January 2005
141
(CDCl3) d: 160.6, 134.0, 130.9, 125.2 (q, JCFꢁ274.7 Hz), 120.0, 111.8,
111.4, 110.6, 76.4, 55.8, 28.4 (q, 2JCFꢁ40.8 Hz), MS (EI) 318, 320, HR-MS
(EI) Calcd for C11H6BrF3N2O (Mꢂ) 317.9616, Found 317.9608, IR (neat)
2199.42 cmꢃ1
.
General Procedure for the Synthesis of Diazirinyl (E)-b-Bromo-
styrene (4) Compound 2 (30.0 mg, 0.081 mmol), in EtOH (0.25 ml), was
added to a solution of diethyl phosphite (1.1 eq) and sodium methoxide solu-
tion (28%, 1.1 eq) in EtOH. The reaction mixture was stirred at room tem-
perature for 1 h. After concentration, the residue was purified with silica gel
column chromatography (hexane) to afford colorless oil.
(E)-b-Bromo-4-(3-trifluoromethyl-3H-diazirin-3-yl)styrene (4a): Yield
1
96%, H-NMR (CDCl3) d: 7.32 (d, 2H, Jꢁ8.3 Hz), 7.14 (d, 2H, Jꢁ8.3 Hz),
7.09 (d, 1H, Jꢁ14.2 Hz), 6.84 (d, 1H, Jꢁ14.2 Hz). 13C-NMR (CDCl3) d:
137.1, 136.1, 135.4, 128.9, 126.9, 126.3, 122.0 (q, JCFꢁ274.8 Hz), 110.4,
108.4, 28.4 (q, 2JCFꢁ40.8 Hz), MS (EI) 290, 292, HR-MS (EI) Calcd for
C10H6BrF3N2 (Mꢂ) 289.9666, Found 289.9657.
(E)-b-Bromo-2-methoxy-4-(3-trifluoromethyl-3H-diazirin-3-yl)styrene
Fig. 1. Stereoselective Synthesis of Diazirinyl (E)- and (Z)-b-Bromo-
1
(4b): Yield 72%, H-NMR (CDCl3) d: 7.90 (d, 1H, Jꢁ8.0 Hz), 7.22 (d, 1H,
styrene
Jꢁ14.3 Hz), 6.97 (d, 1H, Jꢁ14.3 Hz), 6.75 (d, 1H, Jꢁ8.0 Hz), 6.59 (s, 1H),
3.86 (s, 3H). 13C-NMR (CDCl3) d: 156.6, 132.0, 130.0, 128.2, 126.3, 122.0
(q, JCFꢁ274.7 Hz), 118.9, 109.9, 108.7, 55.6, 28.4 (q, 2JCFꢁ40.8 Hz). MS
(EI) 320, 322, HR-MS (EI) Calcd for C11H8BrF3N2O (Mꢂ) 319.9772, Found
319.9777.
mer was calculated at less than 3% from NMR analysis.
Stereoselective hydrogenolysis was applied to introduce deu-
terium by commercially available reagents. It has been re-
ported that hydrogen of solvent, has been utilized for the syn-
(E)-b-Bromo-b-deutrium-4-(3-trifluoromethyl-3H-diazirin-3-yl)styrene
1
(4c): Yield 89%, H-NMR (CDCl3) d: 7.32 (d, 2H, Jꢁ8.3 Hz), 7.14 (d, 2H,
Jꢁ8.3 Hz), 7.09 (d, 1H, Jꢁ14.2 Hz), 6.84 (d, 1H, Jꢁ14.2 Hz). 13C-NMR
thesis of (E)-b-bromostyrene. The reaction, performed with (CDCl3) d: 137.1, 136.1, 135.4, 128.9, 126.9, 126.3, 122.0 (q,
2
JCFꢁ274.8 Hz), 110.4, 108.4 (t, JCDꢁ28.8 Hz), 28.4 (q, JCFꢁ40.8 Hz), MS
unlabeled diethylphosphonate in labeled CD3OD solution,
produced deuterated compound 5c at a rate of over 90%. On
the other hand, deuterated (Z)-compound 5d was obtained
with (n-Bu)3SnD and unlabeled Pd catalysis in unlabeled sol-
vent at a rate of over 95% deuterium incorporation.
(EI) 291, 293, HR-MS (EI) Calcd for C10H5DBrF3N2 (Mꢂ) 290.9728, Found
290.9734.
