Table 1.
Optimization studies to access α-haloglycines 4a-c in one-pot.[a]
 | ||||
|---|---|---|---|---|
| Entry | Promoter (eq.) | Temp | Time | Yield (%)[b] |
| 1 | AcCI (3.0) | RT | 48 h | 4b (62) |
| AcOH (0.1) | 60 °C | 11 h | 4b (100) | |
| 2 | SOCI2 (3.0) | RT | 15 h | 4b (100) |
| 60 °C | 6 h | 4b (100) | ||
| 3 | SiCI4 (1.5) | 35 °C | 24 h | 4b (100) |
| 4[c] | BCI3 (1.0) | 0 °C | 24 h | 4b (0) |
| 5 | TMSCl (3.0) | RT | 60 h | 4b (89) |
| 6 | (CO)2Cl2 (3.0) | RT | 18 h | 4b (94) |
| 7 | AcBr (3.0) | RT | 6.5 h | 4c (100) |
| AcOH (0.1) | ||||
| 8 | SOBr2 (3.0) | −20 °C | 15 mins | 4c (100) |
| 9 | TMSBr (3.0) | RT | 4 h | 4c (100) |
| 10[d] | BzF (3.0) | 0 °C to 60 °C | 72 h | 4a (0) |
| BzOH (0.1) | ||||
| 11 | Et2NSF3 (3.0) | 0 °C to RT | 72 h | 4a (0) |
| 12[e] | Et2NSF3 (3.0) | 40 °C then −78 °C | 15 h then 2 h | 4a (100) |
| AcOH(0.1) | ||||
[a]
1H NMR recorded in CD3CN, aH: 4a (F), δ = 5.95 ppm (dd, J = 9.5, 53.7 Hz); 4b (Cl), δ = 6.18 ppm (d, J = 10.4 Hz); 4c (Br), δ = 6.39 ppm (d, J = 10.8 Hz).
[b]
Yields determined by 1H NMR on crude reaction mixtures using mesitylene as internal standard.
[c]
Complete decompostion of starting material Cbz-carbamate 2 was observed in presence of BCl3.
[d]
Hemiaminal 3 was formed (≈ 25 % conv.).
[e]
Experiment run in in a a stepwise manner in CH2Cl2 for the condensation-deoxyfluorination.