A. Kos´ciołowicz, M. D. Rozwadowska / Tetrahedron: Asymmetry 17 (2006) 1444–1448
1447
1), 213 (74), 165 (100), 150 (9), 137 (5). Anal. Calcd for
C13H19NO3S: (269.1) C, 57.97; H, 7.12; N, 5.20; S, 11.88.
Found: C, 57.80; H, 7.18; N, 5.33; S, 12.16.
reaction mixture was heated at 110 ꢁC for 24 h under the
argon atmosphere. During that time an additional amount
of K2CO3 (66 mg, 0.48 mmol) and 2-bromo-1,1-diethoxy-
etane (0.7 mmol, 0.1 ml) were added. After completion of
the reaction, the mixture was poured into ice and after
reaching rt. the mixture was extracted three times with
ethyl ether. The organic extracts were dried and the solvent
was evaporated to afford crude 11, which after purification
by silica gel column chromatography yielded oily amine 11.
Yield: 62%; [a]D = ꢀ29.6 (c 0.8, CHCl3); IR (KBr), m
(cmꢀ1): 2974, 1517, 1262, 1139. 1H NMR (CDCl3): d
1.15–1.21 (m, 6H, 2 · CH2CH3), 1.36 (d, J = 6.59 Hz,
3H, CH3CH), 1.60 (br s, 1H, disappears on treatment with
D2O, NH), 2.53–2.67 (dABq, J = ca. 5, 12.1 Hz, 2H,
CH2NH ), 3.44–3.76 (m, 5H, 2 · CH3CH2, CH(OEt)2),
3.87 (s, 3H, OCH3), 3.89 (s, 3H, OCH3), 4.58 (t,
J = 5.76 Hz, 1H, CHCH3), 6.82 (m, 2H, ArH), 6.90 (s,
1H, ArH). 13C NMR (CDCl3): d 15.33, 24.22, 49.78,
55.84, 57.99, 62.01, 62.52, 101.91, 109.34, 110.86, 118.85,
137.48, 147.92, 149.03. EI MS m/z (%): 297 (M+, 2.9),
281 (6), 236 (2), 206 (11), 180 (21), 165 (100), 150 (5), 103
(32). Anal. Calcd for C16H27NO4: (297.2) C, 64.60; H,
9.16; N, 4.71. Found: C, 64.60; H, 9.32; N, 4.75.
4.1.2. (RS,S)-(ꢀ)-N-[1-(3,4-Dimethoxyphenylethyl)]-2-meth-
ylpropanesulfinamide 9. A solution of aldimine 8 (26 mg,
0.096 mmol) in anhydrous THF (2.5 ml) was cooled to
ꢀ27 ꢁC under an argon atmosphere. Methylmagnesium
bromide (3 M in diethyl ether) (0.32 ml, 0.96 mmol) was
then added and the reaction mixture stirred at ꢀ27 ꢁC for
4 h, after which 20% NH4Cl (2 ml) was added and after
reaching rt the phases were separated. The aqueous phase
was extracted three times with ethyl ether. The combined
organic extracts were dried over anhydrous Na2SO4 and
the solvent evaporated. The crude reaction product was
purified by silica gel column chromatography (CH2Cl2/
MeOH 0.3%). Yield: 89%, dr 97:3 (after crystallization
from i-Pr2O/hexane dr 99:1); mp 111–113 ꢁC;
[a]D = ꢀ100.0 (c 1.105, CHCl3). IR (KBr), m (cmꢀ1):
1
3209, 2974, 1520, 1266, 1063. H NMR (CDCl3): d 1.21
(s, 9H, C(CH3)3), 1.52 (d, J = 6.59 Hz, 3H, CH3CH),
3.35 (d, 1H, disappears on treatment with D2O, NH),
3.87 (s, 6H, 2 · OCH3), 4.52 (m, 1H, CHCH3; after treat-
ment with D2O: q, J = 6.59 Hz), 6.81–6.90 (m, 3H, ArH).
13C NMR (CDCl3): d 22.64, 25.18, 54.30, 55.44, 55.81,
55.88, 109.99, 110.91, 119.04, 135.83, 148.26, 148.86. EI
MS m/z (%): 285 (M+, 0.6), 229 (6), 213 (2), 179 (1), 165
(100), 150 (5). Anal. Calcd for C14H23NSO3: (285.1) C,
58.92; H, 8.13; N, 4.91; S, 11.21. Found: C, 58.94; H,
8.15; N, 4.88; S, 10.95.
