The Journal of Organic Chemistry
Article
CDCl3) δ (ppm) 7.38 (d, J = 8.0 Hz, 2H), 7.24 (d, J = 8.0 Hz, 2H),
3.70 (s, 3H), 3.57 (d, J = 20.0 Hz, 1H), 3.01 (d, J = 20.0 Hz, 1H), 2.91
(bs, 1H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3) 172.67, 166.84,
140.77, 129.77, 127.64, 125.85, 81.54, 53.79, 46.18, 35.90, 21.74;
HRMS (ESI) calcd for C13H14NO4 [M + H]+ 248.0917, found
248.0902.
Methyl 3-oxo-1-(2-(trifluoromethyl)phenyl)-2-oxa-6-
azabicyclo[3.1.0]hexane-5-carboxylate (4k): brown oil; 231 mg,
77% yield; H NMR (400 MHz, CDCl3) δ (ppm) 7.78−7.62 (comp,
4H), 3.71 (s, 3H), 3.56 (d, J = 20.0 Hz, 1H), 3.01 (d, J = 20.0 Hz, 1H),
2.85 (bs, 1H); 13C NMR (100 MHz, CDCl3) 172.20, 167.23, 132.80,
131.56 (d, J = 5.0 Hz), 129.45 (q, J = 32.0 Hz), 127.81 (q, J = 5.0 Hz),
127.06, 125.38, 122.66, 79.67, 53.91, 46.02, 34.89; HRMS (ESI) calcd
for C13H11F3NO4 [M + H]+ 302.0635, found 302.0627.
tert-Butyl 3-oxo-1-(2-(trifluoromethyl)phenyl)-2-oxa-6-
azabicyclo[3.1.0]hexane-5-carboxylate (4l): brown oil; 281 mg,
82% yield; 1H NMR (400 MHz, CDCl3) δ (ppm) 8.19 (d, J = 8.0 Hz,
1H), 7.80−7.67 (comp, 3H), 3.70 (d, J = 20.0 Hz, 1H), 2.97 (d, J =
20.0 Hz, 1H), 2.74 (bs, 1H), 1.28 (s, 9H); 13C NMR (100 MHz,
CDCl3) 172.68, 165.23, 132.58, 131.33 (d, J = 3.3 Hz), 129.74 (q, J =
32.0 Hz), 127.72 (q, J = 5.2 Hz), 127.4, 125.36, 122.64, 84.57, 79. 34,
46.70, 34.93, 27.93; HRMS (ESI) calcd for C16H17F3NO4 [M + H]+
344.1104, found 344.1107.
1
Methyl 1-(4-fluorophenyl)-3-oxo-2-oxa-6-azabicyclo[3.1.0]-
hexane-5-carboxylate (4c): white solid; mp 147−150 °C; 49 mg,
1
19.5% yield; H NMR (400 MHz, CDCl3) δ (ppm) 7.50 (m, 2H),
7.11 (m, 2H), 3.68 (s, 3H), 3.57 (d, J = 20.0 Hz, 1H), 3.01 (d, J = 20.0
Hz, 1H), 2.99 (bs, 1); 13C NMR (100 MHz, CDCl3) 172.54, 166.69,
165.25 (d, J = 25.0 Hz), 129.94 (d, J = 8.0 Hz), 124.96 (d, J = 3.0 Hz),
116.21 (d, J = 22.0 Hz), 80.82, 53.85, 46.23, 35.82; HRMS (ESI) calcd
for C12H11FNO4 [M + H]+ 252.0667, found 252.0671.
Methyl 1-(4-chlorophenyl)-3-oxo-2-oxa-6-azabicyclo[3.1.0]-
hexane-5-carboxylate (4d): yellow solid; mp 135−136 °C; 87 mg,
1
32.5% yield; H NMR (400 MHz, CDCl3) δ (ppm) 7.44 (q, J = 8.0
Methyl 4-methyl-1-(2-nitrophenyl)-3-oxo-2-oxa-6-
azabicyclo[3.1.0]hexane-5-carboxylate (4m): cis + trans: 260
mg, 89% yield; trans:cis = 1:1 (trans and cis relative chemistry was
determined by 1D-NoE experiment).10 trans-4 m: yellow oil; 1H
NMR (400 MHz, CDCl3) δ (ppm) 8.14 (d, J = 8.0 Hz, 1H), 7.80−
7.67 (comp, 3H), 3.85 (q, J = 8.0 Hz, 1H), 3.72 (s, 3H), 2.80 (bs, 1H),
1.48 (d, J = 8.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) 175.42,
167.65, 147.73, 134.46, 132.12, 131.91, 125.95, 124.94, 77.30, 54.05,
Hz, 4H), 3.72 (s, 3H), 3.61 (d, J = 20.0 Hz, 1H), 3.03 (d, J = 20.0 Hz,
1H), 2.91 (bs, 1H); 13C NMR (100 MHz, CDCl3) 172.28, 166.58,
136.75, 129.36, 129.09, 127.52, 80.69, 53.94, 46.46, 35.85; HRMS
(ESI) calcd for C12H11ClNO4 [M + H]+ 268.0371, found 268.0382.
