P,N Ligand for Rh-Catalyzed Asymmetric Hydroboration
J . Org. Chem., Vol. 67, No. 9, 2002 2775
(R)-3,5-Di-ter t-bu tyl-2-(3′-m eth yl-2′-p yr id yl)p h en yl Tr i-
flu or om et h a n esu lfon a t e (2). (R)-3,5-Di-tert-butyl-2-(3′-
methyl-2′-pyridyl)phenol30,43a (R)-(1) (297 mg, 1.0 mmol) was
dissolved in dry dichloromethane (5 mL) under nitrogen at
rate, 0.3 mL/min) tR ) 9.82 min, tS )11.20 min. F or (R)-3:
HPLC (column: analytical Daicel OD-H, solvent, hexane/2-
propanol ) 99:1; UV lamp, 254 nm; flow rate, 0.4 mL/min) tR
) 6.41 min, tS ) 7.28 min.
room temperature in
a
three-necked round-bottom flask.
2-(2′-Dip h en ylp h osp h in o-4′,6′-d i-ter t-bu tyl-1′-p h en yl)-
3-m eth ylp yr id in e32 (p yp h os) (4). Racemic 3,5-di-tert-butyl-
2-(3′-methyl-2′-pyridyl)phenyl trifluoromethanesulfonate (1)
(1.07 g, 2.5 mmol), palladium(II) acetate (56 mg, 0.25 mmol),
and triphenylphosphine (1.51 g, 5.8 mmol) were dissolved in
dry DMF (10 mL) under nitrogen. The solution was heated to
110-115 °C for 4.5 days, and the color of the solution was
changed from yellow to red. The reaction was cooled, and DMF
was removed under reduced pressure. The residue was purified
by column chromatography on silica gel using a solvent
mixture of (hexane/ethyl acetate ) 6:1, Rf ) 0.6) as eluent to
obtain the crude product. This crude product was then purified
by column chromatography on silica gel with eluent (toluene/
ethyl acetate ) 20:1) to afford the pure 2-(2′-diphenylphos-
phino-4′,6′-di-tert-butyl-1′-phenyl)-3-methylpyridine (pyphos)
(4) (790 mg, 68%) as a white solid: mp 135-136 °C; Rf ) 0.6
Pyridine (0.26 mL, 3.0 mmol) and trifluoromethanesulfonic
anhydride (triflic anhydride) (0.18 mL, 1.1 mmol) in dry
dichloromethane (3 mL) were then added slowly to the reaction
mixture. White fumes evolved, and the color of the solution
was changed from yellow to orange. The reaction mixture was
stirred at room temperature for 2 h. Water (5 mL) was added,
and the aqueous phase was extracted with dichloromethane
(20 mL × 3). The combined organic extract was washed with
water and brine, dried over MgSO4, and rotary-evaporated.
The resultant brown residue was purified by column chroma-
tography on silica gel using a solvent mixture (hexane/ethyl
acetate ) 5:1) as the eluent to afford (R)-3,5-di-tert-butyl-2-
(3′-methyl-2′-pyridyl)phenyl trifluoromethanesulfonate (R)-(2)
(408 mg, 95%) as white solids: Rf ) 0.6 (hexane/ethyl acetate
) 4:1); mp 96-98 °C; HPLC (column: analytical Daicel OD-
H, solvent, hexane/2-propanol ) 995:5; UV lamp, 254 nm; flow
1
(toluene/ethyl acetate ) 15:1); H NMR (300 MHz, CDCl3) δ
rate, 0.3 mL/min) tR ) 11.20 min; [R]20 ) +2.3 (c ) 0.6,
1.13 (s, 9 H), 1.17 (s, 9 H), 1.94 (s, 3 H), 7.04-7.30 (m, 13 H),
7.60 (d, 1 H, J ) 2.0 Hz), 8.34 (d, 1 H, J ) 4.3 Hz); 13C NMR
(75 MHz, CDCl3) δ 19.9, 31.1, 32.4, 34.8, 37.2, 125.8, 127.9,
128 (d, J CP ) 8.0 Hz), 128.2 (d, J CP ) 4.6 Hz), 130.1, 131.2 (d,
J CP ) 7.6 Hz), 131.1 (d, J CP ) 7.5 Hz), 133.4 (d, J CP ) 19.3
Hz), 134.0 (d, J CP ) 20.0 Hz), 137.1 (d, J CP ) 8.7 Hz), 138.0
(d, J CP ) 9.3 Hz), 138.2, 145.1, 147.1 (d, J CP ) 5.6 Hz), 149.7;
31P NMR (162 MHz, CDCl3) δ -11.60; MS (EI) m/z (relative
intensity) 465 (M+, 80), 450 (88), 408 (100), 388 (82), 374 (22),
358 (35), 342 (23); HRMS (ESIMS) calcd for C32H36NPH+
466.2658, found 466.2622.
