A simple resolution procedure using the Staudinger reaction for the preparation of P-stereogenic phosphine oxides

Article abstract of DOI:10.1021/jo015909u

The resolution of a variety of (±)-P-stereogenic phosphines is achieved by exploiting the Staudinger reaction of a (±)-phosphine with enantiopure (1S,2R)-O-(tert-butyldimethylsilyl)isobornyl-10-sulfonyl azide. The resulting mixtures of diastereomeric phosphinimines are generally separable by fractional crystallization or flash chromatography. Subsequent acid-catalyzed hydrolysis provides the corresponding optically pure phosphine oxides in high yields.

Full text of DOI:10.1021/jo015909u

7478
J . Org. Chem. 2001, 66, 7478-7486
A Sim p le Resolu tion P r oced u r e Usin g th e Sta u d in ger Rea ction for
th e P r ep a r a tion of P -Ster eogen ic P h osp h in e Oxid es
Neil G. Andersen,† Philip D. Ramsden,‡ Daqing Che,§ Masood Parvez, and Brian A. Keay*
Department of Chemistry, University of Calgary, Calgary, AB, Canada, T2N 1N4
keay@ucalgary.ca
Received J uly 10, 2001
The resolution of a variety of (()-P-stereogenic phosphines is achieved by exploiting the Staudinger
reaction of a (()-phosphine with enantiopure (1S,2R)-O-(tert-butyldimethylsilyl)isobornyl-10-sulfonyl
azide. The resulting mixtures of diastereomeric phosphinimines are generally separable by fractional
crystallization or flash chromatography. Subsequent acid-catalyzed hydrolysis provides the
corresponding optically pure phosphine oxides in high yields.
In tr od u ction
developed to stereospecifically reduce P-stereogenic phos-
phine oxides to the corresponding phosphines with either
retention or inversion of configuration,6 new methods for
the preparation of optically pure phosphine oxides are
highly valuable. Of the few strategies reported for
obtaining enantiomerically pure phosphines via resolu-
tion techniques, the most popular these days uses ortho-
metalated palladium(II)-amine complexes.,7,8,9 The main
disadvantage of this strategy is that it requires the use
of stoichiometric amounts of palladium, which is quite
expensive. On a project involving the preparation of
electron deficient phosphines containing an axis of chiral-
ity, we required a method for resolving the enantiomers
of BINAPFu 1.10 Upon exhausting several of the known
methods for phosphine resolution without success,11 it
was necessary to design a new optical resolution proce-
dure to obtain the enantiopure BINAPFu ligand. We
The use of enantiomerically pure phosphine ligands in
asymmetric syntheses mediated by transition metals has
become very popular among the various strategies avail-
able for performing asymmetric transformations.1 There-
fore, much effort has been directed toward the rational
design, synthesis, and testing of new enantiomerically
pure phosphines for various synthetic purposes. A large
number of enantiomerically pure phosphines are now
available commercially, and many other ligands have
been reported in the literature.1d,2 The vast majority of
these compounds have carbon-based central or axial
chirality rather than P-stereogenic phosphorus atoms.
However, efforts to use P-stereogenic phosphines in
enantioselective transformations have been infrequent
due, in part, to the relative difficulty of obtaining these
compounds by resolution procedures or diastereoselective
synthesis.3 While there have been several recent ad-
vances in the diastereoselective synthesis of P-stereogenic
materials,4,5 there are still relatively few resolution
methods available for obtaining enantiomerically pure
tertiary phosphines. Since reliable methods have been
(6) (a) Marsi, K. L. J . Org. Chem. 1974, 39, 265. (b) Naumann, K.;
Zon, G.; Mislow, K. J . Am. Chem. Soc. 1969, 91, 2788. (c) Horner, L.;
Balzer, W.-D.; Tetrahedron Lett. 1965, 1157.
(7) For a review, see: (a) Wild, S. B. Coord. Chem. Rev. 1997, 166,
291. For recent examples, see: (b) Albert, J .; Cadena, J . M.; Granell,
J .; Muller, G.; Panyella, D.; Sanudo, C. Eur. J . Inorg. Chem. 2000,
1283. (c) Albert, J .; Bosque, R.; Cadena, J . M.; Granell, J . R.; Muller,
G.; Ordinas, J . I. Tetrahedron: Asymm. 2000, 11, 3335. (d) Albert, J .;
Cadena, J . M.; Delgado, S.; Granell, J . R. Organomet. Chem. 2000,
603, 235. (e) Albert, J .; Cadena, J . M.; Granell, J . R.; Solans, X.; Font-
Bardia, M. Tetrahedron Asymm. 2000, 11, 1943. (f) Dunina, V. V.;
Kuz′mina, L. G.; Rubina, M. Y.; Grishin, Y. K.; Veits, Y. A.; Kazakova,
E. I. Tetrahedron Asymm. 1999, 10, 1483. (g) Albert, J .; Cadena, J .
M.; Granell, J .; Muller, G.; Ordinas, J . I.; Panyella, D.; Puerta, C.;
Sanudo, C.; Valerga, P. Organometallics 1999, 18, 3511.
(8) For recent resolutions of phosphine oxides involving cocrystal-
lization with (S)-mandelic acid, see: (a) Wang, F.; Polavarapu, P. L.
J . Org. Chem. 2000, 65, 7561. (b) Drabowicz, J .; Lyzwa, P.; Omelanc-
zuk, J .; Pietrusiewicz, K. M.; Mikolajczyk, M. Tetrahedron: Asymm.
1999, 10, 2757.
(9) For a resolution of phosphines involving the formation of covalent
diastereomers, see: Vedejs, E.; Donde, Y. J . Am. Chem. Soc. 1997, 119,
9293.
(10) Andersen, N. G.; Parvez, M.; Keay, B. A. Org. Lett. 2000, 2,
2817.
(11) (a) Takaya, H.; Mashima, K.; Koyano, K.; Yagi, M.; Kumoba-
yashi, H.; Taketomi, T.; Akutagawa, S.; Noyori, R. J . Org. Chem. 1986,
51, 629. (b) Tani, K.; Brown, L. D.; Ahmed, J .; Ibers, J . A.; Yokota, M.;
Nakamura, A.; Otsuka, S. J . Am. Chem. Soc. 1977, 99, 7876. (c)
Otsuka, S.; Nakamura, A.; Kano, T.; Tani, K. J . Am. Chem. Soc. 1971,
93, 4301. (d) Roberts, N. K.; Wild, S. B. J . Chem. Soc., Dalton Trans.
1979, 2015. (e) Alcock, N. W.; Brown, J . M.; Hulmes, D. I. Tetra-
hedron: Asymm. 1993, 4, 743. (f) Leung, P. H.; Willis, A. C.; Wild, S.
B. Inorg. Chem. 1992, 31, 1406. (g) Gurusamy, N.; Berlin, K. D. J .
Am. Chem. Soc. 1982, 104, 3114. (h) Marsi, K. L.; Tuinstra, H. J . Org.
Chem. 1975, 40, 1843.
* To whom correspondence should be addressed. Phone: 403-220-
5354, Fax: 403-284-1372.
† Current address: Department of Chemistry, Stanford University,
Stanford, CA, 94305.
‡ Current address: Department of Chemistry, University of Toronto,
Toronto, ON, Canada, M5S 3H6.
§ Current address: Brantford Chemicals Inc., P.O. Box 1976,
Brantford, ON, Canada, N3T 5W5.
(1) (a) Zhang, X. Enantiomer 1999, 4, 541. (b) Williams, J . M. J .
Catalysis in Asymmetric Synthesis; Blackwell Science, Inc.: Malden,
MA, 1999 and references therein. (c) Stephenson, G. R. Advanced
Asymmetric Synthesis; Chapman & Hall: New York, 1996 and refer-
ences therein. (d) Seyden-Penne, J . Chiral Auxiliaries and Ligands in
Asymmetric Synthesis; J ohn Wiley & Sons: New York, 1995 and
references therein. (e) Blystone, S. L. Chem. Rev. 1989, 89, 1663. (f)
Brunner, H. Synthesis 1988, 645.
(2) (a) Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley
& Sons: New York, 1994; Chapter 2. (b) Ojima, I. Catalytic Asymmetric
Synthesis; VCH Publishers: Weinheim, 1993; Chapter 1. (c) Morrison,
J . D. Asymmetric Synthesis: Academic Press: New York, 1985; Vol.
5, Chapter 1.
(3) (a) Pietrusiewicz, K. M.; Zablocka, M. Chem. Rev. 1994, 94, 1375.
(b) Pietrusiewicz, K. M. Phosphorus, Sulfur Silicon Relat. Elem. 1996,
573. (c) Holz, J .; Quirmbach, M.; Bo¨rner, A. Synthesis 1997, 983.
(4) For recent advances in the diastereoselective synthesis of P-
stereogenic materials, see: Kolodiazhnyi, O. I. Tetrahedron: Asymm.
1998, 9, 1279 and references therein.
(5) Wolfe, B.; Livinghouse, T. J . Am. Chem. Soc. 1998, 120, 5116.
