mg, 70%) as white solids: Rf ) 0.6
1
(hexane/ethyl acetate ) 5:1); mp 135-137 °C; H NMR (300
HRMS (ESIMS) calcd for
756.2980.
C
47H47NPPd+ 756.2973, found
MHz, CDCl3) δ 1.13 (s, 9 H), 1.17 (s, 9 H), 1.94 (s, 3 H), 7.04-
7.30 (m, 13 H), 7.60 (d, 1 H, J ) 2.0 Hz), 8.34 (d, 1 H, J ) 4.3
Hz); 13C NMR (75 MHz, CDCl3) δ 19.9, 31.1, 32.4, 34.8, 37.2,
125.8, 127.9, 128 (d, J CP ) 8.0 Hz), 128.2 (d, J CP ) 4.6 Hz),
130.1, 131.2 (d, J CP ) 7.6 Hz), 131.1 (d, J CP ) 7.5 Hz), 133.4
(R)-2-(2′-Dip h en ylp h osp h in o-4′,6′-d i-ter t-bu tyl-1′-p h en -
yl)-3-m eth ylp yr id in e (p yp h os) ((R)-4). (R,R)-[Dimethyl(1-
phenylethyl)aminato-C2,N]-[2-(2′-diphenylphosphino-4′,6′-di-
tert-butyl-1′-phenyl)-3-methylpyridine]palladium(II) hexafluoro-
phosphate (R,R)-8 (450 mg, 0.5 mmol) was dissolved in
dichloromethane (10 mL) followed by the addition of 1,2-
diphenylphosphinoethane (dppe) (200 mg, 0.5 mmol). The
reaction mixture was stirred at room temperature overnight.
Water (50 mL) was added, the solution was extracted with
dichloromethane (3 × 10 mL), and the combined organic phase
was washed with brine and dried over magnesium sulfate.
Rotary evaporation of the solvent gave a pale yellow residue
that was purified by short column chromatography on silica
gel using a solvent mixture of hexane/ethyl acetate (5:1) to
afford (R)-(4) (423 mg, 91%) as white solids.
(d, J CP ) 19.3 Hz), 134.0 (d, J CP ) 20.0 Hz), 137.1 (d, J CP
8.7 Hz), 138.0 (d, J CP ) 9.3 Hz), 138.2, 145.1, 147.1 (d, J CP
)
)
5.6 Hz), 149.7; 31P NMR (162 MHz, CDCl3) δ -11.60; MS (EI)
m/z (relative intensity) 465 (M+, 80), 450 (88), 408 (100), 388
(82), 374 (22), 358 (35), 342 (23); [R]20 ) +98.2 (c ) 0.5,
D
CHCl3).
(S)-2-(2′-Dip h en ylp h osp h in o-4′,6′-d i-ter t-bu tyl-1′-p h en -
yl)-3-m eth ylp yr id in e (p yp h os) ((S)-4). The general proce-
dure of reduction phosphine oxide for was used. (S)-2-(2′-
Diphenylphosphinyl-4′,6′-di-tert-butyl-1′-phenyl)-3-methyl-
pyridine (S)-9 (30 mg, 0.06 mmol), dry toluene (3 mL),
trichlorosilane (0.45 mL, 0.6 mmol), and triethylamine (0.88
mL, 0.66 mmol) were used to afford the (S)-2-(2′-diphenylphos-
phino-4′,6′-di-tert-butyl-1′-phenyl)-3-methylpyridine (pyphos)
2-(2′-Dip h en ylp h osp h in yl-4′,6′-d i-ter t-bu tyl-1′-p h en yl)-
3-m eth ylp yr id in e (9). 2-(2′-Diphenylphosphino-4′,6′-di-tert-
butyl-1′-phenyl)-3-methylpyridine32 (pyphos) 4 (300 mg, 0.65
mmol) was dissolved in acetone (15 mL) followed by the
addition of hydrogen peroxide (2 mL), and the solution was
stirred at room temperature for 5 min. The aqueous phase was
extracted by dichloromethane (10 mL × 3), and the combined
organic extract was washed with water and brine and dried
over MgSO4. The solvent was removed by rotary evaporation,
and the residue was purified by short column chromatography
on silica gel using a solvent mixture (hexane/ethyl acetate )
1:1) as the eluent to yield 2-(2′-diphenylphosphinyl-4′,6′-di-
tert-butyl-1′-phenyl)-3-methylpyridine 9 (306 mg, 98%) as
white solids: Rf ) 0.2 (hexane/ethyl acetate ) 1:1); mp 181-
(S)-4 (20 mg, 70%) as white solids: [R]20 ) -97.0 (c ) 0.5,
D
CHCl3).
