Asymmetric Synthesis of Aryl Benzyl Sulfoxides by Vanadium-Catalysed Oxidation
FULL PAPER
SCH
1
6
2
), 2.40 (s, 3 H, Ar-CH
42.03, 139.93, 130.77, 129.96, 129.72, 128.85, 128.58, 124.86,
4.08, 21.86 ppm. M.p. 165.3–165.8 °C. HPLC: t (R) = 44.4 min,
(S) = 51.9 min (Chiracel OD-H; flow rate = 1.0 mLmin ; hex-
3
) ppm. 13C NMR (75 MHz): δ =
63.80 ppm. M.p. 166.6–167.6 °C. HPLC: t
r r
(R) = 44.4 min, t (S)
–
1
= 50.1 min (Chiracel OD-H; flow rate = 0.5 mLmin ; hexane/2-
2
0
[21] 20
r
propanol 94:6; 10 °C). [α]
D 3 D
= –65 (c = 0.2, CHCl ) {ref. [α] =
–
1
t
r
–80 (c = 1.6, CHCl ) for (S) Ͼ99% ee}.
3
20
ane/2-propanol 98:2; 20 °C). [α]
D
= –235.2 (c = 0.7, acetone)
D
= –179.1 (c = 1.3, acetone) for (S) 94%ee}.
(
S)-(–)-Benzyl Phenyl Sulfoxide (2h):[17d] The crude product con-
[
20]
20
{
ref. [α]
tained a mixture of sulfoxide and sulfone (70:30). Purification by
(S)-(–)-4-Chlorobenzyl 4Ј-Tolyl Sulfoxide (2c): The crude product
chromatography afforded the product as a white solid (110 mg,
contained a mixture of sulfoxide and sulfone (53:47). Purification
by chromatography afforded the product as a white solid (124 mg,
1
5
1%, 91% ee). H NMR (300 MHz): δ = 7.58–7.21 (m, 6 H, Ar-
H), 7.01–6.91 (m, 2 H, Ar-H), 4.15–3.95 (ABq, J = 12.6 Hz, 2 H,
4
8
8%, 98% ee). IR (KBr): ν˜ = 2962, 2345, 1596, 1147, 1038,
13
SCH
1
1
2
) ppm. C NMR (75 MHz): δ = 142.86, 131.16, 130.35,
29.10, 128.84, 128.44, 128.24, 124.42, 63.57 ppm. M.p. 137.6–
38.9 °C. HPLC: t (R) = 28.0 min, t (S) = 34.6 min (Chiracel OD-
–1 1
02 cm . H NMR (300 MHz): δ = 7.28–7.20 (m, 6 H, Ar-H), 6.91
), 2.40 (s, 3 H, Ar-
) ppm. 13C NMR (75 MHz): δ = 142.22, 139.52, 134.72,
(d, J = 7.6 Hz, 2 H, Ar-H), 3.98 (s, 2 H, SCH
2
r
r
CH
3
–1
H; flow rate = 1.0 mLmin ; hexane/2-propanol 98:2; 20 °C).
1
32.06, 130.08, 128.97, 128.02, 124.79, 62.87, 21.87 ppm.
13ClOS (264.77): calcd. C 63.51, H 4.95, Cl, 13.39, S 12.11;
found C 63.66, H 4.99, Cl 13.15, S 12.18. M.p. 164.2–166.0 °C.
HPLC: t (R) = 34.5 min, t (S) = 40.9 min (Chiracel OD-H; flow
rate = 0.5 mLmin ; hexane/2-propanol 93:7; 10 °C). [α]
20
[17d]
20
[α]
D
= –135.9 (c = 0.49, acetone) {ref.
D
[α] = –169.8 (c = 1.0,
14
C H
acetone) for (S) 79% ee}.
(
S)-(–)-Benzyl tert-Butyl Sulfoxide (2i):[22] The crude product con-
r
r
–1
20
tained a mixture of sulfoxide and sulfone (95:5). Purification by
chromatography afforded the product as a white solid with a low
D
= –140
(c = 0.5, CHCl
3
).
