Resolution and stereochemistry of tert-butylphenylphosphinous acid-borane

Article abstract of DOI:10.1021/jo061896e

(Chemical Equation Presented) A combined use of ephedrine and cinchonine as resolving agents enabled facile resolution of racemic tert- butylphenylphosphinous acid-borane (1) into the two enantiomers in ca. 31-32% yield each. The resolved 1 served as a mo

Full text of DOI:10.1021/jo061896e

Resolution and Stereochemistry of tert-Butylphenylphosphinous
Acid-Borane
Marek Stankevicˇ†,‡ and K. Michał Pietrusiewicz*,‡
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, 01-224 Warsaw, Poland,
and Department of Organic Chemistry, Maria Curie-Skłodowska UniVersity, ul. Gliniana 33,
20-614 Lublin, Poland
michal@hermes.umcs.lublin.pl
ReceiVed September 13, 2006
A combined use of ephedrine and cinchonine as resolving agents enabled facile resolution of racemic
tert-butylphenylphosphinous acid-borane (1) into the two enantiomers in ca. 31-32% yield each. The
resolved 1 served as a model substrate to study stereoselective synthetic transformations of phosphinous
acid-boranes yielding optically active phosphinite-borane, boranatophosphinous-sulfonic anhydride,
secondary phosphine-borane, tertiary phosphine-borane, secondary phosphine oxide, and phosphinic
halides. By the judicious choice of the reaction paths, either enantiomer of tert-butylphenylphosphine-
borane and of tert-butylmethylphenylphosphine-borane could be stereoselectively obtained from a single
enantiomer of 1.
Introduction
transition metals is continuously growing.2 Synthesis of such
ligands has progressed rapidly in the past two decades due in
great part to the development of methodologies based on
phosphine-borane chemistry.3 Among the important intermedi-
Chiral organophosphorus compounds such as tertiary diphos-
phines and monophosphines are widely utilized in the field of
asymmetric synthesis as chiral ligands and as chiral catalysts.1
Especially valuable are enantiopure phosphine ligands that
possess a chirality center at the phosphorus atom, and the use
of such compounds in asymmetric reactions catalyzed by
(2) For recent publications, see: (a) Chen, W.; Mbafor, W.; Roberts,
S. M.; Whittall, J. J. Am. Chem. Soc. 2006, 128, 3922-3923. (b) Imamoto,
T.; Itoh, T.; Yamanoi, Y.; Narui, R.; Yoshida, K. Tetrahedron: Asymmetry
2006, 17, 560-565. (c) Christ, M. L.; Zabłocka, M.; Spencer, S.; Lavender,
R. J.; Lemaire, M.; Majoral, J.-P. J. Mol. Catal. A: Chem. 2006, 245, 210-
216. (d) Liu, D.; Zhang, X. Eur. J. Org. Chem. 2005, 646-649. (e) Miller,
K. M.; Jamison, T. F. Org. Lett. 2005, 7, 3077-3080. (f) Hoge, G.; Samas,
B. Tetrahedron: Asymmetry 2004, 15, 2155-2157. (g) Pakulski, Z.;
Demchuk, O. M.; Frelek, J.; Luboradzki, R.; Pietrusiewicz, K. M. Eur. J.
Org. Chem. 2004, 3913-3918.
* Corresponding author. Tel.: +48 81 537 5679. Fax: +48 22 632 6681.
† Polish Academy of Sciences.
‡ Maria Curie-Skłodowska University.
(1) (a) Yamanoi, Y.; Imamoto, T. ReV. Heteroatom Chem. 1999, 20,
227-248. (b) Lagasse, F.; Kagan, H. B. Chem. Pharm. Bull. 2000, 48,
315-324.
10.1021/jo061896e CCC: $37.00 © 2007 American Chemical Society
Published on Web 12/29/2006
816
J. Org. Chem. 2007, 72, 816-822

tert-Butylphenylphosphinous Acid-Borane
ates in the field are resolved methyl4 and menthyl5 phosphinite-
boranes, which formally should be viewed as chiral esters of
phosphinous acid-boranes. In contrast to the esters, the parent
phosphinous acid-boranes have not attracted much attention
in the past,6 and only very recently, the ready access to these
compounds has been offered7,8 and their reactivity profile has
been revealed.9 They can be used as convenient precursors to a
large variety of phosphorus compounds such as phosphinite-
boranes, sec-phosphine-boranes, tert-phosphine-boranes, chlo-
rophosphine-boranes, stable boranatophosphinous anhydrides,
as well as mixed boranatophosphinous-carboxylic and bo-
ranatophosphinous-sulfonic anhydrides, oxaphosphaborolidines,
sec-phosphine oxides, phosphinic halides, and others.9 Since the
unsymmetrically substituted phosphinous acid-boranes are
chiral and bear a stereogenic center at phosphorus, we consid-
ered it important to develop a gram-scale access to resolved
phosphinous acid-boranes to further expand the synthetic
potential of this class of compounds and to study the stereo-
chemistry of their conversions into other optically active
phosphorus-stereogenic organophosphorus compounds.
