Table 1. Identification of the Optimum Conditions and the Best-Suited Chiral Amine Leaving Group for the Ammonium Ylide-Mediated Synthesis of 3b.
| entry | amine | base (equiv) | cond.a | yieldb (%) | drc (trans/cis) | er (trans)d |
|---|---|---|---|---|---|---|
| 1 | Me3N | K2CO3 (4×) | A | traces | ||
| 2 | Me3N | Cs2CO3 (4×) | A | 69 | 3.3:1 | |
| 3 | Me3N | t-BuOK (2×) | A | 76 | 13:1 | |
| 4 | Me3N | DBU (3×) | A | 55 | 2.8:1 | |
| 5 | Me3N | Cs2CO3 (5×) | B | 86 | 2.5:1 | |
| 6 | QD1 | Cs2CO3 (5×) | C | 9 | 6:1 | n.d. |
| 7 | QD2 | Cs2CO3 (5×) | C | 79 | 1.8:1 | 2:98 |
| 8 | QD3 | Cs2CO3 (5×) | C | 59 | 3.3:1 | 2.5:97.5 |
| 9 | QD4 | Cs2CO3 (5×) | C | n.d. | ||
| 10 | Q1 | Cs2CO3 (5×) | C | 3 | 3.1:1 | n.d. |
| 11 | Q2 | Cs2CO3 (5×) | C | 85 | 2.5:1 | >99.8:0.2 |
| 12 | Q3 | Cs2CO3 (5×) | C | 57 | 2.7:1 | 99.5:0.5 |
| 13 | Q4 | Cs2CO3 (5×) | C | n.d. | ||
| 14 | Q2 | Cs2CO3 (6×) | D | 98 | >40:1 | >99.8:0.2 |
a
All reactions were carried out using 0.1 mmol 5a in CH2Cl2 (A: with 1 equiv 1a, rt, 24 h; B: with 1.5 equiv 1a, rt, 24 h; C: with 2.5 equiv 1a, rt, 72 h; D: with 2.5 equiv 1a, reflux, 96 h.
b
Isolated yields.
c
Determined by NMR analysis of the crude product.
d
Determined by HPLC using a chiral stationary phase.