A. K. Nadipuram, S. M. Kerwin / Tetrahedron 62 (2006) 3798–3808
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159.6, 140.8, 136.7, 118.1, 44.8, 33.4, 29.3, 21.9, 19.4;
HRMS m/z 171.0924 (calculated 171.0922, C11H11N2).
along with 2.5 mg (10% yield) of 22e. Compound 19e: H
NMR (300 MHz, CDCl3) d 7.71 (s, 1H), 7.66 (s, 1H), 7.42
(d, JZ0.9 Hz, 1H), 6.80 (d, JZ0.9 Hz, 1H), 5.83 (ddt, JZ
16.8, 10.5, 6 Hz), 5.09–5.00 (m, 2H), 2.77 (t, JZ7.2 Hz,
2H), 2.41 (q, JZ7.2 Hz, 2H); HRMS (CI) m/z 207.0689
(calculated 207.0689, C11H12N2Cl). Compound 22e: 1H
NMR (300 MHz, CDCl3) d 8.35 (d, JZ2.4 Hz, 1H), 8.27 (d,
JZ2.4 Hz, 1H), 6.81 (s, 1H), 5.93 (m, 1H), 5.19 (dt, JZ
17.4, 1 Hz, 1H), 5.09 (dt, JZ10.5, 1 Hz, 1H), 4.37 (d, JZ
9.9 Hz, 1H), 3.70 (d, JZ9.9 Hz, 1H), 2.6–2.4 (m, 4H);
HRMS (CI) m/z 185.1074 (calculated 185.1079, C12H13N2).
4.4.4. 5-Chloro-8-phenyl-imidazo[1,2-a]pyridine, (19a).
Following the general procedure above with 9a in
chlorobenzene, 13 mg (39% yield) of 19a was obtained as
a yellow oil: 1H NMR (400 MHz, CDCl3) d 7.00 (d, 1H, JZ
7.6 Hz, H6), 7.30 (d, 1H, JZ8 Hz, H7), 7.40–7.44 (m, 1H,
para-H), 7.48–7.52 (m, 2H, meta-H), 7.78 (d, 1H, JZ
1.2 Hz, H2), 7.85 (d, 1H, JZ1.2 Hz, H3), 7.93–7.96 (m, 2H,
ortho-H); 13C NMR (75 MHz, CDCl3) d 112.1 (C2), 112.4
(C6), 123.3 (C7), 125.1 (C8), 128.6 (para-C), 128.7 (ortho-
C), 129.0 (meta-C), 129.2 (C5), 133.9 (C3), 135.9 (ipso-C),
144.8 (C9); HRMS (CI) m/z 229.0530 (calculated 229.0533,
C13H10N2Cl).
4.5. General procedure for thermolysis in DMF
4.5.1. (Z)-1-(2-Chlorovinyl)-2-(3-methoxyprop-1-ynyl)-
1H-imidazole (20d) and 2-[(Z)-2-chloro-3-methoxy-
prop-1-enyl]-1-[(Z)-2-chlorovinyl]-1H-imidazole (21d).
To a solution of 9d (25 mg, 0.155 mmol) in dry, degassed
DMF (5 ml) was added tetramethylammonium chloride
(48 mg, 0.44 mmol) and TFA (32 ml, 0.44 mmol). The
mixture was stirred at 80 8C overnight. Upon disappearance
of 9d (by TLC), the solvent was evaporated and the residue
diluted with CH2Cl2 (5 ml) and washed with satd NaHCO3
solution (2!5 ml) and brine (5 ml). The organic extracts
were combined, dried and the solvent evaporated. The
residue was purified by flash chromatography (0–70%
EtOAc/hexanes) to afford 3 mg (10% yield) of 20d as a
yellow oil and 13 mg (36% yield) of 21d as a yellow oil.
Compound 20d: 1H NMR (400 MHz, CD2Cl2) d 7.87
(d, JZ1.6 Hz, 1H), 7.26 (d, JZ6.8 Hz, 1H), 7.10 (br s, 1H),
6.02 (d, JZ6.2 Hz, 1H), 4.35 (s, 2H), 3.42 (s, 3H); 13C
NMR (100 MHz, CD2Cl2) d 132.1, 130.4, 123.4, 119.7,
108.6, 91.1, 75.3, 60.4, 58.1; HRMS m/z 197.0483
4.4.5. 5-Chloro-7-phenyl-imidazo[1,2-a]pyridine (19b).
Following the general procedure above starting with 9b in
CH2Cl2, 6 mg (18% yield) of 19b was obtained as a tan solid
along with 2 mg (7% yield) of 22b. Compound 19b:
mp 102–103 8C; 1H NMR (400 MHz, CDCl3) d 7.81 (t, JZ1
Hz, 1H), 7.77 (s, 1H), 7.74 (d, JZ1 Hz, 1H), 7.65–7.63 (m,
2H), 7.51–7.47 (m, 2H), 7.44–7.34 (m, 1H), 7.21 (d, JZ
1.2 Hz, 1H); 13C NMR (125 MHz, CDCl3) d 146.5, 138.2,
137.9, 134.4, 129.2, 128.6, 126.8, 126.4, 112.9, 111.9,
111.1; HRMS m/z 229.0532 (calculated 229.0533,
C13H10ClN2). Compound 22b: 1H NMR (400 MHz,
CDCl3) d 8.43 (d, JZ2.8 Hz, 1H), 8.35 (d, JZ2.8 Hz,
1H), 7.87–7.84 (m, 2H), 7.52–7.47 (m, 3H), 7.33 (s, 1H),
4.51 (d, JZ10.8 Hz, 1H), 4.18 (d, JZ10.8 Hz, 1H); HRMS
(CI) m/z 207.0920 (calculated 207.0922, C14H11N2).