[2-(2′-Dip h en ylp h osp h in o-4′,6′-d i-ter t-bu tyl-1′-p h en yl)-
3-m eth ylpyr idin e]-[1,5-cyclootadien e]r h odiu m (I) Hexaflu -
or op h osp h a t e (10). 2-(2′-Diphenylphosphino-4′,6′-di-tert-
butyl-1′-phenyl)-3-methylpyridine (pyphos) (4) (10 mg, 0.022
mmol) was dissolved in dichloromethane (1 mL) under nitro-
gen. [Rh(COD)Cl]2 was added, and the color of the solution
turned yellow. The solution was stirred for 5 min at room
temperature, and ammonium hexafluorophosphate (3.4 mg,
0.022 mmol) was added together with minimal amount of
water. The reaction was stirred vigorously at room tempera-
ture for 30 min, and the solvent was removed by reduced
pressure. The brown solid was washed with a minimal amount
of water and dried again. Minimal dichloromethane was added
followed by the addition of diethyl ether under nitrogen
atmosphere. Orange crystals formed after refrigeration over-
1
183 °C; H NMR (300 MHz, CDCl3) δ 1.08 (s, 9 H), 1.19 (s, 9
H), 2.12 (s, 3 H), 8.68 (dd, 1 H, J ) 8.3 Hz, 4.2 Hz), 7.23-7.49
(m, 10 H), 7.69-7.75 (m, 2 H), 7.80 (d, 2 H, J ) 2.1 Hz); 13C
NMR (75 MHz, CDCl3) δ 20.6, 29.6, 31.0, 32.4, 34.7, 37.6,
122.8, 127.7 (d, J CP ) 12.2 Hz), 128.0 (d, J CP ) 12.1 Hz), 128.4

P,N Ligand for Rh-Catalyzed Asymmetric Hydroboration
J . Org. Chem., Vol. 67, No. 9, 2002 2777
night and were collected by filtration to yield [2-(2′-diphen-
ylphosphino-4′,6′-di-tert-butyl-1′-phenyl)-3-methylpyridine][1,5-
cyclootadiene]rhodium(I) hexafluorophosphate (10) (14.5 mg,
82%): 1H NMR (300 MHz, CDCl3) δ 1.13 (s, 9 H), 1.36 (s, 9
H), 1.43 (s, 3 H), 1.77-1.82 (m, 4 H), 2.43-2.55 (m, 4 H), 3.56-
3.58 (m, 1 H), 3.89-3.91 (m, 1 H), 5.20-5.22 (m, 1 H), 5.46-
5.48 (m, 1 H), 6.96-7.03 (m, 3 H), 7.27-7.52 (m, 10 H), 7.77
(d, 1 H, J ) 1.6 Hz), 8.69 (d, 1 H, J ) 5.3 Hz); 13C NMR (75
MHz, CDCl3) δ 19.7, 26.1, 28.1, 31.1, 32.2, 32.8, 35.3, 35.7,
38.1, 76.4 (d, J ) 13.1 Hz), 78.3 (d, J ) 11.9 Hz), 100.5 (d, J
) 14.3 Hz), 106.7 (d, J ) 14.1 Hz), 123.9, 124.4 (d, J CP ) 7.0
Hz), 124.9, 125.5 ((d, J CP ) 4.6 Hz), 126.4, 126.6, 127.2, 128.0,
128.7 (d, J CP ) 9.6 Hz), 131.5 (d, J CP ) 25.7 Hz), 133.2 (d, J CP
) 9.4 Hz), 136.3, 138.3 (d, J CP ) 19.6 Hz), 139.7, 148.1, 149.8
(d, J CP ) 8.4 Hz), 152.5 (d, J CP ) 7.1 Hz), 157.6 (d, J CP ) 9.4
Hz); 31P NMR (162 MHz, CDCl3) δ 35.22 (d, J PRh ) 143.9 Hz),
-143.12 (heptet, J PF ) 712.8 Hz); MS (FAB) m/z (relative
intensity) 822 (M+ + 1, 20); HRMS (ESIMS) calcd for C40H48F6-
NP2RhH+ 822.2292, found 822.2285. X-ray crystals were grown
under the solvent mixture of dichloromethane/diethyl ether.
