1434
V. D. Sio et al. / Tetrahedron: Asymmetry 21 (2010) 1432–1435
As already found for catalyst 7 (Table 1, entries 4 and 5), the
gel flash chromatography by elution with chloroform (99% yield).
1H NMR d 2.73 (s, 3H), 4.82 (s, 2H), 7.25–7.35 (m, 5H), 7.50–7.67
(m, 3H), 8.28 (d, 1H, J = 7.8 Hz), 8.42 (s, 1H). 13C NMR d 43.0,
64.0, 123.1, 126.2, 126.8, 127.6, 129.1, 130.2, 130.5, 131.8, 137.5,
presence of a secondary amine functionality seemed to be respon-
sible for the failure of the procedure by using ligand 9 as an activa-
tor, since the rapid decomposition of allyl trichlorosilane was again
detected (Table 3, entries 1 and 2). Conversely, the employment of
10 proved to be successful for the occurrence of the process, result-
ing, more importantly, in a notable enhancement of the yields in all
the reported entries. As regards the level of enantioselectivity, the
best results were again given by electron-poor aromatic and het-
ero-aromatic aldehydes (up to 90% ee, entries 4–6), as well as ali-
phatic aldehydes (72% ee, entry 7).
146.6, 159.0. ESI-MS m/z 258 [MH]+. [
a]D = +190.3 (c 1.0, CHCl3).
Ee 99%. Anal. Calcd for C15H15NOS: C, 70.01; H, 5.87; N, 5.44; S,
12.46. Found: C, 70.23; H, 5.62; N, 5.67; S, 12.71.
4.3. One-pot synthesis of (R)-(+)-N-(2-(methylsulfinyl)benzyl)-
(phenyl)methanamine 7
To
(54.0 mg, 0.32 mmol, 99% ee) in MeOH (3.5 mL), benzylamine
(77.0 L, 0.70 mmol) and acetic acid (27.5 L, 0.48 mmol) wer-
a solution of (R)-(+)-2-(methylsulfinyl)benzaldehyde 1
3. Conclusion
l
l
eadded at room temperature. The mixture was stirred for 1 h and
then NaBH3CN (60.3 mg, 0.96 mmol) was added. At the end of
the reaction, it was quenched with saturated aqueous NaHCO3
(3.0 mL), and the mixture was extracted with 10 Â 3 mL of CH2Cl2
and dried over anhydrous Na2SO4. After removing the solvent un-
der reduced pressure, the crude oil was purified by silica gel flash
chromatography by elution with chloroform (97% yield). 1H NMR d
1.70 (br s, 1H), 2.82 (s, 3H), 3.75 (d, 1H, J = 12.7 Hz), 3.76 (s, 2H),
3.96 (d, 1H, J = 12.7 Hz), 7.25–7.35 (m, 6H), 7.43 (dt, 1H,
J = 7.5 Hz, J = 1.1 Hz), 7.51 (t, 1H, J = 7.5 Hz), 8.07 (d, 1H,
J = 7.7 Hz). 13C NMR d 43.2, 49.4, 52.3, 122.7, 126.2, 127.1, 127.5,
127.9, 128.2, 129.6, 130.1, 138.5, 144.9. ESI-MS m/z 260 [MH]+.
In conclusion, easily available chiral 2-methylsulfinyl benzalde-
hyde proved to be a valuable starting material for the synthesis of a
variety of new mono- and polydentate imino- and amino-sulfox-
ides through appropriate elaboration of the aldehyde functionality.
Furthermore, an accurate evaluation of their catalytic properties, as
activators, allowed the achievement of new catalytic procedures
for the asymmetric allylation of aldehydes with allyl trichlorosi-
lane proceeding in moderate yields and moderate to high ees.
4. Experimental
4.1. General
[a]D = +29.6 (c 0.2, CHCl3). Ee 99%. Anal. Calcd for C15H17NOS: C,
69.46; H, 6.61; N, 5.40; S, 12.36. Found: C, 69.73; H, 6.42; N,
5.65; S, 12.10.
All reactions were performed in oven-dried (140 °C) or flame-
dried glassware under an atmosphere of dry nitrogen. All the sol-
vents for the reactions were of reagent grade and were dried and
distilled immediately before use (dichloromethane from calcium
hydride, diethyl ether from lithium aluminium hydride). Column
chromatographic purification of products was carried out using Sil-
ica Gel 60 (70–230 mesh, Merck). The reagents (Aldrich and Fluka)
were used without further purification. The NMR spectra were re-
corded on a Bruker DRX 400 (400 MHz, 1H; 100 MHz, 13C). Spectra
were referenced to residual chloroform (7.26 ppm, 1H, 77.23 ppm,
13C). Chemical shifts are reported in parts per million (ppm), mul-
tiplicities are indicated by s (singlet), d (doublet), t (triplet), q
(quartet), quint (quintept), m (multiplet) and br (broad). Coupling
constants, J, are reported in Hz. Yields are given for isolated prod-
ucts showing one spot on a TLC plate and no impurities detectable
in the NMR spectrum. Mass spectrometry analysis was carried out
using an electrospray spectrometer Waters 4 micro quadrupole.
