Synthesis of Novel 1,4-Bissulfonamide Ligands for Enantioselective Addition of Diethylzinc
(EI) m/z (%): 142.1 (M+-HCl, 2), 125.1 (7), 110.1 (6),
83.1 (6), 72.0 (100). Anal. calcd for C8H20N2Cl2: C
44.66, H 9.37, N 13.02; found C 44.93, H 9.30, N 13.25.
(1R,2S,4R,5S)-1,4-N,N'-Bismethylsulfonamino-2,5-
dimethylcyclohexane (8) White solid, 71% yield
(0.42 g); [α]2D5 -12.8 (c 0.35, THF), m.p.>210 ℃; 1H
NMR (CDCl3, 300 MHz) δ: 4.31 (s, br, 2H), 3.55 (s,
2H), 2.99 (s, 6H), 2.27—2.29 (m, 2H), 172—1.75 (m,
4H), 1.10 (d, J=6.4 Hz, 6H); 13C NMR (DMSO-d6, 75
MHz) δ: 16.8, 31.3, 33.9, 34.7, 54.0; IR (KBr) ν: 3289,
3252, 2-966, 2905, 1473, 1411, 13+13, 1262, 1160, 1100,
General procedure for synthesis of ligands 5—8
Under nitrogen atmosphere, the salt of
(1R,2S,4R,5S)-4 with hydrochloride (430 mg, 2 mmol)
was dissolved in the saturated solution of KOH, and
then extracted with CH2Cl2 (10 mL×3). The organic
phase was dried over anhydrous Na2SO4 and gave the
solution of diamine (1R,2S,4R,5S)-4 in CH2Cl2. Sul-
fonyl chloride (4 mmol in 20 mL CH2Cl2) was added
slowly to the solution of diamine (1R,2S,4R,5S)-4 and
triethylamine (0.56 mL, 2.7 g, 4 mmol) in 30 mL
CH2Cl2 at 0 ℃. The mixture was stirred at room tem-
perature for 48 h and then HCl (20 mL, 1 mol/L, 20
mmol) was added. The organic phase was dried over
anhydrous Na2SO4 and the solvent was removed via
vacuum. The product was purified by flash chromatog-
raphy.
1
982 cm ; MS (ESI) m/z: 299 (M +1). Anal. calcd for
C10H22N2O4S2: C 40.25, H7.43, N 9.39; found C 40.53,
H 7.56, N 9.51.
Synthesis of ligand 9
Under nitrogen atmosphere, dihydrochloride salt of
(±)-4 (430 mg, 2 mmol) was dissolved with 2 mL satu-
rated solution of KOH, and then extracted with CH2Cl2
(10 mL×3). The organic phase was dried over anhy-
drous Na2SO4 and gave the solution of diamine (±)-4
in CH2Cl2. (1S)-(+)-Camphorsulfonyl chloride (1.0 g, 4
mmol in 20 mL CH2Cl2) was added slowly to the so-
lution of diamine (±)-4 and triethylamine (0.56 mL, 2.7
g, 4 mmol) in 30 mL CH2Cl2 at 0 ℃. The mixture was
stirred at room temperature for 48 h and then HCl (20
mL, 1 mol/L, 20 mmol) was added. The organic phase
was dried over anhydrous Na2SO4 and the solvent was
removed. The product was purified by flash chromatog-
raphy. Two white solid, enantiomerically pure sulfona-
mides 5 and 9 were obtained in the yield of 23% and
47% respectively.
(1R,2S,4R,5S)-2,5-Dimethyl-1,4-N,N'-biscamphor-
sulfonamino-2,5-dimethylcyclohexane (5)
White
solid, 53% yield (0.60 g); [α]2D5 +9.9 (c 0.80, THF);
m.p. 169—171 ℃; 1H NMR (CDCl3, 300 MHz) δ: 5.30
(d, J=7.6 Hz, 2H), 3.60—3.62 (m, 2H), 3.00—3.40 (m,
4H), 1.90—2.44 (m, 12H), 1.70—1.73 (m, 4H),
1.38—1.52 (m, 4H), 1.12 (d, J=7.2 Hz, 6H), 0.92 (s,
6H), 1.05 (s, 6H); 13C NMR (CDCl3, 75 MHz) δ: 17.0,
20.0, 20.3, 27.0, 27.4, 34.1, 34.4, 43.2, 43.3, 49.0, 52.3,
54.1, 59.7, 217.0; IR (KBr) v: 3306, 2958, 1736,+1429,
(1S,2R,4S,5R)-2,5-Dimethyl-1,4-N,N'-biscamphor-
sulfonamino-2,5-dimethylcyclohexane (9) 0.53 g,
-1
1324, 1132, 1049 cm ; MS (ESI) m/z: 571 (M +1).
