The Journal of Organic Chemistry
ARTICLE
and the residue was dissolved in dichloromethane. The mixture was
washed with 5% aqueous sodium bicarbonate and brine, filtered, con-
centrated under reduced pressure, and chromatographed on silica gel
using chloroform as eluent. Enantiomers of the resulting 4-aryl-DHPB 9
were separated by HPLC with a Chiralcel OD-H column.
140.7, 140.3, 138.4, 129.4, 125.7, 123.5, 122.3, 121.7, 121.6, 108.3, 55.6,
41.3, 27.5, 21.3. IR (thin film): 2922, 1623, 1471, 1185, 743 cmꢀ1
.
HRMS for C18H18N2S + H+: calcd 295.1269, found 295.0149 [M + 1].
Enantiomers were separated by HPLC with a Chiralcel OD-H column (10%
i-PrOH in hexanes, flow rate 1 mL/min): tR = 10.97 min, tR = 13.67 min.
4-Mesityl-3,4-dihydro-2H-benzo[4,5]thiazolo[3,2-a]pyrimidine (9f).
Following general procedure A, 2-aminobenzothiazole (1.0 mmol, 150
mg), paraformaldehyde (1.0 mmol, 30 mg), 2,4,6-trimethylstyrene
(1.0 mmol, 146 mg), and trifluoroacetic acid (1.0 mmol, 114 mg) in
1 mL of acetonitrile gave 4-mesityl-3,4-dihydro-2H-benzo[4,5]thiazolo-
[3,2-a]pyrimidine (9f) in 45.0% yield (138.5 mg). 1H NMR (600 MHz,
CDCl3): δ 7.27ꢀ7.25 (m, 1H), 6.93ꢀ6.89 (m, 3H), 6.72 (s, 1H),
6.16ꢀ6.15 (m, 1H), 5.39 (t, 1H, J = 6.6 Hz), 3.57ꢀ3.53 (m, 2H), 2.47
(s, 3H), 2.25ꢀ2.17 (m, 4H), 2.05ꢀ1.98 (m, 4H). 13C NMR (150 MHz,
CDCl3): δ 159.3, 140.1, 137.0, 135.5, 134.9, 132.8, 132.0, 130.1, 125.6,
123.8, 121.9, 121.6, 109.1, 53.8, 43.7, 26.4, 20.6, 20.5, 19.6. IR (thin film):
2930, 2372, 2320, 1620, 1471, 742 cmꢀ1. HRMS for C19H20N2S + H+:
calcd 309.1425, found 309.0308 [M + 1]. Enantiomers were separated by
HPLC with a Chiralcel OD-H column (10% i-PrOH in hexanes, flow rate
0.5 mL/min): tR = 17.87 min, tR = 18.50 min.
6-Methyl-4-phenyl-3,4-dihydro-2H-benzo[4,5]thiazolo[3,2-a]pyri-
midine (9b). Following general procedure A, 4-methyl-2-aminoben-
zothiazole (1.0 mmol, 164 mg), paraformaldehyde (1.0 mmol, 30 mg),
styrene (1.0 mmol, 104 mg), and trifluoroacetic acid (1.0 mmol, 114
mg) in 1 mL of acetonitrile gave 6-methyl-4-phenyl-3,4-dihydro-2H-
benzo[4,5]thiazolo[3,2-a]pyrimidine (9b) in 60.5% yield (169.5 mg).
1H NMR (600 MHz, CDCl3): δ 7.36 (t, 2H, J = 8.0 Hz), 7.29ꢀ7.26 (m,
1H), 7.15 (t, 3H, J = 7 Hz), 6.85 (t, 1H, J = 7.5 Hz), 6.77 (d, 1H, J = 7.5
Hz), 5.87 (br s, 1H), 3.47ꢀ3.43 (m, 1H), 3.11ꢀ3.05 (m, 1H),
2.25ꢀ2.30 (m, 4H), 2.05 (d, 1H, J = 13.0 Hz). 13C NMR (150.9
MHz, CDCl3): δ 157.6, 140.2, 137.5, 137.4, 129.5, 125.6, 122.3, 121.6,
108.2, 55.4, 41.2, 27.6, 20.9. IR (thin film): 2928, 2852, 2372, 2320,
1622, 1165, 755 cmꢀ1. HRMS for C17H16N2S + H+: calcd 281.1112,
found 281.1117 [M + 1]. Enantiomers were separated by HPLC with a
Chiralcel OD-H column (10% i-PrOH in hexanes, flow rate 1 mL/min):
tR = 11.45 min, tR = 13.38 min.
