M. Cha6arot et al. / Tetrahedron: Asymmetry 12 (2001) 1147–1150
1149
O
O
COOEt
COOEt
EtOOC
EtOOC
1 (10 mol%)
4.3. General procedure for the catalytic Strecker
reaction
+
toluene,-20°C.
3 days
60%,
The imine (0.5 mmol) was added to a mixture of the
cyanide source (1 mmol, 2 equiv.) and the catalyst (0.05
mmol) in toluene (5 mL) at the required temperature.
The resulting mixture was stirred for the indicated time
and the reaction was quenched by addition of a satu-
rated solution of Na2CO3. The mixture was extracted
with Et2O, the resulting organic layer was dried over
MgSO4 and the solvent was removed in vacuo.
37%e.e.
OH
CN
CHO
+ TMSCN
1 (10 mol%)
toluene, -20°C,
100%,
84% e.e.
2 h
Scheme 4. Other catalytic applications of 1.
Conversions were estimated by NMR analysis of the
crude aminonitrile and the e.e. was measured either by
NMR (formation of a diastereoisomeric salt by adding
(R)-camphor-sulfonic acid as a chiral solvating agent7)
or by chiral HPLC analysis.
3. Conclusion
Although the level of enantioselectivity obtained does
not currently compete with the beautiful recent achieve-
ments in Strecker synthesis, the present work shows a
new facet of the versatility of the heterobimetallic cata-
lysts devised by Shibasaki et al. We believe that the
readily available new member of the family, Sc[(R)-
BINOL]2Li 1,6 deserves further investigation.
4.4. 2-Benzylamino-2-phenylpropionitrile
IR (film): 3320, 3063, 3030, 2984, 2849, 2223, 1958,
1897, 1811, 1603, 1494, 1447, 1372, 1214, 1152, 1075,
1
1037, 863, 765, 700 cm−1. H NMR (200 MHz, CDCl3):
l 7.71 to 7.32 (m, 10H), 3.87 and 3.56 (dd, J=13.0 Hz,
2H), 1.78 (s, 3H). 13C NMR (62.5 MHz, CDCl3): l
139.5, 138.8, 128.7, 128.4, 128.3, 128.0, 127.2, 125.3,
121.1, 60.3, 49.3, 31.1. NMR determination of the e.e.:
The benzylic CH2 appears as an AB system at 3.56
ppm. Upon addition of increasing amounts of the
chiral solvating agent (R)-camphor-sulfonic acid, it
splits into two new AB systems between 3.6 and 4.3
ppm. The relative integration of each system gave the
enantiomeric ratio of the aminonitrile product. HPLC
measurement of the e.e.: cyclohexane/propan-2-ol (99/
1), 0.5 mL/min, tR=12.0 min (minor) and 13.5 min
(major).
4. Experimental
All reactions were carried out in Schlenk tubes, under
inert atmosphere, using freshly distilled solvents. HCN
solutions in toluene were prepared from in situ reaction
of methanol and TMSCN analogously to Ref. 2.
HPLC analysis were performed on a Shimadzu appara-
tus (UV diodes array detector) equipped with a chiral
column Daicel Chiralpak OD (25 cm).
4.1. Preparation of aluminiumꢀ(BINOL)2Li 2
Using standard Schlenk techniques. A solution of AlEt3
(1 M, 26 mL, 0.025 mmol) in toluene was added to
(R)-BINOL (15 mg, 0.05 mmol, 2 equiv.) in dry toluene
(2.5 mL), under an inert atmosphere. After stirring for
1 h at 50°C, the brown solution was cooled and a
solution of n-BuLi in hexanes (1.6 M, 33 mL, 0.025
mmol, 1 equiv.) was added. The mixture was stirred for
a few minutes at room temperature and the solution
was cooled to the desired temperature for the addition
of the reagents
4.5. 2-Benzylamino-2-phenylacetonitrile
Purified by flash chromatography over silica (eluent:
pentane/dichloromethane, 5/95); yield=61%; IR (film):
3331, 2963, 2931, 2857, 2229, 1951, 1886, 1805, 1649,
1600, 1455, 1380, 1265, 1094, 1029, 800, 694 cm−1. H
1
NMR (300 MHz, CDCl3): l 7.55 to 7.24 (m, 10H), 4.74
(s, 1H), 4.0 (dd, 2H), 1.85 (broad s, 1H). 13C NMR
(75.5 MHz, CDCl3): l 138.1, 134.7, 128.9, 128.6, 128.4,
127.6, 127.2, 118.7, 53.4, 51.2. HPLC measurement of
the e.e.: cyclohexane/propan-2-ol (99/1), 0.5 mL/min,
tR=17.1 min (minor, (S)-enantiomer) and 18.0 min
(major, (R)-enantiomer). [h]2D0=+41.1 (c 0.88, CHCl3),
measured on a sample of 58% e.e.
4.2. Preparation of scandiumꢀ(BINOL)2Li 1
A solution of n-BuLi in hexane (1.6 M, 130 mL) was
added at 0°C to a solution of (R)-BINOL (28.5 mg, 0.1
mmol) in Et2O (5 mL). The mixture was stirred for 0.5
h at room temperature before the addition of ScCl3 (8.5
mg, 0.056 mmol) in THF (4 mL). The reaction mixture
was stirred under reflux overnight. Toluene (15 mL)
was added and the solvents were removed in vacuo.
This was repeated twice in order to ensure the best
removal of the polar solvent. The complex was then
dissolved in toluene (5 mL) and cooled to the desired
temperature for the Strecker reaction. Complex 3 was
prepared according to the same procedure but replacing
ScCl3 with TiCl3.
Absolute configuration: 53 mg of this isolated sample
was dissolved in formic acid (1 mL), and dry HCl gas
was bubbled through the solution for 1 h. After stand-
ing overnight at 20°C, the solvent was evaporated. The
obtained a-aminocarboxamide was hydrogenolysed in
methanol (3 mL), with Pd/C (10%, 100 mg) and ammo-
nium formate (150 mg) under reflux for 2 h, the mixture
was filtered through Celite and evaporated. The sample,
in ethanol (1.00 mL), had [h]2D0=+2.13 (lit.8 for the
(R)-enantiomer: [h]2D2=+103 (c 1.2, EtOH)).