SCHEME 1
Herein, we report that by taking advantage of the acidic
properties of phosphinous acid-boranes, it is possible to resolve
them in the classical way by using enantiopure amines as
resolving agents. We have selected tert-butylphenylphosphinous
acid-borane (1) for the model study and have succeeded in
effectively resolving it through its diastereomeric salts with
ephedrine and cinchonine. We will demonstrate that the resolved
1 can be transformed with high stereoselectivity into optically
active phosphinite-borane, tertiary phosphine-borane, second-
ary phosphine-borane, phosphinic halides, and a mixed phos-
phinous acid-borane sulfonic anhydride.
Results and Discussion
Racemic tert-butylphenylphosphinous acid-borane (1) was
synthesized from tert-butylphenylphosphinic chloride by reduc-
tion with BH3-THF in 95% yield as described before.9a
Separation of rac-1 into enantiomers was carried out according
to the protocol shown in Scheme 1.
Dissolving equimolar amounts of rac-1 and (1R,2S)-ephedrine
hemihydrate 210 in DCM and adding hexane until the solution
became slightly cloudy resulted in the precipitation of a
crystalline salt. After 24 h, the crystals were collected and
recrystallized once more from DCM/hexane to yield the
ephedrine salt of 1 of high diastereomeric purity as confirmed
1
by H NMR. Acidic workup of 3 with aqueous HCl afforded
free phosphinous acid borane (S)-1 in 31% overall yield.
Attempted crystallizations of the second phosphorus-epimeric
ephedrine salt of 1 from the mother liquor were unsuccessful.
However, recovering the enriched (R)-1 from the mother liquor
and treating it with an equimolar amount of cinchonine 4 in
the same solvent system resulted in the precipitation of a
crystalline cinchonine salt of 1 that after one additional
recrystallization afforded diastereomerically pure 5 (1H NMR).
Acidic workup of 5 as before furnished enantiomerically pure
(R)-1 in 32% overall yield.
The assignment of the absolute configurations to the resolved
enantiomers of 1 was originally based on our previous chemical
correlation of enriched (S)-1 with (S)-tert-butylmethylphe-
nylphosphine-borane.11 It is now unequivocally confirmed by
the single-crystal X-ray diffraction data obtained for 5
(Figure 1).
(3) For recent reviews concerning phosphine-boranes, see: (a) Brunel,
J. M.; Faure, B.; Maffei, M. Coord. Chem. ReV. 1998, 178-180, 665-
698. (b) Ohff, M.; Holz, J.; Quirmbach, M.; Bo¨rner, A. Synthesis 1998,
1391-1415. (c) Carboni, B.; Monnier, L. Tetrahedron 1999, 55, 1197-
1248.
(4) (a) Juge´, S.; Stephan, M.; Laffitte, J. A.; Geneˆt, J. P. Tetrahedron
Lett. 1990, 31, 6357-6360. (b) Juge´, S.; Stephan, M.; Merdes, R.; Geneˆt,
J. P.; Halut-Desportes, S. J. Chem. Soc., Chem. Commun. 1993, 531-533.
(5) Imamoto, T.; Osiki, T.; Onozawa, T.; Kusumoto, T.; Sato, K. J. Am.
Chem. Soc. 1990, 112, 5244-5252. (b) Hoge, G. J. Am. Chem. Soc. 2003,
125, 10219-10227.
(6) (a) Schmidbaur, H. J. Organomet. Chem. 1980, 200, 287-306.
(b) Ko¨ster, R.; Tsay, Y.-H.; Synoradzki, L. Chem. Ber. 1987, 120, 1117-
1124. (c) Uziel, J.; Ste´phan, M.; Kaloun, E. B.; Geneˆt, J. P.; Juge´, S. Bull.
Soc. Chim. Fr. 1997, 134, 379-389. (d) Nagata, K.; Matsukawa, S.;
Imamoto, T. J. Org. Chem. 2000, 65, 4185-4188.
(7) Stankevicˇ, M.; Pietrusiewicz, K. M. Synlett 2003, 1012-1016.
(8) Stankevicˇ, M.; Andrijewski, G.; Pietrusiewicz, K. M. Synlett 2004,
311-315.
(9) (a) Stankevicˇ, M.; Pietrusiewicz, K. M. Synthesis 2005, 1279-1290.
(b) Pietrusiewicz, K. M.; Stankevicˇ, M. Curr. Org. Chem. 2005, 9, 1883-
1897.
(10) Anhydrous ephedrine failed to provide any crystalline precipitate
with rac-1. However, the addition of a small amount of water to the mixture
of rac-1 and anhydrous ephedrine was found effective in promoting the
desired fractional crystallization of 2a.
