Table 1.
Optimization of Pd-Catalyzed Suzuki-Miyaura Cross-Coupling of Amides
| Entry | Catalyst (mol%) | Boronic Acid (equiv) | Base (equiv) | H2O (equiv) | Yielda (%) |
|---|---|---|---|---|---|
| 1 | 1.5 | 1.2 | 2.0 | 0 | 56 |
| 2 | 1.5 | 1.2 | 2.0 | 5 | >98 |
| 3 | 0.25 | 1.05 | 1.1 | 5 | >98 |
| 4 | 0.05 | 1.05 | 1.1 | 5 | 32 |
| 5b | 0.05 | 2.0 | 1.1 | 5 | 74 |
| 6b,c | 0.05 | 2.0 | 3.0 | 5 | 85 |
| 7b,d | 0.05 | 2.0 | 3.0 | 5 | >98 |
| 8b,d | 0.025 | 2.0 | 3.0 | 5 | 96 |
Conditions: amide 7a, PhC(O)–NPh/Boc, (1.0 equiv), catalyst ([Pd(IPr)(μ-Cl)Cl]2) (x mol%), 4-Tol-B(OH)2 (1.05–2.0 equiv), K2CO3 (1.1–3.0 equiv), H2O (0–5 equiv), THF (0.25 M), 23°C, 12 h.
a
GC/1H NMR yields.
b
0.50 M.
c
Toluene.
d
40°C. See Transparent Methods for full details. IPr, 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene.