Enantioselective acylation using a second-generation P-aryl-2- phosphabicyclo[3.3.0]octane catalyst

Article abstract of DOI:10.1021/jo049112p

The synthesis of P-aryl-2-phosphabicylco[3.3.0]-octane·HBF ₄ salts 3a and 3c is described. Incorporation of the P-3,5-di-tert-butyl-4-methoxyphenyl group in 3c allows use of a less expensive aryl bromide starting material. Deprotonation of the air-stable salts in situ with triethylamine releases the corresponding phosphines 1a and 1c for use in the kinetic resolution of representative secondary alcohols. The method is convenient for small-scale experiments and affords enantioselectivities s close to the values obtained using the free phosphines 1a and 1b in cases where s is ca. 40 or lower.

Full text of DOI:10.1021/jo049112p

borane decomplexation technique in the case of catalysts
1a and 1c, generated in situ from 3a and 3c as described
below.
En a n tioselective Acyla tion Usin g a
Secon d -Gen er a tion
P -Ar yl-2-p h osp h a bicyclo[3.3.0]octa n e
Ca ta lyst
J ames A. MacKay and Edwin Vedejs*
Department of Chemistry, University of Michigan,
Ann Arbor, Michigan 48109
edved@umich.edu
Received May 26, 2004
Our study began with the synthesis of 2c. The starting
arylphosphine 4 was prepared from 4-bromo-2,6-di-tert-
butyl phenol by O-methylation6 and the usual sequence
of bromine-lithium exchange, reaction with PCl3, and
reduction with LiAlH4.1b,c The conversion to the phos-
phine 1c was then carried out by lithiating 4 and reacting
the derived lithiophosphide with the cyclic sulfate 5.1b,c
Subsequent treatment with THF-borane gave the com-
plex 2c in 87% yield. Decomplexation of 2c with pyrro-
lidine afforded the free phosphine 1c, and protonation
with aqueous HBF4 produced the phosphonium tetrafluo-
roborate salt 3c in 90% yield. Crystallization provided
pure precatalyst 3c as a moderately hygroscopic solid,
but no decomposition was observed over 6 months for a
sample that was stored in a vial and frequently opened
to air.
Abstr a ct: The synthesis of P-aryl-2-phosphabicylco[3.3.0]-
octane‚HBF4 salts 3a and 3c is described. Incorporation of
the P-3,5-di-tert-butyl-4-methoxyphenyl group in 3c allows
use of a less expensive aryl bromide starting material.
Deprotonation of the air-stable salts in situ with triethyl-
amine releases the corresponding phosphines 1a and 1c for
use in the kinetic resolution of representative secondary
alcohols. The method is convenient for small-scale experi-
ments and affords enantioselectivities s close to the values
obtained using the free phosphines 1a and 1b in cases where
s is ca. 40 or lower.
In 1993, a report from our laboratory demonstrated
that tri-n-butylphosphine serves as a nucleophilic acy-
lation catalyst,1a a discovery that eventually led to the
development of the enantioselective P-aryl-2-phospha-
bicyclo[3.3.0]octane (“PBO”) catalysts 1a ,b.1b,c The 3,5-
di-tert-butylphenyl derivative 1b was preferred for most
applications because it is more effective for enantiose-
lective acyl transfer compared to 1a . However, the
synthesis of 1b starts from the expensive 3,5-di-tert-butyl-
1-bromobenzene.2 An analogue 1c has now been prepared
from the cheaper 2,6-di-tert-butyl-4-bromophenol and has
been tested in acyl transfer reactions.
We have also reevaluated the methodology for prepar-
ing catalyst solutions containing 1a ,b. In the last step of
our published route, phosphorus was protected by com-
plexation with borane3 to allow isolation and purification.
