Notes
J . Org. Chem., Vol. 63, No. 9, 1998 3135
mL). The solvents were removed from the filtrate under reduced
pressure to afford desired phosphinite 2 (1.45 g, 90.0% yield):
1H NMR (CDCl3) δ 7.50-7.43 (m, 8 H), 7.36-7.26 (m, 12 H),
4.22-4.20 (m, 2 H), 2.15 (m, 2 H), 1.82-1.66 (m, 8 H), 1.59-
1.53 (m, 2 H), 1.28-1.21 (m, 2H); 31P NMR (CDCl3) δ P ) 106.7;
13C NMR (CDCl3) δ 143.18-142.70 (m), 130.38-130.07 (m),
128.90 (s, 128.18-128.08 (m), 85.56 (d, J ) 17.9 Hz), 49.29 (d,
J ) 6.52 Hz), 33.78 (d, J ) 5.61 Hz), 27.06 (s), 22.59 (s). MS
m/z: 538, 461, 383, 353, 337, 201, 185, 151, 135, 77; HRMS calcd
for C34H36O2P2 (M+) 538.2190, found 538.2156.
transition metals. However, compared with the potential
nine-membered chelated bidentate ligands reported by
Grubbs,3b Miyano,9 and Kumada,10 our new bisphosphin-
ites 2 and 3 display the highest reactivities and enanti-
oselectivities in the rhodium-catalyzed asymmetric hy-
drogenation of R-(acylamino)acrylic acids.
Con clu sion s
(1R,1′R)-Bicyclop en tyl-(2R,2′R)-d iol (4). Under nitrogen,
to a solution of diol 2 (2.5 g, 14.7 mmol), benzioc acid (7.26 g,
59.4 mmol), and triphenylphosphine (15.6 g, 59.5 mmol) in THF
(50 mL) was added diethyl azodicarboxylate (9.4 mL, 59.7 mmol)
dropwise at 0 °C. After stirring overnight at room temperature,
the solution was concentrated and the residue was chromato-
graphed on silica gel to afford the benzoate ester. The benzoate
ester was directly used for hydrolysis. A mixture of NaOMe,
which was made from sodium (3.35 g, 0.15 mol) and MeOH (560
mL), and benzoate ester in MeOH was stirred overnight at room
temperature. After evaporation of MeOH, the residue was
diluted with ether and water and acidified with 10% aqueous
hydrochloric acid. The mixture was extracted with methylene
chloride, and the combined organic layer was dried over sodium
sulfate. After evaporation of solution, the residue was purified
by chromatography on silica gel. Diol 4 was obtained as a solid
(1.0 g, 40% total yield): [R]25D ) -54.0 (c, 1.07, CHCl3); 1H NMR
(CDCl3) δ 4.30-4.28 (m, 2H), 1.87-1.49 (m, 14 H); 13C NMR
(CDCl3) δ 74.21, 45.59, 35.23, 28.27, 21.62. MS m/z 152, 134,
121, 108, 67, 41, 37; HRMS calcd for C10H17O (M+ - OH)
153.1279, found 153.1238.
The mechanism of asymmetric hydrogenation of de-
hydroamino acids has been examined intensively.11 It
is generally accepted that a chiral ligand which can form
a rigid ligand-metal complex is essential for effective
chiral recognition. The most difficult part of research in
asymmetric catalysis is to find effective new ligand
scaffolds. Our study shows that the new class of phos-
phinites 2 and 3, which could potentially form nine-
membered chelated complexes with rhodium, gave re-
markably high selectivities for the hydrogenation of
dehydroamino acids. The key element of this system is
that the two cyclopentane rings in the backbone restrict
the conformational flexibility of the nine-membered ring,
and the four stereogenic carbon centers in the backbone
dictate the orientation of four P-phenyl groups. Other
chiral ligands based on this framework are under study
and will be reported in due course.