4-Mesityl-6-methyl-3,4-dihydro-2H-benzo[4,5]thiazolo[3,2-a]pyri-
midine (9g). Following general procedure A, 4-methyl-2-aminoben-
zothiazole (1.0 mmol, 150 mg), paraformaldehyde (1.0 mmol, 30 mg),
2,4,6-trimethylstyrene (1.0 mmol, 146 mg), and trifluoroacetic acid
(1.0 mmol, 114 mg) in 1 mL of acetonitrile gave 4-mesityl-6-methyl-3,
4-dihydro-2H-benzo[4,5]thiazolo[3,2-a]pyrimidine (9g) in 62.0% yield
(200 mg). 1H NMR (600 MHz, CDCl3): δ 7.11 (d, 1H, J = 7.8 Hz), 6.89
(s, 1H), 6.83 (t, 1H, J = 7.8 Hz), 6.76ꢀ6.75 (m, 2H), 5.83 (br s, 1H),
3.55ꢀ3.51 (m, 1H), 3.26 (dt, 1H, J = 11.4, 3.0 Hz), 2.83 (s, 3H), 3.24
(s, 3H), 2.15 (m, 4H), 2.10 (s, 3H), 1.98ꢀ1.95 (m, 1H). 13C NMR
(150 MHz, CDCl3): δ 159.0, 139.5, 137.2, 136.6, 136.1, 134.0, 132.3,
130.6, 130.3, 123.0, 121.8, 120.0, 119.8, 56.1, 42.5, 27.0, 20.5, 20.1, 20.0,
19.0. IR (thin film): 3060, 2960, 2850, 1471, 758 cmꢀ1. HRMS for
C20H22N2S + H+: calcd 323.1582, found 323.0483 [M + 1]. Enantio-
mers were separated by HPLC with a Chiralcel OD-H column (10%
i-PrOH in hexanes, flow rate 1 mL/min): tR = 7.69, tR = 10.38 min.
General Procedure B: Kinetic Resolution of 1-Phenylethanol.
To a mixture of 1-phenylethanol (0.030 mL, 0.25 mmol), diisopropylethy-
lamine (24 mg, 0.75 equiv) and catalyst 8 or 9 (2.5 μmol, 1 mol %) in
CH2Cl2 (1.0 mL) was added isobutyric anhydride (0.031 mL, 0.75 equiv) at
room temperature. The resulting mixture was stirred at this temperature.
After production of the corresponding ester was checked by TLC, water was
added. The mixture was extracted with ether, dried over MgSO4, concen-
trated, and chromatographed on silica gel to separate the remaining alcohol
from the resulting ester. The resulting ester was saponified by using 2 M
aqueous KOH and neutralized by addition of 1 M aqueous HCl to yield the
corresponding alcohol. The enantiomeric excess of these alcohols
thus obtained was independently determined by chiral HPLC analysis
(Chiralcel OD-H column). The selectivity value S was calculated using the
equation S = ln((1 ꢀ CHPLC)(1 ꢀ eeA))/ln((1 ꢀ CHPLC)(1 + eeA)).
General Procedure C: Asymmetric Rearrangement of
Azlactone Carbonates or Acetates 10, Benzofuran Deriva-
tive 12, and Indol Derivative 14. A solution of the substrate
carbonate or acetate (0.1 mmol, 0.2 M solution in CH2Cl2) under argon
was cooled to the required temperature, and the chiral catalyst (0.05
mmol, 0.5 mL, 0.01 M solution in CH2Cl2, 5 mol %) was added. After
the specified time, aqueous 0.1 M HCl (5 mL) was added and the
aqueous phase was extracted with Et2O (three times), dried (MgSO4),
and concentrated in vacuo. The product was then purified by
column chromatography. The spectroscopic data (1H and 13C NMR
and IR) of the resulting rearrangement products 11a,12 11b,12 11c,12
11d,22a 11e,12 11f,12 and 11j12 were in good agreement with those
reported. The absolute stereochemistry of the products 11a,12 11b,12
11c,12 11f,12 11j,12 13,27 and 1522a was determined by comparison of
4-(p-tolyl)-3,4-dihydro-2H-benzo[4,5]thiazolo[3,2-a]pyrimidine (9c).