10.1021/jo015909u CCC: $20.00 © 2001 American Chemical Society
Published on Web 10/10/2001

Preparation of P-Stereogenic Phosphine Oxides
J . Org. Chem., Vol. 66, No. 22, 2001 7479
Sch em e 1
Sch em e 2a
a
Conditions: (a) 2 equiv of MeI, CHCl3, rt, 24 h. (b) 5 equiv of
LiAlH4, Et2O, reflux, 6 h.
conceived that a Staudinger12 reaction between a racemic
phosphine (()-2 and an enantiopure organoazide 3 should
provide a 1:1 mixture of diastereomeric phosphinimines
4a and 4b if the PdN bond rotational barrier was low
enough to prevent geometrical isomerism (Scheme 1). A
literature survey revealed that the PdN rotational bar-
rier for simple phosphinimines has been calculated to be
ca. 2.54 kcal/mol.13 Hence it was rationalized that PdN
geometrical isomerism would likely not complicate the
proposed resolution technique. By judicious choice of
the organoazide, the diastereomers formed from the
Staudinger reaction would be separable by column chro-
matography or crystallization. Once separated the phos-
phinimines would be hydrolyzed to provide optically pure
phosphine oxides. We herein provide a full account of our
new resolution procedure14 via the Staudinger reaction
for application with either P-stereogenic phosphines or
phosphines within molecules containing an axis of chiral-
ity.
Syn th esis of P -Ster eogen ic P h osp h in es. Unfortu-
nately, a commercial source of (()-P-stereogenic tertiary
phosphines could not be identified and thus these ma-
terials had to be synthesized according to known general
methods.15 Phosphines containing two alkyl substituents,
one of which was methyl, and an aryl group were
prepared via LiAlH4 reduction of a suitably substituted
phosphonium salt 6 (Scheme 2) that was generated from
phosphine 5. In this manner, racemic phosphines 7-9
were prepared and exhibited physical and spectral prop-
erties consistent with the literature.16
Sch em e 3a
a
Conditions: (a) 1.0 equiv of MeMgBr, Et2O, -40 °C, 1 h, 85%.
(b) 2.2 equiv of HCl (1.0 M solution in Et2O), 0 °C, 1 h. (c) 1.2
equiv of RMgBr, Et2O, -40 °C, 3 h, 32-67% (two steps).
variety of freshly prepared aryl Grignard reagents af-
forded racemic phosphines 13-17 in 32-67% yield.18-22
Triaryl phosphine 1820 was prepared in a similar step-
wise manner with the exception that 1-naphthylmagne-
sium bromide was used in place of MeMgBr (step a,
Scheme 3) and biphenyl was used in 10 instead of a
phenyl ring.
Attem pted Resolu tion of Cycloh exylm eth ylph en yl-
p h osp h in e (7) Usin g Va r iou s Or ga n o Azid es. Efforts
were directed at identifying an organoazide resolving
agent, which would be highly general for a wide variety
of racemic phosphines. To this end, (+)-neomenthyl azide
(19),23 3â-azido-5R-cholestane (20),24 6-azido-6-deoxy-
1,2,3,4-di-O-isopropylidene-R-D-galactopyranose (21),25 and
(1S)-10-camphorsulfonyl azide (22)26 were prepared ac-
cording to literature procedures and screened as potential
Phosphines bearing two or more aryl substituents were
prepared in a stepwise fashion starting with phos-
phonamidous chloride reagent 1017 (Scheme 3). Treat-
ment of compound 10 with 1 equiv of MeMgBr (Et2O, -40
°C, 1 h) afforded phosphonamide 11 in 85% yield.
Subsequent reaction with 2.2 equiv of anhydrous HCl (1.0
M solution in Et2O) furnished chloromethylphenylphos-
phine (12).18 Treatment of 12 (ether, -40 °C) with a
(12) Staudinger, H.; Hauser, E. Helv. Chem. Acta 1921, 4, 861. (b)
Staudinger, H.; Meyer, J . Helv. Chem. Acta 1919, 2, 635. (c) For a
review on the Staudinger reaction, see: Gololobov, Y. G.; Kasukhin,
L. F. Tetrahedron 1992, 48, 1353.
(13) Koketsu, J .; Ninomiya, Y.; Suzuki, Y.; Koga, N. Inorg. Chem.
1997, 36, 694.
(18) Duff, J . M.; Shaw, B. L. J . Chem. Soc., Dalton Trans. 1972,
2219.
(19) Serreqi, A. N.; Kazlauskas, R. J . J . Org. Chem. 1994, 59, 7609.
(20) Luckenbach, R. Phosphorus 1971, 1, 77.
(21) Pescher, P.; Caude, M.; Rosset, R.; Tambute´, A.; Oliveros, L.
Nouv. J . Chim. 1985, 9, 621.
(14) Andersen, N. G.; Ramsden, P. D.; Che, D.; Parvez, M.; Keay,
B. A. Org. Lett. 1999, 1, 2009.
(15) (a) Payne, N. C.; Stephan, D. W. Can. J . Chem. 1980, 58, 15.
(b) Bestman, H. J .; Lienert, J .; Heid, E. Chem. Ber. 1982, 115, 3875.
(c) Wittig, G.; Braun, H.; Cristau, H. Liebigs Ann. Chem. 1971, 751,
17.
(16) Wolfsberger, W. Z. Naturforsch., B: Chem Sci. 1988, 43, 295.
(17) Cowley, A. H.; Dewar, M. J . S.; J ackson, W. R.; J ennings, W.
B. J . Am. Chem. Soc. 1970, 92, 5206.
(22) Tani, K.; Brown, L. D.; Ahmed, J .; Ibers, J . A.; Yokota, M.;
Nakamura, A.; Otsuka, S. J . Am. Chem. Soc. 1977, 99, 7876.
(23) Viaud, M. C.; Rollin, P. Synthesis 1990, 130.
(24) Davis, A. P.; Dresen, S.; Lawless, L. J . Tetrahedron Lett. 1997,
38, 4305.
(25) Szarek, W. A.; J ones, J . K. N. Can. J . Chem. 1965, 43, 2345.
(26) (1S)-(+)-10-camphorsulfonyl azide can be prepared in one step
from (1S)-(+)-10-camphorsulfonyl chloride, see: Cremlyn, R.; Burrell,
K.; Fish, K.; Hough, I.; Mason, D. Phosphorus Sulfur 1982, 12, 197.

7480 J . Org. Chem., Vol. 66, No. 22, 2001
Andersen et al.
Sch em e 4
Sch em e 5a
a
Conditions: 2.4 equiv NaBH4, H2O, rt, 1 h, 95%. (b) 3.3 equiv
TBSCl, Et3N, DMF, rt, 3 h. (c) 6.0 equiv SOCl2, C6H6, DMF, reflux,
12 h. (d) 3.2 equiv NaN3, DMA, H2O, 60 °C, 12 h, 57% (3 steps).
1). Dissolving this mixture in petroleum ether and cooling
the resulting solution to -5 °C resulted in the precipita-
tion of diastereomerically pure phosphinimine 28a in
excellent yield. A second crop of crystals taken from the
mother liquor afforded compound 28b as thick colorless
prisms with a melting point of 147-149 °C (total yield
was 94%). Similar results were obtained using petroleum
ether as a crystallization solvent for phosphinimines 29a
and 29b (entry 2). However, phosphine 9 could not be
fully resolved by this technique (entry 3). For this
phosphinimine mixture, a single crystallization from
petroleum ether provided pure compound 30a in 43%
yield leaving a ca. 7:1 ratio of diastereomers in the
mother liquor. Under these circumstances, phosphin-
imine 30b could not be further purified by crystallization.
Many of the phosphinimine diastereomers were readily
separable by simple flash chromatography on silica gel
using mixtures of hexanes/ethyl acetate as eluent (entries
4-6, 8-9).28 With isomerically pure phosphinimines 28-
36 in hand, an investigation of the hydrolytic cleavage
of these materials to provide the corresponding enan-
tiopure phosphine oxides was initiated.
Treatment of phosphinimine 28a with 3 M H2SO4
solution in refluxing dioxane smoothly afforded cyclo-
hexylmethylphenylphosphine oxide (37) in 93% isolated
yield after chromatographic removal of the sulfonamide
byproduct 46 (Table 2, entry 1). The optical rotation of
compound 37, measured in MeOH at 20 °C, was +19.2,
which compares very favorably to the reported R20D value
of +19.0.29 Moreover, since the absolute stereochemistry
of phosphine oxide 37 has been previously established
by Mislow and co-workers,29 it can be concluded that the
R isomer was obtained from phosphinimine 28a in
reasonably high optical purity. Similar hydrolytic cleav-
age of isomerically pure phosphinimines 29-36 provided
optically active phosphine oxides 38-45, respectively
(Table 2). In general, the phosphine oxides obtained from
the hydrolysis procedure exhibited optical rotation val-
ues, which closely matched the known specific rotations
reported in the literature. Hence, it may be concluded
that the phosphine oxide products obtained using this
method are generally of high stereochemical purity. The
stereochemical purity of phosphine oxides 38, 41, and 44,
resolving agents. Unfortunately, azides 19-21 were
unsuccessful in this endeavor. Treatment of cyclohexyl-
methylphenylphosphine (7) with (1S)-10-camphorsulfonyl
azide (22) gave a 1:1 mixture of diastereomeric phos-
1
phinimines 23a and 23b (by H and 31P NMR) (Scheme
4), but unfortunately, the two diastereomers could not
be separated. Attention was focused on derivatizing azide
22 in hopes of identifying a more general phosphine
resolving agent.