The free phosphines 2a ,b were then released as needed
by warming with pyrrolidine followed by filtration chro-
matography. This procedure was relatively simple, but
attempts to quantify the amount of free phosphine or to
transfer the material often resulted in partial oxida-
tion, especially in small-scale experiments.4 We were
therefore interested in the recent report of Fu et al. where
air-stable trialkylphosphonium tetrafluoroborate salts
were used as versatile sources of air-sensitive trialkyl-
phosphines.5 We have compared this approach with the
The P-phenyl precatalyst 3a was obtained by a similar
approach. Thus, the free phosphine 1a was generated
by decomplexation of 2a with warm pyrrolidine, and
aqueous HBF4 in CH2Cl2 was added. Removal of solvent
afforded phosphonium tetrafluoroborate 3a as a white
powder that was contaminated with a small amount of
unreacted phosphine borane, but crystallization gave
pure 3a in 86% yield. The crystalline salt was exposed
(4) The best procedure from the borane complex is to decomplex a
substantial amount of the phosphine borane and to immediately divide
it between several reactions. Alternatively, the phosphine can be stored
in the solid state or in hydrocarbon solution, but both methods of
storage require rigorous exclusion of air, and oxidation has been
observed over extended periods of time. Solutions of PBO catalysts in
deoxygenated toluene or benzene can be stored outside the glovebox
in a flask under a good rubber septum for 1-2 months before the
phosphine oxide is observable by 31P NMR.
(1) (a) Vedejs, E.; Diver, S. T. J . Am. Chem. Soc. 1993, 115, 3358.
(b) Vedejs, E.; Daugulis, O. J . Am. Chem. Soc. 1999, 121, 5813. (c)
Vedejs, E.; Daugulis, O. J . Am. Chem. Soc. 2003, 125, 4166. (d) Vedejs,
E.; MacKay, J . A. Org. Lett. 2001, 3, 535.
(2) 3,5-Di-tert-butylbromobenzene is commercially available from
Aldrich for $130/5 g.
(3) For selected reviews on phosphine boranes, see: (a) Brunel, J .
M.; Faure, B.; Maffei, M. Coord. Chem. Rev. 1998, 180, 665. (b) Ohff,
M.; Holz, J .; Quirmbach, M.; Borner, A. Synthesis 1998, 1391.
(5) Netherton, M. R.; Fu, G. C. Org. Lett. 2001, 3, 4295.
(6) Miller, B. J . Org. Chem. 1965, 30, 1964.
10.1021/jo049112p CCC: $27.50 © 2004 American Chemical Society
Published on Web 09/04/2004
6934
J . Org. Chem. 2004, 69, 6934-6937

TABLE 1. En a n tioselective Acyla tion s Ca ta lyzed by 3a a
TABLE 2. En a n tioselective Acyla tion s Ca ta lyzed by 3ca
cat. time conv
T
s
s
T
s
s
entry alcohol
R
solvent (%)
(h)
(%) (°C) (3c) (1b)b
entry alcohol
R
solvent
(°C) (3a /Et3N) (1a )
1
2
3
4
5
6
7
8
9
6
6
6
7
8
8
9
10
10
11
12
i-Pr toluene
3-Py toluene
3-Pyc toluene
i-Pr heptane
6
1
2
2
1.5
0.17 58
4.5
9.5
35
rt 30
(35)
1
2
3
4
5
6
7
6
7
8
6
7
8
9
i-Pr toluene
i-Pr toluene
rt
rt
rt
21
13
24
23
16
47
16
(21)b
(11)b
(24)b
(20)
rt
7
28 -40
52 -40 40
19
49
48 -40 65
57 rt
46 -40 82
52 -40 34
55 -40 49
8.1
Ph
toluene
(55)
(10)
3-Pyc 3:1 t-AmOH/DCMd -25
3-Pyc 3:1 t-AmOH/DCMd -25
3-Pyc 3:1 t-AmOH/DCMd -25
3-Pyc 3:1 t-AmOH/DCMd -25
i-Pr toluene 15 139
rt 13
Ph
i-Pr heptane
Ph toluene
toluene
9
1
4
2
5
7
3.5
16
1
45.5
13
64
rt 10.2 (10)
(145)
5.2 (6.9)
(57)
(17)
a
i-Pr heptane
i-Pr heptane
i-Pr heptane
(99)
(52)
(82)
All reactions used 0.1 M substrate in the given solvent with a
10
11
ca. 1:2 ratio of precatalyst/Et3N and 2.5 equiv of anhydride unless
noted. Reference 1c. c 0.5 equiv of anhydride and 1 equiv of Et3N.
b
d
t-AmOH ) tert-amyl alcohol; DCM ) CH2Cl2.
a
Reactions used 0.1 M substrate and ca. 1:2 3c/Et3N and 2.5
equiv of anhydride unless noted. Reference 1c. c 1 equiv of
b
anhydride.
to the air for 1 week and was found to be mildly hy-
groscopic, but no decomposition was observed.
