A Novel Phosphinamide Catalyst for the Asymmetric Reduction of Ketones by Borane

Full text of DOI:10.1021/jo980674g

6068
J . Org. Chem. 1998, 63, 6068-6071
A Novel P h osp h in a m id e Ca ta lyst for th e
Asym m etr ic Red u ction of Keton es by
Bor a n e
Mark P. Gamble, Athene R. C. Smith, and
Martin Wills*
Department of Chemistry, University of Warwick,
Coventry, CV4 7AL, U.K.
conversion to the target phosphinamide 1 in 70% yield.
The application of 1 as a catalyst for the reduction of
ketones was first tested using R-chloroacetophenone as
substrate, since this has been demonstrated by ourselves3c
and others7e,8 to be a particularly good substrate in
preliminary work (Scheme 1, Table 1).3c As has been
demonstrated in previous studies, the best results were
obtained at elevated temperature in toluene solution.
Using 10 mol % of 1 at ca. 110 °C enantiomeric excesses
of up to 94.4% were recorded, and yields were generally
excellent.
Received April 10, 1998
In tr od u ction
The reduction of ketones to enantiomerically enriched
alcohols is a pivotal transformation in synthetic organic
chemistry.1 Many asymmetric catalysts have been de-
veloped for the reduction of ketones by borane, most
significantly the oxazaborolidines, which have been
extensively reviewed.2 We have recently published the
results of some of our ongoing studies of phosphinamide
catalysts3 that, in contrast to oxazaborolidines, exert a
catalytic effect primarily through Lewis base interaction
of the phosphinamide oxygen atom with the borane
reducing agent.4 While they are thus effective catalysts,
asymmetric inductions have remained modest because
there is no facility for the control of the conformation of
the ketone during the reduction. In a recent paper, we
reported an improvement to the reduction system through
the incorporation of a proximal hydroxyl group in the
catalyst.3c Other researchers have reported related
catalysts that also give excellent results.5 This hydroxyl
group reacts with a molecule of borane to give a complex
in which a boron-centered Lewis acid center is available
to bind the ketone during the reduction process. In this
paper, we describe an optimized catalyst 1 and procedure
for its use in asymmetric carbonyl reductions.
Our optimized procedure for the reaction is sum-
marized as follows: the catalyst and the borane were
combined in toluene and heated to the required temper-
ature, and then a solution of the ketone in toluene was
added dropwise over 10-15 min. Analysis by TLC
showed that the reaction was complete some 10-20 min
after the addition of the ketone had been completed, at
which point the reaction was cooled and worked up. The
asymmetric induction remained high even at tempera-
tures as low as 70 °C but dropped sharply thereafter. The
catalyst did not appear to decompose under the reaction
conditions and could be recovered and reused after the
reaction without any apparant decrease in reactivity.
Although routine precautions were taken to ensure
dryness (i.e., azeotroping catalyst with toluene, the use
of freshly distilled dry toluene, flame-dried glassware),
the reaction could be performed without any of the above
precautions with only a small drop in selectivity (90% ee
for the chloroacetophenone reduction) and no change in
the reaction time. This underlines the robustness and
practicality that characterize phosphinamide reagents.
To confirm that the catalyst was not decomposing
under the reaction conditions, to give, for example, an
oxazaborolidine, we conducted a number of enlightening
experiments. In the first, a solution of catalyst 1 and
borane (10 equiv relative to 1) were heated together for
20 min and then allowed to cool to room temperature.