It was postulated that increasing the steric size of the
functional group at C-2 in azide 22 might indeed result
in the production of a better, more stereodifferentiated
resolving agent. (+)-CSA monohydrate (24) was reduced
with NaBH4 to give exclusively the exo alcohol 2527
(Scheme 5). Silylation of 25 followed by heating the
sodium salt of silyl ether 26 with SOCl2 (benzene, 12 h)
furnished the corresponding sulfonyl chloride (not shown)
which immediately reacted with NaN3 in aqueous solu-
tion to provide the desired (1S,2R)-O-(tert-butyldi-
methylsilyl)isobornyl-10-sulfonyl azide (27) in 57% over-
all yield. With sulfonyl azide 27 in hand, attention was
focused on the optical resolution P-stereogenic phos-
phines 7-9 and 13-18.
Op tica l Resolu tion of P -Ster eogen ic P h osp h in es
w ith Isobor n yl Su lfon yl Azid e 27. The phosphin-
imines formed using sulfonyl azide 27 were found to be
stable toward flash chromatography on silica gel and
prolonged storage under an ambient atmosphere. In
addition, the diastereomeric phosphinimines produced
from the reaction of racemic phosphines 7-9 and 13-
18 with enantiopure azide 27 were readily separable by
fractional crystallization or flash chromatography on
silica gel (Table 1). For example, the phosphinimine
mixture obtained upon treatment of phosphine 7 with
azide 27 showed two strong singlets of equal intensity
in the 31P NMR spectrum at 23.3 and 23.2 ppm corre-
sponding to compounds 28a and 28b, respectively (entry
(28) The first isomer to elute from the column was designated as
phosphinimine “a ” while the other diastereomer was designated as the
“b” isomer.
(29) Korpium, O.; Lewis, R. A.; Chickos, J .; Mislow, K. J . Am. Chem.
Soc. 1968, 90, 4842.
(27) Dimmel, D. R.; Fu, W. Y. J . Org. Chem. 1973, 38, 3782.

Preparation of P-Stereogenic Phosphine Oxides
J . Org. Chem., Vol. 66, No. 22, 2001 7481
Ta ble 1. Resolu tion of P -Ster eogen ic P h osp h in es w ith Su lfon yl Azid e 27
entry
SM
R1
R2
productsa
separation method
yield (%)b
1
2
3
4
5
6
7
8
9
7
8
9
13
14
15
16
17
18
Me
Me
Me
Me
Me
Me
Me
Me
1-Np
C6H11
C5H9
CH(CH3)2
1-Np
2-Me-1-Np
2-MeO-1-Np
2-Np
9-phenanthryl
p-PhC6H4
28a and 28b
29a and 29b
30a and 30b
31a and 31b
32a and 32b
33a and 33b
34a and 34b
35a and 35b
36a and 36b
crystallization
crystallization
crystallizationc
chromatography
chromatography
chromatography
crystallization
chromatography
chromatography
94
90
87
94
91
95
87
89
89
a
b
Diastereomer to elute first or crystallize first designated “a ”. Combined isolated yield of both diastereomers. c Not fully separated.
Ta ble 2. Hyd r olysis of Isom er ica lly P u r e P h osp h in im in es
expt R20
D;
SM
R1
R2
product
[c] (g/100 mL)a
lit. R20
yield (%)b,c
SM config
D
1
2
3
4
5
6
7
8
9
28a
29b
30a
31a
32b
33a
34a
35a
36b
Me
Me
Me
Me
Me
Me
Me
Me
1-Np
C6H11
C5H9
CH(CH3)2
1-Np
2-Me-1-Np
2-MeO-1-Np
2-Np
9-phenanthryl
p-PhC6H4
37
38
39
40
41
42
43
44
45
+19.2;
[0.93]
[1.62]
[1.00]
[2.92]
[1.50]
[1.58]
[0.90]
[1.14]
[0.62]d
+19.028
- -
93 (R)
93
94 (S)
96 (S)
94
91 (S)
96 (S)
99
S
- -
R
R
- -
R
R
- -
S
+33.3;
-22.6;
+19.8;
-73.6;
+128.0;
-12.0;
+71.4;
+26.9;
-21.230
+18.631
- -
+128.019
-12.028
- -
+27.0d,22
93 (R)
a
b
c
d
Rotation in methanol except as noted. Isolated yields. Phosphorus configuration assigned according to literature correlation.
Rotation in CHCl3.
for which specific rotation data has not been reported,30
is assumed to be high on the basis of the good agreement
observed in the optical rotation data for known oxides
37, 39,31 40,32 42, 43, and 45 (Table 2). Also, the
phosphine oxides obtained from the hydrolysis of the
opposite phosphinimine diastereomers, 29a , 32b, and
35a provided oxides 38, 41, and 44, respectively, with
optical rotations equal in magnitude but opposite in sign
to those reported in Table 2. It is clear from the data
presented in Table 2 that the absolute configuration of
the product cannot be predicted based on which phos-
phinimine diastereomer is hydrolyzed.
To investigate the stereochemical course of the phos-
phinimine hydrolysis step, a single-crystal X-ray struc-
ture determination of compound 30a was undertaken.33
Since (1S,2R)-O-(tert-butyldimethylsilyl)isobornyl-10-sul-
fonyl azide (27) was used to prepare phosphinimine 30a ,
it was unambiguously concluded from the X-ray analysis
that the phosphorus stereocenter was of R configuration.
Since the hydrolysis of phosphinimine 30a provided (-)-
isopropylmethylphenylphosphine oxide (39), known to be
of S configuration,31 it can be concluded that the hydroly-
sis proceeds stereospecifically with inversion at phos-
phorus.34 Having shown that the hydrolysis step occurs
with inversion of configuration, many of the stereochem-
ical configurations of phosphinimines 28-36 may be
assigned (Table 2) based on the optical rotation data
reported for oxides 37-45 (vide supra).
Resolu tion of Axially Ster eogen ic Biden tate P h os-
p h in es. In addition to demonstrating the synthetic
(33) See Figure S1, Supporting Information. X-ray crystallographic
analysis was performed by Dr. M. Parvez at the University of Calgary.
The following crystal parameters were obtained: orthorhombic P212121
(No. 19); a ) 12.337(4) Å, b ) 12.833(3) Å, c ) 18.751(2) Å, V ) 2969(1)
Å3; Z ) 4; R ) 0.0459; wR ) 0.1208; Flack parameter ) -0.03(2).
Bijvoet analysis was performed. A refinement of the inverted structure
was carried out and converged with R ) 0.0543, wR ) 0.1427 with
Flack parameter ) 1.03(3) and was therefore rejected as the absolute
configuration present in the crystal.
(34) While the hydrolysis of phosphinimines under basic conditions
has been shown to occur with inversion of configuration at phosphorus,
such a relationship has not been previously established for acidic
media. For more information, see: Horner, L.; Winkler, H. Tetrahedron
Lett. 1964, 3, 175.
(30) Unfortunately, assignment of the absolute configuration to
phosphine oxide products 38, 41, and 44 was not possible since the
relationship between rotation sign and configuration has not been
deduced for these materials.
(31) Byrne, L. T.; Engelhardt, L. M.; J acobsen, G. E.; Leung, W.-P.;
Papasergio, R. I.; Raston, C. L.; Skelton, B. W.; Twiss, P.; White, A.
H. J . Chem. Soc., Dalton Trans. 1989, 105.
(32) Luchenbach, R.; Phosphorus 1972, 5, 223.

7482 J . Org. Chem., Vol. 66, No. 22, 2001
Andersen et al.
Sch em e 6
utility of resolving agent 27 toward a variety of P-
stereogenic phosphines, a project was undertaken to
apply the Staudinger reaction in the resolution of C2-
symmetric diphosphines. Treatment of (()-BINAPFu 1
with 2 equiv of enantiopure azide 22 smoothly provided
a 1:1 mixture of diastereomeric phosphinimines 47a and
47b in near quantitative yield (Scheme 6). Phosphin-
imines 47a and 47b could be readily separated by flash
chromatography on silica gel using a 9:1 CHCl3/CH3CN
eluent mixture.
Racemic BINAPFu (1) could also be resolved with 2
molar equiv of azide 27; a 1:1 mixture of easily separable
(by column chromatography) diastereomeric phosphin-
imines 48a and 48b were obtained (Scheme 6).
Application of resolving agent 27 to Sannicolo`’s
BITIANP35 ligand 49 was also successful giving phos-
phinimines 50a and 50b, which were separable by flash
chromatography. Hydrolysis of phosphinimines 47, 48,
and 50 after separation provided the enantiomerically
pure bis-phosphine oxides of (S)-BINAPFu and (S)-
BITIANP, respectively, as evidenced by optical rotation
measurements.
ucts 52 and 53 had been isolated. This surprising result
was initially attributed to partial air oxidation under the
reaction conditions. Subsequent experimentation, with
rigorous exclusion of oxygen, revealed that the source of
oxidation must be internal to the reaction mixture.