4.4.6. 5-Chloro-7-propyl-imidazo[1,2-a]pyridine (19c).
Following the general procedure above starting with 9c in
CH2Cl2, 6 mg (12% yield) of 19c was obtained as a yellow
oil along with 6 mg (14% yield) of 22c. Compound 19c: 1H
NMR (400 MHz, CDCl3) d 7.69 (s, 1H), 7.64 (s, 1H), 7.36
(s, 1H), 6.76 (s, 1H), 2.63 (t, JZ7.6 Hz, 2H), 1.69 (sextet,
JZ6 Hz, 2H), 0.97 (t, JZ6 Hz, 3H); 13C NMR (125 MHz,
CDCl3) d 146.5, 140.5, 133.4, 125.7, 114.0, 113.8, 110.8,
37.3, 23.4, 13.6; HRMS m/z 195.0689 (calculated 195.0689,
C10H12ClN2). Compound 22c: 1H NMR (400 MHz, CDCl3)
d 8.34 (d, JZ3 Hz, 1H), 8.26 (d, JZ3 Hz, 1H), 6.78 (t, JZ
2 Hz, 1H), 4.37 (d, JZ10.8 Hz, 1H), 3.96 (d, JZ10.8 Hz,
1H), 2.55–2.27 (m, 2H), 1.88–1.77 (m, 2H), 1.104 (t, JZ
8 Hz, 3H); HRMS (CI) m/z 173.1083 (calculated 173.1078,
C11H13N2).
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(calculated 197.0482, C9H10ClN2O). Compound 21d: H
NMR (500 MHz, CD2Cl2) d 7.52 (d, JZ1 Hz, 1H), 7.20 (br
s, 1H), 6.98 (d, JZ6 Hz, 1H), 6.63 (t, JZ1.5 Hz, 1H), 6.18
(d, JZ6 Hz, 1H), 4.14 (d, JZ1.5 Hz, 2H), 3.42 (s, 3H); 13C
NMR (125 MHz, CD2Cl2) d 142.4, 136.1, 129.9, 123.9,
119.5, 113.3, 112.3, 76.1, 58.7; HRMS m/z 233.0235
(calculated 233.0242, C9H11Cl2N2O).
4.5.2. (Z)-1-(2-Chlorovinyl)-2-(2-phenylethynyl)-1H-imi-
dazole (20b). Following the general procedure above with
9b and employing 1.2 equiv of conc HCl in place of
Me4NCl and TFA, 18 mg (69% yield) of 20b was obtained
as a yellow oil: 1H NMR (300 MHz, CD2Cl2) d 7.92 (d, JZ
1.5 Hz, 1H), 7.58–7.55 (m, 2H), 7.41–7.32 (m, 4H), 7.19 (d,
JZ1.5 Hz, 1H), 6.00 (d, JZ6.6 Hz, 1H); 13C NMR
(75 MHz, CDCl3) d 132.6, 131.8, 130.03, 129.5, 128.5,
123.0, 121.2, 119.2, 107.9, 94.5, 77.7; HRMS (CI) m/z
229.0533 (calculated 229.0531, C10H12ClN2)
4.4.7. 5-Chloro-7-(methoxymethyl)-imidazo[1,2-a]-
pyridine (19d). Following the general procedure above
with 9d in chlorobenzene, 7 mg (15% yield) of 19d was
obtained as yellow oil along with 8.5 mg (15% yield) of
16d. Compound 19d: 1H NMR (500 MHz, CDCl3) d 7.73 (s,
1H, H3), 7.68 (s, 1H, H2), 7.49 (s, 1H, H8), 6.92 (d, JZ
4.5.3. (Z)-1-(2-Chlorovinyl)-2-(pent-1-ynyl)-1H-imidazole
(20c). Following the general procedure above with 9b and
employing 1.2 equiv of conc HCl in place of Me4NCl and
TFA, 20 mg (56% yield) of 20c was obtained as a yellow oil
1 Hz, 1H, H6), 4.46 (s, 2H, CH2O), 3.40 (s, 3H, CH3O); 13
C
NMR (125 MHz, CDCl3) d 146.1 (C9), 136.0 (C7), 134.1
(C3), 126.3 (C5), 113.9 (C8), 111.6 (C6), 111.4 (C2),
73.1 (CH2O), 53.4 (CH3O); HRMS (CI) m/z 197.0489
(calculated 197.0482, C9H9ClN2O).
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along with 5 mg (14% yield) of 19c. Compound 20c: H
NMR (300 MHz, CD2Cl2) d 7.84 (d, JZ1.5 Hz, 1H), 7.25 (d,
JZ6.6 Hz, 1H), 7.03 (d, JZ1.2 Hz, 1H), 5.96 (d, JZ6 Hz,
1H), 2.45, (t, JZ6.9 Hz, 2H), 1.67 (quintet, JZ7.5 Hz, 2H),
1.04 (t, JZ7.2 Hz, 3H); 13C NMR (75 MHz, CD2Cl2) d
133.5, 129.9, 123.5, 118.9, 107.4, 96.6, 70.1, 22.1, 21.6,
4.4.8. 7-(But-3-enyl)-5-chloro-imidazo[1,2-a]pyridine
(19e). Following the general procedure above with 9e in
CH2Cl2, 2 mg (8% yield) of 19e was obtained as a yellow oil