The potential of using the resolved phosphinous acid-boranes
as convenient precursors to other synthetically useful enan-
tiopure organophosphorus compounds was demonstrated first
by reacting (S)-1 at oxygen in the straightforward conversions
of (S)-1 into (S)-methyl tert-butylphenylphosphinite-borane (6)
(11) Muci, A. R.; Campos, K. R.; Evans, D. A. J. Am. Chem. Soc. 1995,
117, 9075-9076.
J. Org. Chem, Vol. 72, No. 3, 2007 817

Stankevicˇ and Pietrusiewicz
FIGURE 1. ORTEP view of cinchonine salt of (R)-1.
by comparison with the known compounds11 and confirmed the
expected full retention of configurations in both steps.12
SCHEME 2
According to the lower track of Scheme 3, anhydride (S)-7
was reduced by sodium borohydride in ethanol with the clean
inversion of configuration13 and afforded enantiomerically pure
(S)-8 in 96% yield. Methylation of the lithiated (S)-8 as stated
previously gave (R)-9 in 89% yield. Thus, as indicated in
Scheme 3, the two synthetic paths are complementary and
demonstrate the practical possibility of achieving the fully
stereoselective synthesis of either enantiomer of a secondary
phosphine-borane and a tertiary phosphine-borane from a
single enantiomer of the resolved phosphinous acid-borane.
The stereochemistry of the conversions of the resolved 1 into
its acid halide derivatives was studied next. The reaction of (S)-1
with mesyl chloride in the presence of an excess of triethylamine
hydrochloride gave the optically active chlorophosphine-borane
(R)-10 in 56% yield (Scheme 4). This conversion was found to
occur with predominant inversion of configuration at P, although
it was accompanied by a considerable loss of configurational
integrity of the phosphorus center as evidenced by the pertinent
chemical correlation with methyl phosphinite-borane (S)-6
obtained previously (Scheme 4).
In turn, reaction of (S)-1 with NaH and hexachloroacetone
as the chlorinating agent resulted in the loss of the borane
protecting group and led to the exclusive formation of (S)-tert-
butylphenylphosphinic chloride (11) (Scheme 5). Comparing
the optical rotation of the obtained (S)-11 with the pertinent
literature data14 indicated that the studied conversion occurred
with the predominant inversion of configuration and gave the
phosphinic chloride of 45% optical purity.
and into (S)-tert-butylphenylboranatophosphinous methane-
sulfonic anhydride (7) by means of simple alkylation and
acylation reactions, respectively (Scheme 2).
O-Methylation of (S)-1 was best achieved with methyl iodide
in the presence of potassium carbonate in boiling acetone and
afforded the desired ester (S)-6 in 92% isolated yield. In turn,
treatment of (S)-1 with mesyl chloride in the presence of
triethylamine in DCM gave the mixed anhydride (S)-7 in 78%
isolated yield. As the two reactions took place at the oxygen
center, the configuration at P remained intact, and the (S)
absolute configuration was assigned to the two products (i.e.,
the same as in the starting phosphinous acid-borane).
With the readily available enantiopure 6 and 7 in hand, the
fully stereoselective synthesis of the two enantiomers of a
secondary phosphine-borane and a tertiary phosphine-borane
could then be carried out as delineated in Scheme 3.
Treatment of (S)-6 with lithium in THF/NH3 at low temper-
ature resulted in the cleavage of the ester bond leading to (R)-
tert-butylphenylphosphine-borane (8) in 58% yield. Deproto-
nation of 8 at low temperature and quenching of the resulting
lithiated sec-phosphine borane with methyl iodide afforded (S)-
tert-butylmethylphenylphosphine-borane (9). The optical purity
(op) and the absolute configuration of 8 and 9 were determined
Similarly, treatment of (S)-1 with bromine or iodine as
halogenating agents led to the formation of (S)-tert-butylphe-
(12) Oshiki, T.; Hikosaka, T.; Imamoto, T. Tetrahedron Lett. 1991, 32,
3371-3374.
(13) Skrzypczyn´ski, Z.; Michalski, J. J. Org. Chem. 1988, 53, 4549-
4551.
(14) Omelan´czuk, J. J. Chem. Soc., Chem. Commun. 1992, 1718-1719.
818 J. Org. Chem., Vol. 72, No. 3, 2007

tert-Butylphenylphosphinous Acid-Borane
SCHEME 3
SCHEME 4
SCHEME 5
SCHEME 6
nylphosphinic bromide (12) and (S)-tert-butylphenylphosphinic
iodide (13), respectively (Scheme 5). The absolute configuration
and the optical purity of the obtained (S)-12 was determined
by comparison of its rotation data with the literature value,15
whereas for (S)-13, it was assessed by chemical correlation with
(R)-14 obtained previously16 (Scheme 5).
