Rearrangements of 7-Substituted Norcamphors
J . Org. Chem., Vol. 61, No. 16, 1996 5579
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mp 129-130 °C; H NMR δ 7.21 (br, 1H), 4.30 (s, 1H), 3.69
C7H10NOCl: C, 52.65; H, 6.32; N, 8.78. Found: C, 52.51; H,
6.30; N, 8.71.
(br, 1H), 2.70 (ddd, J ) 18.0, 4.8, 2.1 Hz, 1H), 2.59 (m, 1H),
2.30-1.71 (br, 5H); 13C NMR δ 170.1, 63.1, 58.0, 40.7, 40.3,
32.0, 26.4. Anal. Calcd for C7H10NOCl: C, 52.65; H, 6.32; N,
8.78. Found: C, 52.27; H, 6.29; N, 8.64.
a n ti-8-Br om o-2-aza-3-oxobicyclo[3.2.1]octan e (33). From
ketone 31 (200 mg, 1.05 mmol) in acetic acid (15 mL) after 1.5
h there was obtained 196 mg (92%) of crude lactam 33.
Chromatography, Rf ) 0.63 (THF), gave 151 mg (70%) of white
solid lactam, mp 109-110 °C (ether/hexanes); 1H NMR δ 7.50
(br, 1H), 4.30 (s, 1H), 3.70 (t, J ) 3.0 Hz, 1H), 2.70 (m, 1H),
2.60 (br, 1H), 2.30-1.82 (br, 5H); 13C NMR δ 169.6, 52.8, 50.4,
49.0, 44.0, 39.2, 32.6. Anal. Calcd for C7H10NOBr: C, 41.18;
H, 4.94; N, 6.87. Found: C, 40.84, H, 5.08; N, 6.78.
syn -8-Br om o-3-a za -2-oxobicyclo[3.2.1]octa n e (20) a n d
syn -8-Br om o-2-a za -3-oxobicyclo[3.2.1]octa n e (21). From
ketone 19 (100 mg, 0.53 mmol) in chloroform (15 mL) after 4
h there was obtained according to the general procedure 65
mg (60%) of a mixture of lactams. Chromatography, Rf ) 0.28
(EtOAc), gave 37 mg (34%). Recrystallization (EtOAc) gave
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lactam 20, mp 133-134 °C; H NMR δ 5.99 (br, 1H), 4.22 (t,
J ) 4.2 Hz, 1H), 3.76 (dd, J ) 11.4, 3.0 Hz, 1H), 3.14 (d, J )
11.4 Hz, 1H), 2.90, (t, J ) 3.9 Hz, 1H), 2.53 (br, 1H), 2.13-
1.85 (br, 4H); 13C NMR δ 173.7, 49.6, 48.6, 46.7, 36.9, 29.2,
26.5. Anal. Calcd for C7H10NOBr: C, 41.18; H, 4.94; N, 6.87.
Found: C, 41.19, H, 5.03; N, 6.90.
a n ti-8-(p-Tolu en esu lfon yloxy)-2-aza-3-oxobicyclo[3.2.1]-
octa n e (36). From ketone 34 (15 mg, 0.53 mmol) in acetic
acid (5 mL) after 1 h there was obtained 11 mg (70%) of crude
lactam 36. Chromatography, Rf ) 0.28 (EtOAc), gave 6 mg
(38%) of pure 24 as a white solid, mp 178-179 °C; 1H NMR δ
7.81 (br, J ) 8.1 Hz, 2H), 7.38 (d, J ) 8.1 Hz, 2 H), 6.90 (br,
1H), 4.76 (s, 1H), 3.67 (br, 1H), 2.61 (ddd, J ) 18, 2.1, 1.8 Hz,
1H), 2.49 (br, 4H), 2.30 (dd, J ) 18, 1.8 Hz, 1H), 2.07-1.6 (m,
4H); 13C NMR δ 169.5, 144.8, 132.9, 129.6, 127.2, 83.8, 55.0,
39.2, 36.7, 31.9, 26.5, 21.2. Anal. Calcd for C14H17NO4S: C,
56.93; H, 5.80; N, 4.74. Found: C, 57.14; H, 5.72; N, 4.69.
syn -8-(p-Tolu en esu lfon yloxy)-3-a za -2-oxobicyclo[3.2.1]-
octa n e (23) a n d syn -8-(p-Tolu en esu lfon yloxy)-2-a za -3-
oxobicyclo[3.2.1]octa n e (24). From ketone 22 (150 mg, 0.54
mmol) in chloroform (20 mL) after 2 h according to the general
procedure there was obtained 130 mg (82%) of a mixture of
lactams. Chromatography, Rf ) 0.18 (EtOAc), gave 82 mg
(52%) of a white solid mixture. Recrystallization gave lactam
23, mp 169-169 °C; 1H NMR δ 7.81 (d, J ) 8.1 Hz, 2H), 7.35
(d, J ) 8.1 Hz, 2H), 5.60 (br, 1H), 4.85 (dd, J ) 5.1, 4.8 Hz,
1H), 3.65 (dd, J ) 11.4, 3.0 Hz, 1H), 3.06 (d, J ) 11.1 Hz, 1H),
2.57 (t, J ) 4.8, 5.1 Hz, 2H), 2.47 (s, 3H), 2.05-1.60 (br, 4H);
13C NMR δ 172.2, 144.8, 132.8, 129.5, 127.7, 79.3, 45.3, 44.5,
33.6, 25.6, 24.7, 21.2. Anal. Calcd for C14H17NO4S: C, 56.93;
H, 5.80; N, 4.74. Found: C, 57.14; H, 5.72; N, 4.69.