4.1.5. (S)-(ꢀ)-Salsolidine 1. A solution of aminoacetal
(40 mg, 0.13 mmol) and 5 M aqueous HCl (1.3 ml) were
stirred overnight at rt. The mixture was basified with 20%
aqueous NaOH and extracted three times with dichloro-
methane. The combined organic extracts were dried over
anhydrous Na2SO4 and evaporated to give a solid
(27 mg), which was dissolved in dichloromethane (6 ml)
and cooled to 0 ꢁC. To this solution NaBH4 (60 mg,
1,6 mmol) was added along with the slow introduction of
trifluoroacetic acid (0.93 ml, 12.2 mmol) in dichlorometh-
ane (2 ml). The reaction was stirred at rt for 24 h, then
the solvent was removed under reduced pressure. The
resultant precipitate was dissolved in water (4 ml), basified
with 20% aqueous NaOH and extracted three times with
dichloromethane. The organic extract was dried over anhy-
drous Na2SO4 and evaporated yielding levorotatory (ꢀ)-
salsolidine 1 as an oil. Yield: 55%, ee 98% (HPLC). This
was dissolved in methanolic HCl to give crystalline hydro-
4.1.3. (S)-(ꢀ)-1-(3,4-Dimethoxyphenyl)ethylamine hydro-
chloride 10ÆHCl. Sulfinamide 9 (90 mg, 0.32 mmol ) was
dissolved in EtOH (2 ml) and the solution cooled to 0 ꢁC.
Concentrated HCl (94 ll) was added and the reaction mix-
ture stirred at room temperature for ca. 2 h. Saturated
K2CO3 (7 ml) was added, and the reaction mixture
extracted twice with ethyl acetate. The combined organic
extracts were dried over anhydrous Na2SO4 and solvents
evaporated. To the crude reaction product, a 3% solution
of HCl in MeOH (2 ml) was added and after 1 h the sol-
vents were evaporated. The residue was washed a few times
with ethyl acetate and dried in air to provide a white solid
(65 mg). Yield: 92%; mp 201–203 ꢁC (lit.21 214–215 ꢁC for
racemic 10ÆHCl), [a]D = ꢀ6.9 (c 0.7, MeOH). IR (KBr), m
chloride salt, 1ÆHCl; mp 230–232 ꢁC, [a]D = ꢀ25.9 (c 0.32,
22
EtOH), lit.22 mp 235–236 ꢁC, ½aꢁD ¼ ꢀ18 (c 1, EtOH),
23
1
½aꢁD ¼ ꢀ26:6 (c 4, EtOH). H NMR (DMSO-d6): d 1.55
(d, J = 6.59 Hz, 3H, CHCH3), 2.90 (m, 2H, CH2CH2NH),
3.23 (m, 1H, CHHNH), 3.38 (m, 1H, CHHNH), 3.71 (s,
6H, 2 · OCH3), 4.43 (q, J = 6.59 Hz, 1H, CHCH3), 6.76
(s, 1H, ArH), 6.80 (s, 1H, ArH).
1
(cmꢀ1): 3000, 2696, 1514, 1262. H NMR (DMSO-d6): d
1.49 (d, J = 6.8 Hz, 3H, CHCH3), 3.75 (s, 3H, OCH3),
3.78 (s, 3H, OCH3), 4.31 (q, J = 6.8 Hz 1H, CHCH3),
6.98–6.99 (m, 2H, ArH), 7.22 (d, 1H, ArH), 8.44 (s, 1H,
disappears on treatment with D2O, NH). 13C NMR
(DMSO-d6): 20.77, 49.84, 55.58, 55.65, 110.89, 111.58,
119.07, 131.76, 148.69, 148.74. EI MS m/z (%): 181
(M+ꢀHCl, 18), 166 (100), 150 (15), 139 (14), 105 (5). Anal.
Calcd for C10H15NO2ÆHClÆ1/3H2O: (223.5) C, 53.68; H,
7.51; N, 6.26. Found: C, 53.44; H, 7.74; N, 6.17.
Acknowledgements
This work was supported by research Grant from the State
Committee for Scientific Research during 2003–2006 (KBN
Grant No. 4T09A 07824).
4.1.4.
phenyl)ethylamine 11. To
(S)-(ꢀ)-N-(2,2-Diethoxyethyl)-1-(3,4-dimethoxy-
solution of amine 10
a
(100 mg, 0.52 mmol), prepared from the amine hydrochlo-
ride 10ÆHCl by treatment with 20% NaOH, in DMF (3 ml),
anhydrous K2CO3 (66 mg, 0.48 mmol) was added followed
by 2-bromo-1,1-diethoxyethane (0.7 mmol, 0,1 ml). The
References
1. Zhou, P.; Chen, B.-C.; Davis, F. A. Tetrahedron 2004, 60,
8003–8030.