Methyl 1-(4-bromophenyl)-3-oxo-2-oxa-6-azabicyclo[3.1.0]-
hexane-5-carboxylate (4e): yellow solid; mp 148−150 °C; 138 mg,
1
44.4% yield; H NMR (400 MHz, CDCl3) δ (ppm) 7.58 (d, J = 8.0
Hz, 2H), 7.39 (d, J = 8.0 Hz, 2H), 3.72 (s, 3H), 3.58 (d, J = 20.0 Hz,
1H), 3.03 (d, J = 20.0 Hz, 1H), 2.90 (bs, 1H); 13C NMR (100 MHz,
CDCl3) 172.26, 166.56, 132.32, 129.30, 128.04, 125.00, 80.74, 53.95,
46.46, 35.85; HRMS (ESI) calcd for C12H11BrNO4 [M + H]+
311.9866, found 311.9874.
1
50.30, 39.82, 11.86. cis-4 m: yellow solid; mp 117−119 °C; H NMR
(400 MHz, CDCl3) δ (ppm) 8.14 (d, J = 8.0 Hz, 1H), 7.80−7.67
(comp, 3H), 3.85 (q, J = 8.0 Hz, 1H), 3.72 (s, 3H), 2.80 (bs, 1H), 1.48
(d, J = 8.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) 176.78, 167.65,
147.75, 134.36, 132.21, 131.99, 125.78, 125.37, 79.46, 53.66, 49.05,
43.35, 14.21; HRMS (ESI) calcd for C13H13N2O6 [M + H]+ 293.0768,
found 293.0771.
M e t h y l 1 - ( 4 - a c e t o x y p h e n y l ) - 3 - o x o - 2 - o x a - 6 -
azabicyclo[3.1.0]hexane-5-carboxylate (4f): yellow oil; 144 mg,
1
49.5% yield; H NMR (400 MHz, CDCl3) δ (ppm) 7.54 (d, J = 8.0
Hz, 2H), 7.19 (d, J = 8.0 Hz, 2H), 3.73 (s, 3H), 3.58 (d, J = 20.0 Hz,
1H), 3.04 (d, J = 20.0 Hz, 1H), 2.89 (bs, 1H), 2.33 (s, 3H); 13C NMR
(100 MHz, CDCl3) 171.97, 169.01, 166.22, 151.94, 128.55, 126.07,
121.93, 80.48, 53.52, 46.11, 35.53, 21.16; HRMS (ESI) calcd for
C14H14NO6 [M + H]+ 292.0816, found 292.0833.
Methyl 1-(2-nitrophenyl)-3-oxo-2-oxa-6-azabicyclo[3.1.0]-
hexane-5-carboxylate (4g): colorless crystal (after crystallization
in DCM, EtOAc, and hexanes); mp 155−156 °C; 250 mg, 90% yield;
1H NMR (400 MHz, CDCl3) δ (ppm) 8.17 (d, J = 8.0 Hz, 1H), 7.82−
7.69 (comp, 3H), 3.74 (d, J = 16.0 Hz, 1H), 3.72 (s, 3H), 3.03 (d, J =
16.0 Hz, 1H), 2.80 (bs, 1H); 13C NMR (100 MHz, CDCl3) 172.45,
167.54, 147.73, 134.48, 132.16, 131.91, 126.02, 124.91, 78.89, 54.07,
46.53, 34.99; HRMS (ESI) calcd for C12H11N2O6 [M + H]+ 279.0612,
found 279.0611.
tert-Butyl 1-(2-nitrophenyl)-3-oxo-2-oxa-6-azabicyclo[3.1.0]-
hexane-5-carboxylate (4h): brown oil; 294 mg, 92% yield; 1H
NMR (400 MHz, CDCl3) δ (ppm) 8.19 (d, J = 8.0 Hz, 1H), 7.80−
7.67 (comp, 3H), 3.70 (d, J = 20.0 Hz, 1H), 2.97 (d, J = 20.0 Hz, 1H),
2.74 (bs, 1H), 1.28 (s, 9H); 13C NMR (100 MHz, CDCl3) 172.60,
165.23, 147.11, 134.10, 131.64, 131.60, 125.49, 125.06, 84.15, 78.33,
46.83, 34.72, 27.53; HRMS (ESI) calcd for C15H17N2O6 [M + H]+
321.1081, found 321.1077.