Similar results were obtained in the attempted resolution
of (()-MeOBIPHEP 56 using azide 27 (Scheme 7). Bis-
phosphinimine product 57 was obtained in 19% yield
after extensive chromatographic purification while prod-
ucts 58-60 could not be obtained in analytically pure
form.
The resolution of 2,2′-bis(di-2-furylphosphino)-1,1′-
binaphthalene 51a was successful using resolving agent
27. The diastereomers formed were easily separated and
converted to their corresponding phosphine oxides upon
treatment with 3 M sulfuric acid.37
The competitive formation of phosphine oxide products
54, 55, 59, and 60 can be rationalized by considering the
mechanism of the Staudinger reaction (Scheme 8). The
first step involves nucleophilic attack of the phosphine
on the terminal nitrogen of the azide reactant 27 produc-
ing a triazo intermediate 61. Although some intermedi-
ates of type 61 have been isolated,38 such compounds
normally decompose rapidly through a four-membered
transition state 6239 to provide the phosphinimine prod-
uct 52, 53 or 57, 58 with the expulsion of N2 gas. It is
postulated that due to steric hindrance, a four-membered
cyclic transition state 62 is not easily attained upon
reacting BINAP 51 or MeOBIPHEP 56 with sulfonyl
azide 27 through intermediate 61 (Scheme 8). Instead,
a six-membered cyclic transition state 63 is possible
leading to oxygen transfer from the sulfonyl moiety to
the phosphorus atom. Such a hypothesis is consistent
Interestingly, the resolution of (()-BINAP 51 and (()-
MeOBIPHEP 5636 using sulfonyl azide 27 did not proceed
as planned. Treatment of racemic BINAP 51 with 2
equiv. of azide 27 afforded a mixture of four phosphin-
imine products 52-55 (Scheme 7). Fortunately, these
materials could be separated by preparative TLC and
1
were identified on the basis of their H, 31P, and 13C NMR
spectra. A mixture of mono-phosphine oxide, mono-
phosphinimine 54 and 55, and bis-phosphinimine prod-
(35) (a) Benincori, T.; Brenna, E.; Sannicolo`, F.; Trimarco, L.;
Antognazza, P.; Cesarotti, E.; Demartin, F.; Pilati, T. J . Org. Chem.
1996, 61, 6244. (b) Tietze, L. F.; Thede. K.; Sannicolo`, F. J . Chem. Soc.,
Chem. Commun. 1999, 1811. (c) Tietze, L. F.; Thede. K.; Schimpf, R.;
Sannicolo`, F. J . Chem. Soc., Chem. Commun. 2000, 583.
(36) The (()-MeOBIPHEP ligand was prepared by Dr. D. Che
according to literature proceedure. See: Schmid, R.; Foricher, M.;
Cereghetti, M.; Scho¨nholzer, P. Helv. Chim. Acta 1991, 74, 370.
(37) Andersen, N. G.; McDonald, R.; Keay, B. A. Tetrahedron:
Asymm. 2001, 12, 263.
(38) (a) Leffler, J . E.; Tsuno, Y. J . Org. Chem. 1963, 28, 902. (b)
Leffler, J . E.; Hosenberg, U.; Tsuno, Y.; Forsblad, I. J . Org. Chem. 1961,
26, 4811.
(39) Leffler, J . E.; Temple, R. D. J . Am. Chem. Soc. 1967, 89, 5235.

Preparation of P-Stereogenic Phosphine Oxides
J . Org. Chem., Vol. 66, No. 22, 2001 7483
Sch em e 7
Sch em e 8
limited for axially stereogenic diphosphines such as
BINAP 51 and MeOBIPHEP 56; however, BINAPFu,
TetFuBINAP, and BITIANP could be resolved via this
procedure. In principle, the Staudinger resolution method
should be applicable to tertiary phosphines bearing
substituents other than alkyl and aryl groups and work
is currently in progress to test this hypothesis.
Exp er im en ta l Section
Gen er a l Deta ils. Infrared spectra were recorded on a FT-
IR spectrometer. Solid samples were handled as pressed KBr
pellets or as CCl4 thin films while liquid samples were
analyzed neat between NaCl plates. Nuclear magnetic reso-
nance (NMR) spectra were recorded on a 200 MHz (1H), 50
MHz (13C), 400 MHz (1H), 100 MHz (13C), 81 MHz (31P), or 162
MHz (31P) spectrometer. All spectra were obtained in CDCl3
unless otherwise mentioned and the chemical shifts (ppm) are
relative to the CHCl3 peak as an internal reference (7.27 ppm
for 1H and 77.00 for 13C). The external standard for 31P NMR
spectra was a solution of 30% H3PO4 in D2O. Low resolution
MS, HRMS, and FAB-MS analyses were obtained at the
University of Calgary. All melting and boiling points are
uncorrected. Boiling points are uncorrected and refer to
measured air-bath temperatures using a Kugelrohr short path
distillation apparatus. Optical rotation data was obtained on
a polarimeter using a quartz cell with a 10 cm path length.
Elemental analyses were performed by Ms. D. Fox at the
University of Calgary. X-ray structure determination was
performed by Dr. M. Parvez (University of Calgary) using a
diffractometer with graphite monochromated Mo-KR radia-
tion.
with 31P NMR studies of the (()-BINAP/azide 27 reaction
mixture, which showed the formation of all four products
52-55 prior to workup. Sulfonamide 46 was also ob-
tained from the reaction mixture and presumably formed
via hydration of intermediate 64.
Con clu sion s
Cyclohexylmethylphenylphosphine15a (7), cyclopentylmeth-
ylphenylphosphine16 (8), isopropylmethylphenylphosphine16
(9), chloro(diisopropylamino)phenylphosphine17 (10), chloro-
methylphenylphosphine18 (12), methyl-1-naphthylphenylphos-
phine18 (13), methyl(2-methoxy-1-naphthyl)phenylphosphine19
(15), methyl-2-naphthylphenylphosphine20 (16), methyl-9-
phenanthrylphenylphosphine21 (17), 4-biphenyl-1-naphthyl-
phenylphosphine22 (18), sodium (1S,2R)-isobornyl-10-sul-
fonate27 (25), BITIANP35 (49), and MeOBIPHEP36 (56) were
prepared according to known procedures and exhibited spectral
By use of the Staudinger reaction between racemic
tertiary phosphines and an enantiomerically pure organo-
azides 22 or 27, a 1:1 mixture of diastereomeric phos-
phinimines can be formed and separated by either
crystallization or flash chromatography. Subsequent
hydrolysis of the isomerically pure phosphinimines gives
enantiopure phosphine oxides with inversion of config-
uration at phosphorus. Although this method works very
well for P-stereogenic systems, its use is somewhat

7484 J . Org. Chem., Vol. 66, No. 22, 2001
Andersen et al.
properties consistent with those reported in the literature. (R)-
Cyclohexylphenylphosphine oxide29 (37), (S)-isopropylmeth-
ylphenyl phosphine oxide31 (39), (S)-methyl-1-naphthylphen-
ylphosphine oxide32 (40), methyl(2-methyl-1-naphthyl)phenyl-
phosphine oxide40 (41) (S)-methyl(2-methoxy-1-naphthyl)phen-
ylphosphine oxide19 (42), (S)-methyl-2-naphthylphenylphos-
phine oxide29 (43), methyl-9-phenanthrylphenylphosphine ox-
ide21 (44), and (R)-4-biphenyl-1-naphthylphenylphosphine ox-
ide22 (45) exhibited physical and spectral properties consistent
with those reported in the literature.
reduced pressure gives the crude phosphinimine mixture,
which may be purified by fractional crystallization or flash
chromatography.
(SP )-[(1S,2R)-O-(ter t-Bu tyld im eth ylsilyl)isobor n yl-10-
su lfon a m id yl]cycloh exylm et h ylp h en ylp h osp h in im in e
(28a ) a n d (RP )-[(1S,2R)-O-(ter t-Bu t yld im et h ylsilyl)iso-
bornyl-10-sulfonamidyl]cyclohexylmethylphenylphosphin-
im in e (28b). Phosphinimines 28a and 28b were prepared
according to the general procedure using cyclohexylmethyl-
phenylphosphine15a 7 (1.07 g, 5.20 mmol) and azide 27 (2.04
g, 5.46 mmol). Separation of the product diastereomers was
achieved by recrystallization from petroleum ether. The first
diastereomer to crystallize, compound 28a , was obtained as
fine, colorless needles (1.39 g, 49%) and exhibited the following
Meth yl (2-Meth yl-1-n a p h th yl)p h en ylp h osp h in e (14).
