Herrbach et al.
solution of this compound in 1 mL of methanol at 0 °C was
added 0.5 mL of concd HCl and the solution was stirred at 35
°C for 1 h. After being cooled to 0 °C, the solution was
neutralized by concd sodium hydroxide, extracted by methyl-
ene chloride, dried over magnesium sulfate, and concentrated.
The crude material was injected on HPLC, using a Chiracel
OJ column. A calibration curve was previously elaborated with
racemic 6 to determine the yields. The ee was determined by
the difference of the two peak areas (hexane/propan-2-ol 95/5,
flow rate 1 mL/min, (+)-6 RT ) 9 min, (-)-6 RT ) 15 min).
2-Am in op h en ylbor on ic Acid (3d ). To a stirred solution
of BCl3 in CH2Cl2 (1 M, 9 mL, 9 mmol) at -78 °C was added
dropwise a solution of pinacol (2-aminophenyl)boronate 3b
(300 mg, 1.37 mmol) in CH2Cl2 (1.4 mL). The mixture was
stirred at -78 °C for 15 min, allowed to warm to 25 °C, and
stirred at 25 °C for 3 h. The solution was then concentrated
under reduced pressure and methanol (3 mL) was carefully
added. Trimethyl borate and methanol were removed by
evaporation under vacuum. Water (10 mL) and diethyl ether
(10 mL) were added, and the aqueous layer was separated and
washed with 2 × 15 mL of diethyl ether. Removal of water
under vacuum and recrystallization from MeOH/CHCl3 gave
boronic acid 3d 23 (96 mg, 52%).
P in a col [2-(1-(Met h oxym et h oxy)m et h yl-1-et h ylp r op -
1-yl)p h en yl]bor on a te (4d ). Compound 4a (241 mg, 0.69
mmol) was submitted to a classical palladium-catalyzed
borylation,18a using triethylamine (386 µL, 2.8 mmol), palla-
dium(II) acetate (7.8 mg, 0.035 mmol), PCy2(o-biph) (48.5 mg,
0.14 mmol), and pinacolborane (301 µL, 2.1 mmol), to afford
4d as an oil (171 mg, 71%); 1H NMR (300 MHz, CDCl3) δ 0.69
(t, 6H), 1.38 (s, 12H), 1.88 (m, 4H), 3.33 (s, 3H), 3.84 (s, 2H),
4.62 (s, 2H), 7.15-7.30 (m, 3H), 7.44 (d, J ) 7.2 Hz, 1H) ppm;
13C NMR (75.5 MHz, CDCl3) δ 8.2, 24.7, 28.4, 46.3, 55.2, 70.6,
83.7, 96.8, 124.7, 127.1, 128.7, 133.7, 148.3 ppm; IR (film) ν
2975, 1594 cm-1; HRMS (LSIMS) calcd for C20H34BO4 [(M +
H)+] 349.2550, found 349.2559.
(t, J ) 9.0 Hz, 1H), 7.22-7.32 (m, 4H), 7.46 (m, 2H), 7.79 (m,
2H), 7.93 (m, 2H) ppm; 31P NMR (121.5 MHz, CDCl3) δ -26.1
ppm; 13C NMR (75.5 MHz, CDCl3) δ 10.1 (d, J C-P ) 11.9 Hz),
10.6 (d, J C-P ) 15.2 Hz), 21.2 (d, J C-P ) 15 Hz), 21.3 (d, J C-P
) 11.5 Hz), 43.7, 119.2, 123.4, 125.8, 126.0, 126.4, 127.3, 127.7,
128.0, 128.1, 129.2, 133.9, 134.6, 136.8 (d, J C-P ) 16.5 Hz),
144.4 (d, J C-P ) 30.2 Hz), 150.0 ppm (observed complexity due
to P-C splitting); IR (film) ν 2957, 1594 cm-1; HRMS (LSIMS)
calcd for C26H29NP [(M + H)+] 386.2038, found 386.2038.
(S)-(-)-2-(o-An isole)-1-(d icycloh exylp h osp h a n yl)fer -
r ocen e, Tetr a flu or obor ic Acid Sa lt (14). A flame-dried
round-bottom flask was charged with (SP,SS)-2-(o-anisole)-1-
(p-tolylsulfinyl)ferrocene (13, 159 mg, 0.371 mmol), THF (2
mL) was added, and the reaction was cooled to -78 °C.