Benzyl 4-methyl-1-(2-nitrophenyl)-3-oxo-2-oxa-6-
azabicyclo[3.1.0]hexane-5-carboxylate (4n): cis + trans: 305 mg,
83% yield; trans:cis = 3:1 (trans and cis relative chemistry was
1
determined by comparison the analogue H NMR specrta with 4m).
trans-4n: yellow oil; 1H NMR (400 MHz, CDCl3) δ (ppm) 8.08 (d, J
= 8.0 Hz, 1H), 7.75−7.14 (comp, 8H), 5.16 (d, J = 12.0 Hz, 1H), 5.01
(d, J = 12.0 Hz, 1H), 3.91 (q, J = 8.0 Hz, 1H), 2.65 (bs, 1H), 1.47 (d, J
= 8.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) 175.35, 166.89, 147.57,
134.72, 134.32, 131.97, 131.79, 129.11, 129.04, 128.73, 125.98, 124.98,
1
77.25, 68.81, 50.41, 39.83, 11.90. cis-4n: yellow oil; H NMR (400
MHz, CDCl3) δ (ppm) 8.06 (d, J = 8.0 Hz, 1H), 7.69−7.08 (comp,
8H), 5.09 (d, J = 12.0 Hz, 1H), 4.97 (d, J = 12.0 Hz, 1H), 3.18 (q, J =
8.0 Hz, 1H), 2.80 (bs, 1H), 1.82 (d, J = 8.0 Hz, 3H); 13C NMR (100
MHz, CDCl3) 176.83, 166.69, 147.55, 134.53, 134.62, 132.09, 131.83,
129.09, 129.01, 128.86, 125.97, 125.80, 79.45, 68.61, 49.01, 43.47,
14.18; HRMS (ESI) calcd for C19H17N2O6 [M + H]+ 369.1081, found
369.1062.
Methyl 1-(2-nitrophenyl)-3-oxo-4-phenyl-2-oxa-6-
azabicyclo[3.1.0]hexane-5-carboxylate (4o): white solid; mp
189−191 °C; 202 mg, 57% yield; trans:cis > 20:1 (trans and cis
1
relative chemistry was determined by 1D-NoE experiment); H NMR
(400 MHz, CDCl3) δ (ppm) 8.19 (d, J = 8.0 Hz, 1H), 7.75−7.38
(comp, 8H), 5.14 (s, 1H), 3.72 (s, 3H), 2.80 (bs, 1H); 13C NMR (100
MHz, CDCl3) 172.84, 167.39, 147.72, 134.53, 133.25, 132.24, 131.97,
129.69, 129.18, 128.71, 126.06, 124.79, 54.20, 50.78, 50.19; HRMS
(ESI) calcd for C18H15N2O6 [M + H]+ 355.0925, found 355.0905.
General Procedure for Rearrangement Reactions of TIPS-
Protected Enoldiazoacetate 1 with Nitrile Oxides 2g. To an
oven-dried flask containing a magnetic stirring bar, 4 Å molecular
sieves (100 mg), Rh2(pfb)4 (2.0 mol %), and nitrile oxide 2g (1.0
mmol) in dichloromethane (5.0 mL) was added enol diazoacetate 1
(1.2 mmol) in dichloromethane (3.0 mL) over 1 h via a syringe pump
at 0 °C. After addition was complete, the reaction solution was stirred
for another 2 h at room temperature, and then DCM was removed
under reduced pressure and the crude reaction mixture was subjected
to NMR analysis: 100% conversion to 7; 1H NMR (400 MHz, CDCl3)
δ (ppm) 8.23−7.78 (comp, 4H), 3.73 (s, 3H), 3.43 (d, J = 16.0 Hz,
1H), 2.97 (d, J = 16.0 Hz, 1H), 1.24 (m, 3H), 1.02 (m, 18H); 13C
M e t h y l 1 - ( 2 , 4 - d i n i t r o p h e n y l ) - 3 - o x o - 2 - o x a- 6 -
azabicyclo[3.1.0]hexane-5-carboxylate (4i): yellow solid; mp
1
168−170 °C; 261 mg, 81% yield; H NMR (400 MHz, CDCl3) δ
(ppm) 8.95−8.09 (comp, 3H), 3.78 (d, J = 20.0 Hz, 1H), 3.72 (s, 3H),
3.07 (d, J = 16.0 Hz, 1H), 2.84 (bs, 1H); 13C NMR (100 MHz,
CDCl3) 171.90, 167.11, 149.48, 148.16, 133.76, 131.02, 128.36,
121.33, 54.26, 47.01, 34.98; HRMS (ESI) calcd for C12H10N3O8 [M +
H]+ 324.0462, found 324.0469.
tert-Butyl 1-(2,4-dinitrophenyl)-3-oxo-2-oxa-6-
azabicyclo[3.1.0]hexane-5-carboxylate (4j): dark brown oil; 321
1
mg, 88% yield; H NMR (400 MHz, CDCl3) δ (ppm) 8.20−7.67
(comp, 3H), 3.70 (d, J = 20.0 Hz, 1H), 2.97 (d, J = 20.0 Hz, 1H), 2.74
(bs, 1H), 1.28 (s, 9H); 13C NMR (100 MHz, CDCl3) 172.20, 165.49,
149.41, 147.89, 133.83, 131.59, 128.37, 121.22, 85.25, 47.67, 35.06,
28.02; HRMS (ESI) calcd for C15H16N3O8 [M + H]+ 366.0932, found
366.09312.
D
dx.doi.org/10.1021/jo3006733 | J. Org. Chem. XXXX, XXX, XXX−XXX