To a solution of chloromethylphenylphosphine18 (12) (0.238 g,
1.5 mmol) in dry Et2O (10 mL) at -40 °C was added a freshly
prepared solution of 2-methyl-1-naphthylmagnesium bromide
(0.080 M solution in THF, 20 mL, 1.6 mmol). The resulting
mixture was warmed to room temperature and stirred for a 3
h period. The mixture was quenched with 10% HCl and
extracted with Et2O. The combined organic extracts were dried
(MgSO4) and concentrated under reduced pressure to afford a
thick yellow oil. The product was purified by flash chroma-
tography (19:1 hexanes:benzene) to afford the analytically pure
14 (0.246 g, 62%). mp 190-191 °C (CHCl3); IR (KBr) 2954,
analytical data: R20 -39.7 (c 0.86, CHCl3); mp 175-177 °C
D
(petroleum ether); IR (KBr) 2930, 1452, 1110 cm-1; H NMR
1
(200 MHz) δ 0.06 (s, 3H), 0.16 (s, 3H), 0.82 (s, 3H), 0.91 (s,
9H4), 1.00 (s, 3H), 1.07-1.90 (m, 15H), 2.04 (d, J ) 11.2 Hz),
1.91-2.24 (m, 3H), 2.81 (d, J ) 13.8 Hz, 1H), 3.70 (dd, J )
13.8, 2.0 Hz, 1H), 4.19 (m, 1H), 7.66-7.45 (m, 3H), 7.72-7.90
(m, 2H); 13C NMR (50 MHz) ppm -4.9, -4.4, 10.3 (d, J ) 58
Hz), 17.9, 20.3, 20.9, 25.0 (d, J ) 3 Hz), 25.1 (d, J ) 3 Hz),
25.6, 26.0, 26.2, 27.4, 28.1, 38.7 (d, J ) 71 Hz), 42.2, 44.6, 48.5,
50.4, 53.8 (d, J ) 5 Hz), 76.3, 127.7 (d, J ) 86 Hz), 128.7 (d,
J ) 12 Hz), 131.1 (d, J ) 9 Hz), 134.2 (d, J ) 3 Hz); 31P NMR
(81 MHz) ppm +23.3; mass spectrum, m/z (relative intensity,
%) 551 (0.2, M+), 536 (1, M+ - CH3), 494 (53, M+ - C4H9), 268
1114, 748 cm-1 1H NMR (400 MHz) δ 1.94 (d, J ) 4.8 Hz,
;
3H), 2.80 (s, 3H), 7.20-7.54 (m, 8H), 7.88 (d, J ) 8.3 Hz, 2H),
8.38 (dd, J ) 8.5, 3.6 Hz, 1H); 13C NMR (100 MHz) ppm 10.8
(d, J ) 17 Hz), 24.3 (d, J ) 26 Hz), 125.2, 126.4, 126.8 (d, J )
2 Hz), 128.1 (d, J ) 17 Hz), 128.9 (d, J ) 4 Hz), 129.4, 129.6
(d, J ) 15 Hz), 129.9 (d, J ) 6 Hz), 131.2, 131.8 (d, J ) 20
Hz), 133.4 (d, J ) 3 Hz), 136.4 (d, J ) 7 Hz), 142.9 (d, J ) 13
Hz), 145.4 (d, J ) 22 Hz); 31P NMR (162 MHz) ppm -41.4;
mass spectrum, m/z (relative intensity, %) 264 (26, M+), 263
(100, M+ - H), 215 (13), 170 (7). Exact mass calcd for
(64), 73 (100). Exact mass calcd for C25H41NO3PSSi (M+
-
C4H9): 494.2314. Found: 494.2339. Compound 28b was
recovered from the mother liquor by recrystallization (1.30 g,
45%) as colorless prisms and exhibited the following charac-
teristics: R20 -10.0 (c 1.06, CHCl3); mp 147-149 °C (petro-
D
leum ether); IR (KBr) 2930, 1452, 1110 cm-1; H NMR (200
1
C
18H17P: 264.1068. Found: 264.1066.
MHz) δ 0.06 (s, 3H), 0.14 (s, 3H), 0.85 (s, 3H), 0.87 (s, 9H),
0.99 (s, 3H), 1.02-1.98 (m, 15H), 1.98-2.26 (m, 3H), 2.03 (d,
J ) 13 Hz, 3H), 2.81 (d, J ) 13.8 Hz, 1H), 3.67 (dd, J ) 13.8,
2.4 Hz, 1H), 4.10 (m, 1H), 7.41-7.64 (m, 3H), 7.70-7.82 (m,
2H); 13C NMR (50 MHz) ppm -4.9, -4.4, 10.3 (d, J ) 59 Hz),
17.9, 20.3, 20.9, 25.0 (d, J ) 3 Hz), 25.2 (d, J ) 3 Hz), 25.6,
26.0, 26.2, 27.4, 28.3, 38.7 (d, J ) 72 Hz), 42.2, 44.6, 48.5, 50.4,
53.9 (d, J ) 5 Hz), 76.4, 127.7 (d, J ) 86 Hz), 128.7 (d, J ) 12
Hz), 131.1 (d, J ) 10 Hz), 132.3 (d, J ) 3 Hz); 31P NMR (81
MHz) ppm 23.2; mass spectrum, m/z (relative intensity, %) 551
(0.2, M+), 536 (1, M+ - CH3), 494 (53, M+ - C4H9), 268 (64),
73 (100). Exact mass calcd for C25H41NO3PSSi (M+ - C4H9):
494.2314. Found: 494.2365.
(Sa x)-[(1S,2R )-O-(t er t -Bu t yld im e t h ylsilyl)isob or n yl-
10-su lfon am idyl]-[3,3′-bin aph th o[2,1-b]fu r an ]-2,2′-diylbis-
[d ip h en ylp h osp h in im in e] (48a ) a n d (Ra x)-[(1S,2R)-O-
(ter t-Bu tyldim eth ylsilyl)isobor n yl-10-su lfon am idyl]-[3,3′-
b in a p h t h o[2,1-b]fu r a n ]-2,2′d iylb is[d ip h en ylp h osp h in -
im in e] (48b). To a solution of racemic BINAPFu10 (1) (0.242
g, 0.345 mmol) in DME (2.5 mL) was added a solution of azide
27 (0.284 g, 0.759 mmol) in 7.5 mL of DME. The resulting
mixture was heated to reflux under a N2 atmosphere for 12 h.
The cooled mixture was then concentrated in vacuo to afford
a thick yellow oil. Separation of the product diastereomers was
achieved by column chromatography (3:1, hexanes:ethyl ace-
tate). The first isomer to elute from the column, compound
48a , was obtained as white solid (0.224 g, 49%), which gave
the following analytical data: mp 196-198 °C (CH3CN/H2O);
IR (KBr) 2954, 1437, 1120 cm-1; 1H NMR (400 MHz) δ -0.27
(s, 3H), -0.10 (s, 3H), 0.57 (s, 3H), 0.70 (s, 9H), 0.79 (s, 3H),
1.28-1.37 (m, 2H), 1.38-1.63 (m, 4H), 1.70-1.86 (m, 1H), 2.01
(d, J ) 13.6 Hz, 1H), 2.83 (d, J ) 13.6 Hz, 1H), 3.85 (m, 1H),
6.72-6.87 (m, 2H), 7.03-7.15 (m, 1H), 7.29-7.43 (m, 1H),
7.44-7.70 (m, 7H), 7.78-7.90 (m, 5H); 13C NMR (100 MHz)
ppm -4.7, -4.3, 18.1, 20.5, 21.1, 26.4, 27.8, 29.0, 42.8, 44.8,
48.8, 50.6, 53.4 (d, J ) 5 Hz), 76.4, 112.7, 122.2 (d, J ) 8 Hz),
123.6, 125.9, 127.0 (d, J ) 105 Hz), 127.2 (d, J ) 15 Hz), 128.0,
128.1 (d, J ) 10 Hz), 128.3 (d, J ) 105 Hz), 129.0, 129.2, 129.3,
130.2, 131.2, 132.8 (d, J ) 3 Hz), 133.3 (d, J ) 3 Hz), 133.9 (d,
J ) 12 Hz), 134.1 (d, J ) 10 Hz), 140.8 (d, J ) 151 Hz), 156.1
(d, J ) 9 Hz); 31P NMR (162 MHz) ppm +4.9; FAB-MS, m/z
(relative intensity, %) 1393 (2, M+H+). Phosphinimine 48b was
(1S,2R)-O-(ter t-Bu t yld im et h ylsilyl)isob or n yl-10-su l-
fon yl Azid e (27). To a solution of sodium (1S,2R)-isobornyl-
10-sulfonate27 25 (5.56 g, 21.7 mmol) in DMF (150 mL) and
Et3N (15 mL) was added TBSCl (10.84 g, 71.92 mmol). The
resulting mixture was stirred for 3 h at room temperature,
and the solvents were removed in vacuo (55 °C, 0.05 mmHg).
The residue was taken up into ether, filtered through a pad
of Celite, and concentrated under reduced pressure to afford
a thick orange oily residue. The crude silyl ether was dissolved
in benzene (150 mL), and DMF (5 drops) was added followed
by SOCl2 (9.5 mL, 0.13 mmol). The resulting solution was
heated to reflux for 12 h, quenched with saturated brine, and
extracted with ether. The combined organic extracts were dried
(MgSO4), filtered, and concentrated in vacuo to afford the
desired product (7.76 g, 82% from compound 25). The crude
sulfonyl chloride was dissolved in DMA (80 mL) and H2O (40
mL). To the solution was added NaN3 (4.54 g, 69.8 mmol), and
the resulting mixture was heated to 60 °C for 12 h. The cooled
mixture was then extracted with Et2O, washed with brine,
dried (MgSO4), and concentrated to furnish a light yellow oil.