Finally, decomplexation of (S)-1 by HBF4 etherate17 was
found to occur with the expected retention of configuration at
P and yielded (S)-15 (Scheme 6). Somewhat less expectedly,
however, the isolated (S)-15 was found to be not optically pure
(83% op) as revealed by the comparison of its specific rotation
with the known literature values.18
(18) (a) Drabowicz, J.; Łyz˘wa, P.; Omelan´czuk, J.; Pietrusiewicz,
K. M.; Mikołajczyk, M. Tetrahedron: Asymmetry 1999, 10, 2757-2863.
(b) Haynes, R. K.; Au-Yeung, T.-L.; Chan, W.-K.; Lam, W.-L.; Li, Z.-Y.;
Yeung, L.-L.; Chan, A. S. C.; Li, P.; Koen, M.; Mitchell, C. R.; Vonwiller,
S. C. Eur. J. Org. Chem. 2000, 3205-3216. (c) Leyris, A.; Nuel, D.;
Giordano, L.; Achard, M.; Buono, G. Tetrahedron Lett. 2005, 46, 8677-
8680.
(15) Haynes, R.; Lam, W. W.-L.; Williams, I. D.; Yeung, L.-L. Chem.s
Eur. J. 1997, 3, 2052-2057.
(16) Au-Yeung, T.-L.; Chan, K.-Y.; Chan, W.-K.; Haynes, R. K.;
Williams, I. D.; Yeung, L. L. Tetrahedron Lett. 2001, 42, 453-456.
(17) McKinstry, L.; Livinghouse, T. Tetrahedron Lett. 1994, 35, 9319-
9322.
J. Org. Chem, Vol. 72, No. 3, 2007 819

Stankevicˇ and Pietrusiewicz
was added. After 5 min, methyl iodide (0.426 g, 3 mmol) was
added, and the reaction mixture was heated under reflux for 3 h.
The reaction mixture was allowed to cool to room temperature,
inorganic salt was filtered off, and the filtrate was evaporated to
dryness. The residue was subjected to separation by flash chroma-
tography with hexane/ethyl acetate (6:1) as an eluent and yielded
Conclusion
The efficient resolution of racemic tert-butylphenylphosphi-
nous acid-borane (1) through the combined use of cinchonine
and ephedrine as the resolving agents has been achieved. Use
of the resolved 1 in the model syntheses of optically active
phosphinite-borane, boranatophosphinous-sulfonic anhydride,
secondary phosphine-borane, tertiary phosphine-borane, sec-
ondary phosphine oxide, and phosphinic halides demonstrated
the potential of resolved phosphinous acid-boranes as conve-
nient substrates for the synthesis of a variety of other phosphorus-
stereogenic compounds. The fully stereoselective syntheses of
both enantiomers of tert-butylphenylphosphine-borane 8 and
of tert-butylmethylphenylphosphine-borane 9 from a single
enantiomer of the resolved phosphinous acid-borane 1 highlight
this potential the best. In the course of these syntheses, the fully
regio- and stereoselective reduction of mixed boranatophosphi-
nous-sulfonic anhydride by sodium borohydride was ac-
complished.
0.058 g of (S)-6 (92%) as a white solid. [R]22 -119.2 (c 1.02,
D
CHCl3) (100% op);19 1H NMR (200 MHz, CDCl3) δ -0.1-1.6
(bm, 3H), 1.1 (d, JP-H) 14.2 Hz, 9H), 3.7 (d, JP-H) 11.1 Hz, 3H),
7.4-7.6 (m, 3H), 7.6-7.8 (m, 2H); 13C NMR (50 MHz, CDCl3) δ
24.2 (d, JP-C ) 3.0 Hz); 32.1 (d, JP-C ) 43.5 Hz); 54.7 (d, JP-C
)
4.3 Hz); 128.1 (d, JP-C ) 9.4 Hz); 131.4 (d, JP-C ) 2.7 Hz);
131.8 (d, JP-C ) 9.5 Hz); 31P NMR (202 MHz, CDCl3) δ 127.6;
HRMS for C11H20BONaP (M + Na+): Calcd: 233.1237. Found:
233.1235.