(E)-b-Bromo-b-deutrium-2-methoxy-4-(3-trifluoromethyl-3H-diazirin-3-
yl)styrene (4d): Yield 56%, 1H-NMR (CDCl3) d: 7.90 (d, 1H, Jꢁ8.0 Hz),
7.25 (1H, s), 6.75 (d, 1H, Jꢁ8.0 Hz), 6.59 (1H, s), 3.86 (3H, s). 13C-NMR
(CDCl3) d: 156.6, 131.8, 129.9, 128.2, 126.2, 122.0 (q, JCFꢁ274.7 Hz),
118.9, 109.7 (t, JCDꢁ31.2 Hz), 108.7, 55.6, 28.4 (q, 2JCFꢁ40.8 Hz), MS (EI)
Experimental
IR spectra were recorded with a JASCO IR spectrophotometer. NMR 321, 323, HR-MS (EI) Calcd for C11H7DBrF3N2O (Mꢂ) 320.9834, Found
spectra were recorded on a JEOL ECA-500 instrument (1H 500 MHz, 13C
125 MHz), and chemical shifts are expressed in ppm downfield from tetra-
320.9840.
General Procedure for the Synthesis of Diazirinyl (Z)-b-Bromostyrene
methylsilane. Mass spectra were recorded on JEOL JNM-LA400 mass spec- (5) To a stirred solution of compound 2 (23.8 mg, 0.06 mmol), in dry ben-
trometers. CD3OD and (n-Bu)3SnD were purchased from Cambridge Isotope zene (0.5 ml), was added Pd(PPh3)4 (4 mol%) and (n-Bu)3SnH (2.3 eq), suc-
Laboratories and Aldrich, respectively. All other solvents were reagent grade
and distilled using the appropriate methods.
cessively, and the mixture was stirred at room temperature for 50 min. After
the reaction was completed, it was diluted with hexane and washed with
General Procedure for the Synthesis of Diazirinyl b,b-Dibromo- water and brine. The hexane extract was dried over MgSO4, and the solvent
styrene (2) To an ice cold stirred solution of 1a (0.443 g, 2.07 mmol) and was removed under reduced pressure. The residue was purified with silica
CBr4 (1.5 eq), in dry CH2Cl2, was added PPh3 (3.0 eq) in CH2Cl2. The reac- gel column chromatography (hexane) to afford colorless oil.
tion mixture was stirred at room temperature for 2 h and concentrated. The
residue was purified with silica gel column chromatography (hexane) to give
colorless oil.
(Z)-b-Bromo-4-(3-trifluoromethyl-3H-diazirin-3-yl)styrene (5a): Yield
1
87%, H-NMR (CDCl3) d: 7.71 (d, 1H, Jꢁ7.9 Hz), 7.19 (d, 1H, Jꢁ7.9 Hz),
7.06 (d, 1H, Jꢁ8.3 Hz), 6.52 (d, 1H, Jꢁ8.3 Hz). 13C-NMR (CDCl3) d: 136.2,
b,b-Dibromo-4-(3-trifluoromethyl-3H-diazirin-3-yl)styrene (2a): Yield 131.2, 129.2, 128.9, 126.2, 122.0 (d, JCFꢁ274.7 Hz), 108.3, 28.4 (d,
97%, 1H-NMR (CDCl3) d: 7.57 (d, 2H, Jꢁ8.3 Hz), 7.47 (s, 1H), 7.18 (d, 2H,
Jꢁ8.3 Hz), 13C-NMR (CDCl3) d: 136.55, 135.56, 129.51, 129.24, 128.70, (Mꢂ) 289.9666, Found 289.9660.
126.40, 121.97, (q, JCFꢁ274.6 Hz), 91.61, 28.36 (q, 2JCFꢁ40.8 Hz), MS (EI)
(Z)-b-Bromo-2-methoxy-4-(3-trifluoromethyl-3H-diazirin-3-yl)styrene
2JCFꢁ39.6 Hz), MS (EI) 290, 292, HR-MS (EI) Calcd for C10H6BrF3N2
368, 370, 372, HR-MS (EI) Calcd for C10H5Br2F3N2 (Mꢂ) 367.8772, Found (5b): Yield 83%, H-NMR (CDCl3) d: 7.90 (d, 1H, Jꢁ8.0 Hz), 7.22 (d, 1H,
1
367.8765.
