Copper(I)-Assisted Synthesis of Se-N Heterocycles
J . Org. Chem., Vol. 65, No. 24, 2000 8157
N-(2-Br om o-r,r-d im et h ylb en zen em et h yl)a cet a m id e
(19). To a stirred solution of 13 (976 mg, 4.56 mmol) in CH2Cl2
(20 mL) was added first Et3N (555 mg, 765 µL, 5.5 mmol) and
then acetyl chloride (429 mg, 390 µL, 5.5 mmol) at 15 °C. The
reaction mixture was stirred for 14 h at room temperature,
diluted with CH2Cl2 (25 mL), washed first with water (25 mL),
saturated aqueous NaHCO3 solution (25 mL), and brine (25
mL). The organic phase was dried (MgSO4) and concentrated
to provide 19 as a white powder (1.04 g, 89%): 1H NMR (200
MHz) δ 1.77 (s, 6H), 1.93 (s, 3H), 6.0 (br s, 1H), 7.04 (m, 1H),
7.27 (m, 1H), 7.51 (m, 2H); 13C NMR (50 MHz) δ 23.4, 27.9,
55.8, 120.6, 127.5, 128.3, 135.4, 143.4, 168.9; MS (CI) m/z 258/
256 (100, MH+), 176 (100); HRMS calcd for C11H1579BrNO
(MH+) 256.0337, found m/z 256.0333; calcd for C11H1581BrNO
258.0317, found m/z 258.0307.
Chromatography of the crude product on silica gel afforded
21 [Rf (hexane/EtOAc ) 4:1) ) 0.5] and 3,3-dimethylindolin
22 [Rf (hexane/EtOAc ) 4:1) ) 0.45] in colorless crystals.
21: 115 mg, 51% (Table 4, entry 1) and 154 mg, 68% (Table
4, entry 2), mp: 86 °C (hexane). 1H NMR (200 MHz) δ 1.26 (s,
6H), 3.22 (br s, 2H), 3.45 (br s, 1H), 6.95-7.15 (m, 3H), 7.40
(m, 1H); 13C NMR (50 MHz) δ 28.5, 33.0, 61.4, 125.5, 125.9,
126.8, 127.9, 129.9, 143.2; 77Se-NMR (95 MHz) δ 693; MS (EI)
m/z 227 (64, M+), 183 (100). Anal. Calcd for C10H13NSe: C,
53.10; H, 5.79; N, 6.19. Found: C, 53.24; H, 5.77; N, 6.17.
3,3-Dim eth ylin d olin (22): mp 33 °C (lit.42 mp 32-33.5 °C);
1H NMR (200 MHz) δ 1.34 (s, 6H), 3.35 (s, 2H), 3.70 (br s,
1H), 6.70 (m, 1H), 6.81 (m, 1H), 7.10 (m, 2H); 13C NMR (50
MHz) δ 27.3, 41.5, 61.5, 109.6, 118.8, 122.0, 127.3, 138.5, 150.4;
MS (EI) m/z 147 (20, M+).
3,3-Dim eth yl-1,2-ben zisoth ia zolin e (20). To a solution of
KSCN (116 mg, 1.2 mmol) and 13 (214 mg, 1 mmol) in a
mixture of THF (1 mL) and DMF (4 mL) was added at room
temperature CuI (190 mg, 1 mmol) in one portion, followed
by Et3N (303 mg, 420 µL, 3 mmol) 2 min later. After being
heated for 2 h at 80 °C, the reaction mixture was treated
according to general procedure 1 to afford 20 as a slightly
yellow oil (36 mg, 22%): 1H NMR (200 MHz) δ 1.48 (s, 6H),
7.07 (m, 2H), 7.17 (m, 2H); 13C NMR (50 MHz) δ 25.9, 69.6,
120.1, 122.2, 125.4, 127.9, 144.3, 146.4; MS (EI) m/z 165 (20,
M+), 150 (100), 109 (20); HRMS (EI) calcd for C9H11NS (M+)
165.0612, found m/z 165.0629.
3,3-Dim eth yl-1,2-ben zisoselen azolin e (15). Gen er al P r o-
ced u r e 1. To a solution of KSeCN (173 mg, 1.2 mmol) and 13
(214 mg, 1 mmol) in DMF (5 mL) was added at room
temperature CuI (38 mg, 0.2 mmol for entries 2-3 in Table 1;
190 mg, 1 mmol, entries 4-5 in Table 1) in one portion, for
entry 5 followed by Et3N (303 mg, 420 µL, 3 mmol) 2 min later.
The reaction mixture was stirred for 24 h at room temperature.
To determine the conversion of 13, 150 µL of the reaction
mixture was diluted in 500 µL of acetone-d6, and the signals
1
of the dimethyl group in the H NMR integrated: Amine 13:
1.6-1.8 ppm, 15: 1.5 ppm. To isolate 15, the mixture was
diluted with water (80 mL) and EtOAc (80 mL). After filtration
through a pad of Celite, the organic phase was washed with
water (5 × 50 mL) and brine (50 mL), dried (MgSO4), and
concentrated. Flash chromatography (cyclohexane/EtOAc )
9:1, Rf ) 0.35) provided 15 in pale yellow crystals (32 mg, 15%,
Table 1, entry 2; 85 mg, 40%, entry 4; 174 mg, 82%, entry 5):
mp 38.5-39.5 °C; 1H NMR (200 MHz) δ 1.50 (s, 6H), 4.10 (br
s, 1H), 7.02-7.34 (m, 4H); 13C NMR (50 MHz) δ 26.6, 70.8,
123.6, 124.4, 126.2, 128.1, 139.5, 149.6; 77Se-NMR (47.7 MHz)
δ 756.4. MS (EI) m/z 213 (30, M+), 198 (100). Anal. Calcd for
C9H11NSe: C, 50.95; H, 5.22; N, 6.60. Found C, 51.01; H, 5.17;
N, 6.61.