(S)-tert-Butylphenylphosphinous Acid-Borane Methanesulfo-
nyl Anhydride (7). In a flask equipped with magnetic stirrer and
a drying tube (CaCl2) (S)-1 (0.059 g, 0.3 mmol) was placed 15 mL
of DCM. Then was added triethylamine (0.036 g, 0.36 mmol) and
after 5 min, mesyl chloride (0.069 g, 0.60 mmol). The reaction
mixture was stirred at room temperature for 3 h. Then, the mixture
was filtered to remove triethylammonium salt, the filtrate was
evaporated to dryness, and the residue was purified by flash
chromatography using hexane/ethyl acetate 6:1 as eluent to give
Experimental Procedures
0.064 g of (S)-7 (78%) as a waxy solid. [R]22 -130.6 (c 1.10,
D
Resolution of Racemic tert-Butylphenylphosphinous Acid-
Borane (1). A sample of racemic tert-butylphenylphosphinous
acid-borane (1) (0.980 g, 5 mmol) was dissolved in DCM
(10 mL), and then (1R,2S)-ephedrine hemihydrate 2 (0.871 g, 5
mmol) was added. After homogenization of the mixture, hexane
was added until the clear solution became slightly cloudy and it
was left overnight. The formed precipitate was filtered off and
recrystallized from hexane-DCM to give 0.614 g of diastereo-
merically pure (1H NMR) salt 3 (34%). The mother liquor was
evaporated to dryness, and the residue was dissolved in DCM (10
mL). A total of 10 mL of 10% hydrochloric acid was then added,
and the mixture was stirred at room temperature for 0.5 h. Then,
the two phases were separated, and the aqueous phase was washed
3 times with DCM (20 mL). The collected organic phases were
dried over anhydrous MgSO4, filtered, and evaporated on a rotary
evaporator. The resulting enriched phosphinous acid-borane 1 was
dissolved in 10 mL of DCM, and cinchonine 4 (1.030 g, 3.5 mmol)
was added with a few drops of methanol to make all cinchonine
dissolved. Then, hexane was added until the mixture became slightly
cloudy. The solvents were allowed to evaporate slowly at room
temperature in an open flask (24 h). The resulting crystalline
precipitate was filtered off and recrystallized from DCM-hexane
to afford diastereomerically pure (1H NMR) cinchonine salt 5 (0.833
g, 34%). The diastereomerically pure ephedrine salt (0.666 g, 1.85
mmol) 3 was dissolved in DCM (20 mL), and 10 mL of 10%
hydrochloric acid was added. The resulting mixture was extracted
6 times with 20 mL of DCM, and the combined organic layers
were dried over anhydrous MgSO4 and evaporated to give 0.333 g
CHCl3) (100% op);19 1H NMR (200 MHz, CDCl3) δ 0.2-1.9 (bm,
3H), 1.2 (d, JP-H) 15.6 Hz, 9H), 3.5 (s, 3H), 7.5-7.7 (m, 3H),
7.8-7.9 (m, 2H); 13C NMR (50 MHz, CDCl3) δ 24.0 (d, JP-C
)
3.5 Hz); 33.8 (d, JP-C ) 33.7 Hz); 47.2; 126.7 (d, JP-C ) 47.6
Hz); 128.4 (d, JP-C ) 10.4 Hz); 131.8 (d, JP-C ) 10.9 Hz); 132.6
(d, JP-C ) 2.8 Hz); 31P NMR (202 MHz, CDCl3) δ 144.7; Anal.
Calcd for C11H20BO3PS: C 48.20, H 7.35, S 11.70. Found: C 48.09,
H 7.37, S 11.57.
Conversion of (S)-tert-Butylphenylphosphinous Acid-Borane
Methyl Ester (6) to (R)-tert-Butylphenylphosphine-Borane (8)
and to (S)-tert-Butylmethylphenylphosphine-Borane (9). A flask
equipped with magnetic stirrer, argon inlet, and a dry ice condenser
was cooled to - 78 °C. Then, 20 mL of ammonia was condensed,
and lithium (0.12 g, 1.66 mmol) was added. After lithium was
dissolved, (S)-6 (0.058 g, 0.28 mmol) in 5 mL of THF was added,
and the reaction mixture was allowed to stir at this temperature for
1 h. Then, acetic acid (2 mL) was added, and ammonia was
evaporated. The residue was washed with DCM, the inorganic phase
was filtered off, and the filtrate was evaporated to dryness. The
residue was purified by flash chromatography using hexane/ethyl
acetate (6:1) as eluent to yield 0.029 g of (R)-8 (58%) as an oil.
[R]22 -6.4 (c 1.12, CHCl3) (100% op);19 1H NMR (200 MHz,
D
CDCl3) δ -0.1-1.7 (bm, 3H), 1.2 (d, JP-H) 14.8 Hz, 9H), 5.1
(dq, JP-H ) 368 Hz, 1H), 7.4-7.7 (m, 5H); 13C NMR (50 MHz,
CDCl3) δ 26.5 (d, JP-C ) 2.9 Hz); 28.5 (d, JP-C ) 32.5 Hz); 124.7
(d, JP-C ) 51.0 Hz); 128.5 (d, JP-C ) 9.7 Hz); 131.5 (d, JP-C
)
3.5 Hz); 133.9 (d, JP-C ) 7.7 Hz); 31P NMR (202 MHz, CDCl3) δ
32.0; Anal. Calcd for C10H18BP: C 66.71, H 10.08. Found: C 66.83,
H 10.21. In a flask equipped with magnetic stirrer and argon inlet
was placed (S)-8 (0.029 g, 0.16 mmol) in 15 mL of dry THF. Then,
the mixture was cooled to -78 °C, and 1.6 M n-BuLi (0.1 mL,
0.48 mmol) was added. After 15 min, methyl iodide (0.068 g, 0.48
mmol) was added, and the reaction mixture was allowed to stir at
this temperature for 2 h. Then, 0.5 mL of 10% hydrochloric acid
was added, and the reaction mixture was allowed to warm to room
temperature. The mixture was extracted 3 times with DCM (20
mL), and the combined extracts were dried over anhydrous MgSO4,
filtered, and evaporated to dryness. The residue was purified by
flash chromatography using hexane/ethyl acetate (6:1) as eluent to
of (S)-1 (92%) as a glassy solid. [R]22 -44.2 (c 1.15, CHCl3)
D
(100% op);8 1H NMR (200 MHz, CDCl3) δ 0.0-1.7 (bm, 3H), 1.1
(d, JP-H ) 14.66 Hz, 9H), 4.5 (bs, 1H), 7.4-7.6 (m, 3H), 7.7-7.9
(m, 2H); 13C NMR (50 MHz, CDCl3) δ 23.9 (d, JP-C ) 3.44 Hz),
31.7 (d, JP-C ) 41.1 Hz), 127.9 (d, JP-C ) 10.1 Hz), 131.2; 131.4
(d, JP-C ) 10.4 Hz); 31P NMR (161 MHz, CDCl3) δ 114.4;
Anal. Calcd for C10H18BOP: C 61.27, H 9.26. Found: C 61.26, H
9.08.