Dicyclohexylchlorophosphine (0.286 mL, 1.3 mmol) and a
solution of tert-butyllithium in hexane (1.5 M, 0.742 mL, 1.11
mmol) were added sequentially dropwise. The reaction mixture
was stirred at -78 °C for 30 min. A solution of borane-methyl
sulfide complex in THF (2.0 M, 0.925 mL, 1.85 mmol) was then
added dropwise. The solution was allowed to warm to 25 °C,
and stirred for 1 h at that temperature, followed by quenching
with a 2 M NaOH solution and extraction with diethyl ether.
The organic layer was washed with brine, dried over magne-
sium sulfate, filtered, and concentrated under reduced pres-
sure. The crude material was purified by flash chromatography
(silical gel, heptane/ethyl acetate 9/1, then 4/1) to afford 14
borane complex (125 mg, 67% yield). This compound (35.2 mg,
0.07 mmol) was charged in a flame-dried round-bottom flask,
DABCO (78.6 mg, 1.4 mmol) and toluene (1.5 mL) were added,
and the reaction mixture was stirred at 60 °C for 1 h. The
solution was cooled to 25 °C and concentrated under reduced
pressure. CH2Cl2 (5 mL) and tetrafluoroboric acid (48% aque-
ous solution, 5 mL) were added to the residue and the solution
was stirred for 30 min. After separation, the organic layer was
dried over magnesium sulfate and concentrated under vacuum
to afford phosphonium 14 (39 mg, 96.3%); [R]23 -3.4 (c 1.5,
D
CHCl3); 1H NMR (300 MHz, CDCl3) δ 0.83-2.53 (m, 22H), 3.84
(s, 3H), 4.46 (s, 5H), 4.78 (m, 1H), 4.82 (m, 2H), 5.92 and 7.58
(br d, J H-P ) 498 Hz, 1H), 6.94 (d, J ) 8.1 Hz, 1H), 7.10 (t, J
) 7.2 Hz, 1H), 7.40 (t, J ) 8.4, 1H), 7.64 (dd, J ) 7.5, 2.1 Hz,
1H) ppm; 31P NMR (121.5 MHz, CDCl3) δ 22.7 ppm; 13C NMR
(75.5 MHz, CDCl3) δ 25.0, 25.1, 26.1, 26.2, 26.3, 26.4, 26.6,
26.7, 27.8, 28.2, 30.5, 31.1, 31.2, 31.8, 55.6, 71.8, 72.7 (d, J C-P
) 9.8 Hz), 73.7 (d, J C-P ) 12.1 Hz), 75.8 (d, J C-P ) 9.8 Hz),
111.1, 121.4, 122.5, 130.4, 133.0, 156.8 ppm (observed com-
(+)-2-N,N-Dim eth yla m in o-2′-d im eth ylp h osp h in o-1,1′-
bin a p h th yl (7e). A round-bottom flask was charged with (-)-
2-N,N-(dimethylamino)-2′-bromo-1,1′-binaphthyl (10, 500 mg,
1.34 mmol) and purged with argon. THF (10 mL) was added,
the resulting solution was cooled to -78 °C, and a solution of
n-butyllithium in hexane (1.6 M, 0.913 mL, 1.5 mmol) was
added dropwise. The solution was stirred at -78 °C for 1 h.
Dimethylchlorophosphine (0.137 mL, 1.7 mmol) was added
dropwise and the reaction mixture was stirred for 1 h at -78
°C, allowed to warm to 25 °C, and stirred for 17 h at 25 °C. A
saturated aqueous ammonium chloride solution was added and
the reaction mixture was extracted with methylene chloride
(3 × 10 mL). The combined organic extracts were dried over
anhydrous magnesium sulfate, filtered, and concentrated
under vacuum. The crude material was recrystallized from
methylene chloride/methanol to give (+)-7e as colorless crys-
plexity due to P-C splitting); IR (film) ν 2930, 1450 cm-1
;
HRMS (ESI) calcd for C29H38FeOP [(M - BF4)+] 489.2010,
found 489.2020.