The product was purified by column chromatography (15:1,
hexanes:ethyl acetate) to afford 6.13 g (70%) of azide 27 as a
colorless oil: R20 -36.2 (c 5.5, CHCl3); IR (KBr) 2954, 2131
D
(N3) cm-1; 1H NMR (200 MHz) δ 0.08 (s, 3H), 0.11 (s, 3H), 0.89
(s, 3H), 0.90 (s, 9H), 1.05 (s, 3H), 1.06-1.47 (m, 3H), 1.49-
1.86 (m, 3H), 1.88-2.10 (m, 1H), 3.12 (d, J ) 14.0 Hz, 1H),
3.97 (d, J ) 14.0 Hz, 1H), 4.06 (m, 1H); 13C NMR (50 MHz)
ppm -5.4, -4.1, 17.8, 20.1, 20.6, 25.8, 27.2, 28.6, 41., 44.5,
49.3, 50.4, 54.9, 75.8; mass spectrum, m/z (relative intensity,
%) 345 (1, M+ - N2), 288 (44), 115 (66), 73 (100). Exact mass
calcd for C12H22N3O3SSi (M+ - C4H9): 316.1151. Found:
316.1120.
Gen er a l P r oced u r e for th e P r ep a r a tion of P h osp h in -
im in es Usin g Azid e 27. To a solution of the tertiary phos-
phine (1.0 mmol) in dry THF (10 mL) is cautiously added a
solution of azide 27 (1.1 mmol) in THF (5 mL) at ambient
temperature. The mixture is then heated to 60 °C under an
inert atmosphere for 12 h. Removal of the solvent under
(40) Pescher, P.; Caude, M.; Rosset, R.; Tambute´, A. J . Chromatogr.
1986, 371, 159.

Preparation of P-Stereogenic Phosphine Oxides
J . Org. Chem., Vol. 66, No. 22, 2001 7485
obtained as a pale yellow solid (0.198 g, 43%), which was
recrystallized from CH3CN/H2O as long white needles with the
following properties: mp 176-178 °C (CH3CN/H2O); IR (KBr)
2954, 1438, 1118 cm-1; 1H NMR (400 MHz) δ 0.05 (s, 3H), 0.11
(s, 3H), 0.35 (s, 3H), 0.81 (s, 3H), 0.91 (s, 9H), 1.07-1.78 (m,
7H), 1.99 (d, J ) 13.3 Hz, 1H), 2.85 (d, J ) 13.3 Hz, 1H), 3.90
(m, 1H), 6.56-6.77 (m, 2H), 7.04 (t, J ) 7.1 Hz, 1H), 7.30-
7.47 (m, 4H), 7.51 (td, J ) 7.3, 3.2 Hz, 2H), 7.59 (td, J ) 6.9,
1.7 Hz, 1H), 7.66 (d, J ) 9.1 Hz, 1H), 7.71 (d, J ) 8.2 Hz, 1H),
7.78 (d, J ) 7.4 Hz, 1H), 7.81 (d, J ) 7.5 Hz, 1H), 7.87 (d, J )
9.1 Hz, 1H), 7.91 (d, J ) 8.0 Hz, 1H); 13C NMR (100 MHz)
ppm -4.2, 18., 20.5, 20.9, 26.7, 27.6, 29.5, 42.7, 44.9, 48.8, 50.7,
54.3 (d, J ) 2 Hz), 76.6, 113.1, 122.1 (d, J ) 8 Hz), 123.8, 125.8,
126.3 (d, J ) 107 Hz), 126.9 (d, J ) 16 Hz), 127.8, 127.8 (d, J
) 105 Hz), 128.0 (d, J ) 9 Hz), 128.9, 129.1 (d, J ) 14 Hz),
129.5, 130.0, 131.2, 132.6 (d, J ) 3 Hz), 133.2 (d, J ) 3 Hz),
133.7 (d, J ) 12 Hz), 134.1 (d, J ) 12 Hz), 140.9 (d, J ) 145
Hz), 156.1 (d, J ) 9 Hz); 31P NMR (162 MHz) ppm +5.8; FAB-
MS, m/z (relative intensity, %) 1393 (2, M + H+). Anal. Calcd
for C80H94N2O8P2S2Si2 + 2H2O: C, 67.20; H, 6.91; N, 1.96.
Found: C, 67.36; H, 6.80; N, 2.01. To establish absolute
stereochemistry, phosphinimine 48a (0.155 g, 0.111 mmol) was
subjected to acid hydrolysis, according to the general procedure
for the preparation of phosphine oxides from phosphinimines
to afford (S)-2,2′-bis(diphenylphosphinyl)-3,3′-binaphtho[2,1-
establish absolute stereochemistry, phosphinimine 50a (0.110
g, 0.083 mmol) was subjected to acid hydrolysis, according to
the general procedure for the preparation of phosphine oxides
from phosphinimines, to afford (S)-2,2′-bis(diphenylphos-
phinyl)-3,3′-bibenzo[b]thiophene (0.050 g, 91%) with R22
D
-324.2 (lit.35 R25 -329.0).
D
Rea ction of (()-BINAP (51) w ith (1S,2R)-O-(ter t-Bu tyl-
d im eth ylsilyl)isobor n yl-10-su lfon yl Azid e (27). To a solu-
tion of racemic BINAP (51) (0.247 g, 0.397 mmol) in degassed
toluene (10 mL) was added azide 27 (0.326 g, 0.873 mmol),
and the mixture was heated to reflux under an argon atmo-
sphere for 48 h. The cooled mixture was concentrated under
reduced pressure to afford a thick yellow oil. 31P NMR analysis
of the crude material showed the complete consumption of
starting material to yield four products 52-55 in an ap-
proximate 2:2:3:3 ratio. Subjecting the mixture to flash chro-
matography (4:1, hexanes:ethyl acetate) afforded bis-phos-
phinimine products 52 and 53 in isomerically pure form along
with a third fraction containing compounds 54 and 55. The
first isomer to elute from the column, compound 52, was
obtained as a colorless film (0.940 g, 18%) with the following
properties: mp 176-178 °C (CHCl3); IR (KBr) 2926, 1438, 1085
cm-1; 1H NMR (400 MHz) δ 0.04 (s, 3H), 0.10 (s, 3H), 0.50 (s,
3H), 0.91 (s, 3H), 0.93 (s, 3H), 1.27 (m, 1H), 1.37-1.65 (m, 6H),
1.71 (d, J ) 13.6 Hz, 1H), 2.78 (d, J ) 13.6 Hz, 1Hb), 3.91 (m,
1H), 6.87-6.99 (m, 2H), 7.14 (t, J ) 7.1 Hz, 1H), 7.35-7.51
(m, 5H), 7.55 (td, J ) 7.9, 1.4 Hz, 2H), 7.69 (d, J ) 7.3 Hz,
2H), 7.72 (d, J ) 7.3 Hz, 2H), 7.82 (t, J ) 7.1 Hz, 2H); 13C
NMR (100 MHz) ppm -4.1, -3.9, 18.4, 20.8, 21.1, 26.7, 27.7,
29.7, 43.0, 44.9, 48.9, 50.9, 53.8 (d, J ) 4 Hz), 76.8 (CH), 124.2
(d, J ) 114 Hz), 127.3, 128.2 (d, J ) 13 Hz), 128.5 (d, J ) 10
Hz), 128.7, 128.7 (d, J ) 101 Hz), 128.8, 128.8 (d, J ) 14 Hz),
129.0, 129.9 (d, J ) 14 Hz), 130.9 (d, J ) 95 Hz), 131.9 (d, J
) 3 Hz), 132.5 (d, J ) 3 Hz), 133.9 (d, J ) 13 Hz), 134.0 (d, J
) 11 Hz), 134.4 (d, J ) 2 Hz), 134.9 (d, J ) 12 Hz), 142.8 (dd,
J ) 6, 4 Hz); 31P NMR (162 MHz) ppm +15.9; FAB-MS, m/z
(relative intensity, %) 1313 (4, M + H+). Bis-phosphinimine
53 was obtained as a colorless amorphous solid (0.105 g, 20%)
with the following characteristics: mp 148-151 °C (CHCl3);
b]furan (0.076 g, 93%) with R22 -170.4.
D
(Sa x)-[(1S,2R)-O-(ter t-Bu tyld im eth ylsilyl)isobor n yl-10-
su lfon a m id yl]-[3,3′-b ib en zo[b]t h iop h en e]-2,2′-d iylb is-
[d ip h en ylp h osp h in im in e] (50a ) a n d (Ra x)-[(1S,2R)-O-
(ter t-Bu tyldim eth ylsilyl)isobor n yl-10-su lfon am idyl]-[3,3′-
b ib e n zo[b]t h iop h e n e ]-2,2′-d iylb is[d ip h e n ylp h osp h in -
im in e] (50b). To a solution of racemic BITIANP35 (49) (0.247
g, 0.389 mmol) in THF (2.5 mL) was added a solution of azide
27 (0.320 g, 0.855 mmol) in 7.5 mL of THF. The resulting
mixture was heated to reflux under a N2 atmosphere for 24 h.
The cooled mixture was then concentrated in vacuo to afford
a thick yellow oil. Separation of the product diastereomers was
achieved by column chromatography (3:1, hexanes:ethyl ace-
tate). The first isomer to elute from the column, compound
50a , was obtained as a white solid (0.240 g, 47%), which gave
the following analytical data: mp 277-279 °C (CH3CN/H2O);
1
IR (KBr) 2926, 1438, 1120, 1086 cm-1; H NMR (400 MHz) δ
-0.18 (s, 3H), -0.05 (s, 3H), 0.69 (s, 3H), 0.81 (s, 3H), 0.98 (s,
3H), 1.11-1.30 (m, 2H), 1.42-1.66 (m, 5H), 2.02 (d, J ) 13.8
Hz, 1H), 2.70 (d, J ) 13.8 Hz, 1H), 3.85 (m, 1H), 7.15 (td, J )
8.9, 3.6 Hz, 4H), 7.23 (d, J ) 6.7 Hz, 1H), 7.40 (td, J ) 7.6, 3.1
Hz, 2H), 7.45-7.57 (m, 3H), 7.64-7.74 (m, 4H), 7.82 (t, J )
8.4 Hz, 2H); 13C NMR (100 MHz) ppm -4.2, 18.2, 20.9, 21.5,
26.6, 27.7, 29.2, 43.1, 44.7, 49.1, 50.7, 53.3 (d, J ) 8 Hz, CH2),
76.6, 124.3 (d, J ) 116 Hz), 127.4, 128.2, 128.5, 128.5 (d, J )
6 Hz), 128.6, 128.7 (d, J ) 96 Hz), 128.8, 128.9, 129.0, 129.5
(d, J ) 16 Hz), 131.0 (d, J ) 98 Hz), 132.3 (d, J ) 3 Hz), 133.7
(d, J ) 11 Hz, 134.2 (d, J ) 12 Hz), 134.3, 134.8 (d, J ) 12
Hz), 143.2 (t, J ) 5 Hz); 31P NMR (162 MHz) ppm +14.6; FAB-
MS, m/z (relative intensity, %) 1313 (6, M + H+). The third
fraction obtained from the column contained a mixture of
compounds 54 and 55. This mixture was separated by repeated
preparative TLC (7:3 CHCl3/CH3CN). The less polar fraction,
compound 54, was obtained as a colorless solid (0.118 g, 30%)
and exhibited the following analytical data: mp 212-214 °C
(CHCl3); IR (KBr) 2951, 1437, 1118 cm-1; 1H NMR (400 MHz)
δ 0.07 (s, 3H), 0.13 (s, 3H), 0.52 (s, 3H), 0.89 (s, 3H), 0.91 (s,
3H), 1.33-1.44 (m, 1H), 1.50-1.71 (m, 5H), 1.88-1.98 (m, 1H),
2.22 (d, J ) 13.4 Hz, 1H), 3.45 (d, J ) 13.4 Hz, 1H), 4.07 (m,
1H), 6.29 (d, J ) 8.5 Hz, 1H), 6.44 (td, J ) 8.5, 1.3 Hz, 1H),
6.65 (td, J ) 8.0, 3.6 Hz, 2H), 6.89 (td, J ) 8.4, 1.6 Hz, 1H),
7.05-7.25 (m, 7H), 7.36-7.71 (m, 13H), 7.73 (t, J ) 8.2 Hz,
2H), 7.97 (dd, J ) 8.4, 2.1 Hz, 1H), 8.19 (d, J ) 13.1 Hz, 1H),
8.22 (d, J ) 13.1 Hz, 1H), 8.33-8.45 (m, 2H); 13C NMR (100
MHz) ppm -4.3, -4.2, 18.4, 20.8, 21.1, 26.5, 27.7, 29.0, 42.7,
44.9, 48.8, 50.8, 53.8 (d, J ) 4 Hz), 76.9, 125.8, 126.5 (d, J )
129 Hz), 127.3, 127.4, 127.7, 127.9 (d, J ) 6 Hz), 128.0, 128.1
(d, J ) 5 Hz), 128.2, 128.3, 128.4, 128.6, 128.7, 128.8 (d, J )
115 Hz), 128.9, 129.6, 130.6 (d, J ) 13 Hz), 131.1 (d, J ) 3
Hz), 131.4 (d, J ) 3 Hz), 131.5 (d, J ) 9 Hz), 131.6 (d, J ) 98
Hz), 132.0 (d, J ) 3 Hz), 132.4 (d, J ) 3 Hz), 132.68 (d, J ) 12
Hz), 132.72 (d, J ) 9 Hz), 133.1, 133.5 (d, J ) 11 Hz), 133.6
1
IR (KBr) 2927, 1438, 1121, 1086 cm-1; H NMR (400 MHz) δ
-0.05 (s, 3H), -0.01 (s, 3H), 0.67 (s, 3H), 0.84 (s, 9H), 0.90 (s,
3H), 1.38 (m, 1H), 1.62 (m, 5H), 2.02 (m, 1H), 2.17 (d, J )
13.8 Hz, 1H), 3.01 (d, J ) 13.8 Hz, 1H), 3.95 (m, 1H), 7.00 (td,
J ) 7.7, 3.2 Hz), 7.20 (t, J ) 7.4 Hz), 7.32 (d, J ) 8.2 Hz), 7.38
(t, J ) 7.5 Hz), 7.50 (td, J ) 7.5, 3.3 Hz), 7.60 (d, J ) 7.4 Hz),
7.63 (d, J ) 7.5 Hz), 7.75 (d, J ) 8.2 Hz), 7.78 (d, J ) 7.4 Hz);
13C NMR (100 MHz) ppm -4.4, -4.1, 18.3, 20.8, 21.3, 26.5,
27.7, 29.2, 42.8, 44.9, 48.9, 50.7, 53.5 (d, J ) 7 Hz), 76.7, 122.2
(d, J ) 2 Hz), 125.6, 125.8, 127.7, 127.8 (d, J ) 123 Hz), 127.9
(d, J ) 102 Hz), 128.2 (d, J ) 13 Hz), 129.1 (d, J ) 13 Hz),
129.6 (d, J ) 104 Hz), 132.7 (d, J ) 3 Hz), 133.3 (d, J ) 3 Hz),
133.7 (d, J ) 12 Hz), 133.9 (d, J ) 12 Hz), 140.4 (dd, J ) 7, 2
Hz), 141.6 (d, J ) 13 Hz), 142.2 (d, J ) 7 Hz); 31P NMR (162
MHz) ppm +8.1; FAB-MS, m/z (relative intensity, %) 1325 (2,
M + H+). Anal. Calcd for C72H90N2O6P2S4Si2 + H2O: C, 64.35;
H, 6.90; N, 2.08. Found: C, 64.57; H, 6.69; N, 2.18. Phosphin-
imine 50b was obtained as a colorless solid (0.208 g, 40%) with
the following properties: mp 220-222 °C (CH3CN/H2O); IR
(KBr) 2927, 1438, 1122, 1086 cm-1; 1H NMR (400 MHz) δ 0.05
(s, 3H), 0.15 (s, 3H), 0.52 (s, 3H), 0.86 (s, 3H), 0.92 (s, 9H),
1.21 (m, 1H), 1.35-1.70 (m, 6H), 2.01 (d, J ) 13.7 Hz, 1H),
3.01 (d, J ) 13.7 Hz, 1H), 3.94 (m, 1H), 6.88 (td, J ) 7.7, 3.4
Hz), 7.14 (d, J ) 8.1 Hz), 7.18 (d, J ) 7.7 Hz), 7.25 (d, J ) 8.7
Hz), 7.31-7.42 (m, 3H), 7.51 (dt, J ) 7.6, 3.3 Hz), 7.57-7.63
(m, 1H), 7.74 (d, J ) 7.7 Hz), 7.77 (d, J ) 7.3 Hz); 13C NMR
(100 MHz) ppm -4.2, -4.0, 18.4, 20.7, 21.1, 26.7, 27.7, 29.4,
42.8, 44.9, 48.9, 50.7, 54.1 (d, J ) 3 Hz), 76.7, 122.4, 125.2,
125.4, 127.3 (d, J ) 104 Hz), 127.5, 127.8 (d, J ) 124 Hz),
128.0 (d, J ) 13 Hz), 128.7 (d, J ) 100 Hz), 129.0 (d, J ) 13
Hz), 132.5 (d, J ) 3 Hz), 133.3 (d, J ) 3 Hz), 133.3 (d, J ) 12
Hz), 134.4 (d, J ) 11 Hz), 140.0 (dd, J ) 8, 2 Hz), 141.3 (d, J
) 14 Hz), 142.3 (d, J ) 7 Hz); 31P NMR (162 MHz) ppm +9.8;
FAB-MS, m/z (relative intensity, %) 1325 (2, M + H+). To

7486 J . Org. Chem., Vol. 66, No. 22, 2001
Andersen et al.