Gen er a l P r oced u r e 2. To a solution of KSeCN (173 mg,
1.2 mmol) and 13 (214 mg, 1 mmol) in DMF (5 mL) was added
at room temperature the metal salt in one portion, followed
by Et3N (303 mg, 420 µL, 3 mmol) 2 min later. After 24 and
40 h, respectively, a sample of 15 µL of the reaction mixture
was diluted in 500 µL of acetone-d6, and the signals of the
dimethyl group in the 1H NMR for 13 (1.6-1.8 ppm) and 15
(1.5 ppm) were integrated.
3,4-Dih yd r o-4,4-d im et h yl-2H -1,2-b en zot h ia zin e (23).
Compound 23 was prepared starting from a solution of 14 (228
mg, 1 mmol) and KSCN (194 mg, 2 mmol) in THF/DMF (5
mL, 1:4). CuI (190 mg, 1 mmol) was added in one portion,
followed 2 min later by Et3N (303 mg, 417 µL, 3 mmol).
Treatment of the reaction mixture, after heating for 2 h at 80
°C according to the procedure described for 21, afforded 23 as
1
colorless crystals (54 mg, 30%): mp 92 °C (hexane); H NMR
(200 MHz) δ 1.28 (s, 6H), 3.17 (br s, 2H), 6.86 (m, 1H), 7.04
(m, 2H), 7.36 (m, 1H); 13C NMR (50 MHz) δ 29.1, 31.5, 59.9,
121.8, 125.2, 126.6, 127.8, 134.7, 140.5; MS (EI) m/z 179 (80,
M+), 149 (100), 134 (80); HRMS (EI) calcd for C10H13NS (M+)
179.0769, found m/z 179.0782.
2-(1′-Meth yl-1′-eth yla m in o)p h en ylselen ocya n a te (16d ).
To a stirred solution of 15 (106 mg, 0.5 mmol) in acetonitrile
(5 mL) was added NaCN (75 mg, 1.5 mmol). The homogeneous
reaction mixture was stirred for 1 h at room temperature and
was then diluted with water (20 mL) and EtOAc (20 mL). The
organic phase was washed with water (5 × 20 mL), dried
(Na2SO4), and concentrated to afford 16d as a colorless oil
(purity according to the 1H and 13C NMR ∼90%, the product
contains ∼10% 1543): 1H NMR (200 MHz) δ 1.52 (s, 6H), 1.85
(br s, 2H), 7.10-7.28 (m, 3H), 7.91 (m, 1H), trace of 15 (about
10%) at 1.48 (s); 13C NMR (50 MHz) δ 30.5, 54.4, 112.1, 125.9,
126.2, 127.6, 128.6, 131.4, 146.2, trace of 15 at 26 ppm. MS
(EI) m/z 240 (22, M+), 225 (50), 198 (100), 183 (50).
Gen er a l P r oced u r e 3. The reactions were performed as
described in the General Procedure for Table 1, except for the
variation of the solvent (5 mL) as given in each entry of Table
3. The product distribution was determined by 1H NMR
analysis on the crude reaction mixture obtained after the
treatment as described before (see Table 1).
3,4-Dih yd r o-4,4-d im eth yl-2H-1,2-ben zoselen a zin e (21).
Gen er a l P r oced u r e 4. To a stirred solution of 14 (228 mg, 1
mmol) and KSeCN (144-720 mg, 1-5 mmol, see Table 4) in
DMF (entries 1-4, 5 mL), respectively, acetonitrile (entry 5),
or THF (entry 6) was added CuI (190 mg, 1 mmol) in one
portion, followed 2 min later by Et3N (303 mg, 417 µL, 3 mmol).
The reaction mixture was stirred at room temperature for 24
h and was then diluted with EtOAc (25 mL) and a solution of
NaCN (147 mg, 3 mmol) in water (25 mL). After the mixture
was stirred for 5 min, the organic phase was separated, and
the aqueous phase was extracted again with EtOAc (25 mL).
The combined organic phases were washed with water (5 ×
40 mL) and brine (40 mL), dried (Na2SO4), and concentrated.
To determine the conversion of 14 and the ratio of 21 to 22,
20 mg of the crude product were dissolved in CDCl3 and the
signals of the dimethyl group in the 1H NMR integrated at
1.26 ppm (21), 1.29 ppm (22), and 1.45 ppm (14).
Ack n ow led gm en t. The authors are indebted to and
thank Dr. J ean Chaudie`re, who initiated the project,
and Dr. Marc Moutet for their fruitful collaboration and
many stimulating discussions. We also gratefully ac-
knowledge J ean-Claude Michel and J acques Baudry for
their excellent technical support.
J O000418F
(42) Abramovitch, R. A.; Brown, R. A. Org. Prep. Proced. 1969, 1,
39.
(43) Attempts to purify the crude product by chromatography over
silica gel or alumina resulted in decomposition.