Table 1. Optimization Study of the Cyclocarbonylative Sonogashira Reaction Between 2-Ethynylbenzamide 1 and Iodobenzene 2a.
selectivityc (%) |
|||||||
---|---|---|---|---|---|---|---|
entrya | solvent | T (°C) | t (h) | conversionb (%) | 3a | 4a | 5a |
1 | CH2Cl2 | 100 | 4 | 80 | 57 (34) | 43 (21) | |
2 | CH2Cl2 | 100 | 8 | 78 | 39 | 61 | |
3d | CH2Cl2 | 100 | 4 | 69 | 28 | 72 | |
4 | CH2Cl2 | 70 | 24 | 79 | 29 | 71 | |
5 | CH2Cl2 | 50 | 24 | 78 | 21 | 79 (42) | |
6 | THF | 100 | 4 | 94 | 29 | 71 (44) | |
7 | THF | 50 | 24 | 79 | 21 | 79 | |
8 | THF | 30 | 24 | 16 | 26 | 74 | |
9 | CH3CN | 100 | 4 | 85 | 78 | 22 | |
10 | CH3CN | 50 | 24 | 83 | 38 | 62 | |
11 | DMF | 100 | 4 | 100 | 33 | 32 | 35 |
All reactions were carried with 2-ethynylbenzamide 1 (1.0 mmol), iodobenzene 2a (1.0 mmol), CO (20 atm), PdCl2(PPh3)2 (0.4 mol %), Et3N (1.5 mL), and the solvent (4.0 mL), unless otherwise stated.
Conversion was determined by the 1H NMR peak integration on the crude product.
Selectivity was estimated by 1H NMR spectroscopy; isolated yields of pure products are reported in parentheses.
Reaction performed with 1 mol % of PdCl2(PPh3)2.