exo-6-Br om o-a n ti-8-(m et h oxyca r b on yl)-2-a za -3-oxo-
bicyclo[3.2.1]octa n e (39). From ketone 37 (200 mg, 0.81
mmol) in acetic acid (15 mL) after 2 h there was obtained 167
mg (79%) of crude lactam 39. Recrystallization (EtOAc) gave
a n ti-8-(Met h oxyca r b on yl)-3-a za -2-oxob icyclo[3.2.1]-
oct a n e (26) a n d a n ti-8-(Met h oxyca r b on yl)-2-a za -3-
oxobicyclo[3.2.1]octa n e (27). From ketone 25 (100 mg, 0.6
mmol) in chloroform (15 mL) after 2 h according to the general
procedure there was obtained 43 mg (39%) of a mixture of
crude lactams 26 and 27. Chromatography, Rf ) 0.13 (ether),
afforded 34 mg (31%) of a 66:34 mixture of the lactams, mp
102-112 °C. Data for lactam 26: 1H NMR δ 6.61 (br, 1H),
3.67 (s, 3H), 3.39 (dd, J ) 11.4, 3.9 Hz, 1H), 3.05 (dt, 11.1, 2.0
Hz, 1H), 2.93 (br, 1H), 2.90 (s, 1H), 2.81 (m, 1H), 2.30-1.56
(m, 4H); 13C NMR δ 175.2, 171.7, 51.6, 49.0, 47.8, 45.3, 35.0,
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148 mg (64%) of white solid, mp 164.5-165.5 °C; H NMR δ
6.93 (br, 1H), 4.24 (dd, J ) 7.8 Hz, 1H), 4.14 (br, 1H), 3.77 (s,
3H), 3.29 (m, 1H), 2.97 (s, 1H), 2.88-2.60 (m, 3H), 2.50 (dd, J
) 18, 1.8 Hz, 1H); 13C NMR δ 170.3, 169.8, 53.6, 51.6, 50.3,
48.0, 47.3, 47.2, 40.4. Anal. Calcd for C9H12NO3Br: C, 41.24;
H, 4.61; N, 5.34. Found: C, 41.17, H, 4.69; N, 5.33.
Gen er a l P r oced u r e for th e Sch m id t Rea ction s. To a
cold (0 °C) chloroform solution of sodium azide (2 equiv) in
concentrated sulfuric acid (1 mL/mmol) was added dropwise
a solution of the ketone in chloroform.. After the mixture was
stirred at 25 °C for the indicated time (Table 2), the reaction
was basified with sodium bicarbonate or sodium hydroxide
solution and extracted with chloroform. The combined organic
layers were washed with water, dried over MgSO4, and filtered.
Removal of solvent gave a crude mixture; lactam products were
obtained by chromatography using the appropriate amount of
ether. Lactam ratios are reported in Table 2. Cleavage
products, which primarily remained in the water layer, were
not purified or characterized.
29.1, 27.1. Anal. of the mixture of lactams Calcd for C9H13
-
NO3: C, 59.00; H, 7.15; N, 7.65. Found: C, 58.66; H, 7.07; N,
7.63.
a n ti-8-Ch lor o-3-a za -2-oxobicyclo[3.2.1]octa n e (29) a n d
a n ti-8-Ch lor o-2-a za -3-oxobicyclo[3.2.1]octa n e (30). From
ketone 28 (48 mg, 0.346 mmol) in chloroform (15 mL) after 5
h there was obtained according to the general procedure 29 g
(53%) of a mixture of lactams. Chromatography, Rf ) 0.20
(EtOAc), gave 16 mg (29%) of a white solid mixture of lactams,
mp 145-146.5 °C. Data for lactam 29: 1H NMR δ 6.53 (br,
1H), 4.38 (s, 1H), 3.42 (dd, J ) 11.1, 4.0 Hz, 1H), 3.08 (dt, J )
11.1, 2.1 Hz, 1H), 2.82 (d, J ) 4.8 Hz, 1H), 2.69 (br, 1H), 2.43-
1.65 (m, 4H); 13C NMR δ 174.3, 61.4, 50.9, 47.5, 41.1, 28.1,
25.7. Anal. Calcd for C7H10NOCl: C, 52.65; H, 6.32; N, 8.78.
Found: C, 52.39; H, 6.36; N, 8.60.