(2R,2′R)-Bis(d ip h en ylp h osp h in oxy)-(1R,1′R)-d icyclop en -
ta n e (5). This compound was made in a similar fashion as
phosphinite 2 (1.20 g, 74.4% yield): 1H NMR (CDCl3) δ 7.48-
7.40 (m, 8 H), 7.35-7.27 (m, 12 H), 4.11-4.09 (m, 2 H), 1.86-
1.70 (m, 8 H), 1.58-1.50 (m, 4 H), 1.50-1.30 (m, 2H); 31P NMR
(CDCl3) δ 106.1; 13C NMR (CDCl3) δ 143.79-142.70 (m), 131.19-
127.99 (m), 83.44 (dd, J 1 ) 2.01 Hz, J 2 ) 19.4 Hz), 46.03 (d, J )
6.44 Hz), 33.42 (d, J ) 4.98 Hz), 28.30 (s), 21.58 (s). MS m/z
538, 461, 383, 353, 337, 269, 201, 185, 151, 135, 77; HRMS calcd
for C34H36O2P2 (M+) 538.2190, found 538.2159.
Exp er im en ta l Section
Gen er a l. All reactions and manipulations were performed
in a nitrogen-filled glovebox or using standard Schlenk tech-
niques. Toluene, benzene, and tetrahydrofuran (THF) were
distilled from sodium benzophenone ketyl under nitrogen. Me-
thylene chloride and 1,2-dichloroethane were distilled from
CaH2. Methanol, ethnaol, and 2-propanol were distilled from
Mg under nitrogen. Column chromatography was performed
using EM Silica gel 60 (230-400 mesh).
Gen er a l P r oced u r e for Asym m etr ic Hyd r ogen a tion . In
a glovebox, to a solution of [Rh(COD)2]BF4 (5.0 mg, 0.012 mmol)
in MeOH (10 mL) was added chiral ligand 2 (0.15 mL of 0.1 M
solution in toluene, 0.015 mmol). After stirring the mixture for
30 min, the dehydroamino acid (1.2 mmol) was added. The
hydrogenation was performed at room temperature under 1 atm
of hydrogen for 24 h. The reaction mixture was treated with
CH2N2 and then concentrated in vacuo. The residue was passed
through a short silica gel column to remove the catalyst. The
enantiomeric excesses were measured by capillary GC or HPLC.
The absolute configuration of products was determined by
comparing the observed rotation with the reported value.8d,j
Deter m in a tion of En a n tiom er ic Excess. Ch ir a l ca p il-
la r y GC used the following: column, Chirasil-VAL III FSOT;
dimensions, 25 m × 0.25 mm (i.d.); carrier gas, He (1 mL/min).
The racemic products were obtained by hydrogenation of sub-
strates with an achiral catalyst. The following is the retention
time for the racemic products.
R-Acetamidoacrylic acid and its methyl ester were purchased
from Aldrich and used as received. All other substrates,
â-isopropyl-R-acetoamidoacrylic acid,12 R-benzoamidocinnamic
acid,13 methyl R-benzoamidocinnamate,14 â-aryl-R-acetoami-
doacrylic acid,15 and their methyl esters,14 were prepared by
standard Erlenmeyer procedures. (1R,1′R)-Bicyclopentyl-(2S,2′S)-
diol (3) was made according to the previous reported procedure.2
(2S,2′S)-Bis(d ip h en ylp h osp h in oxy)-(1R,1′R)-d icyclop en -
ta n e (2). To a solution of (1R,1′R)-bicyclopentyl-(2S,2′S)-diol
(3) (0.51 g, 3.0 mmol) and DMAP (36 mg, 0.3 mmol) in CH2Cl2
(5 mL) was added pyridine (4.86 mL, 60 mmol) under stirring.
Then the mixture was cooled to 0 °C, and a solution of ClPPh2
(1.24 mL, 6.9 mmol) in CH2Cl2 (10 mL) was added dropwise.