Following general procedure A, 2-aminobenzothiazole (1.0 mmol, 150
mg), paraformaldehyde (1.0 mmol, 30 mg), 4-methylstyrene (1 mmol,
118.0 mg), and trifluoroacetic acid (1.0 mmol, 114 mg) in 1 mL of
acetonitrile gave 4-(p-tolyl)-3,4-dihydro-2H-benzo[4,5]thiazolo[3,2-
1
a]pyrimidine (9c) in 55.5% yield (155.5 mg). H NMR (600 MHz,
CDCl3): δ 7.29 (d, 1H, J = 6.6 Hz), 7.15 (d, 2H, J = 8.4 Hz), 7.10 (d, 2H,
J = 8.4 Hz), 7.00 (t, 1H, J = 7.2 Hz), 6.93 (t, 1H, J = 7.8 Hz), 6.47 (d, 1H,
J = 7.8 Hz), 5.17 (d, 1H, J = 5.4 Hz), 3.52ꢀ3.49 (m, 1H), 3.31ꢀ3.26 (m,
1H), 2.32 (s, 3H), 2.32ꢀ2.22 (m, 1H), 1.99ꢀ1.97 (m, 1H). 13C NMR
(125 MHz, CDCl3): δ 157.5, 140.2, 137.6, 137.4, 129.5, 125.6, 122.3,
121.6, 121.6, 108.2, 55.42, 41.3, 27.6, 20.9. IR (thin film): 2924, 1625,
1587, 1471, 1192, 742 cmꢀ1. HRMS for C17H16N2S + H+: calcd
281.1112, found 281.1117 [M + 1]. Enantiomers were separated by
HPLC with a Chiralcel OD-H column (10% i-PrOH in hexanes, flow rate
1 mL/min): tR = 11.10 min, tR = 15.66 min.
6-Methyl-4-(o-tolyl)-3,4-dihydro-2H-benzo[4,5]thiazolo[3,2-a]pyri-
midine (9d). Following general procedure A, 4-methyl-2-aminoben-
zothiazole (1.0 mmol, 164 mg), paraformaldehyde (1.0 mmol, 30 mg),
2-methylstyrene (1.0 mmol, 118 mg), and trifluoroacetic acid (1.0
mmol, 114 mg) in 1 mL of acetonitrile gave 6-methyl-4-(o-tolyl)-3,
4-dihydro-2H-benzo[4,5]thiazolo[3,2-a]pyrimidine (9d) in 62.0% yield
(182.6 mg). 1H NMR (600 MHz, CDCl3): δ 7.23ꢀ7.12 (m, 4H), 7.03
(d, 1H, J = 7.8 Hz), 6.83 (t, 1H, J = 7.8 Hz), 6.75 (d, 1H, J = 7.8 Hz), 5.92
(d, 1H, J = 6 Hz), 3.47ꢀ3.44 (m, 1H), 3.16ꢀ3.10 (m, 1H), 2.21 (s, 3H),
2.20ꢀ2.18 (m, 1H), 1.98ꢀ1.65 (m, 1H). 13C NMR (150 MHz, CDCl3):
δ 157.4, 140.0, 138.5, 132.3, 131.3, 130.3, 127.6, 126.6, 126.2, 121.7,
119.9, 119.3, 55.1, 40.9, 25.1, 19.4, 18.6. IR (thin film): 2921, 2854, 2320,
1621, 724 cmꢀ1. HRMS for C18H18N2S + H+: calcd 295.1269, found
295.0318 [M + 1]. Enantiomers were separated by HPLC with a
Chiralcel OD-H column (10% i-PrOH in hexanes, flow rate 1 mL/min):
tR = 9.46 min, tR = 13.13 min.
4-(3,5-Dimethylphenyl)-3,4-dihydro-2H-benzo[4,5]thiazolo[3,2-a]-
pyrimidine (9e). Following general procedure A, 2-aminobenzothiazole
(1.0 mmol, 150 mg), paraformaldehyde (1.0 mmol, 30 mg), 3,5-
dimethylstyrene (1.0 mmol, 132 mg), and trifluoroacetic acid (1.0
mmol, 114 mg) in 1 mL of acetonitrile gave 4-(3,5-dimethylphenyl)-
3,4-dihydro-2H-benzo[4,5]thiazolo[3,2-a]pyrimidine (9e) in 43.5%
1
yield (127.0 mg). H NMR (600 MHz, CDCl3): δ 7.29 (d, 1H, J =
7.2 Hz), 7.02 (t, 1H, J = 6.6 Hz), 6.95 (d, 1H, J = 6.6 Hz), 6.91 (s, 1H),
6.81 (s, 1H), 6.50 (d, 1H, J = 8.4 Hz), 5.14 (br d, 1H, J = 5.4 Hz),
3.52ꢀ3.49 (m, 1H), 3.35ꢀ3.29 (m, 1H), 2.28 (s, 6H), 2.24ꢀ2.20
(m, 1H), 1.98ꢀ1.96 (m, 1H). 13C NMR (150 MHz, CDCl3): δ 157.7,
6683
dx.doi.org/10.1021/jo200984n |J. Org. Chem. 2011, 76, 6678–6685