Dropwise addition of chloroacetophenone (10 equiv rela-
tive to 1) resulted in reduction to give a product of 11.5%
ee (21% yield). In contrast, the same reaction using an
oxazaborolidine gave a product of 97% ee under these
conditions.7c
The reaction of commercially available S-diphenylpro-
linol with dimethyl phosphite and triethylamine in the
presence of carbon tetrachloride gave the N-(O,O-di-
methylphosphoryl derivative 2 in 76% yield.5,6 Treat-
ment of 2 with an excess of p-anisylmagnesium bromide
at 70 °C (oil bath temperature) for 2-3 h resulted in clean
(1) (a) Noyori, R. Asymmetric Catalysis in Organic Synthesis; J ohn
Wiley and Sons Ltd.: New York, 1994. (b) Catalytic Asymmetric
Synthesis; Ojima, I., Ed.; VCH Press: Berlin, 1993. (c) Singh, V. K.
Synthesis 1992, 605.
(2) (a) Deloux, L.; Srebnik, M. Chem. Rev. 1993, 93, 763. (b)
Wallbaum, S.; Martens, J . Tetrahedron 1992, 3, 1475.
(3) (a) Burns, B.; Studley, J . R.; Wills, M. Tetrahedron Lett. 1993,
34, 7105. (b) Burns, B.; King, N. P.; Studley, J . R.; Tye, H.; Wills, M.
Tetrahedron: Asymmetry 1994, 5, 801. (c) Gamble, M. P.; Studley, J .
R.; Wills, M. Tetrahedron Lett. 1996, 37, 2853. (d) Gamble, M. P.;
Studley, J . R.; Wills, M. Tetrahedron: Asymmetry 1996, 7, 3071. (e)
Burns, B.; Gamble, M. P.; Simm, A. R. C.; Studley, J . R.; Alcock, N.
W.; Wills, M. Tetrahedron: Asymmetry 1997, 8, 73.
(4) Similar Lewis base effects of phosphoramides in C-C bond-
forming reactions have been reported: (a) Denmark, S. E.; Winter, S.
B. D. Synlett 1997, 1087. (b) Denmark, S. E.; Coe, D. M.; Pratt, N. E.;
Griedel, B. D. J . Org. Chem. 1994, 59, 6161. (c) Iseki, K.; Kuroki, Y.;
Takahashi, M.; Kobayashi, Y. Tetrahedron Lett. 1996, 37, 5149.
(5) Hulst, R.; Heres, H.; Peper, N. C. M. W.; Kellogg, R. M.
Tetrahedron: Asymmetry 1996, 7, 1373. Kellogg reports excellent
results using compounds related to 2 as catalysts. In our hands, the
use of 10 mol % of 2 in the reduction of chloroacetophenone gave a
product of 38% ee. Compound 2 decomposed slowly under the reaction
conditions.
We also carried out a number of NMR experiments.
The in situ 11B NMR spectra of a solution of 1 before and
after treatment with a 10-fold excess of BH3‚SMe2 in
(7) (a) Brunel, J . M.; Maffei, M.; Buono, G. Tetrahedron: Asymmetry
1993, 4, 2255. (b) Mathre, D. J .; Thompson, A. S.; Douglas, A. W.;
Hoogsteen, K., Carroll, J . D.; Corley, E. G.; Grabowski, E. J . J . J . Org.
Chem. 1993, 58, 2880. (c) Stone, G. B. Tetrahedron: Asymmetry 1994,
5, 465. (d) Douglas, A. W.; Tscaen, D. M.; Reamer, R. A.; Shi, Y.-T.
Tetrahedron: Asymmetry 1996, 7, 1303. (e) O’Neil, I. A.; Turner, C.
D.; Kalindjian, S. B. Synlett 1997, 777.
(8) (a) Chiodi, O.; Fotiadu, F.; Sylvestre, M.; and Buono, G.
Tetrahedron Lett. 1996, 37, 39. (b) Peper, V.; Martens, J . Tetrahedron
Lett. 1996, 37, 8351.
(6) Atherton, F. R.; Oppenshaw, H. T.; Todd, A. R. J . Chem. Soc.
1945, 660.