The mixture was stirred at 0 °C for 5 h, followed by 48 h at
room temperature. Then the reaction mixture was concentrated
under vacuum and excess chlorodiphenylphosphine, pyridine
HCl salt, and phosphorus impurities were removed by filtration
through basic alumina (1 × 5 cm), eluted with ether (3 × 20
N-Acetylp h en yla la n in e m eth yl ester :8j (capillary GC, 150
°C, isothermal) (R) t1 ) 14.66 min, (S) t2 ) 16.23 min; 1H NMR
(CDCl3) δ 7.34-7.06 (m, 5H), 5.93 (br, 1H), 4.93-4.83 (m, 1H),
3.72 (m, 3H), 3.14-3.06 (m, 2H), 1.98 (s, 3H).
(9) Miyano, S.; Nawa, M.; Mori, A.; Hashimoto, H. Bull. Chem. Soc.
J pn. 1984, 57, 2171.
(10) Tamao, K.; Yamamoto, H.; Matsumoto, H.; Miyake, N.; Hayashi,
T.; Kumada, M. Tetrahedron Lett. 1977, 1389.
N-Acetyla la n in e m eth yl ester :8j (capillary GC, 100 °C,
isothermal) (R) t1 ) 5.56 min, (S) t2 ) 6.73 min; 1H NMR (CDCl3)
δ 6.07 (br, 1H), 4.60 (q, J ) 7.21 Hz, 1H), 3.75 (s, 3H), 2.01 (s,
3H), 1.40 (d, J ) 7.10 Hz, 3H).
(11) (a) Chan, A. S. C.; Pluth, J . J .; Halpern, J . J . Am. Chem. Soc.
1980, 102, 5952. (b) Yawabata, Y.; Tanaka, M.; Ogata, I. Chem. Lett.
1976, 1213. (c) Halpern, J . Pure Appl. Chem. 1983, 55, 99. (d) Brown,
J . M.; Chaloner, P. A.; Morris, G. A.; J . Chem. Soc., Perkin Trans 2
1987, 1583. (e) Halpern, J . Inorg. Chim. Acta 1981, 50, 11. (f) Landis,
C. R.; Halpern, J . J . Am. Chem. Soc. 1987, 109, 1746.
(12) Doherty, D. G.; Tietzman, J . E.; Bergmann, M. J . Biol. Chem.
1943, 147, 617.
(13) (a) Gillespie, H. B.; Snyder, H. R. Organic Synthesis; Wiley:
New York, 1941; Collect. Vol. 1, p 489. (b) Vineyard, B. D.; Knowles,
W. S.; Sabacky, M. J .; Bachman, G. L.; Weinkauff, D. J . J . Am. Chem.
Soc. 1977, 99, 9, 5946.
N-Acetyl-m -br om op h en yla la n in e m eth yl ester :8j (capil-
lary GC, 180 °C, isothermal) (R) t1 ) 14.14 min, (S) t2 ) 15.09
min; 1H NMR (CDCl3) δ 7.50-7.00 (m, 4 H), 6.03-5.98 (br, 1H),
4.89-4.79 (m, 1H), 3.80 (s, 3H), 3.08 (m, 2H), 1.85 (s, 3H).
N-Ben zoylp h en yla la n in e m eth yl ester :8j (capillary GC,
180 °C, isothermal) (R) t1 ) 35.65 min, (S) t2 ) 37.13 min; 1H
NMR (CDCl3) δ 7.80-7.10 (m, 10 H), 6.65-6.55 (br, 1H), 5.14-
5.05 (m, 1 H), 3.76 (s, 3H), 3.36-3.17 (m, 2H).
(14) Glaser, R.; Vainas, B. J . Organomet. Chem. 1976, 121, 249.
(15) Herbst, R. M.; Shemin, D. Organic Synthesis; Wiley: New York,
1943; Collect. Vol. 2, p 1.
N-Acetylleu cin e m eth yl ester :8j (capillary GC, 110 °C,
isothermal) (R) t1 ) 16.1 min, (S) t2 ) 19.4min; 1H NMR (CDCl3)