PBO tetrafluoroborate salt 3a was tested as a precata-
lyst in several acylation reactions via in situ deprotona-
tion with Et3N (Table 1). Alcohols 6 and 7 were initially
chosen as representative substrates from the aryl alkyl
carbinol series, and their isobutyroylations using the in
situ 3a /Et3N method proceeded with selectivities similar
to those observed for reactions catalyzed by preformed
1a (from 2a and pyrrolidine, entries 1 and 2). The
benzoylation of 8 with 3a /Et3N also occurred with selec-
tivity comparable to that of the preformed phosphine
catalyst 1a .
In addition, several other substrates were tested in
nicotinoylation reactions with nicotinic anhydride.7 This
reagent was expected to mimic the steric effect of benzoic
anhydride but to react faster due to the electron-
withdrawing effect of pyridine nitrogen. Indeed, the
reactions were considerably faster (ca. 5-fold) and were
conveniently conducted using 0.5 equiv of the anhydride,
in contrast to the benzoylations where 2.5 equiv of the
anhydride was necessary. The nicotinoylations were
performed in 3:1 tert-amyl alcohol/CH2Cl2 at -25 °C,
entries 4-7, with CH2Cl2 added to prevent freezing of
tert-amyl alcohol at low temperatures and to provide
solubility for nicotinic anhydride. Aryl alkyl carbinols
6-9 all exhibited high selectivities, with a particularly
high value of s ) 47 obtained for the hindered substrate
8, although this substrate exhibited even better selectiv-
ity with catalyst 1a under the same conditions.
the catalyst 1c in situ (Table 2). The isobutyroylation of
6 at rt worked well, and s ) 30 was observed, marginally
lower than the value of s ) 35 obtained with the
preformed catalyst 1b (entry 1). In contrast, the results
using nicotinic anhydride were relatively poor (entries 2
and 3), suggesting that this reagent is not well matched
for use with catalyst 1b. A similar drop in enantioselec-
tivity has been observed in our earlier studies for reac-
tions where benzoic anhydride was activated by catalyst
1b, as also shown in the example of entry 8 vs entry 9.
On the other hand, the benzoylation of the hindered
alcohol 8 proceeded with similar, modest selectivity using
either catalyst (entries 5 and 6). No further experiments
were performed with nicotinic or benzoic anhydrides in
this series.
A number of isobutyroylations were studied (entries
4, 5-7, and 9-11) and afforded selectivities comparable
to those obtained with the previously optimized catalyst
1b at room temperature. However, differences between
3c/Et3N and 1b became apparent at lower temperatures.
Three isobutyroylation reactions of benzylic alcohols were
conducted in heptane at -40 °C (entries 4, 7, and 9), the
optimized conditions for catalyst 1b. All three examples
gave high selectivities with 3c/Et3N, but the s values
were diminished compared to those using 1b. Two
additional substrates 11 and 12 were isobutyroylated
with precatalyst 3c in heptane at -40 °C to represent
the allylic alcohol category as previously reported.1b,c
Alcohol 11 reacted with s ) 34 (compare to s ) 52 using
catalyst 1b)1b-d and 12 gave s ) 49 (compare to s ) 82
using catalyst 1b).1d
Clearly, the in situ generation of phosphine 1c from
3c /Et3N serves as an effective source of the acylation
catalyst 1c for the kinetic resolution of aryl alkyl
carbinols and allylic alcohols for those reactions where s
is below ca. 40. Somewhat lower s values observed with
precatalyst 3c compared to preformed catalyst 1b are
probably due to intrinsic differences between the two aryl
groups. Interference by the Et3N and the derived Et3N‚
HBF4 may be a factor in some of the most highly selective
low-temperature reactions, but the findings of Table 1
suggest that the in situ procedure does not cause sub-
stantial deterioration of enantioselectivities compared to
the use of preformed catalyst when enantioselctivites s
are in the range of 10-40.