S0022-3263(98)00674-4 CCC: $15.00 © 1998 American Chemical Society
Published on Web 08/05/1998

Notes
J . Org. Chem., Vol. 63, No. 17, 1998 6069
Sch em e 1a
a
Reagents and conditions: (i) 10 mol % of 1, 1.05 equiv of
BH3‚SMe2, toluene, 40-110 °C; see Table 1.
F igu r e 2.
Ta ble 1. Red u ction of r-Ch lor oa cetop h en on e: Effect
The application of 1 to the synthesis of a range of
alcohols in enantiomerically enriched form through the
reduction of the corresponding ketones was investigated
(Figure 1). While R-chloroacetophenone remained the
optimal substrate, the results were generally good to
excellent. Although the presence of an electron-with-
drawing group at the R-position of the ketone was
beneficial (4, 5, 13, and 14), the electron density of the
aromatic ring appeared to have no significant effect on
selectivity (cf. 6 vs 8 and the 11 vs 14). The products 13
and 14 may in principle be cyclized to the corresponding
epoxides, which represent potential precursors to the
drugs denopamine and salbutamol.
Aryl/alkyl ketones were the best substrates, although
dialiphatic ketones could also be reduced in good yield
and enantioselectivity (cf. 16 and 17). The selectivity of
reduction was reversed in the case of the reduction of
the trichloromethyl substituted acetophenone adduct, in
agreement with Corey’s observations on the relative
steric sizes of the groups bordering the ketone.9
Diols could be obtained in very high enantiopurity at
the cost of diastereoselectivity due to the mathematical
combination of two selective reactions upon the same
molecule. Reduction of benzil proceeded in moderate
diastereoselectivity (threo/erythro 86:14). The ee of the
chiral (threo) isomer 18 was established by conversion
to the diacetate followed by analysis with the shift
reagent Eu(hfc)3.10a Reduction of 1,2-dibenzoylethane
proceeded to give the R,R enantiomer with moderate
distereoselectivity (R/S/meso 84:16) but with an apparent
ee of >90% as judged by the 19F NMR analysis of the bis
(R)-MTPA ester.10b
of Tem p er a tu r e
entry
T/°C
110
100
80-85
70-75
60-65
40-50
yield/%
% ee
1
2
3
4
5
6
91
89
88
80
69
62
94.4
94.3
93.3
92.8
80.1
13.5
toluene-d8 at room temperature and at elevated temper-
ature (110 °C, 20 min) were compared with the corre-
sponding spectra of a solution of diphenylprolinol treated
under the same conditions. The 11B NMR showed no
peaks corresponding to the formation of an oxazaboroli-
dine (these were seen in the control experiment).7a,b,d
These observations are in agreement with those of Buono,
who reported no cleavage of the N-P bond upon treat-
ment of a cyclic oxazaphospholidine oxide with excess
borane.8a No decomposition of 1 was observed by 31P
NMR after the above mixture had been cooled and
quenched with deuterium oxide.
We have previously suggested that the actual catalytic
species is a complex such as 20, which is formed by the
reaction of 1 with 1 equiv of borane.3c This may exist as
the discrete species 20 or as a dialkoxyborane (Figure
2)12 or perhaps even a more complex polymeric species.
The system contains both a Lewis base and Lewis acid
site, which interact with a molecule of borane and ketone,
respectively. Thus, the reagents are effectively held
within reactive distance and activated by the requisite
electron-donating and -withdrawing properties of the
groups involved, as shown in Figure 3. Following the
hydride transfer step the alkoxyborane reduction product
dissociates from the catalyst, and the latter then renters
the catalytic cycle. The high temperature required for
the best results in this process may be due to the
acceleration of this dissociation process, which thus
(9) (a) Corey, E. J .; Link, J . O.; Sarshar, S.; Shao, Y. Tetrahedron
Lett. 1992, 33, 7103. (b) Corey, E. J .; Link, J . O. J . Am. Chem. Soc.
1992, 114, 1906.
(10) (a) Prasad, K. R. K.; J oshi, N. N. J . Org. Chem. 1996, 61, 3888.
