Table 4.
Optimization of Pd-catalyzed Suzuki-Miyaura cross-coupling of 2-B(pin)-substituted allylic acetate 1a.
| ||||||
|---|---|---|---|---|---|---|
| Entry | Pd/ligand[a] | Base[b] | Solvent[c] | Conc.(M)[d] | Time (h) | yield (%)[e] |
| 1 | Pd(OAc)2/PPh3 (15 mol %, 1:2) | Cs2CO3 | THF | 0.022 | 24 | 90[f] |
| 2 | Pd(OAc)2/PPh3 (10 mol %, 1:2) | Cs2CO3 | THF | 0.022 | 48 | 62 |
| 3 | Pd(OAc)2/P(o-Tol)3 (10 mol %, 1:2) | Cs2CO3 | THF | 0.022 | 48 | 20 |
| 4 | Pd(OAc)2/DPPP (10 mol %, 1:1) | Cs2CO3 | THF | 0.022 | 48 | 32 |
| 5 | Pd(OAc)2/DPPE (10 mol %, 1:1) | Cs2CO3 | THF | 0.022 | 48 | 27 |
| 6 | Pd(OAc)2/DPPF (10 mol %, 1:1) | Cs2CO3 | THF | 0.022 | 48 | 62 |
| 7 | Pd(OAc)2/P(t-Bu)3 (10 mol %, 1:1) | Cs2CO3 | THF | 0.022 | 48 | 80 |
| 8 | Pd(PPh3)4 (10 mol %) | Cs2CO3 | THF | 0.022 | 36 | 87 |
| 9 | PdCl2(PPh3)2/PPh3 (10 mol %, 1:1) | Cs2CO3 | THF | 0.08 | 24 | 71 |
| 10 | PdCl2(PPh3)2/PPh3 (10 mol %, 1:1) | Cs2CO3 | Dioxane | 0.08 | 18 | 61 |
| 11 | PdCl2(PPh3)2/PPh3 (10 mol %, 1:1) | CsF | Dioxane | 0.08 | 18 | 25 |
| 12 | PdCl2(PPh3)2/PPh3 (10 mol %, 1:1) | K3PO4 | toluene | 0.08 | 24 | 52 |
| 13 | Pd(OAc)2/PPh3 (10 mol %, 1:3) | Cs2CO3 | toluene | 0.17 | 4 | 96[f] |
| 14 | Pd(OAc)2/PPh3 (5 mol %, 1:3) | Cs2CO3 | toluene | 0.17 | 18 | 95[f],[g] |
| 15 | PdCl2(PPh3)2/PPh3 (5 mol %, 1:1) | Cs2CO3 | toluene | 0.17 | 18 | 93[f],[g] |
| 16 | Pd(PPh3)4 (10 mol %) | Cs2CO3 | toluene | 0.17 | 18 | 96[f],[g] |
mol % of Pd and molar ratio of Pd to phosphine provided in parenthesis.
3 equiv of base and iodobenzene used unless otherwise noted.
10:1 ratio of solvent to H2O.
Ratio of 1a (mmol)/solvent (mL).
Yield determined by 1H NMR integration of the crude reaction mixture using 1,4-dimethoxybenzene as the internal standard.
Yield of isolated and purified products.
2 equiv of Cs2CO3 and iodobenzene used.