3-Aza -2-oxobicyclo[3.2.1]octa n e (4).6 From norcamphor
1 (500 mg, 4.45 mmol) in CHCl3 (15 mL) after 1 h there was
obtained 217 mg (39%) of lactam 4.
syn -8-Meth oxy-3-aza-2-oxobicyclo[3.2.1]octan e (14) an d
syn -8-Meth oxy-2-aza-3-oxobicyclo[3.2.1]octan e (15). From
ketone 13 (280 mg, 2.0 mmol), sodium azide (1.5 equiv) and
sulfuric acid (1 mL) in chloroform (15 mL) after 1 h there was
afforded 223 mg (72%) of a mixture of lactams. Chromatog-
raphy, Rf ) 0.40 (THF/ether 1:1), afforded 148 mg of lactams
as an oil. Data for 14: 1H NMR δ 6.82 (br, 1H), 3.75 (dd, J )
4.5, 4.8 Hz, 1H), 3.51 (dd, J ) 11.0, 3.3 Hz, 1H), 3.38 (s, 3H),
2.91 (dt, J ) 11.0, 1.8 Hz, 1H), 2.70 (t, J ) 4.5 Hz, 1H), 2.30
(m, 1H), 1.93-1.70 (m, 4H); 13C NMR δ 174.7, 81.1, 57.1, 44.9,
a n ti-8-Br om o-3-aza-2-oxobicyclo[3.2.1]octan e (32). From
ketone 31 (342 mg, 1.81 mmol) in chloroform (25 mL) after 12
h there was obtained according to the general procedure 210
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mg (57%) of crude lactam 32, mp 140.5-142 °C (EtOAc), H
NMR δ 6.77 (br, 1H), 4.45 (s, 1H), 3.42 (dd, J ) 11.1, 3.3 Hz,
1H), 3.05 (d, J ) 11.4 Hz, 1H), 2.87 (d, J ) 5.1 Hz, 1H), 2.75
(br, 1H), 2.43-1.65 (m, 4H); 13C NMR δ 174.5, 52.7, 52.0, 48.3,
42.1, 29.2, 26.5. Anal. Calcd for C7H10NOBr: C, 41.18; H,
4.94; N, 6.87. Found: C, 41.03, H, 5.01; N, 6.78.
44.6, 33.1, 26.4, 25.9. Anal. of the mixture calcd for C8H13
-
NO2: C, 61.91; H, 8.44, N, 9.02. Found: C, 61.99; H, 8.31; N,
9.07.
a n ti-8-(p-Tolu en esu lfon yloxy)-3-aza-2-oxobicyclo[3.2.1]-
octa n e (35) a n d a n ti-8-(p-Tolu en esu lfon yloxy)-2-a za -3-
oxobicyclo[3.2.1]octa n e (36). From ketone 34 (100 mg,
0.357 mmol) in chloroform (20 mL) after 2 h there was obtained
according to the general procedure 63 mg (64%) of crude
lactams. Chromatography, Rf ) 0.28 (EtOAc), gave 42 mg
(40%) of white solid mixture, mp 153-155 °C. Data for lactam
35: 1H NMR δ 7.78 (d, J ) 8.4 Hz, 2H), 7.35 (d, J ) 8.4 Hz,
2 H), 5.78 (br, 1H), 4.85 (br, 1H), 3.37 (dd, J ) 11.1, 3.6 Hz,
1H), 3.02 (d, J ) 11.1 Hz, 1H), 2.60 (br, 2H), 2.47 (s, 3H), 2.20-
2.00 (br, 4H); 13C NMR δ 173.3, 132.9, 129.6, 127.2, 82.7, 47.8,
46.1, 38.0, 28.1, 25.7, 21.2. Anal. of the mixture of lactams
syn -8-Ch lor o-3-a za -2-oxobicyclo[3.2.1]octa n e (17) a n d
syn -8-Ch lor o-2-a za -3-oxobicyclo[3.2.1]octa n e (18). From
ketone 16 (800 mg, 5.54 mmol) in chloroform (30 mL) after 24
h there was obtained according to the general procedure 364
mg (47%) of a mixture of lactams, which was purified by
recrystallization (EtOAc) to afford 250 mg (28%) of white
crystals. Further recrystallization gave lactam 17, mp 161.5-
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163 °C, H NMR δ 6.59 (br, 1H), 4.21 (t, J ) 4.5 Hz, 1H), 3.72
(dd, J ) 11.4, 3.3 Hz, 1H), 3.07 (d, J ) 11.4 Hz, 1H), 2.81 (t,
J ) 4.5 Hz, 1H), 2.50 (br, 1H), 2.14-1.82 (m, 4H); 13C NMR δ
173.1, 57.7, 48.8, 45.0, 36.2, 27.9, 26.1. Anal. Calcd for