D
1
CHCl3); H NMR (300 MHz, CDCl3) δ 1.16 (s, 9 H), 1.36 (s, 9
H), 2.12 (s, 3 H), 7.20 (s, 1 H), 7.23 (dd, 1 H, J ) 7.8 Hz, 4.8
Hz), 7.57 (d, 1 H, J ) 8.0 Hz), 7.63 (d, 1 H, J ) 0.8 Hz), 8.53
(d, 1 H, J ) 4.0 Hz); 13C NMR (75 MHz, CDCl3) δ 19.1, 29.7,
31.1, 35.1, 37.5, 115.4, 118.2 (q, J CF ) 317.6 Hz), 124.4, 132.7,
133.1, 138.3, 146.4, 148.2, 150.5, 152.1, 152.5; MS (EI) m/z
(relative intensity) 430 (M+ + 1, 74), 414 (52), 296 (19), 281
(100), 266 (22); HRMS (ESIMS) calcd for C21H26F3NO3SH+
430.1658, found 430.1647.
(S)-3,5-Di-ter t-bu tyl-2-(3′-m eth yl-2′-p yr id yl)p h en yl Tr i-
flu or om eth a n esu lfon a te (S)-(2). (S)-3,5-Di-tert-butyl-2-(3′-
methyl-2′-pyridyl)phenol30,43a (S)-(1) (65 mg, 0.22 mmol) was
used to yield the (S)-3,5-di-tert-butyl-2-(3′-methyl-2′-pyridyl)-
phenyl trifluoromethanesulfonate (S)-(2) (85 mg, 90%, 100%ee)
according to the above procedure. HPLC (column: analytical
Daicel OD-H, solvent, hexane/2-propanol ) 995:5; UV lamp,
Di-µ-ch lor ob is[(R)-d im et h yl(1-p h en ylet h yl)a m in a t o-
C2,N]d ip a lla d iu m (II) (5).36 Palladium(II) dichloride (618 mg,
3.5 mmol) and lithium chloride (348 mg, 7.0 mmol) were
dissolved in methanol (15 mL) at 60 °C. The solution was then
stirred for 1 h until a deep red solution was obtained. The
solution was filtered and treated with (R)-N,N-dimethylphen-
ylethylamine (1.2 g, 8.1 mmol). The yellow precipitate formed
was filtered at room temperature, washed with methanol, and
dried under reduced pressure to obtain di-µ-chlorobis[(R)-
dimethyl(1-phenylethyl)aminato-C2,N]dipalladium(II) (885 mg,
88%) as yellow solid: MS (FAB) m/z (relative intensity) 581
254 nm; flow rate, 0.3 mL/min) tR ) 9.82 min; [R]20 ) -2.2 (c
D
) 0.6, CHCl3).
(R)-(3,5-Di-ter t-bu tyl-2-(3′-m eth yl-2′-pyr idyl)ph en yl Non -
a flu or obu ta n esu lfon a te (R)-(3). (R)-3,5-Di-tert-butyl-2-(3′-
methyl-2′-pyridyl)phenol30,43a (R)-(1) (594 mg, 2.0 mmol) in
anhydrous ether (3 mL) was added to NaH (120 mg, 2.7 mmol)
in anhydrous ether (7 mL) at 0 °C. Nonafluorobutanesulfonyl
fluoride (1.2 g, 4.0 mmol) was then added under nitrogen at 0
°C. After complete addition, the reaction mixture was heated
to reflux for 2 h. The reaction mixture was then cooled and
added with water (20 mL). The aqueous phase was extracted
by diethyl ether (50 mL × 2). The combined organic phase was
washed with water and brine and dried over MgSO4. The
solvent was removed by rotary evaporation, and the residue
was purified by column chromatography on silica gel using a
solvent mixture (hexane/ethyl acetate ) 5:1) as the eluent to
yield the (R)-3,5-di-tert-butyl-2-(3′-methyl-2′-pyridyl)phenyl
nonafluorobutanesulfonate (R)-(3) (984 mg, 85%) as light
yellow solids: Rf ) 0.6 (hexane/ethyl acetate ) 5:1); mp 48-
50 °C; HPLC (column: analytical Daicel OD-H, solvent,
hexane/2-propanol ) 99:1; UV lamp, 254 nm; flow rate, 0.4
mL/min) tR ) 6.67 min; [R]20D ) +2.2 (c ) 0.7, CHCl3); 1H NMR
(300 MHz, CDCl3) δ 1.16 (s, 9 H), 1.36 (s, 9 H), 2.11 (s, 3 H),
7.22 (d, 1 H, J ) 0.9 Hz), 7.24 (dd, 1 H, J ) 3.8 Hz, 7.4 Hz),
7.55 (d, 1 H, J ) 7.5 Hz), 7.63 (d, 1 H, J ) 1.6 Hz), 8.52 (d, 1
H, J ) 3.9 Hz); 13C NMR (75 MHz, CDCl3) δ 19.2, 31.1, 32.3,
35.1, 37.1, 109.2-118.9 (m), 115.1, 123.1, 124.5, 129.3, 133.9,
137.6, 146.0, 148.0, 150.4, 152.7, 155.2; MS (FAB) m/z (relative
intensity) 580 (M+ + 1, 60), 564 (10), 297 (30), 282 (100), 266
(33); HRMS (ESIMS) calcd for C24H26F9NO3SH+ 580.1562,
found 580.1536.
