J.-H. Xie, Q.-L. Zhou et al.
FULL PAPERS
mined using a Perkin–Elmer 241 MC
polarimeter. HRMS were recorded on
APEXII and ZAB-HS spectrometer.
GC analyses were performed using a
Hewlett Packard Model HP 6890
Series. HPLC analyses were per-
formed using
a
Hewlett Packard
Model HP 1100 instrument. X-ray dif-
fraction analysis was performed on a
Bruker Smart-1000 X-ray diffraction
meter.
Synthesis of N-Methylated Spiro
Aminophosphoine Ligands (R)-1e and
1f
Synthesis of (R)-1e: Ethyl chlorofor-
mate (60 mg, 0.55 mmol) was added
slowly to a dry Schlenk tube contain-
ing
a solution of (R)-1c (300 mg,
0.47 mmol) and pyridine (120 mL,
1.49 mmol) in 2 mL dry toluene at 08C
under nitrogen atmosphere. When the
Figure 6. Stereochemistry of the hydrogenation of acetophenone.
addition was complete, the reaction
mixture was stirred at room tempera-
offering the chiral secondary alcohols with high enantiose-
lectivities (up to 97% ee) and high activities (TON up to
10000, TOF up to 37200 hꢀ1). The active catalyst is iridium
dihydride containing one chiral spiro aminophosphine
ligand, which was slowly transformed to an inactive iridium
dihydride complex with two ligands. The 3,5-di-tert-butyl
groups on the P-phenyl rings of the ligand (R)-1c play an
important role for controlling the enantioselectivity of the
catalyst and preventing the formation of inactive iridium
complexes. Investigations on the active catalyst species and
the reaction rate support the reaction mechanism involving
a six-membered cyclic transition state. The iridium complex
of chiral spiro aminophosphine ligand (R)-1c represents a
highly efficient iridium catalyst for the asymmetric hydroge-
nation of simple ketones and a,b-unsaturated ketones, and
has a high potential for application in other asymmetric hy-
drogenation reactions.
ture overnight. After dilution with 20 mL ethyl acetate, the mixture was
washed sequentially with 5% HCl and brine and dried with anhydrous
Na2SO4. The organic solution was then concentrated in vacuum to afford
a white solid. This white solid was dissolved in 3 mL dry THF and was
added to a suspension of LiAlH4 (64 mg, 1.69 mmol) in 1 mL dry THF at
08C. After the addition was complete, the mixture was stirred under
reflux overnight. The mixture was cooled to 08C and a small amount of
water was carefully added to quench the reaction. After dilution with
20 mL ethyl acetate, the reaction mixture was washed sequentially with
20 mL 5% NaOH and brine and dried with anhydrous Na2SO4. The sol-
vent was removed in vacuum and the obtained crude product was sepa-
rated by chromatography on silica gel (petroleum ether/ethyl acetate/trie-
thylamine=20:1:0.2) to afford (R)-1e (267 mg, 87%) as an oil (which
20
solidified after standing at room temperature for a long time). ½aꢁD
=
+142 (c=0.16, CH2Cl2). 1H NMR (400 MHz, CDCl3): d=6.69–7.32 (m,
11H, Ar-H), 6.09 (d, J=8.0 Hz, 1H, Ar-H), 2.92–3.10 (m, 4H, CH2),
2.10–2.39 (m, 5H, CH2, NH), 2.07 (s, 3H, NCH3), 1.24 (s, 18H, C
ACHTUNGTRENNUNG(CH3)3),
1.16 ppm (s, 18H,
CACHTUNGTRENNUNG
(CH3)3). 31P NMR (162 MHz, CDCl3): d=
ꢀ20.03 ppm (s). 13C NMR (100 MHz, CDCl3): d=151.8 (d, J=25.3 Hz),
148.9 (d, J=7.1 Hz), 148.7 (d, J=6.1 Hz), 144.3 (d, J=2.9 Hz), 143.0,
142.9, 137.6 (d, J=12.1 Hz), 134.7 (d, J=13.0 Hz), 133.7, 133.5, 133.1 (d,
J=2.0 Hz), 133.0, 131.4 (d, J=3.0 Hz), 127.2, 127.0, 126.6, 126.4, 125.9,
124.8, 121.2, 120.1, 112.6, 106.8, 60.5 (d, J=3.2 Hz), 38.0 (d, J=3.6 Hz),
34.3, 33.8, 33.6, 30.4, 30.3, 28.7, 28.3 ppm. HRMS (ESI) calcd for
C46H61NP [M+H]+: 658.4536; found: 658.4544.