Next, the more highly substituted precatalyst 3c was
tested in acylation reactions with Et3N added to release
In summary, we have prepared air-stable PBO tet-
(7) Badgett, C. O. J . Am. Chem. Soc. 1947, 69, 2231.
rafluoroborate salts (3a and 3c) as precursors to PBO
J . Org. Chem, Vol. 69, No. 20, 2004 6935

catalysts. In accord with the Fu precedent,5 these salts
are trivial to handle, even on a small scale, and serve as
convenient precatalysts for PBO-catalyzed kinetic resolu-
tions. The stability of the salts allows accurate quanti-
fication of the precatalyst in air, and in situ deprotonation
with Et3N releases the free phosphines in typical acyla-
tion experiments. Precatalyst 3a usually gives products
with enantioselectivities comparable to those with 1a .
Precatalyst 3c affords similar room-temperature enan-
tioselectivity compared to the optimized PBO catalyst 1b,
but the beneficial effect of lower reaction temperatures
is more pronounced for 1b. Overall, the in situ generation
of 1a and 1c is competitive with many of the recently
described alternatives for nonenzymatic kinetic resolu-
tion of unsaturated alcohol substrates.8
solution of freshly distilled PCl3 (4.5 mL, 51.3 mmol) in THF
(85 mL) at -78 °C over ca. 70 min. After being stirred for 30
min at -78 °C, the mixture was warmed to room temperature
and was stirred for 1.5 h. Assay by 31P NMR (unlocked, crude
reaction mixture) showed the presence of ArPCl2 (δP ) 166.1
ppm). The crude solution of ArPCl2 was added dropwise to a
stirred suspension of LiAlH4 (7.7 g, 202.8 mmol) in ether (150
mL) at -78 °C via cannula over 1 h. After addition, the
suspension was warmed to room temperature (1 h) and then
carefully quenched at 0 °C with degassed (N2 purge, 1 h)
NH4Cl solution in water (ca. 70 mL of 1:1 saturated solution/
H2O). The supernatant liquid was transferred via cannula onto
MgSO4 in an N2-purged flask; the Al salt residue was shaken
with ether (2 × 100 mL; all transfers with cannula under N2
pressure); and all the organic layers were combined over MgSO4.
The liquid was decanted away from MgSO4 (cannula), and the
precipitate was washed with ether (50 mL). Solvents were
evaporated (N2 stream), and the residue was distilled in vacuo
through a 10-cm Vigreaux column (STENCH!). The first fraction
was collected at 60-64 °C/0.1 mm, 650 mg and was impure; the
second fraction was collected at 64-68 °C/ 0.1 mm, 3.3 g and
was ca. 85% pure 4 (contaminated with the arene from replace-
ment of Br by H). This product was used in the subsequent step
without additional purification: 500 MHz NMR (C6D6, ppm) δ
7.54 (2 H, d, J ) 8.1 Hz) 3.84 (2 H, d, J ) 97.8 Hz) 3.38 (3 H, s)
1.43 (18 H, s); 31P NMR (161.9 MHz {H}, C6D6, ppm) δ -122.6.
