1128
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 5, May, 2004
Belokon et al.
Table 1. Yield and enantiomeric purity of Oꢀacetylmandelonitrile
based on the results of reaction under conditions of phase transꢀ
fer catalysis by compounds 1—11
was performed on a 3700 chromatograph (Russia) with a
40 m × 0.23 mm quartz capillary column (2,6ꢀdiꢀnꢀpentylꢀ3ꢀ
trifluoroacetylꢀγꢀcyclodextrin as the chiral phase, film thickness
0.12 µm). The yield and the enantiomeric purity of the obtained
Oꢀacetylmandelonitrile were determined under isothermal conꢀ
ditions at a column temperature of 105 °C with helium as the
carrier gas. The column was preliminarily calibrated against the
starting compound and the racemic product.
Run
Solvent
Catalyst
(mol.%)
Yielda
ееa,b
%
1
2
3
Toluene
Water
Toluene—water
—
—
—
3
—
27
0
—
0
Compounds 1—5,12 6,5 7,5 8,13 and 9 14 were prepared by
reported procedures, while complex 10 was synthesized by analꢀ
ogy with complex 9 starting from 4,6ꢀdiformyldibenzo[b,d]furan.
4,6ꢀDi[(4R,5R)ꢀ4,5ꢀbis(isopropyloxycarbonyl)ꢀ1,3ꢀdioxolanꢀ
2ꢀyl]dibenzo[b,d]furan (12). 4,6ꢀDiformyldibenzofuran (1 g,
4.46 mmol) in 20 mL of benzene, diisopropyl (R)ꢀtartrate
(1.88 mL, 8.92 mmol), and pꢀtoluenesulfonic acid (0.0154 g,
0.01 mmol) were placed in a twoꢀnecked flask equipped with a
Dean—Stark trap and a reflux condenser. The reaction mixture
was refluxed for 48 h and neutralized with a saturated solution of
NaHCO3, the organic layer was concentrated, and product
12 was recrystallized from MeOH. Yield 0.7 g (24%), m.p.
103—105 °C, [α]D20 –49.5 (c 1, CHC13). Found (%): C, 62.18;
H, 6.07. C34H40O13. Calculated (%): C, 62.19; H, 6.14.
1H NMR, δ: 1.23, 1.28 (both d, 6 H each, 3J = 6.8 Hz); 1.36 (d,
12 H, 3J = 5.8 Hz); 4.85, 4.98 (both d, 2 H each, 3J ≈ 3 Hz); 5.18
(br.m, 4 H); 6.85 (s, 2 H); 7.39 (t, 2 H, 3J = 7.3 Hz, 3J =
7.5 Hz); 7.83 (d, 2 H, 3J = 7.3 Hz); 7.98 (d, 2 H, 3J = 7.5 Hz).
4,6ꢀDi{(4R,5R)ꢀ4,5ꢀbis[hydroxy(diphenyl)methyl]ꢀ1,3ꢀdiꢀ
оxolanꢀ2ꢀyl}dibenzo[b,d]furan (10). Metallic Mg (0.28 g,
12.00 mmol) was placed in an argonꢀfilled twoꢀnecked flask,
THF (10 mL) was added, and a solution of PhBr (1.88 g,
12 mmol) in 60 mL of THF was slowly added. Then a solution of
diester 12 (0.9 g, 1.37 mmol) in 30 mL of THF was added with
stirring and cooling (0 °C). After a temperature of ~20 °C was
reached, the reaction mixture was refluxed for 2 h and neutralꢀ
ized with a saturated solution of NH4Cl. The organic layer was
separated, concentrated, and recrystallized from MeOH. Yield
(9 : 1)
4
5
6
The same
1 (5)
90
100
90
0
0
0
«»
«»
2 (3) + Bu4NBr (3)
3 (5)
7
«»
4 (5)
90
0
8
9
«»
«»
«»
«»
«»
5 (5) + imidazole (10)
60
75
75
0
20 (S)
25 (S)
0
0
0
6 (1)
7 (2)
8 (5)
9 (5)
10 (5)
11 (5)
6 (1)
7 (2)
10
11
12
13
14
15
16
90 (50c)
90 (40c)
90
«»
«»
95
20
30
0
Toluene
The same
52 (S)
74 (S)
a The yield and enantiomeric purity were determined by GLC
on a chiral column calibrated preliminarily against the starting
compound and the racemic product.
