Table 2.
Optimisation of the transformation of cyclobutanol major-1c to the cyclised product 3ca
| Entry | Solvent (mL) | Brønsted Acid (mL) | Yield 3c [%]b |
|---|---|---|---|
| 1c | – | – | traces |
| 2 | CHCl3 (0.75) | Py•HF (0.75) | 57 |
| 3 | CHCl3 (1.0) | Py•HF (1.0) | 68 |
| 4 | CHCl3 (0.5) | Py•HF (1.0) | 70 |
| 5 | – | Py•HF (1.0) | 72 |
| 6 | CHCl3 (1.0) | HFIP (1.0) | 13 |
| 7 | – | HFIP (1.0) | 55 |
| 8 | – | HFIP (2.0) | 71 (70) |
| 9d | – | HFIP (2.0) | (48) |
aStandard reaction conditions: Intermediate 2c was prepared according to the procedure described in Table 1 on a 0.2 mmol scale. Additional solvent and/or Brønsted acid was added after 18 h. The reaction was stirred for an additional 24 h at rt.
bDetermined by 19F NMR using ethyl 2-fluoroacetate as internal standard. Isolated yield in parentheses.
c2c was prepared with an amine:HF ratio of 1:6.5. No solvent nor acid activator was added after 18 h.
d3c was prepared stepwise, isolating IIIc and 2c. The stepwise synthesis was performed on a 0.5 mmol scale. Full details provided in the ESI.