1
melting point (83 mg, 42%, 56% ee). H NMR (300 MHz): δ =
(S)-(–)-4-Methylbenzyl 4Ј-Tolyl Sulfoxide (2d): The crude product
7
.41–7.25 (m, 5 H, Ar-H), 3.85–3.60 (ABq, J = 12.8 Hz, 2 H,
contained a mixture of sulfoxide and sulfone (66:34). Purification
by chromatography afforded the product as a white solid (110 mg,
13
SCH
1
7
2
), 1.33 (s, 9 H, C–CH
34.08, 132.08, 130.92, 130.06, 55.77, 55.03, 25.13 ppm. M.p. 71.9–
3.3 °C. HPLC: t (R) = 18.5 min, t (S) = 23.4 min (Chiracel OD-
3
) ppm. C NMR (75 MHz): δ =
1
45%, Ͼ99% ee). H NMR (300 MHz): δ = 7.32–7.17 (m, 4 H, Ar-
r
r
H), 7.04 (d, J = 7.0 Hz, 2 H, Ar-H), 6.85 (d, J = 7.2 Hz, 2 H, Ar-
H), 4.07–3.88 (ABq, J = 12.5 Hz, 2 H, SCH ), 2.40 (s, 3 H, Ar-
CH
) ppm. 13C NMR (75 MHz): δ = 141.93, 140.13, 138.43,
30.66, 129.95, 129.58, 126.62, 124.89, 63.91, 21.86, 21.61 ppm.
16OS (244.35): calcd. C 73.73, H 6.55, S 13.12; found C 73.62,
H 6.55, S 13.39. M.p. 140.2–140.9 °C. HPLC: t (R) = 75.6 min, t
–1
H; flow rate = 1.0 mLmin ; hexane/2-propanol 96:4; 10 °C).
[α] = –128 (c = 0.6, CHCl ) {ref. [α] = –220 (c = 1.7, CHCl )
D 3 D 3
2
20
[20]
20
3
for (S) 94% ee}.
1
(S)-(–)-Benzyl Methyl Sulfoxide (2j):[21] The crude product con-
tained a mixture of sulfoxide and sulfone (83:17). Purification by
chromatography afforded the product as a clear oil (105 mg, 76%,
14
C H
r
r
–1
(
2
S) = 83.0 min (Chiracel OD-H; flow rate = 1.0 mLmin ; hexane/
-propanol 98:2; 0 °C). [α]2
0
= –43 (c = 0.5, CHCl
).
1
10% ee). H NMR (300 MHz): δ = 7.43–7.21 (m, 5 H, Ar-H), 4.10–
D
3
3
.90 (ABq, J = 12.8 Hz, 2 H, SCH
2
), 2.46 (s, 9 H, S–CH
C NMR (75 MHz): δ = 130.43, 130.23, 129.39, 128.85, 60.64,
7.65 ppm. HPLC: t (R) = 51.3 min, t (S) = 58.3 min (Chiracel
3
) ppm.
(
R)-(–)-2-Methoxybenzyl 4Ј-Tolyl Sulfoxide (3e): The crude product
1
3
contained a mixture of sulfoxide and sulfone (69:31). Purification
by chromatography afforded the product as a clear oil (130 mg,
5
3
r
r
–
1
OD-H; flow rate = 1.0 mLmin ; hexane/2-propanol 96:4; 0 °C).
1
0%, Ͼ99% ee). H NMR (300 MHz): δ = 7.34–7.18 (m, 5 H, Ar-
2
0
[20]
α]
D 3
[ = 5 (c = 0.5, CHCl ) {ref. = +19.5 (c = 4.6, EtOH) for (S)
H), 6.97–6.91 (m, 1 H, Ar-H), 6.90–6.77 (m, 2 H, Ar-H), 4.14–3.93
ABq, J = 12.7 Hz, 2 H, SCH ), 3.73 (s, 3 H, Ar-OCH ), 2.40 (s, 3
H, Ar-CH
) ppm. 13C NMR (75 MHz): δ = 158.03, 141.67, 140.96,
32.55, 130.18, 129.71, 124.85, 120.79, 118.64, 110.65, 59.37, 55.68,
1.82 ppm. C14 S (260.35): calcd. C 69.20, H 6.19, S 12.32;
19% ee}.