1
Anal. calcd for C28H46N2O6S2: C 58.92, H 8.12, N 4.91;
found C 58.67, H 8.19, N 4.74.
[α]2D5 +18.3 (c 1.24, THF); m.p. 134—136 ℃; H
NMR (CDCl3, 300 MHz) δ: 5.20 (s, 2H), 3.18—3.21 (m,
2H), 2.90—3.40 (m, 4H), 1.90—2.50 (m, 12H),
1.35—1.70 (m, 8H), 1.16 (d, J=7.0 Hz, 6H), 0.91 (s,
6H), 1.02 (s, 6H); 13C NMR (CDCl3, 75 MHz) δ: 15.9,
20.3, 20.4, 27.0, 27.4, 30.1, 39.1, 42.7, 43.0, 43.2, 49.2,
49.7, 59.6, 217.4; IR (KBr) v: 3293, 2964, 1743, 1535,
(1R,2S,4R,5S)-1,4-N,N-Bis(p-methylphenylsulfon-
amino)-2,5-dimethylcyclohexane (6)
White solid,
92% yield (0.83 g); [α]2D5 -22.7 (c 3.16, THF); m.p.
195—197 ℃ ; 1H NMR (CDCl3, 300 MHz) δ:
7.93—7.96 (d, J=8.3 Hz, 4H), 7.29—7.31 (d, J=8.3
Hz, 4H), 4.85 (s, br, 2H), 3.22—3.28 (m, 2H), 2.43 (s,
6H), 1.74—1.86 (m, 2H), 1.40—1.42 (m, 4H), 0.82 (d,
J=6.7 Hz, 6H); 13C NMR (CDCl3, 75 MHz) δ: 16.5,
21.9, 33.3, 33.8, 53.7, 127.8, 129.1, 138.3, 143.7; IR
(KBr) v: 3362, 3264, 3064, 2964, 1598, 1431, 1345,
-1
1454, 1416, 1392, 1127, 1261, 1095 cm ; MS (ESI)
m/z: 571 (M++1). Anal. calcd for C28H46N2O6S2: C
58.92, H 8.12, N 4.91; found C 58.73, H 8.05, N 4.86.
General procedure for enantioselective addition of
dialkylzinc to aldehydes in the presence of titanium
isopropoxide
-1
1263, 1161, 1093, 1055, 971 cm ; MS (ESI) m/z: 451
(M++1). Anal. calcd for C22H30N2O4S2: C 58.64, H
Diethylzinc (1.2 mmol, 0.88 mmol/mL in n-hexane)
was dropped slowly to the toluene solution of the chiral
sulfonamide 6 (0.1 mmol) under the nitrogen. The solu-
tion was stirred for 20 min at room temperature. After
the flask was cooled to -78 ℃, a solution of titanium
tetraisopropoxide (1.2 mmol, 1.0 mol/L in hexane) was
added slowly by a syringe. After 30 min, the aldehyde
(1.0 mmol) was dropwise added and the resulting mix-
ture was kept under smooth stirring for 24 h at -25 ℃,
after which the reaction was quenched by the addition
of 2 mol/L HCl and then extracted with ethyl acetate.
The organic phase was dried over Na2SO4 and removed
the solvent. After purification by preparative silica gel
6.71, N 6.22; found C 58.90, H 6.44, N 6.54.
(1R,2S,4R,5S)-1,4-N,N'-Bisphenylsulfonamino-2,5-
dimethylcyclohexane (7) White solid, 95% yield
(0.80 g); [α]2D5 -17.8 (c 3.14, THF). m.p.>210 ℃; 1H
NMR (CDCl3, 300 MHz) δ: 7.84—7.87 (m, 4H),
7.53—7.58 (m, 6H), 4.54 (s, 2H), 3.23—3.28 (m, 2H),
1.45—1.87 (m, 6H), 0.81—0.83 (d, J=7.0 Hz, 6H); 13
C
NMR (DMSO-d6, 75 MHz) δ: 16.4, 31.3, 33.7, 54.1,
127.3, 129.8, 132.9, 142.4; IR (KBr) v: 3358, 3260,
3061, 3-059, 2963, 2888, 1452, 13+30, 1262, 1162, 1093,
1
949 cm ; MS (ESI) m/z: 423 (M +1). Anal. calcd for
C20H26N2O4S2: C 56.85, H 6.20, N 6.63; found C 56.70,
H 6.27, N 6.32.
Chin. J. Chem. 2011, 29, 1697— 1702
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1701