Jꢁ8.0 Hz), 6.82 (d, 1H, Jꢁ8.0 Hz), 6.52 (d, 1H, Jꢁ8.0 Hz), 6.61 (s, 1H),
b,b-Dibromo-2-methoxy-4-(3-trifluoromethyl-3H-diazirin-3-yl)styrene
3.84 (3H, s). 13C-NMR (CDCl3) d: 156.96, 130.29, 129.83, 126.95, 125.49,
(2b): Yield 85%, 1H-NMR (CDCl3) d: 7.72 (d, 1H, Jꢁ8.0 Hz), 7.54 (s, 1H),
122.05 (q,
JCFꢁ274.7 Hz), 118.23, 108.66, 108.21, 55.63, 28.4 (q,
6.80 (d, 1H, Jꢁ8.0 Hz), 6.58 (s, 1H), 3.84 (s, 3H), 13C-NMR (CDCl3) d: 2JCFꢁ40.8 Hz), MS (EI) 320, 322, HR-MS (EI) Calcd for C11H8BrF3N2O
132.1, 131.4, 130.7, 129.5, 125.9, 122.0 (q, JCFꢁ274.7 Hz), 118.4, 109.9, (Mꢂ) 319.9772, Found 319.9780.
2
108.3, 91.4, 55.6, 28.4 (q, JCFꢁ40.8 Hz), MS (EI) 398, 400, 402, HR-MS
(Z)-b-Bromo-b-deutrium-4-(3-trifluoromethyl-3H-diazirin-3-yl)styrene
(EI) Calcd for C11H7Br2F3N2O (Mꢂ) 397.8877, Found 397.8868.
(5c): Yield 70%, H-NMR (CDCl3) d: 7.71 (d, 2H, Jꢁ8.3 Hz), 7.19 (d, 2H,
1
General Procedure for the Synthesis of Diazirinyl 1-Bromo-2- Jꢁ8.3 Hz), 7.06 (s, 1H, Jꢁ8.3 Hz), 13C-NMR (CDCl3) d: 136.2, 131.2,
phenylethyne (3) Compound 2 was dissolved in DMSO. DBU (3 eq) was 129.2, 128.9, 126.2, 122.0 (d, JCFꢁ274.7 Hz), 108.09 (t, JCDꢁ30.5 Hz), 28.4
added to the solution. The reaction mixture was stirred at room temperature
for 1 h, then purified with silica gel column chromatography (hexane) to af-
ford a colorless oil.
(d, 2JCFꢁ39.6 Hz), MS (EI) 291, 293, HR-MS (EI) Calcd for C10H5DBrF3N2
(Mꢂ) 290.9728, Found 290.9725.
(Z)-b-Bromo-b-deutrium-2-methoxy-4-(3-trifluoromethyl-3H-diazirin-3-
1-Bromo-2-[4-(3-trifluoromethyl-3H-diazirin-3-yl)phenyl]ethyne
(3a): yl)styrene (5d): Yield 64%, 1H-NMR (CDCl3) d: 7.91 (d, 1H, Jꢁ8.0 Hz),
Yield 84%, 1H-NMR (CDCl3) d: 7.46 (d, 2H, Jꢁ7.9 Hz), 7.12 (d, 2H,
7.22 (1H, s), 6.82 (d, 1H, Jꢁ8.0 Hz), 6.61 (1H, s), 3.84 (3H, s), 13C-NMR
(CDCl3) d: 157.0, 130.3, 129.8, 126.8, 125.5, 122.1 (q, JCFꢁ274.7 Hz),
118.2, 108.4 (t, JCDꢁ28.2 Hz), 108.20, 55.63, 28.4 (q, 2JCFꢁ40.8 Hz) MS
Jꢁ7.9 Hz), 1.55 (s, 1H), 13C-NMR (CDCl3) d: 132.3, 129.4, 126.3, 124.2,
2
121.9 (q, JCFꢁ274.7 Hz), 78.9, 52.5, 28.4 (q, JCFꢁ40.8 Hz), MS (EI) 288,
290, HR-MS (EI) Calcd for C10H4BrF3N2 (Mꢂ) 287.9510, Found 287.9520 (EI) 321, 323, HR-MS (EI) Calcd for C11H7DBrF3N2O (Mꢂ) 320.9834,
IR (neat) 2206 cmꢃ1
.
Found 320.9830.
1-Bromo-2-[2-methoxy-4-(3-trifluoromethyl-3H-diazirin-3-yl)-
phenyl]ethyne (3b): Yield 68%, 1H-NMR (CDCl3) d: 7.42 (d, 1H,
Jꢁ8.0 Hz), 6.74 (d, 1H, Jꢁ8.0 Hz), 6.57 (s, 1H), 3.88 (s, 3H), 13C-NMR
Acknowledgments This research was partially supported by the Min-
istry of Education, Science, Sports and Culture, Grant-in-Aid for Encour-