(
2
3
3
Kinetic Resolution. General Procedure: Vanadyl acetylacetonate
(2.6 mg, 0.01 mmol) and the ligand (S)-4a (7.1 mg, 0.015 mmol)
in dichloromethane were stirred in a 25 mL round-bottomed flask
(1 mL) for 5 min. Racemic sulfoxide 2 (1.0 mmol) in dichlorometh-
ane (1 mL) was then added and the reaction mixture was stirred
for a further 5 min. Hydrogen peroxide (30% w/w, 0.8 mmol) was
added portionwise over 70 min. The reaction mixture was then
stirred for a further 30 min. The reaction was quenched by the ad-
dition of water (5 mL). The layers were separated and the aqueous
layer was washed with dichloromethane (3 mL). The combined or-
ganic layers were washed with brine (5 mL), dried and concentrated
under reduced pressure. The ratio of sulfoxide/sulfone in the crude
1
2
16 2
H O
found C 68.90, H 6.15, S 12.35. HPLC: t
=
propanol 90:10; 10 °C). [α]
r
(R) = 79.0 min, t
116.0 min (Chiracel OD-H; flow rate = 0.5 mLmin ; hexane/2-
r
(S)
–1
2
0
D
3
= +30 (c = 1.1, CHCl ).
(S)-(–)-4-Methoxybenzyl 4Ј-Tolyl Sulfoxide (2f): The crude product
contained a mixture of sulfoxide and sulfone (62:38). Purification
by chromatography afforded the product as a white solid (135 mg,
5
H), 6.93–6.90 (m, 1 H, Ar-H), 6.88–6.77 (m, 2 H, Ar-H), 4.29–3.97
(
H, Ar-CH
1
1
2%, Ͼ99% ee). H NMR (300 MHz): δ = 7.37–7.17 (m, 5 H, Ar-
ABq, J = 12.7 Hz, 2 H, SCH
2
), 3.69 (s, 3 H, Ar-OCH
) ppm. 1 C NMR (75 MHz): δ = 159.97, 141.93, 140.00,
3
3
), 2.39 (s, 3
1
3
product was determined by H NMR spectroscopy. The product
was purified by flash chromatography on silica gel.
31.97, 129.95, 124.91, 121.57, 114.27, 63.38, 55.66, 21.86 ppm.
14 16 2
C H O
S (260.35): calcd. 69.20, H 6.19, S 12.32; found C 69.47,
(
S)-(–)-4-Fluorobenzyl 4Ј-Tolyl Sulfoxide (2a): The crude product
H 6.09, S 12.30 ppm. M.p. 124–125.1 °C. HPLC: t
r
(R) = 33.4 min,
contained a mixture of sulfoxide and sulfone (30:70). Purification
by chromatography afforded the product as a white solid (52 mg,
2
–
1
r
t (S) = 41.0 min (Chiracel OD-H; flow rate = 0.5 mLmin ; hex-
2
0
ane/2-propanol 90:10; 10 °C). [α]
D
3
= –87 (c = 0.2, CHCl ).
1%, 98% ee). Analytical data as previously reported.
(
S)-(–)-Benzyl 4Ј-Bromophenyl Sulfoxide (2g):[22] The crude product
contained a mixture of sulfoxide and sulfone (45:55). Purification
(
S)- (–)-Benzyl 4Ј-Tolyl Sulfoxide (2b): The crude product con-
tained a mixture of sulfoxide and sulfone (36:64). Purification by
chromatography afforded the product as a white solid (54 mg, 23%,
9
by chromatography afforded the product as a white solid (121 mg,
1
4
1%, Ͼ99% ee). H NMR (300 MHz): δ = 7.61–7.51 (m, 2 H, Ar-
2% ee). Analytical data as previously reported.
H), 7.35–7.15 (m, 5 H, Ar-H), 7.01–6.94 (m, 2 H, Ar-H), 4.22–3.95
ABq, J = 12.6 Hz, 2 H, SCH
) ppm. 13C NMR (75 MHz): δ =
42.19, 132.42, 130.78, 128.97, 128.85, 128.73, 126.44, 126.04,
(
1
2
(S)-(–)-4-Chlorobenzyl 4Ј-Tolyl Sulfoxide (2c): The crude product
contained a mixture of sulfoxide and sulfone (20:80). Purification
Eur. J. Org. Chem. 2006, 4500–4509
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4507