HPLC analyses were performed with Waters Associates equipment
(Waters 2487 Dual l absorbance Detector) and using a CHIRALPAK
AD, CHIRALCEL OD, CHIRALCEL OB, CHIRALCEL AS, CHIRALCEL OD-
H, CHIRALCEL AS-H, CHIRALCEL AD-H column with hexane/isopro-
pyl alcohol mixtures and flow rates as indicated. Chiral GC (Supelco
b-DEX 120) analyses were performed with FOCUS GC/FID Thermo
Scientific. The HPLC and GC methods were calibrated with the cor-
responding racemic mixtures. Optical rotations were measured
with a JASCO DIP-1000 polarimeter. Elemental analyses were per-
formed with FLASHEA 1112 series-Thermo Scientific for CHNS-O.
4.4. Synthesis of (R)-(+)-N-(2-(methylsulfinyl)benzyl)-N-methyl-
(phenyl)methanamine 8
To a solution of (R)-(+)-N-(2-(methylsulfinyl)benzyl)(phenyl)-
methanamine 7 (55.0 mg, 0.21 mmol, 99% ee) in CH3CN (4.5 mL),
formaldehyde (156.4 lL, 2.10 mmol) and acetic acid (27.0 lL,
0.32 mmol) were added at room temperature. The mixture was
stirred for 1 h and then NaBH3CN (52.8 mg, 0.84 mmol) was added.
At the end of the reaction, it was quenched with saturated aqueous
NaHCO3 (3.0 mL), and the mixture was extracted with 10 Â 3 mL of
CH2Cl2 and dried over anhydrous Na2SO4. After removing the sol-
vent under reduced pressure, the crude oil was purified by silica
gel flash chromatography by elution with chloroform (99% yield).
1H NMR d 1.92 (s, 3H), 2.76 (s, 3H), 3.20 (d, 1H, J = 12.8 Hz), 3.47
(d, 1H, J = 12.6 Hz), 3.65 (d, 1H, J = 12.6 Hz), 4.03 (d, 1H,
J = 12.8 Hz), 7.23–7.55 (m, 8H), 8.06 (dd, 1H, J = 7.8 Hz, J = 1.2 Hz).
13C NMR d 39.0, 42.8, 58.9, 61.4, 71.2, 122.9, 126.4, 127.2, 127.3,
128.1, 128.4, 128.5, 128.6, 128.7, 129.6, 136.4, 144.8. ESI-MS m/z
274 [MH]+. [
a]D = +55.5 (c 1.0, CHCl3). Ee 99%. Anal. Calcd for
C16H19NOS: C, 70.29; H, 7.00; N, 5.12; S, 11.73. Found: C, 70.58;
H, 7.21; N, 5.01; S, 11.87.
4.5. Synthesisof(R,R)-(+)-N1,N2-bis-(2-(methylsulfinyl)-benzyl)-
ethane-1,2-diamine
4.2. Synthesis of (R)-(+)-N-(2-(methylsulfinyl)benzylidene)-
(phenyl)methanamine 6
To a solution of (R,R)-(+)-N1,N2-bis-(2-(methylsulfinyl)-benzyl-
idene)-ethane-1,2-diamine (116.0 mg, 0.32 mmol) in MeOH
(3.5 mL), NaBH3CN (60.3 mg, 0.96 mmol) was added. At the end
of the reaction, it was quenched with saturated aqueous NaHCO3
(3.0 mL), and the mixture was extracted with 10 Â 3 mL of CH2Cl2
and dried over anhydrous Na2SO4. After removing the solvent un-
der reduced pressure, the crude oil was purified by silica gel flash
chromatography with chloroform. Yield: 87%. 1H NMR d 1.85 (br s,
2H), 2.70 (s, 4H), 2.75 (s, 6H), 3.73 (d, 2H), 3.90 (d, 2H), 7.26 (d, 2H),
7.39 (t, 2H), 7.48 (t, 2H), 8.00 (d, 2H). 13C NMR d 28.6, 42.9, 47.5,
49.6, 122.7, 127.8, 128.1, 129.7, 136.1, 144.5. ESI-MS m/z 365
To
(53.0 mg, 0.32 mmol, 99% ee) in MeOH (3.0 mL), benzylamine
(84.0 L, 0.77 mmol) and acetic acid (27.5 L, 0.48 mmol) were
a solution of (R)-(+)-2-(methylsulfinyl)benzaldehyde 1
l
l
added at room temperature and the mixture was stirred for 1 h.
At the end of the reaction, it was quenched with saturated aqueous
NaHCO3 (3.0 mL), and the mixture was extracted with 10 Â 3 mL of
CH2Cl2 and dried over anhydrous Na2SO4. After removing the sol-
vent under reduced pressure, the crude oil was purified by silica