b The product configuration is given in parentheses.
c For the reaction carried out at –10 °C.
compounds 4—6 (runs 7—9) and also by cationic comꢀ
plex 7 (runs 10). The process is catalyzed equally effiꢀ
ciently by diol 8, its derivatives 9 and 10, and by quaterꢀ
nary ammonium salt 11, which are classical catalysts of
asymmetric phase transfer catalysis.
Although the catalysts used were chiral enantiomeric
compounds, asymmetric induction was observed only with
complexes 6 and 7. The quaternary ammonium salt of
cinchonidine 11, which efficiently catalyzes the asymꢀ
metric formation of the C—C bond under phase transfer
conditions, did not show stereodifferentiation either.9—11
The asymmetric induction observed in the reaction
carried out in the toluene—water system (see Table 1,
runs 9 and 10) was lower than that in toluene (runs 15
and 16), although the yield was substantially higher under
the phase transfer conditions.
20
0.19 g (14%), dec.p. 232 °C, [α]D +159.3 (c 0.5, CHC13).
Found (%): C, 80.71; H, 5.42. C70H56O9. Calculated (%):
C, 80.75; H, 5.42. 1H NMR, δ: 2.41, 3.54 (both s, 2 H each);
3
3
5.35 (d, 2 H, J = 4.4 Hz); 5.54 (d, 2 H, J = 4.0 Hz); 6.14 (s,
2 H); 7.07—7.39 (m, 32 H); 7.44 (t, 4 H, 3J = 7.5 Hz); 7.61 (m,
8 H); 7.82 (d, 2 H, J = 7.5 Hz). 13C NMR, δ: 79.27 (2 CH);
3
79.65 (2 CH); 81.22 (2 CH); 82.02 (2 CH); 102.47 (2 CH);
121.58 (2 C); 122.05 (2 CH); 123.25 (2 CH); 124.79 (2 C);
126.90 (2 C); 127.14 (2 CH); 127.17 (2 CH); 127.38 (t); 127.90
(2 C); 128.17 (2 CH); 128.22 (2 CH); 128.42 (4 CH); 128.50
(4 CH); 144.16 (2 C); 144.52 (2 C); 145.36 (2 C); 145.40 (2 C);
154.18 (2 C).
Preparation of Oꢀacetylmandelonitrile (general procedure).
Water (0.5 mL) was added to finely ground KCN (0.2 g,
3.1 mmol), the mixture was stirred until a homogeneous suspenꢀ
sion formed, and 4.5 mL of toluene and the catalyst were added.
Then PhCHO (0.1 mL, 0.1044 g, 0.984 mmol) and Ac2O
(0.2 mL, 0.217 g, 2.13 mmol) were successively introduced with
stirring. The reaction mixture was stirred for 2.5 h and filtered
through a silica gel layer, the product being washed out with an
AcOEt—hexane mixture (1 : 5).
We hope that optimization of the reation conditions
and catalyst structures would allow one to attain high
asymmetric induction and high yields in the synthesis of
Oꢀacetyl derivatives of cyanohydrins with asymmetric
phase transfer catalysis.
Experimental
The reactant addition and the experimental procedure for
the reaction in toluene are similar to those described above for
the toluene—water system except that a suspension of finely
ground KCN in toluene was used.
Commercial chemicals and catalyst 11 (Aldrich) and 4,6ꢀdiꢀ
formyldibenzo[b,d]furan (Acros) were used. GLC analysis