578
J. Liu et al. / Tetrahedron: Asymmetry 22 (2011) 575–579
saturated NaHCO3 and brine and dried over anhydrous Na2SO4, fil-
tered, and evaporated under reduced pressure. The crude product
was purified by flash column chromatography with petroleum
ether to afford compound 5c; colorless oil, yield: 96%. The synthe-
sis of 4c from 5c is similar to that of 4a; colorless oil, yield: 36%;
4.2.3. (R)-(2-(tert-Butylsulfinyl) phenyl) (2,4,6–trimethylbenz-
yl) sulfane 4f
White solid, yield: 33% (from 7); ½a D20
¼ þ206:6 (c 1.0, CH2Cl2);
ꢂ
1H NMR (CDCl3, 300 MHz) d = 7.87–7.84 (m, 1H), 7.48–7.42 (m,
3H), 6.86 (s, 2H), 4.13 (q, J = 10.7 Hz, 2H), 2.37 (s, 6H), 2.26 (s,
3H), 1.22 (s, 9H). 13C NMR (CDCl3, 75 MHz): d = 142.4, 137.6,
137.4, 137.3, 131.5, 131.2, 129.1, 128.9, 127.4, 127.0, 58.4, 35.3,
23.2, 20.9, 19.5. HRMS (ESI): [M+Na]+, calcd for C20H26NaOS2:
369.1317, found: 369.1324.
½
a 2D0
ꢂ
¼ þ191:4 (c 1.1, CH2Cl2); 1H NMR (CDCl3, 300 MHz):
d = 7.90–7.87 (m, 1H), 7.56–7.51 (m, 2H), 7.44–7.38 (m, 1H), 1.28
(s, 9H), 1.17 (s, 9H). 13C NMR (CDCl3, 75 MHz): d = 147.0, 138.3,
132.7, 130.2, 128.9, 127.3, 58.5, 48.7, 30.9, 23.4. HRMS (ESI):
[M+Na]+, calcd for C14H22NaOS2: 293.1004, found: 293.1006.
4.2.4. (R)-Benzyl (2-(tert-butylsulfinyl)-3-methoxyphenyl)
4.2. Typical procedure for synthesis of ligands 4d–k
sulfane 4g
Colorless oil, yield: 25% (from 7); ½a D20
¼ þ70:2 (c 1.5, CH2Cl2);
ꢂ
Under an argon atmosphere, to a solution of substituted bromo-
benzene (2.2 mmol) in THF (10 mL) was added dropwise n-BuLi
(1.0 mL, 2.5 mmol) at ꢀ78 °C and the mixture was stirred for
30 min. A solution of (R)-tert-butyl tert-butanethiosulfinate 6
(0.39 g, 2.0 mmol) in THF (2 mL) was then added dropwise to the
reaction mixture at ꢀ78 °C. The temperature was allowed to slowly
warm to room temperature. The reaction mixture was stirred
overnight at room temperature, and then evaporated under
reduced pressure. Saturated NH4Cl (10 mL) was added, and
extracted with CH2Cl2 (10 mL ꢁ 3). The combined organic layers
were washed with brine and dried over anhydrous Na2SO4, filtered,
and evaporated under reduced pressure. The residue was purified
by column chromatography with petroleum ether/EtOAc (4:1,
V/V) to afford 7.13
Under an argon atmosphere, to a solution of 7 (1.0 mmol) in
THF (5 mL) was added dropwise either n-BuLi (0.5 mL, 1.25 mmol,
2.5 M solution in hexane) or LDA (1.1 mmol) at ꢀ78 °C, and the
mixture was stirred for 1 h at ꢀ50 °C. Under an argon flow, ele-
mental sulfur (S8) (64 mg, 2.0 mmol) was added to the reaction
mixture at ꢀ78 °C, and the temperature was allowed to slowly
warm to room temperature. The reaction mixture was stirred over-
night at room temperature, and then evaporated under reduced
pressure. Saturated NH4Cl (10 mL) was added, and extracted with
CH2Cl2 (10 mL ꢁ 3). The combined organic layers were washed
with brine and dried over anhydrous Na2SO4, filtered, and evapo-
rated under reduced pressure to give crude 8. The residue was used
without any further purification. Crude 8 was added to a solution
of NaOH (100 mg, 2.5 mmol) in EtOH (5 mL), stirred for 20 min,
after which ArCH2Br (1.0 mmol) was added, and stirred overnight
at room temperature. The reaction mixture was evaporated under
reduced pressure. The residue was purified by column chromatog-
raphy with petroleum ether/EtOAc (4:1, V/V) to afford the desired
ligand.
1H NMR (CDCl3, 300 MHz): d = 7.37–7.35 (m, 2H), 7.32–7.22 (m,
4H), 6.91 (d, J = 8.03 Hz, 1H), 6.74 (d, J = 8.28 Hz, 1H), 4.13 (s,
2H), 3.82 (s, 3H), 1.36 (s, 9H). 13C NMR (CDCl3, 75 MHz):
d = 159.9, 136.3, 131.9, 129.0, 128.5, 127.3, 125.5, 120.6, 109.4,
60.1, 55.7, 38.6, 31.6, 24.7. HRMS (ESI): [M+Na]+, calcd for
C18H22NaO2S2: 357.0953, found: 357.0952.