The X-ray crystal data have been deposited in Cambridge
Crystallographic Data Centre (CCDC 179715).
6.4 Hz), 6.90 (d, 2 H, J ) 8.6 Hz), 7.31 (d, 2 H, J ) 8.6 Hz);
MS (EI) m/z (relative intensity) 152 (M+, 100), 137 (42), 107
(30); [R]20D ) + 45.8 (c ) 1.0, CHCl3); GC-MS (column: Alltech
â-cyclodextrin chiral column (50 m × 0.25 mm); flow rate, 2
mL/min (helium); temperature program, 120 °C (60 min)) tR
) 42.2 min, tS ) 48.3 min.
1-(4-Meth ylp h en yl)eth a n ol (13).51 The general procedure
of catalytic asymmetric hydroboration was used. (R)-2-(2′-
Diphenylphosphino-4′,6′-di-tert-butyl-1′-phenyl)-3-methylpyri-
dine (pyphos) (R)-4 (1.8 mg, 3.8 µmol), Rh(COD)2BF4 (1.5 mg,
3.8 µmol), 4-methylstyrene (50 µL, 0.38 mmol), catecholborane
(1.0 M in THF, 0.46 mL, 0.46 mmol), and dry THF (1.5 mL)
were used to yield (R)-1-(4-methylphenyl)ethanol (13) (38 mg,
74%, 93% ee) as a colorless oil: Rf ) 0.5 (hexane/diethyl ether
) 1:1); 1H NMR (300 MHz, CDCl3) δ 1.47 (d, 3 H, J ) 6.5 Hz),
1.86 (brs, 1 H), 2.34 (s, 3 H), 4.85 (q, 1 H, J ) 6.5 Hz), 7.19 (d,
2 H, J ) 8.2 Hz), 7.29 (d, 2 H, J ) 8.2 Hz); MS (EI): m/z
(relative intensity) 136 (M+, 100), 121 (78), 91 (22); [R]20
)
D
+49.8 (c ) 0.5, CHCl3); HPLC (column: analytical Daicel OD-
H, solvent, hexane/2-propanol ) 99:1; UV lamp, 254 nm; flow
rate, 0.6 mL/min) tR ) 21.48 min, tS ) 22.74 min.
1-(4-Ch lor op h en yl)eth a n ol (14).52 The general procedure
of catalytic asymmetric hydroboration was used. (R)-2-(2′-
Diphenylphosphino-4′,6′-di-tert-butyl-1′-phenyl)-3-methylpyri-
dine (pyphos) (R)-4 (1.8 mg, 3.8 µmol), Rh(COD)2BF4 (1.5 mg,
3.8 µmol), 4-chlorostyrene (46 µL, 0.38 mmol), catecholborane
(1.0 M in THF, 0.46 mL, 0.46 mmol), and dry THF (1.5 mL)
were used to yield (R)-1-(4-chlorophenyl)ethanol (14) (42 mg,
70%, 79% ee) as a colorless oil: Rf ) 0.5 (hexane/ethyl acetate
) 4:1); 1H NMR (300 MHz, CDCl3) δ 1.47 (d, 3 H, J ) 6.6 Hz),
1.71 (brs, 1 H), 4.85 (q, 1 H, J ) 6.6 Hz), 7.10-7.39 (m, 4 H);
MS (EI): m/z (relative intensity) 158 (M+, 22), 156 (M+, 100);
Gen er a l P r oced u r e for Ca ta lytic Asym m etr ic Hy-
dr obor ation . 1-P h en yleth an ol (11).51 (R)-2-(2′-Diphenylphos-
phino-4′,6′-di-tert-butyl-1′-phenyl)-3-methylpyridine (pyphos)
(R)-4 (1.8 mg, 3.8 µmol) and Rh(COD)2BF4 (1.5 mg, 3.8 µmol)
were dissolved in dry THF (1.5 mL) under nitrogen at room
temperature. The solution was stirred for 5 min at room
temperature and cooled to 0 °C followed by the addition of
styrene (43 µL, 0.38 mmol). The catecholborane (1.0 M in THF,
0.46 mL, 0.46 mmol) was then added, and the color of the
solution was changed from yellow to orange. The reaction was
stirred for 18 h at 0 °C. Ethanol (2 mL) was added at 0 °C
followed by the NaOH solution (3 M, 2.5 mL) and H2O2 (35%,
0.5 mL) and stirred vigorously for 0.5 h at room temperature.
