Table 1.
Formal [3+2]-Cycloaddition Reaction Optimization.
 | |||
|---|---|---|---|
| entry | solvent | 4a:5a | combined 1H NMR yielda |
| 1 | 1,2-DCE | 2.5:1 | 77% |
| 2 | CH2Cl2 | 1.4:1 | 72% |
| 3 | CHCl3 | 2.7:1 | 82% (82%) |
| 4 | TCE | 5.1:1 | 4% |
| 5b | TCE | 1:3.2 | 47% |
| 6c | THF | - | - |
| 7 | MeCN | 1:2.2 | 22% |
| 8 | TFT | 4.7:1 | 52% |
| 9d | hexanes | - | - |
| 10c | acetone | - | - |
| 11e | ethanol | - | - |
| 12f | water | - | - |
| 13f | CHCl3 | 3.8:1 | 57% |
| 14g | CHCl3 | 5.5:1 | 55% |
| 15 | EtOAc | 3.4:1 | 31% |
| 16 | dioxane | 2.0:1 | 64% |
| 17h | CHCl3:hexane (1:1) | 11.5:1 | 23% |
a)
Products are obtained as a mixture of the [3+2] cycloadduct 4a and C–H insertion products 5a favoring the isomer indicated. Combined isolated yield in parenthesis. Reaction conditions 146.2 mg (0.50 mmol) triazole 1a, 247 mL (2.00 mmol) p-xylene, 1.0 mL CH2Cl2, 70 °C, 1.5 h
b)
Reaction time 18 h
c)
Triazole 1a is completely consumed, but produces non-specific decomposition.
d)
No reaction, triazole 1a is not consumed.
e)
O–H insertion product obtained, see the Supporting Information for details.
f)
Microwave heating at 60 °C
g)
microwave heating at 70 °C, 0.5 h, 0.09 M
h)
7% triazole 1a remaining. 1,2-DCE = 1,2-dichloroethane. TFT = α,α,α-trifluorotoluene.
TCE = trichloroethylene, THF = tetrahydrofuran. Hex = hexanes.