(b) Chong, J . M.; Clarke, I. S.; Koch, I.; Olbach, P. C.; Taylor, N. J .
Tetrahedron: Asymmetry 1995, 6, 409.
(11) An alternative method for manipulation of pyridyl ketones:
Corey, E. J .; Helal, C. J . Tetrahedron Lett. 1996, 37, 5675.
(12) DiMare, M. J . Org. Chem. 1996, 61, 8378 and references
therein.
F igu r e 1. Reduction products obtained using catalyst 1.

6070 J . Org. Chem., Vol. 63, No. 17, 1998
Notes
N-(O,O-Dim eth ylp h osp h or yl)-(S)-r,r-d ip h en yl-2-p yr r o-
lid in em eth a n ol (2). Carbon tetrachloride (2.04 mL, 3.25 g,
21.1 mmol) was added dropwise to an ice-cold stirred solution
of (S)-(+)-R,R-diphenyl-2-pyrrolidinemethanol (2.14 g, 8.45 mmol),
dimethyl phosphite (930 mL, 1.12 g, 10.1 mmol), and triethyl-
amine (1.41 mL, 1.03 g, 10.1 mmol) in anhydrous CH2Cl2 (20
mL). The resulting solution was allowed to slowly warm to room
temperature and then stirred for a further 10 h. After this
period, the reaction was quenched with water and the organic
layer separated. The aqueous layer was extracted with CH2-
Cl2, the combined organic layers were washed with saturated
NH4Cl, water, and then brine and dried (MgSO4), and the solvent
was removed in vacuo. The resulting solid was recrystallized
from n-hexane-CH2Cl2 (4:1) to give 2 (2.13 g, 76%) as a white
solid: mp 118-120 °C (from n-hexane-CH2Cl2); [R]D -61.6 (c
0.5, CH2Cl2); υmax/cm-1 3405 (OH), 1233 (PdO); 1H NMR (250
MHz; CDCl3) δ 1.02-1.17 (1H, m), 1.46-1.63 (1H, m), 2.58-
2.70 (1H, m), 3.06-3.18 (1H, m), 3.58 (3H, d, J ) 11.0 Hz), 3.66
(3H, d, J ) 11.0 Hz), 4.72 (1H, dt, J ) 5.2, 8.4 Hz), 5.69 (1H, bs,
exchangeable), 7.20-7.33 (6H, m), 7.40-7.51 (4H, m); 13C NMR
(62.9 MHz; CDCl3) δ 24.9 (d, J ) 5.9 Hz), 30.8 (d, J ) 7.9 Hz),
53.1 (d, J ) 5.9 Hz), 67.6 (d, J ) 4.9 Hz), 80.5, 126.8, 126.9,
127.2, 127.4, 127.7, 128.1, 143.7, 146.1; m/z (CI) 344 (M+ - OH,
100), 183 (98); 31P NMR (162 MHz; CDCl3) δ 15.2. Anal. Calcd
for C19H24NO4P: C, 63.15; H, 6.69; N, 3.88. Found: C, 63.1; H,
6.7; N, 3.9.