4.2.5. (R)-Benzyl (2-(tert-butylsulfinyl)-6-methoxyphenyl)
sulfane 4h
White solid, yield: 28% (from 7); ½a D20
ꢂ
¼ ꢀ35:4 (c 0.8, CH2Cl2); 1H
NMR (CDCl3, 300 MHz): d = 7.49–7.39 (m, 2H), 7.23–7.18 (m, 5H),
6.97–6.94 (m, 1H), 4.00 (s, 2H), 3.90 (s, 3H), 1.18 (s, 9H). 13C NMR
(CDCl3, 75 MHz): d = 159.8, 147.0, 137.1, 129.6, 128.9, 128.3,
127.3, 122.5, 119.3, 112.8, 58.6, 56.1, 39.7, 23.6. HRMS (ESI):
[M+Na]+, calcd for C18H22NaO2S2: 357.0953, found: 357.0962.
4.2.6. (R)-Benzyl (2-(tert-butylsulfinyl)-6-isopropoxyphenyl)
sulfane 4i
Colorless oil, yield: 18% (from 7); ½a D20
¼ ꢀ66:1 (c 0.7, CH2Cl2);
ꢂ
1H NMR (CDCl3, 300 MHz): d = 7.46–7.35 (m, 2H), 7.28–7.18 (m,
5H), 6.99–6.97(m, 1H), 4.73–4.65 (m, 1H), 4.09–4.00 (m, 2H),
1.48–1.44 (m, 6H), 1.18 (s, 9H). 13C NMR (CDCl3, 75 MHz):
d = 158.0, 146.7, 137.0, 129.2, 128.9, 128.3, 127.1, 123.4, 118.9,
115.0, 58.3, 48.5, 39.3, 29.6, 23.4. HRMS (ESI): [M+Na]+, calcd for
C20H26NaO2S2: 385.1266, found: 385.1266.
4.2.7. (R)-Benzyl (2-(tert-butylsulfinyl)-6-(methoxymethoxy)
phenyl) sulfane 4j
Colorless oil, yield: 52% (from 7); ½a D20
¼ ꢀ17:1 (c 0.7, CH2Cl2);
ꢂ
1H NMR (CDCl3, 300 MHz): d = 7.48–7.42 (m, 2H), 7.25–7.16 (m,
6H), 5.22 (s, 2H), 4.02 (s, 2H), 3.54 (s, 3H), 1.19 (s, 9H). 13C NMR
(CDCl3, 75 MHz): d = 158.1, 147.0, 137.0, 129.7, 128.9, 128.4,
127.3, 123.5, 120.7, 116.9, 95.4, 58.6, 56.5, 39.9, 23.5. HRMS (ESI):
[M+Na]+, calcd for C19H24NaO3S2: 387.1059, found: 387.1068.
4.2.1. (R)-Benzyl (2-(tert-butylsulfinyl) phenyl) sulfane 4d
White solid, yield: 34% (from 7); ½a D20
¼ þ207:3 (c 0.5, CH2Cl2);
ꢂ
1H NMR (CDCl3, 300 MHz): d = 7.83–7.80 (m, 1H), 7.41–7.32 (m,
3H), 7.27–7.23 (m, 5H), 4.10 (s, 2H), 1.22 (s, 9H). 13C NMR (CDCl3,
75 MHz): d = 142.1, 136.5, 136.2, 131.4, 131.1, 128.9, 128.5, 127.4,
127.3, 127.1, 58.4, 40.2, 23.2. HRMS (ESI): [M+Na]+, calcd for
4.2.8. (R)-Benzyl (2-(tert-butylsulfinyl)-3,6-dimethoxyphenyl)
sulfane 4k
Colorless oil, yield: 21% (from 7); ½a D20
¼ ꢀ15:3 (c 0.7, CH2Cl2);
ꢂ
1H NMR (CDCl3, 300 MHz): d = 7.27–7.19 (m, 5H), 6.92 (s, 2H),
4.05 (q, J = 13.7, 2H), 3.83 (s, 3H), 3.80 (s, 3H), 1.32 (s, 9H). 13C
NMR (CDCl3, 75 MHz): d = 154.3, 154.1, 137.1, 132.5, 129.1,
128.3, 127.2, 125.9, 115.6, 114.3, 113.9, 59.7, 56.4, 39.9, 25.2.
HRMS (ESI): [M+Na]+, calcd for C19H24NaO3S2: 387.1059, found:
387.1066.
C17H20NaOS2: 327.0848, found: 327.0853.
4.2.2. (R)-(2-(tert-Butylsulfinyl) phenyl) (naphthalene-1-ylmet-
hyl) sulfane 4e
White solid, yield: 29% (from 7); ½a D20
¼ þ269:3 (c 1.0, CH2Cl2);
ꢂ
1H NMR (CDCl3, 300 MHz): d = 8.14 (d, J = 8.3 Hz, 1H), 7.87 (d,
J = 1.3 Hz, 2H), 7.85 (d, J = 1.9 Hz, 1H), 7.57–7.34 (m, 3H), 7.34–
7.30 (m, 4H), 4.56 (q, J = 12.3 Hz, 2H), 1.21 (s, 9H). 13C NMR (CDCl3,
75 MHz): d = 142.7, 136.6, 133.8, 132.2, 131.7, 131.4, 131.1, 128.7,
128.5, 127.7, 127.5, 127.4, 126.3, 125.8, 125.2, 123.7, 58.4, 38.4,
23.3. HRMS (ESI): [M+Na]+, calcd for C21H22NaOS2: 377.1004,
found: 377.1007.
4.3. Typical procedure for the palladium-catalyzed asymmetric
allylic alkylation
Under an argon atmosphere, to a dried Schlenk flask, ligand 4a
(2.9 mg, 5.0 mol %) and [Pd(g
3-C3H5)Cl]2 (1.4 mg, 2.0 mol %) were