Acid (R)-1 was liberated from the cinchonine salt 5 using the
same procedure as described for (S)-(-)-1. [R]22 +44.2 (c 1.02,
D
CHCl3) (100% op);8 Anal. Calcd for C10H18BOP: C 61.27, H 9.26.
Found: C 61.39, H 9.30.
(S)-tert-Butylphenylphosphinous Acid-Borane Methyl Ester
(6). In a flask equipped with a magnetic stirrer, argon inlet, and
reflux condenser was placed (S)-1 (0.059 g, 0.3 mmol) in 15 mL
of acetone. Then, anhydrous potassium carbonate (0.414 g, 3 mmol)
yield 0.028 g of (S)-9 (89%) as a glassy solid. [R]22 +10.6 (c
D
(19) Correlated within this study.
820 J. Org. Chem., Vol. 72, No. 3, 2007

tert-Butylphenylphosphinous Acid-Borane
1.10, CHCl3) (100% op);20 1H NMR (400 MHz, CDCl3) δ 0.3-
1.8 (bm, 3H), 1.1 (d, JP-H ) 14.0 Hz, 9H), 1.6 (d, JP-H ) 9.6 Hz,
3H), 7.4-7.6 (m, 3H), 7.7-7.8 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 5.2 (d, JP-C ) 37.0 Hz); 25.1 (d, JP-C ) 2.5 Hz); 28.5
MHz, CDCl3) δ 24.1; 38.9 (d, JP-C ) 77.4 Hz); 128.3 (d, JP-C )
12.8 Hz); 132.5 (d, JP-C ) 10.0 Hz); 132.8 (d, JP-C ) 2.9 Hz); 31
NMR (161 MHz, CDCl3) δ 74.3.
P
Conversion of (S)-tert-Butylphenylphosphinous Acid-Borane
(1) into (S)-tert-Butylphenylphosphinic Acid Bromide (12). In a
flask equipped with magnetic stirrer and argon inlet was placed
(S)-1 (0.059 g, 0.3 mmol) in 15 mL of dry acetonitrile. Then,
bromine (0.192 g, 1.2 mmol) was added, and the resulting mixture
was stirred at room temperature for 23 h. The mixture was
evaporated to dryness, and the residue was dissolved in a mixture
of ethyl acetate and hexane (1:1, 10 mL). The formed precipitate
was filtered off, and the residue was evaporated to dryness. The
residue was purified by flash chromatography using hexane/ethyl
acetate 2:1 as eluent to give (S)-12 (0.055 g, 70%) as a slightly
(d, JP-C ) 32.8 Hz); 127.6 (d, JP-C ) 50.9 Hz); 128.2 (d, JP-C
)
9.5 Hz); 131.0 (d, JP-C ) 2.6 Hz); 132.8 (d, JP-C ) 8.7 Hz); 31P
NMR (161 MHz, CDCl3) δ 25.1; HRMS for C11H20BNaP (M +
Na+): Calcd: 217.1288 Found: 217.1299.
Conversion of (S)-tert-Butylphenylphosphinous Acid-Borane
Methanesulfonyl Anhydride (7) to (S)-tert-Butylphenylphos-
phine-Borane (8) and to (R)-tert-Butylmethylphenylphosphine-
Borane (9). In a flask equipped with a magnetic stirrer and argon
inlet was placed (S)-7 (0.064 g, 0.23 mmol) in 10 mL of anhydrous
ethanol. Then, NaBH4 (0.089 g, 2.34 mmol) was added, and the
reaction mixture was stirred at room temperature for 45 min. Then,
1 mL of 10% hydrochloric acid was added, and the reaction mixture
was extracted with DCM (3 × 20 mL). The combined organic
phases were dried over anhydrous MgSO4, filtered, and evaporated
to dryness. The residue was purified by flash chromatography using
hexane/ethyl acetate 6:1 as eluent to give 0.040 g of (S)-8 (96%)
yiellow solid. [R]22 -5.6 (c 1.22, CHCl3) (12% op);15 1H NMR
D
(200 MHz, CDCl3) δ 1.3 (d, JP-H ) 19.7 Hz, 9H), 7.5-7.7 (m,
3H), 7.8-8.0 (m, 2H); 13C NMR (50 MHz, CDCl3) δ 24.3; 40.7
(d, JP-C ) 69.5 Hz); 128.2 (d, JP-C ) 12.6 Hz); 132.5 (d, JP-C
)
10.2 Hz); 132.9 (d, JP-C ) 3.2 Hz); 31P NMR (202 MHz, CDCl3)
δ 73.7.