Exp er im en ta l Section
(1R,2R,4S,5S)-4,8,8-Tr im eth yl-2-p h en ylp h osp h a bicyclo-
[3.3.0]octa n e‚HBF 4 (3a ). Phosphine borane 2a 1c (79 mg, 0.30
mmol) was added to a round-bottom flask equipped with a
magnetic stir bar and reflux condenser. The flask was flushed
with N2 for 30 min, and then pyrrolidine (8 mL, distilled from
CaH2) was added. The resulting solution was heated at 50 °C
in an oil bath for 100 min. Pyrrolidine was evaporated (N2
stream), and the residue was filtered through a 10 × 1.2 cm
pad of silica gel (the flask and the column containing silica gel
were purged with N2 for 1 h) in benzene under N2, collecting 50
mL. The solvent was evaporated (N2 stream) and taken up in
CH2Cl2 (3 mL, degassed). Aqueous HBF4 (50 wt %%, 0.3 mL,
2.12 mmol) was added via syringe, and the resulting mixture
was stirred for 15 min. The layers were separated, and the
aqueous layer was extracted with CH2Cl2 (2 × 5 mL). The
organic layers were combined, dried (MgSO4), and filtered.
Removal of solvent (aspirator) provided a white powder. Pure
material (87 mg, 86% yield) was obtained by dual chamber
crystallization from ether/CH2Cl2: mp 136-137 °C; HRMS calcd
for C16H24P+ 247.16160, found m/z 247.1607, error ) 4 ppm; IR
(neat, cm-1) 1033, PH; 500 MHz NMR (CDCl3, ppm) δ 7.91-
7.84 (2 H, m) 7.79-7.74 (1 H, m) 7.65 (2 H, ddd, J ) 7.8, 7.8,
3.4 Hz) 7.57 (1 H, d, J ) 21.0 Hz) 3.57 (1 H, ddd, J ) 9.8, 9.8,
6.2 Hz) 2.95-2.79 (3 H, m) 2.42-2.32 (1 H, m) 2.20-2.12 (1 H,
m) 1.72-1.53 (3 H, m) 1.33 (3 H, d, J ) 6.2 Hz) 1.12 (3 H, s)
0.65 (3 H, s); 13C NMR (100 MHz, CDCl3, ppm) δ 135.1 (d, J )
4.6 Hz), 133.3 (d, J ) 10.7 Hz), 130.4 (d, J ) 13.7 Hz), 115.6 (d,
J ) 73.2 Hz), 54.5 (d, J ) 7.6 Hz), 50.3 (d, J ) 42.7 Hz), 44.2 (d,
J ) 7.6 Hz), 44.1 (d, J ) 3.1 Hz), 42.4 (d, J ) 9.2 Hz), 30.1 (d,
J ) 6.1 Hz), 29.2, 29.0 (d, J ) 58.0 Hz), 25.4 (d, J ) 6.1 Hz),
19.9 (d, J ) 13.7 Hz); 31P NMR (162 MHz {H}, CDCl3, ppm) δ
20.3; 19F NMR (376 MHz, CDCl3, ppm) δ -151.4.
(1R ,2R ,4S ,5S )-4,8,8-T r im e t h y l-2-(3′,5′-d i-t er t -b u t y l-
4′-m et h oxyp h en yl)p h osp h a b icyclo[3.3.0]oct a n e Bor a n e
Com p lex (2c). The compound was prepared by modification of
a literature procedure.1c To a solution of 3,5-di-tert-butyl-4-
methoxyphenylphosphine 4 (252 mg, 0.84 mmol) in THF (6 mL)
was added n-BuLi (0.53 mL of a 1.65 M solution in hexanes,
0.88 mmol, Acros) at 0 °C. The resulting yellow solution was
cooled to -78 °C after being stirred for 10 min. Next, a solution
of cyclic sulfate 51c (164 mg, 0.70 mmol, 99.7%ee) in THF (3 mL)
was added over 4 min via cannula. The yellow solution was
stirred at -78 °C for 10 min. The cooling bath was removed,
and the solution was allowed to warm to room temperature (ca.