N -(Di-p -An isylp h osp h or yl)-(S)-r,r-d ip h e n yl-2-p yr r o-
lid in em eth a n ol (1). p-Anisylmagnesium bromide 2 M in THF
(12.8 mL, 25.6 mmol) was added dropwise to a stirred solution
of N-(O,O-dimethylphosphoryl)-(S)-R,R-diphenyl-2-pyrrolidine-
methanol (2) (2.10 g, 5.81 mmol) in anhydrous THF (50 mL) at
-78 °C under a nitrogen atmosphere. The resulting mixture
was allowed to slowly warm to room temperature over a 3 h
period and then heated at 60 °C for a further 90 min whereupon
the reaction was complete as assayed by thin-layer chromatog-
raphy. The solution was allowed to cool to room temperature
and diluted with water and the THF removed in vacuo. The
residue was acidified with saturated NH4Cl and the aqueous
phase extracted with EtOAc. The combined organic layers were
washed with water and brine and dried (MgSO4), and the solvent
removed in vacuo. The residue was purified by column chro-
matography using EtOAc-CH2Cl2-NEt3 (2:98:0.1) and then
EtOAc-CH2Cl2-NEt3 (5:95:0.1) as the eluants. This gave 1
(2.09 g, 70%) as a white solid that was further purified by
recrystallization from n-hexane-CH2Cl2 (4:1). This gave the
pure product as white solid: mp 169-172 °C (from n-hexane-
CH2Cl2); [R]D -66.6 (c 0.5, CH2Cl2); υmax/cm-1 3230 (OH), 1255
(PdO); 1H NMR (250 MHz; CDCl3) δ 1.06-1.18 (1H, m), 1.25-
1.42 (1H, m), 1.69 (1H, bs, exchangeable), 2.00-2.11 (2H, m),
2.33 (1H, ddd, J ) 7.5, 10.3, 15.6 Hz), 2.64-2.94 (1H, m), 3.84
(3H, s), 3.88 (3H, s), 4.73 (1H, dt, J ) 5.5, 8.3 Hz), 6.87-7.02
(4H, m), 7.21-7.70 (14H, m); 13C NMR (62.9 MHz; CDCl3) δ 24.8
(d, J ) 4.9 Hz), 31.0 (d, J ) 4.9 Hz) 49.8 (d, J ) 4.9 Hz), 55.2,
67.2, 80.0, 113.8 (d, J ) 13.8 Hz), 114.1, 120.9, 121.9, 122.9,
124.0, 126.6, 126.8, 127.0, 127.7, 127.9, 128.7, 133.8 (d, J ) 10.8
Hz) 144.4, 146.1, 162.4 (d, J ) 2.0 Hz); m/z (CI) 514 (M + H+,
2), 236 (100); 31P NMR (162 MHz; CDCl3) δ 34.4. Anal. Calcd
for C31H32NO4P: C, 72.5; H, 6.28; N, 2.73. Found: C, 72.7; H,
6.3; N, 3.0.
F igu r e 3. Stereochemical control in the asymmetric reduc-
tion.
F igu r e 4. Oxazaphospholidine oxide catalysts.
ensures effective catalyst turnover.13a,b In the absence
of an effective turnover the slower uncatalyzed pathway
will dominate, resulting in lower overall yields and
enantioselectivity. An alternative explanation is that an
unproductive species, perhaps a dimer, predominates at
lower temperature.7
Oxazaphospholidine oxides have been reported to be
effective reagents for the asymmetric reduction of ketones
by borane.8 In view of the obvious similarity of these
reagents to our own, we investigated the synthesis and
reactivity of 21 and 22 (Figure 4).8b These were prepared
in a 7:1 diastereoisomeric mixture from the reaction
between diphenylprolinol and phenylphosphonic dichlo-
ride in 70% yield. The configuration of the phosphorus
atom in the major diastereoisomer 21 was confirmed by
single-crystal X-ray analysis.13 Using the individual
isomers 21 and 22, we found that the former was a
superior catalyst in terms of asymmetric induction, giving
a product of 95% ee in the acetophenone reduction (10
mol % catalyst) compared to 75% ee for the latter. In
contrast to 1 the best results for 21 and 22 were achieved
at room temperature in THF solvent. Furthermore, the
oxazaphospholidine oxides were not recoverable after the
reaction. Buono has suggested that these compounds are
ring-opened by cleavage of the P-O bond to give a
catalytic species analogous to 20 (the P-N bond is
retained), which is stable for the lifetime of the reaction
but decomposes upon quenching and workup. It is
therefore clear that the P-O bond cleavage must be
streospecific and that the configuration at the phosphorus
atom contributes to the asymmetric induction in some
manner.3e We are presently investigating modified cata-
lysts based on 1 that contain chiral phosphorus atoms
and that may therefore give improved enantioselectivi-
ties.
