Table 1. Identification of the best-suited SCF3-transfer reagent, catalyst and conditions for the synthesis of 2aa.
 | ||||||
|---|---|---|---|---|---|---|
| Entry | Cat. (mol%) | [CF3S]+ (eq.) | Solv. | Base (eq.) | Yieldb [%] | e.r.c (S : R)d |
| 1 | A2 (5) | I (3) | Et2O | Cs2CO3 (2) | 80 | 82 : 18 |
| 2 | A2 (5) | II (3) | Et2O | Cs2CO3 (1.1) | 70 | 75 : 25 |
| 3 | A2 (5) | III (3) | Et2O | Cs2CO3 (1.1) | 0 | — |
| 4 | A2 (5) | IV (3) | Et2O | Cs2CO3 (1.1) | 0 | — |
| 5 | A1 (5) | I (1.5) | Et2O | Cs2CO3 (1.1) | 77 | 90 : 10 |
| 6 | A1 (5) | I (1.2) | Et2O | K2CO3 (0.2) | 89 | 89 : 11 |
| 7 | A1 (5) | I (1.2) | iPr2O | K2CO3 (0.2) | 85 | 87 : 13 |
| 8 | A1 (5) | I (1.2) | THF | K2CO3 (0.2) | 66 | 76 : 24 |
| 9 | A1 (5) | I (1.2) | CH2Cl2 | K2CO3 (0.2) | 53 | 75 : 25 |
| 10 | A1 (5) | I (1.2) | PhCH3 | K2CO3 (0.2) | 56 | 84 : 16 |
| 11 | A1 (5) | I (1.2) | Et2O | KOAc (0.2) | 25 | 90 : 10 |
| 12 | A1 (5) | I (1.2) | Et2O | NaOPh (0.2) | 71 | 89 : 11 |
| 13 | A1 (5) | I (1.2) | Et2O | K2HPO4 (0.2) | 88 | 90 : 10 |
| 14 | A1 (5) | I (1.05) | Et2Oe | K2HPO4 (0.2) | 82 | 91 : 9 |
| 15f | A1 (5) | I (1.05) | Et2Oe | K2HPO4 (0.2) | 90 | 93 : 7 (98 : 2)g |
| 16f | A1 (5) | I (1.05)h | Et2Oe | K2HPO4 (0.2) | 90 | 95 : 5 |
| 17f,i | A1 (3) | I (1.05) | Et2Oe | K2HPO4 (0.2) | 90 | 93 : 7 |
a
All reactions were run for 20 h at room temperature using 0.1 mmol 1a in the indicated solvent (0.1 M with respect to 1a) with the given reagents and catalysts unless otherwise stated.
b
Isolated yields.
c
Determined by HPLC using a chiral stationary phase.
d
Absolute configuration was determined by X-ray diffraction analysis of single crystals of enantioenriched (S)-2a.21
e
0.05 M with respect to 1a.
f
Run at –20 °C.
g
After recrystallization.
h
Added with a syringe pump over 5 h.
i
1 mmol scale.