Table 7.
Entry | R | P | R1 | R2 | Base | Solvent | Pd-Source | Liganda | drb | Yield |
---|---|---|---|---|---|---|---|---|---|---|
1 | Boc | H | H | NaOtBu | Toluene | Pd(OAc)2 | Dppe | - | 75%c | |
2 | Boc | H | H | Cs2CO3 | DME | Pd(OAc)2 | Dpe-phos | - | 76% | |
3 | Ac | H | H | NaOtBu | Toluene | Pd2(dba)3 | Xantphos | - | 67% | |
4 | Cbz | H | H | Cs2CO3 | DME | Pd(OAc)2 | Dpe-phos | - | 88% | |
5 | Boc | Ph | H | NaOtBu | Toluene | Pd2(dba)3 | Dppb | >20:1 | 60% | |
6 | Boc | Ph | H | Cs2CO3 | Dioxane | Pd(OAc)2 | Dpe-phos | >20:1 | 75% | |
7 | Ac | Ph | H | NaOtBu | Toluene | Pd2(dba)3 | Dppb | >20:1 | 82% | |
8 | Boc | H | Me | Cs2CO3 | Dioxane | Pd(OAc)2 | Dpe-phos | 15:1 | 76% | |
9 | Ac | H | Me | NaOtBu | Toluene | Pd2(dba)3 | Dpe-phos | >20:1 (10:1) | 61% | |
10 | Cbz | H | Me | Cs2CO3 | Dioxane | Pd(OAc)2 | Dpe-phos | 12:1 | 80% |
Conditions: 1.0 equiv amine, 1.1-1.2 equiv R-Br, 1.2-2.3 equiv base, 1 mol % Pd2(dba)3 or 2 mol % Pd(OAc)2, 2-4 mol % ligand, toluene or dioxane or dme (0.25 M), 85-105 °C.
Diastereomeric ratios are for isolated products. Diastereomeric ratios observed in crude reaction mixtures are given in parentheses if they changed upon isolation.
The reaction was conducted at 65 °C.