Sta n d a r d Op tim ized P r oced u r e for th e Ca ta lytic Asym -
m etr ic Red u ction of P r och ir a l Keton es w ith N-(Di-p-
a n isylp h osp h or yl)-(S)-r,r-d ip h en yl-2-p yr r olid in em et h a -
n ol (1). N-(Di-p-anisylphosphoryl)-(S)-R,R-diphenyl-2-pyrrol-
idinemethanol (1) (359 mg, 0.70 mmol) was azetroped in situ
under a nitrogen atmosphere with anhydrous toluene (3 × 4 mL).
The catalyst was then dissolved in anhydrous toluene (14 mL)
to which was added borane-methyl sulfide (2 M in toluene, 3.67
mL, 7.34 mmol), and the mixture was heated to 110 °C. At
approximately 80 °C, a white precipitate forms, which does not
affect the reduction. Once the temperature had stabilized at
110 °C, chloroacetophenone (1.08 g, 6.99 mmol) in anhydrous
toluene (14 mL) was added dropwise via a syringe pump at a
flow rate of 0.5 mL/min. Once all the ketone had been added,
stirring was continued for a further 20 min, whereupon the
reaction was complete as assayed by thin-layer chromatography.
The mixture was allowed to cool to room temperature and
quenched with water. This was acidified with saturated NH4-
In conclusion, we have demonstrated that phosphina-
mide 1 is a readily available, robust, versatile, and
recoverable reagent for the asymmetric catalysis of the
reduction of ketones by borane.
Exp er im en ta l Section
General reagents and conditions have been described in a
previous paper.14
(13) Alcock, N.; Gamble, M. P.; Wills, M. Unpublished results (see
the Supporting Information).
(14) Palmer, M.; Walsgrove, T.; Wills, M. J . Org. Chem. 1997, 62,
5226.

Notes
J . Org. Chem., Vol. 63, No. 17, 1998 6071
Cl and the organic layer separated. The aqueous layer was
extracted with EtOAc, the combined organic layers were washed
with water and brine and dried (MgSO4), and the solvent was
removed in vacuo. The residue was purified by column chro-
matography using light-petroleum-EtOAc-Et3N (89:10:1) as
the eluant. This gave (S)-(+)-2-chloro-1-phenylethanol (971 mg,
89%) in 94.4% ee (see below for determination). The catalyst
could be recovered from the reaction by eluting the column with
EtOAc-CH2Cl2-Et3N (2:97:1) and then EtOAc-CH2Cl2-Et3N
(5:94:1) as the eluants. (S)-(+)-2-Ch lor o-1-p h en yleth a n ol
(4): 94.4% ee (S) by HPLC (Chiralcel OD, ethanol/n-hexane/
diethylamine ) 5:95:0.01:0.5 mL/min) (S isomer 18.8 min, R
isomer 22.3 min); [R]D +47.0 (c 1, cyclohexane) [lit.15a [R]D +49.6
(c 2.8, cyclohexane), (S)]; 1H NMR (250 MHz; CDCl3) δ 2.72 (1H,
bs, exchangeable), 3.64 (1H, dd, J ) 8.7, 11.2 Hz), 3.75 (1H, dd,
J ) 3.5, 11.2 Hz), 4.90 (1H, dd, J ) 3.5, 8.7 Hz), 7.31-7.35 (5H,
m).
