Table 1.
Optimization of the Pd-Catalyzed Annulation of Benzynea
 | ||||
|---|---|---|---|---|
| entry | ligand (mol %) | additive (equiv) |
solvent ratio (toluene/MeCN) |
% yield of 3ab |
| 1 | -------- | -------- | 4:1 | 10 |
| 2 | PPh3 (10) | -------- | 4:1 | 13 |
| 3 | P(o-tolyls)3 (10) | -------- | 4:1 | 50 |
| 4 | dppm (10) | -------- | 4:1 | 66 |
| 5 | dppe (10) | -------- | 4:1 | 30 |
| 6 | dppf (10) | -------- | 4:1 | 25 |
| 7 | L (10)c | -------- | 4:1 | 56 |
| 8 | dppm (5) | -------- | 4:1 | 53 |
| 9 | dppm (10) | Na2CO3 (1) | 4:1 | 73 |
| 10 | dppm (10) | K2CO3(1) | 4:1 | 70 |
| 11 | dppm (10) | Cs2CO3(1) | 4:1 | 67 |
| 12 | dppm (10) | Na2CO3 (2) | 4:1 | 57 |
| 13 | dppm (10) | Na2CO3 (1) | 3:1 | 52 |
| 14 | dppm (10) | Na2CO3 (1) | 6:1 | 49 |
| 15 | dppm (10) | Na2CO3 (1) | 4:1 | 50d |
| 16 | dppm (10) | Na2CO3 (1) | 4:1 | 60e |
a
All reactions were run using substrate 1a (0.25 mmol), 5 mol % of Pd(OAc)2, 2.0 equiv of 2a, 5.0 equiv of CsF, 5 ml of solvent at 110 °C for 16–24 h, unless otherwise specified.
b
Isolated yield.
c
o-(Dicyclohexyl-phosphino)biphenyl.
d
The reaction was conducted at 90 °C for 12 h, at which time the Pd had precipitated out.
e
1.6 Equiv of 2a and 4.0 equiv of CsF were employed.