30 min). Stirring was continued at room temperature for 1 h,
during which time the solution went colorless. The solution was
recooled to -78 °C, and additional n-BuLi (0.53 mL of a 1.65 M
solution in hexanes, 0.88 mmol) was added. The solution turned
orange-yellow and was stirred at -78 °C for 10 min. The solution
was then warmed to room temperature (ca. 30 min) and stirred
for 2 h. Assay by 31P NMR (unlocked, crude reaction mixture)
showed the formation of the desired phosphine (-3.1 ppm) as a
single diastereomer along with unidentified secondary phos-
phines (-60.3 ppm). After addition of borane-THF (2.5 mL of
a 1 M solution in THF), the solution became colorless and was
stirred for 30 min. The solvent was evaporated (N2 stream), HCl
(5 mL of a 5% solution in water) and CH2Cl2 (5 mL) were added,
and the mixture was extracted with CH2Cl2 (3 × 15 mL). The
extracts were combined, dried (MgSO4), and filtered. After
removal of solvent (aspirator), the residue was purified by flash
chromatography (15 × 3 cm), hexanes/toluene 2:1 eluent. Elution
of 375 mL of solvent was followed byproduct in the next 430
mL. Evaporation (aspirator) yielded 245 mg (87%) of 2c.
Analytical TLC, 2:1 hexane/toluene, Rf ) 0.15. Pure material
was obtained by crystallization from hexane: mp 83-85 °C; RD
) +10.6 (c ) 0.58, EtOAc); HRMS calcd for C25H44BNaOP
3,5-Di-ter t-bu tyl-4-m eth oxyp h en ylp h osp h in e (4). A solu-
tion of 3,5-di-tert-butyl-4-methoxybromobenze6 (10.2 g, 34.2
mmol) in THF (150 mL) was slowly added via cannula to a
solution of t-BuLi (45 mL, 1.66 M solution in pentane) at -78
°C. The solution immediately turned yellow and cloudy. After
the solution was stirred for 10 min, a solution of ZnCl2 (fused
under vacuum and diluted to ca. 1 M solution in THF; 50 mL)
was added dropwise via cannula (ca. 10 min) and stirred at -78
°C for 15 min. The cooling bath was removed, and the mixture
was allowed to warm to room temperature and stirred for 30
min. Next, the mixture was transferred via cannula onto a
425.31210, found m/z 425.3118, error ) 1 ppm; IR (neat, cm-1
)
2265, BH; 400 MHz NMR (CDCl3, ppm) δ 7.60 (2 H, d, J ) 11.0
Hz) 3.68 (3 H, s) 2.63-2.41 (3 H, m) 2.29-2.16 (1 H, m) 2.06-
1.94 (1 H, m) 1.87 (1 H, ddd, J ) 15.4, 11.7, 4.0 Hz) 1.55-1.34
(3 H, m) 1.5-0.3 (3 H, br m) 1.43 (18 H, s) 1.20 (3 H, d, J ) 5.9
Hz) 0.98 (3 H, s) 0.46 (3 H, s); 13C NMR (125.7 MHz, CDCl3,
ppm) δ 162.3, 144.1 (d, J ) 10.1 Hz), 131.5 (d, J ) 10.1 Hz),
121.1 (d, J ) 44.9 Hz), 64.5, 56.6 (d, J ) 31.1 Hz), 54.8 (d, J )
2.7 Hz), 44.2, 44.1, 43.2, 36.0 (d, J ) 38.5 Hz), 36.0, 31.9, 30.7
(d, J ) 4.6 Hz), 29.3 (d, J ) 4.6 Hz), 24.1 (d, J ) 4.6 Hz), 20.9
(d, J ) 10.1 Hz); 31P NMR (161.9 MHz, {H}, CDCl3, ppm) δ 31.0,
br m.
(8) (a) Reviews: Fu, G. C. Acc. Chem. Res. 2000, 33, 412. Spivey, A.
C.; Maddaford, A.; Redgrave, A. J . Org. Prep. Proced. Int. 2000, 32,
333. Robinson, D. E. J . E.; Bull, S. D. Tetrahedron: Asymmetry 2003,
14, 1407. (b) Priem, G.; Pelotier, B.; Macdonald, S. J . F. J . Org. Chem.
2003, 68, 3844. Spivey A. C.; Zhu, F. J .; Mitchell, M. B.; Davey, S. G.;
J arvest, R. L. J . Org. Chem. 2003, 68, 7379. Kawabata, T.; Stragies,
R.; Fukaya, T.; Nagaoka, Y.; Schedel, H.; Fuji, K. Tetrahedron Lett.