as an oil. [R]22 +6.5 (c 1.14, CHCl3) (100% op);19 Anal. Calcd
D
Stereochemistry of Conversion of (S)-tert-Butylphenylphos-
phinous Acid-Borane (1) into (S)-tert-Butylphenylphosphinic
Acid Iodide (13). In a flask equipped with magnetic stirrer and
argon inlet was placed (S)-1 (0.059 g, 0.3 mmol) in 15 mL of dry
Et2O. Then, iodine (0.076 g, 1.2 mmol) was added, and the reaction
mixture was stirred at room temperature for 24 h. The reaction
mixture was evaporated to dryness, and the residue was purified
by flash chromatography using hexane/ethyl acetate 2:1 as eluent
for C10H18BP: C 66.71, H 10.08. Found: C 66.74, H 10.05.
(S)-8 (0.040 g, 0.22 mmol) was converted into (R)-9 using the
same prorocol as described previously. The yield of (R)-9 was 83%.
[R]D -10.8 (c 1.09, CHCl3) (100% op).20
Conversion of (S)-tert-Butylphenylphosphinous Acid-Borane
(1) into (R)-tert-Butylphenylchlorophosphine-Borane (10) and
(S)-tert-Butylphenylphosphinous Acid-Borane Methyl Ester (6).
In a flask equipped with a magnetic stirrer, reflux condenser, and
a drying tube (CaCl2) was placed (S)-1 (0.059 g, 0.3 mmol) in 15
mL of DCM. Then was added triethylamine (0.036 g, 0.36 mmol)
and, after 5 min, mesyl chloride (0.069 g, 0.60 mmol). After an
additional 30 min, triethylammonium chloride (0.206 g, 1.5 mmol)
was added, and the reaction mixture was heated under reflux for
3.5 h. Then, the mixture was cooled to room temperature, inorganic
salts were filtered off, the filtrate was evaporated to dryness, and
the residue was purified by flash chromatography using hexane/
ethyl acetate 6:1 as eluent to yield 0.036 g of (R)-10 (56%) as an
oil. [R]22D +56.9 (c 1.10, CHCl3) (45% op);19 1H NMR (200 MHz,
CDCl3) δ 0.3-2.0 (bm, 3H), 1.3 (d, JP-H ) 16.5 Hz, 9H), 7.4-
7.7 (m, 3H), 7.8-8.0 (m, 2H); 13C NMR (50 MHz, CDCl3) δ 24.5
to yield 0.040 g of (S)-13 (78%) as a yiellow solid. [R]22 +57.3
D
(c 1.07, CHCl3) (49% op);19 1H NMR (200 MHz, CDCl3) δ 1.3 (d,
JP-H ) 20.3 Hz, 9H), 7.5-7.7 (m, 3H), 7.8-8.0 (m, 2H); 13C NMR
(50 MHz, CDCl3) δ 24.3; 42.1 (d, JP-C ) 59.6 Hz); 128.0 (d,
JP-C ) 12.2 Hz); 132.2 (d, JP-C ) 10.0 Hz); 132.8 (d, JP-C ) 3.2
Hz); 31P NMR (202 MHz, CDCl3) δ 63.1. In a flask equipped with
magnetic stirrer and argon inlet was placed 10 mL of methanol,
and then sodium (0.046 g, 2 mmol) was added. After sodium was
dissolved, (S)-13 (0.040 g, 0.13 mmol) in 2 mL of methanol was
added, and the resulting mixture was stirred at room temperature
for 16 h. Then, solvent was evaporated, 2 mL of 10% hydrochloric
acid was added to the residue, and the resulting mixture was
extracted with DCM (3 × 20 mL), and the combined extracts were
dried over anhydrous MgSO4, filtered, and evaporated to dryness.