The reaction mixture was extracted with diethyl ether (10 mL
× 3), and the combined organic phase was washed with water
and brine and dried over MgSO4. The residue was purified by
column chromatography on silica gel using a solvent mixture
(hexane/diethyl ether ) 1:1) as the eluent to yield the (R)-1-
phenylethanol (11) (34 mg, 72%, 90% ee) as a colorless oil: Rf
) 0.5 (hexane/diethyl ether ) 1:1); 1H NMR (300 MHz, CDCl3)
δ 1.49 (d, 3 H, J ) 6.4 Hz), 1.91 (brs, 1 H), 4.89 (q, 1 H, J )
6.4 Hz), 7.20-7.40 (m, 5 H); MS (EI): m/z (relative intensity)
[R]20 ) +37.8 (c ) 0.5, CHCl3); HPLC (column: analytical
D
Daicel OD-H, solvent, hexane/2-propanol ) 99:1; UV lamp, 254
nm; flow rate, 0.4 mL/min) tR ) 35.00 min, tS ) 37.38 min.
Absolu te Con figu r a tion Deter m in a tion of p yp h os. The
absolute configuration of pyphos 4 was determined by chemical
correlation of the known configuration of pyridylphenol 1.30,43a
The optically active pyridylphenol (R)-1 underwent trifluo-
romethanesulfonation to yield pyridylphenyl triflate (R)-2
without racemization. Though racemization occurred when
(R)-2 underwent palladium-catalyzed phosphination,32 the
enantiomeric enriched pyphos 4 was obtained when the
reaction was stopped after 1.5 days. The isolated enantiomeric
enriched pyphos was then further oxidized by hydrogen
peroxide to yield the optically enriched phosphine oxide 9 and
analyzed by chiral HPLC using a Daicel OD-H column. The
larger peak area of the chromatogram suggested the R
configuration of pyphos oxide 9. Thus, its retention time was
assigned for (R)-9.
122 (M+, 100), 107 (15), 105 (8), 77 (70); [R]20 ) +45.8 (c )
D
1.3, CH2Cl2); HPLC (solvent, hexane/2-propanol ) 975:25; UV
lamp, 254 nm; flow rate, 0.5 mL/min) tR ) 16.18 min, tS
21.48 min.
)
1-(4-Meth oxyp h en yl)eth a n ol (12).51 The general proce-
dure of catalytic asymmetric hydroboration was used. (R)-2-
(2′-Diphenylphosphino-4′,6′-di-tert-butyl-1′-phenyl)-3-meth-
ylpyridine (pyphos) (R)-4 (1.8 mg, 3.8 µmol), Rh(COD)2BF4 (1.5
mg, 3.8 µmol), 4-methoxystyrene (50 µL, 0.38 mmol), cat-
echolborane (1.0 M in THF, 0.46 mL, 0.46 mmol), and dry THF
(1.5 mL) were used to yield the (R)-1-(4-methoxyphenyl)ethanol
(12) (43 mg, 74%, 94% ee) as a colorless oil: Rf ) 0.4 (hexane/
Ack n ow led gm en t. The work described in this paper
was supported by the Areas of Excellence Scheme
established under the University Grants Committee of
the Hong Kong Special Administrative Region, China
(Project No. AoE/P-10/01).
1
diethyl ether ) 1:1); H NMR (300 MHz, CDCl3) δ 1.47 (d, 3
H, J ) 6.4 Hz), 1.87 (brs, 1 H), 3.80 (s, 3 H), 4.84 (q, 1 H, J )
J O0159542
(52) Akakabe, Y.; Takahashi, M.; Kamezawa, M.; Kikuchi, K.;
Tachibana, H.; Ohtani, T.; Naoshima, Y. J . Chem. Soc., Perkin Trans.
1 1995, 1295-1298.
(51) Hayashi, T.; Matsumoto, Y.; Ito, Y. Tetrahedron: Asymmetry
1991, 2, 601-612.