(R,R)-2,4-Dim et h yl-1-b ip h en ylp h osp h et a n e Bor a n e
Com p lex (18a ). A flame-dried Schlenk tube was charged with
LiAlH4 (1.1 g, 29.6 mmol), diethyl ether (5 mL) was added,
and the solution was cooled to -50 °C and stirred at this
temperature for 30 min. A solution of diethyl 2-biphenylphos-
phonate (15,38 2 g, 6.89 mmol) in 11 mL of diethyl ether was
then introduced dropwise into the Schlenk tube, stirred for
30 min at 0 °C, and allowed to warm to 25 °C for 2 h.Water (5
mL) and 5 mL of NaOH (20% aqueous solution) were intro-
duced dropwise. A white precipitate formed. The supernatant
was cannulated off, dried over magnesium sulfate, and care-
fully evaporated under reduced pressure to furnish the air-
sensitive phosphine 16; 1H NMR (200 MHz, CDCl3) δ 3.28 and
4.29 (d, J H-P) 202 Hz, PH2), 6.95-7.42 (m, 9H); 31P NMR (162
MHz, CDCl3) δ -121.6. This compound was directly introduced
in the next step. To a solution of phosphine 16 (233 mg, 1.25
mmol) and (S,S)-pentane-2,4-diol cyclic sulfate (17a , 208 mg,
1.25 mmol) in diethyl ether (17 mL) at 0 °C was added
dropwise a solution of sec-butyllithium in hexane (0.9 M, 3.1
mL, 2.75 mmol). After the solution was warmed to 25 °C and
stirred for 30 min, excess BH3‚Me2S (2 mmol) was added.
Water was carefully added, the solvent was evaporated, the
residue was dissolved in diethyl ether, and the solution was
washed with water and dried over magnesium sulfate. After
tals (297 mg, 62%); mp ) 228-229 °C; [R]23 128.4 (c1.2,
D
CHCl3); 1H NMR (300 MHz, CDCl3) δ 0.90 (d, J ) 15 Hz, 3H),
1.26 (d, J ) 15 Hz, 3H), 2.47 (s, 6H), 6.84 (d, J ) 8.8 Hz, 1H),
7.07 (t, J ) 8.8, 1H), 7.19-7.32 (m, 3H), 7.42 (t, J ) 6.3 Hz,
1H), 7.48 (d, J ) 9 Hz, 1H), 7.79-7.97 (m, 5H) ppm; 31P (121.5
MHz, CDCl3) δ -55.7 ppm; 13C NMR (75.5 MHz, CDCl3) δ 14.3
(d, J C-P ) 16.7 Hz), 15.2 (d, J C-P ) 11.2 Hz), 43.6, 119.3, 123.4,
125.6, 125.9, 126.1, 126.4, 126.9, 127.7, 127.9, 129.0, 129.4,
133.2, 133.6, 134.4, 139.0 (d, J C-P ) 12.2 Hz), 142.5 (d, J C-P
)
33.4 Hz), 149.7 ppm (observed complexity due to P-C split-
ting); IR (film) ν 2771, 1593 cm-1; HRMS (ESI) calcd for C24H25
NP [(M + H)+] 548.1725, found 548.1732.
-
(+)-2-N,N-Dim eth yla m in o-2′-d ieth ylp h osp h in o-1,1′-bi-
n a p h th yl (7d ). Compound 7d was synthesized as described
above for compound 7e from 10 (500 mg, 1,34 mmol) and
diethylchlorophosphine (0.236 mL, 1.73 mmol). (+)-7d was
obtained as colorless crystals (348 mg, 68%); mp 105 °C; [R]25
D
1
106.5 (c 0.8, CHCl3); H NMR (250 MHz, CDCl3) δ 0.52 (dt, J
) 15, 8.3 Hz, 3H), 1.04 (dt, J ) 15, 7 Hz, 3H), 7.22-7.32 (m,
2H), 1.73 (m, 2H), 2.47 (s, 6H), 6.81 (d, J ) 8.8 Hz, 1H), 7.08
4904 J . Org. Chem., Vol. 68, No. 12, 2003