NMR (67.8 MHz; CDCl3) δ 26.3, 30.2, 44.8, 71.3, 88.7, 126.5,
126.7, 127.4, 128.0, 128.2, 128.3, 129.9, 131.6, 131.7, 132.5, 141.2,
143.6 (d, J ) 4.4 Hz); m/z (CI) 376 (M + H+, 100%); 31P NMR
(162 MHz; CDCl3) δ 36.09. Characterization for the minor
diastereomer 22: mp 157-160 °C; [R]D -64.4 (c 0.28, CH2Cl2);
1H NMR (250 MHz; CDCl3) δ 1.20-1.40 (1H, m), 1.53-2.00 (3H,
m), 2.99-3.24 (2H, m), 4.76 (1H, ddd, J ) 5.2, 11.0, 16.5 Hz),
7.24-7.87 (15H, m); 13C NMR (62.9 MHz; CDCl3) δ 24.6, 30.6
(d, J ) 27.6 Hz), 44.4 (d, J ) 3.9 Hz), 72.6 (d, J ) 8.9 Hz), 89.7,
125.3, 126.3, 126.5, 127.3, 128.0, 128.1, 128.4, 128.6, 129.1, 132.4,
133.1 (d, J ) 10.8 Hz), 142.0 and 144.7; m/z (CI) 376 (M + H+,
55), 236 (100); 31P NMR (162 MHz; CDCl3) δ 34.5. Anal. Calcd
for C23H22NO2P: C, 73.58; H, 5.91; N, 3.73. Found: C, 73.4; H,
5.8; N, 3.7.
The catalytic asymmetric reduction of acetophenone with 21
and 22 was carried out following the procedure described by
Martens.16
Details of the characterization and enantiomeric excess de-
termination of reduction products 5-19 are given in the Sup-
porting Information.
Ack n ow led gm en t. We thank the EPSRC for gener-
ous funding of this project and Dr. J . Ballantine of the
EPSRC service (Swansea) for high-resolution analyses.
(2Sp ,5S)-2,4,4-Tr ip h en yl-3-oxa -1-a za p h osp h or ylbicyclo-
[3.3.0]octa n e (21 a n d 22). Phenylphosphonic dichloride (2.01
g, 1.46 mL, 10.3 mmol) was added dropwise to an ice-cold stirred
solution of (S)-(-)-R,R-diphenylpyrrolidinemethanol (2.38 g, 9.39
mmol) and triethylamine (2.09 g, 2.88 mL, 20.7 mmol) in
anhydrous CH2Cl2 (20 mL). The reaction was allowed to slowly
warm to room temperature and was stirred at this temperature
for a further 12 h. The mixture was filtered and the solvent
Su p p or tin g In for m a tion Ava ila ble: Experimental data
for the synthesis of all compounds related to the novel
compounds 13 and 14, characterization and ee determination
data for compounds 5-19, 1H NMR spectra of 13, 14, and
related synthetic intermediates, X-ray crystallographic data
on 21, and 11B and 31P NMR data from the borane stability
study of 1 (30 pages). This material is contained in libraries
on microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
1
removed in vacuo. The crude H NMR showed a 7:1 mixture of
diastereomers, which was purified by column chromatography
using CH2Cl2-NEt3 (99.9:0.1) and then EtOAc-CH2Cl2-NEt3
(10:90:0.1) as the eluants. This gave 21 and 22 (21: 2.48 g, 70%,
22: 320 mg, 9%) as white powders. These were further purified
by recrystallization from n-hexane-CH2Cl2 (4:1). Major isomer
21: mp 158-161 °C; [R]D -236.4 (c 0.55, CHCl3) [lit.8b [R]D
-235.6 (c 1.15, CHCl3)]; υmax/cm-1 1447, 1241; 1H NMR (270
MHz; CDCl3) δ 1.56-1.84 (4H, m), 2.95-3.03 (1H, m), 3.67-
J O980674G
(15) Corey, E. J .; Shibata, S.; Bakshi, R. K. J . Org. Chem. 1988, 53,
2861.
(16) Peper, V.; Martens, J . Chem. Ber. 1996, 129, 691.
3.79 (1H, m), 4.70 (1H, qu, J ) 6.4 Hz), 7.24-7.61 (15H, m); 13
C