(d, J ) 101 Hz), 134.3 (d, J ) 11 Hz), 134.6 (d, J ) 34 Hz),
134.7 (d, J ) 36 Hz), 134.9 (d, J ) 11 Hz), 141.4 (dd, J ) 8, 5
Hz), 142.2 (dd, J ) 7, 5 Hz); 31P NMR (162 MHz) ppm +12.9
(P-15), +26.1 (P-26); FAB-MS, m/z (relative intensity, %) 984
(47, M + H+). The less polar material, compound 55, was
obtained as a colorless solid (0.107 mg, 27%) with the following
properties: mp 189-191 °C (CHCl3); IR (KBr) 2926, 1437, 1117
cm-1; 1H NMR (400 MHz) δ -0.07 (s, 3H), -0.01 (s, 3H), 0.63
(s, 3H), 0.83 (s, 9H), 0.98 (s, 3H), 1.20-1.40 (m, 1H), 1.47-
1.71 (m, 5H), 1.96-2.07 (m, 1H), 2.33 (d, J ) 13.9 Hz, 1H),
2.98 (d, J ) 13.9 Hz, 1H), 3.93 (m, 1H), 6.36 (d, J ) 8.5 Hz,
1H), 6.50 (t, J ) 7.5 Hz, 1H), 6.96 (td, J ) 7.6, 3.0 Hz, 2H),
7.08-7.26 (m, 7H), 7.28-7.57 (m, 10H), 7.58-7.98 (m, 7H),
8.07 (dd, J ) 12.7, 5.3 Hz, 2H); 13C NMR (100 MHz) ppm -4.3,
-4.2, 18.3, 20.8, 21.4, 26.6, 27.8, 29.0, 42.9, 44.8, 49.0, 50.7,
53.6 (d, J ) 4 Hz, CH2), 76.8, 124.8, 125.9, 127.7 (d, J ) 5
Hz), 127.75 (d, J ) 7 Hz), 127.84, 127.9, 128.0, 128.1 (d, J )
4 Hz), 128.2 (d, J ) 12 Hz), 128.3 (d, J ) 3 Hz), 128.6, 128.7,
128.9 (d, J ) 12 Hz), 129.2 (d, J ) 76 Hz), 129.6 (d, J ) 15
Hz), 130.3 (d, J ) 97 Hz), 131.3 (d, J ) 3 Hz), 131.7 (d, J ) 3
Hz), 131.8 (d, J ) 4 Hz), 131.9 (d, J ) 9 Hz), 132.0 (d, J ) 24
Hz), 132.2 (d, J ) 3 Hz), 132.8 (d, J ) 10 Hz), 132.0 (d, J ) 8
Hz), 133.2, 133.4 (d, J ) 63 Hz), 134.1 (d, J ) 2 Hz), 134.2 (d,
J ) 3 Hz), 134.5 (d, J ) 53 Hz), 134.6 (d, J ) 53 Hz), 134.8 (d,
J ) 10 Hz), 142.6 (dd, J ) 7, 5 Hz), 143.2 (dd, J ) 6, 4 Hz);
31P NMR (162 MHz) ppm +13.2 (P-15), +27.1 (P-26); FAB-
MS, m/z (relative intensity, %) 984 (21, M + H+).
J ) 13 Hz), 128.4 (d, J ) 13 Hz), 128.6 (d, J ) 7 Hz), 128.9 (d,
J ) 17 Hz), 129.5 (dd, J ) 7, 4 Hz), 130.8 (d, J ) 81 Hz), 130.8
(d, J ) 117 Hz), 131.9 (d, J ) 3 Hz), 132.4 (d, J ) 3 Hz), 133.7
(d, J ) 11 Hz), 134.6 (d, J ) 11 Hz), 157.9 (d, J ) 16 Hz); 31
P
NMR (162 MHz) ppm +14.0; FAB-MS, m/z (relative intensity,
%) 1273 (5, M+), 1216 (9, M+ - C4H9), 70 (100).
Gen er a l P r oced u r e for th e Hyd r olysis of Isom er ica lly
P u r e (1S,2R)-O-(ter t-Bu t yld im et h ylsilyl)isob or n yl-10-
su lfon a m id yl P h osp h in im in es To Give En a n tiom er ica lly
P u r e P h osp h in e Oxid es a n d (1S,2R)-O-(ter t-Bu t yld i-
m eth ylsilyl)isobor n yl-10-su lfon a m id e (46). The isomeri-
cally pure phosphinimine starting material (1.0 mmol) in
p-dioxane (20 mL) is treated with 3 M H2SO4 solution (7 mL),
and the resulting mixture is heated to 100 °C for 3 h. The
cooled reaction mixture is quenched with NaHCO3 solution and
extracted with CHCl3. The combined organic extracts are then
dried (MgSO4) and concentrated in vacuo to afford the crude
mixture of the desired phosphine oxide and (1S,2R)-O-(tert-
butyldimethylsilyl)isobornyl-10-sulfonamide (46). Compound
46 can ordinarily be removed from the phosphine oxide product
by flash chromatography (1:1, hexane:ethyl acetate). The
phosphine oxide, which typically remains at the baseline, can
be flushed from the column using 9:1 CHCl3/MeOH as the
eluent. The sulfonamide byproduct 46 exhibits the following
characteristics: mp 113-115 °C (CHCl3); IR (KBr) 3430, 3371,
2929, 1385, 1089 cm-1; 1H NMR (400 MHz) δ 0.07 (s, 3H), 0.10
(s, 3H), 0.87 (s, 3H), 0.90 (s, 9H), 1.02 (s, 3H), 1.02-1.13 (m,
1H), 1.30-1.42 (m, 1H), 1.62-1.80 (m, 4H), 1.90-2.03 (m, 1H),
2.96 (d, J ) 14.0 Hz, 1H), 3.77 (d, J ) 14.0 Hz, 1H), 4.05 (m,
1H), 4.62 (s, 2H); 13C NMR (50 MHz) ppm -4.8, -3.7, 18.3,
20.5, 21.1, 26.3, 27.6, 28.8), 42.3, 44.9, 49.3, 50.6, 54.0, 76.4;
mass spectrum, m/z (relative intensity, %) 290 (1, M+ - C4H9),
Rea ction of (()-BIP HEP (56) w ith (1S,2R)-O-(ter t-
Bu tyld im eth ylsilyl)isobor n yl-10-su lfon yl Azid e (27). To
a solution of racemic MeOBIPHEP36 (56) (0.304 g, 0.546 mmol)
in degassed toluene (10 mL) was added azide 27 (0.448 g, 1.20
mmol). The mixture was then heated to reflux under an argon
atmosphere for 48 h. The cooled mixture was concentrated
under reduced pressure to afford a thick yellow oil. 31P NMR
analysis of the crude material showed the complete consump-
tion of starting material to yield four products 57-60 in an
approximate 2:2:3:3 ratio. Subjecting the mixture to exhaustive
flash chromatography (4:1, hexanes:ethyl acetate) afforded bis-
phosphinimine product 57 and an inseparable mixture of the
diastereomeric bis-phosphinimine 58, and mono-phosphine
oxides 59 and 60. Compound 57 had: IR (KBr) 2928, 1470,
226 (27), 135 (100). Exact mass calcd for C12H24NO3SSi (M+
C4H9): 290.1246. Found: 290.1236.
-
Ack n ow led gm en t. We thank the Natural Sciences
and Engineering Research Council of Canada (NSERC)
for financial support. N.G.A. gratefully acknowledges
receipt of a NSERC scholarship, Ralph Steinhauer
Award of Distinction from the Alberta Heritage Foun-
dation and an Honorary Killam Fellowship. P.D.R.
gratefully acknowledges the receipt of an NSERC sum-
mer studentship.
1110 cm-1 1H NMR (400 MHz) δ 0.05 (s, 3H), 0.08 (s, 3H),
;
0.58 (s, 3H), 0.88 (s, 3H), 0.91 (s, 9H), 1.22-1.31 (m, 1H), 1.45-
1.70 (m, 5H), 1.78-1.92 (m, 1H) 2.08 (d, J ) 13.5 Hz, 1H),
3.29 (d, J ) 13.5 Hz, 1H), 3.47 (s, 3H), 3.99 (m, 1H), 6.81 (d,
J ) 8.1 Hz, 1H), 7.09 (td, J ) 7.5, 3.1 Hz, 2H) 7.15-7.32 (m,
3H), 7.40-7.55 (m, 3H), 7.58 (d, J ) 7.6 Hz, 1H), 7.61 (d, J )
7.8 Hz, 1H), 7.86 (d, J ) 7.1 Hz, 1H), 7.89 (d, J ) 7.1 Hz, 1H);
13C NMR (100 MHz) ppm -3.9, -4.3, 18.4, 20.9, 21.4, 26.6,
27.8, 29.6, 43.0, 44.9, 49.0, 50.8, 53.6 (d, J ) 5 Hz, CH2), 55.5,
76.5, 113.9 (d, J ) 3 Hz, CH), 126.8 (d, J ) 114 Hz), 127.1 (d,
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
tails and data for 29a , 29b, 30a , 31-36 (a ,b), 37-45 and an
ORTEP diagram of 30a . This material is available free of
charge via the Internet at http://pubs.acs.org.
J O015909U