2003, 44, 1545. Kawabata, T.; Stragies, R.; Fukaya, T.; Fuji, K.
Chirality 2003, 15, 71. Griswold, K. S.; Miller, S. J . Tetrahedron 2003,
59, 8869.
(1R ,2R ,4S ,5S )-4,8,8-T r im e t h y l-2-(3′,5′-d i-t er t -b u t y l-
4′-m eth oxyp h en yl)p h osp h a bicyclo[3.3.0]octa n e‚HBF 4 (3c).
6936 J . Org. Chem., Vol. 69, No. 20, 2004

Phosphine borane 2c (320 mg, 0.79 mmol) was added to a round-
bottom flask equipped with a magnetic stir bar and reflux
condenser. The flask was flushed with N2 for 30 min, and
pyrrolidine (25 mL, distilled from CaH2) was then added. The
resulting solution was heated at 50 °C in an oil bath for 100
min. Pyrrolidine was evaporated with an N2 stream, and the
residue was filtered through a 10 × 1.2 cm pad of silica gel (the
flask and the column containing silica gel were purged with N2
for 1 h) in toluene under N2, collecting 50 mL. The solvent was
evaporated (N2 stream) and taken up in CH2Cl2 (12 mL,
degassed). Aqueous HBF4 (50 wt %%, 0.8 mL, 5.53 mmol) was
added via syringe, and the resulting mixture was stirred for 15
min. The layers were separated, and the aqueous layer was
extracted with CH2Cl2 (2 × 5 mL). The organic layers were
combined, dried (MgSO4), and filtered. Removal of solvent
(aspirator) provided a 9:1 mixture of the desired phosphonium
salt and phosphine borane 2c by NMR assay. The phosphine
borane was removed (recovered 28 mg of 2c, 9%) by trituration
with hexanes providing 339 mg (90%) of a white powder. Pure
material was obtained by crystallization from ether: mp 142-
148 °C; HRMS calcd for C25H42OP+ 389.29740, found m/z
389.2976, error ) 1 ppm; IR (neat, cm-1) 1060, PH; 400 MHz
NMR (CDCl3, ppm) δ 7.6 (2 H, d, J ) 15.4 Hz) 7.49 (1 H, d, J )
17.1 Hz) 3.69 (3 H, s) 3.49-3.40 (1 H, m) 2.92-2.76 (2 H, m)
2.73-2.61 (1 H, m) 2.33-2.18 (1 H, m) 2.18-2.05 (1 H, m) 1.68-
1.42 (3 H, m) 1.4 (18 H, s) 1.29 (3 H, d, J ) 6.6 Hz) 1.05 (3 H, s)
0.58 (3 H, s); 13C NMR (100.57 MHz, CDCl3, ppm) δ 166.0, 147.6
(d, J ) 12.2), 132.0 (d, J ) 13.7 Hz), 108.3 (d, J ) 76.3 Hz),
65.2, 54.5 (d, J ) 9.1 Hz), 50.3 (d, J ) 44.2 Hz), 44.3 (d, J ) 6.1
Hz), 44.1 (d, J ) 3.1 Hz), 42.7 (d, J ) 7.6 Hz), 36.5, 31.9, 30.3
(d, J ) 6.1 Hz), 29.5 (d, J ) 6.1 Hz), 29.4 (d, J ) 48.8 Hz), 25.0
(d, J ) 6.1 Hz), 20.2 (d, J ) 12.2 Hz); 31P NMR (161.91 MHz,
{H}, CDCl3, ppm) δ 19.5; 19F NMR (376.3 MHz, CDCl3, ppm) δ
-151.6.
Ack n ow led gm en t. This work was supported by the
National Science Foundation. We also thank Mr. S. A.
Shaw and Ms. N. Tuttle for preparation of cyclic sul-
fate 4.
Su p p or tin g In for m a tion Ava ila ble: Characterization
data and kinetic resolution procedures, general procedure for
benzoylations and nicotinoylations, and NMR spectra for new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O049112P
J . Org. Chem, Vol. 69, No. 20, 2004 6937