(M+, 20), 544 (22), 391 (70), 307 (100); [R]20 ) -53.2 (c ) 0.5,
D
CH2Cl2).
(R,R)- a n d (R,S)-[Dim et h yl(1-p h en ylet h yl)a m in a t o-
C2,N]-[2-(2′-d ip h en ylph osp h in o-4′,6′-d i-ter t-bu tyl-1′-p h en -
yl)-3-m eth ylpyr idin e]palladiu m (II) Hexaflu or oph osph ate
((R,R)-6 a n d (R,S)-6). Di-µ-chlorobis[(R)-dimethyl(1-phenyl-
ethyl)aminato-C2,N]dipalladium(II) (5) (290 mg, 0.5 mmol) and
2-(2′-diphenylphosphino-4′,6′-di-tert-butyl-1′-phenyl)-3-meth-
ylpyridine (4) (465 mg, 1.0 mmol) were dissolved in degassed
methanol (20 mL) under nitrogen and stirred until a clear
solution was obtained. Ammonium hexafluorophosphate (163
mg, 1.0 mmol) in degassed water (15 mL) was then added.
After a half portion of NH4PF6 was added, white precipitate
formed. The suspension was stirred vigorously at room tem-
perature for 1 h. The precipitate was filtered, washed with
water and methanol, and dried under reduced pressure to yield
the (R,S)- and (R,R)-[dimethyl(1-phenylethyl)aminato-C2,N]-
[2-(2′-diphenylphosphino-4′,6′-di-tert-butyl-1′-phenyl)-3-meth-
ylpyridine]palladium(II) hexafluorophosphate (800 mg, 92%)
as white solid: mp 230 °C dec; [R]20D ) +100.5 (c ) 0.5, CHCl3);
1H NMR (300 MHz, CDCl3) δ 1.10 (s, 18 H), 1.22 (s, 18 H),
1.41 (d, 3 H, J ) 6.6 Hz), 1.58 (s, 3 H), 1.62 (s, 3 H), 1.75 (d,
3 H, J ) 6.6 Hz), 2.61 (d, 3 H, J ) 2.4 Hz), 2.79 (d, 3 H, J )
3.3 Hz), 2.86 (d, 3 H, J ) 2.1 Hz), 3.02 (d, 3 H, J ) 3.3 Hz),
3.57 (q, 1 H, J ) 6.6 Hz), 4.87 (q, 1 H, J ) 6.6 Hz), 6.07-6.13
(m, 2 H), 6.38-6.42 (m, 2 H), 6.81-6.99 (m, 10 H), 7.13 (s, 1
H), 7.16 (s, 1 H), 7.25-7.65 (m, 18 H), 7.75 (s, 2 H), 8.68 (dd,
2 H, J ) 9.7, 4.5 Hz); 13C NMR (75 MHz, CDCl3) δ 9.19, 19.8,
19.9, 25.1, 30.8, 32.8, 32.9, 34.9, 38.1, 38.2, 42.0, 47.9, 48.7,
51.6, 72.1, 76.1, 122.0, 123.2, 123.8 (d, J CP ) 11.0 Hz), 124.3
(d, J CP ) 11.1 Hz), 124.6 (d, J CP ) 10.9 Hz), 125.2, 125.7 (d,
Gen er a l P r oced u r es for Ra cem iza tion Exp er im en t:
F or (R)-2. A 5 mL Telfon stopcock flask was charged with
(R)-2 (5 mg, 11 µmol) and dodecane (2 mL) under nitrogen.
The solution was heated to a specific temperature and moni-
tored by HPLC: HPLC (column: analytical Daicel OD-H,
solvent, hexane/2-propanol ) 995:5; UV lamp, 254 nm; flow
J CP ) 5.4 Hz), 126.4, 127.2 (d, J CP ) 5.4 Hz), 127.5 (d, J CP
)