The residue was purified by flash chromatography using ethyl
acetate-methanol 20:1 as eluent to give 0.022 g of (R)-methyl tert-
butylphenylphosphinate (14) (79%) as a white solid. [R]22D -28.5
(c 1.08, CHCl3) (49% op);16 1H NMR (200 MHz, CDCl3) δ 1.2 (d,
JP-H ) 15.9 Hz, 9H), 3.8 (d, JP-H ) 10,9 Hz, 3H), 7.4-7.6 (m,
3H), 7.8-7.9 (m, 2H); 13C NMR (50 MHz, CDCl3): δ 24.2; 32.6
(d, JP-C ) 4.6 Hz); 35.3 (d, JP-C ) 20.9 Hz); 128.3 (d, JP-C
)
P
10.4 Hz); 132.3 (d, JP-C ) 2.8 Hz); 132.5 (d, JP-C ) 10.9 Hz); 31
NMR (161 MHz, CDCl3) δ 121.9. In a flask equipped with
magnetic stirrer and argon inlet, 10 mL of methanol was placed,
and then sodium (0.046 g, 2 mmol) was added. After sodium was
dissolved, (R)-10 (0.036 g, 0.17 mmol) was added, and the mixture
was stirred at room temperature for 16 h. Then, methanol was
evaporated, and 2 mL of 10% hydrochloric acid was added. The
resulting mixture was extracted with DCM (3 × 20 mL), and the
combined extracts were dried over anhydrous MgSO4, filtered, and
evaporated to dryness. The residue was purified by flash chroma-
tography using hexane/ethyl acetate 6:1 as eluent to give 0.033 g
of (S)-6 (93%) as a white solid. [R]22D +24.4 (c 0.99, CHCl3) (49%
op).19
(d, JP-C ) 100.0 Hz); 51.9 (d, JP-C ) 7.1 Hz); 128.3 (d, JP-C
)
12.0 Hz); 132.2 (d, JP-C ) 2.6 Hz); 133.2 (d, JP-C ) 9.6 Hz); 31
P
NMR (161 MHz, CDCl3): δ 55.1; HRMS for C11H17O2NaP (M +
Na+): Calcd: 235.0858; Found: 235.0844.
Conversion of (S)-tert-Butylphenylphosphinous Acid-Borane
(1) into (S)-tert-Butylphenylphosphine Oxide (15). In a flask
equipped with magnetic stirrer and argon inlet was placed (S)-1
(0.059 g, 0.3 mmol) in 15 mL of DCM. Then, tetrafluoroboric acid
diethyl etherate (0.206 mL, 1.5 mmol) was added, and the mixture
was stirred at 0 °C for 1 h. Then, 1 mL of saturated aqueous solution
of NaHCO3 was added, and the resulting mixture was extracted
with DCM (3 × 20 mL), and the combined extracts were dried
over anhydrous MgSO4, filtered, and evaporated to dryness. The
residue was purified by flash chromatography using ethyl acetate-
methanol 20:1 as eluent to give 0.046 g of (S)-15 (85%) as a white
Conversion of (S)-tert-Butylphenylphosphinous Acid-Borane
(1) into (S)-tert-Butylphenylphosphinic Acid Chloride (11). In
a flask equipped with magnetic stirrer and argon inlet was placed
(S)-1 (0.059 g, 0.3 mmol) in 15 mL of dry Et2O. Then was added
sodium hydride (0.009 g, 0.36 mmol) and, after 15 min, hexachlo-
roacetone (0.398 g, 1.5 mmol). After 3 h, the reaction mixture was
evaporated to dryness, and the residue was purified by flash
chromatography using hexane/ethyl acetate 2:1 as eluent to yield
0.049 g of (S)-11 (75%) as a wacky solid. [R]22 +24.4 (c 0.99,
D
CHCl3) (49% op);14 1H NMR (200 MHz, CDCl3) δ 1.3 (d, JP-H
)
solid. [R]22 -35.3 (c 1.21, CHCl3) (83% op);18 1H NMR (200
D
19.1 Hz, 9H), 7.5-7.7 (m, 3H), 7.8-8.0 (m, 2H); 13C NMR (50
MHz, CDCl3) δ 1.2 (d, JP-H ) 16.6 Hz, 9H), 7.0 (d, JP-H ) 454
Hz), 7.4-7.8 (m, 5H); 13C NMR (50 MHz, CDCl3) δ 23.5 (d, JP-C
) 2.0 Hz); 32.0 (d, JP-C ) 68.7 Hz); 128.4 (d, JP-C ) 11.6 Hz);
130.8 (d, JP-C ) 10.0 Hz); 132.4 (d, JP-C ) 2.6 Hz); 31P NMR
(20) Wolfe, B.; Livinghouse, T. J. Am. Chem. Soc. 1998, 120, 5116-
5117.
J. Org. Chem, Vol. 72, No. 3, 2007 821

Stankevicˇ and Pietrusiewicz
(161 MHz, CDCl3) δ 47.7; HRMS for C10H15ONaP (M + Na+):
Calcd: 205.0777. Found: 205.0755.
Supporting Information Available: General experimental
methods and crystallographic information file for 5. This material
is available free of charge via the Internet at http://pubs.acs.org.
Acknowledgment. We express our appreciation to the State
Committee of Scientific Research, Poland (3 T09A 119 26) for
financial support of this study.
JO061896E
822 J. Org. Chem., Vol. 72, No. 3, 2007