Experimental Section
Synthesis of (R)-1 f: The N-dimethylated spiro aminophosphine ligand
(R)-1 f was synthesized from (R)-1e in 86% yield by using same proce-
dure as that for (R)-1e. ½aꢁ2D0 =+135 (c=0.20, CH2Cl2). 1H NMR
(400 MHz, CDCl3): d=6.68–7.18 (m, 12H, Ar-H), 2.89–3.10 (m, 4H,
CH2), 2.65–2.73 (m, 1H, CH2), 2.31–2.38 (m, 1H, CH2), 2.10–2.18 (m,
General
All reactions and manipulations which are sensitive to moisture or air
were performed in an argon-filled glovebox (VAC DRI-LAB HE 493) or
using standard Schlenk techniques. Hydrogen gas (99.999%) was pur-
chased from Boc Gas Inc., Tianjin. PdACHTNUTRGENNUG(OAc)2, [IrACHTUNGTERN(NGUN cod)Cl]2, dppb (1,4-
2H, CH2), 2.06 (s, 6H, NCH3), 1.11 (s, 18H, CACTHNURGTNEG(UN CH3)3), 1.07 ppm (s, 18H,
bis(diphenylphosphino)butane), dppp (1,3-bis(diphenylphosphino)pro-
pane), and ketones were purchased from Aldrich or Acros. Acyclic unsa-
turated ketones and some other substrates were synthesized according to
literature methods. Anhydrous THF and toluene were distilled from
sodium benzophenone ketyl. Anhydrous CH2Cl2, DMSO, iPrOH,
nPrOH, nBuOH, iPr2NEt, and NEt3 were freshly distilled from calcium
hydride. Anhydrous MeOH and EtOH were freshly distilled from mag-
nesium turnings. Melting points were measured on an RY-I apparatus
and are uncorrected. 1H, 13C, and 31P NMR spectra were recorded with a
Varian or Bruker spectrometer at 400 MHz (1H NMR), 100 MHz
(13C NMR), and 162 MHz (31P NMR) in CDCl3 or a Bruker spectrometer
at 300 MHz (1H NMR), 75 MHz (13C NMR), and 121 MHz (31P NMR) in
CDCl3 or CD2Cl2. Chemical shifts were reported in ppm downfield from
internal Me4Si and external 85% H3PO4. Optical rotations were deter-
CACHTUNGTRENNUNG
(100 MHz, CDCl3): d=155.3 (d, J=26.3 Hz), 150.5, 148.8 (d, J=6.1 Hz),
148.6 (d, J=6.0 Hz), 145.3 (d, J=3.4 Hz), 144.9 (d, J=3.1 Hz), 142.9 (d,
J=8.0 Hz), 137.4 (d, J=12.1 Hz), 136.0 (d, J=13.5 Hz), 132.8, (d, J=
2.0 Hz), 132.4 (d, J=21.0 Hz), 127.0, 126.8, 126.0, 125.0, 123.9, 120.6,
120.3, 119.3, 118.7, 118.4, 61.8 (d, J=2.9 Hz), 44.1, 41.5 (d, J=5.8 Hz),
40.5, 33.7 (d, J=6.8 Hz), 30.6, 30.3, 28.7 ppm. HRMS (ESI) calcd for
C47H63NP [M+H]+: 672.4693; found: 672.4695.
Asymmetric Hydrogenation of Ketones
General procedure for asymmetric hydrogenation of ketones (S/C=
1000): The catalyst precursor [Ir
1c (2.3 mg, 3.6 mmol), and nPrOH (1.5 mL) were added to a 30 mL hy-
ACHTUNGTNER(NUNG cod)Cl]2 (1.0 mg, 1.5 mmol), ligand (R)-
906
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2011, 6, 899 – 908