Table 1.
Method development of the TCT-catalyzed Pictet–Spengler reaction for the condensation of tryptamine (1) and 4-tolualdehyde (2a).
| Entry | Solvent | Temp. (°C) | TCT (mol %) | Time (h) | Isolated yield (%) |
| 1 | EtOH | 85 | 20 | 16 | 61a |
| 2 | acetonitrile | 85 | 20 | 16 | 75a |
| 3 | toluene | 110 | 20 | 16 | NRb |
| 4 | DMSO | 100 | 5 | 16 | 45 |
| 5 | DMSO | 100 | 10 | 16 | 68 |
| 6 | DMSO | 100 | 20 | 4 | 85c |
| 7 | DMSO | 100 | 30 | 8 | 78d |
| 8 | DMSO/N2 | 100 | 20 | 8 | 92 |
aStarting material recovered, ban intermediate imine observed as the major product, cfully aromatic β-carboline observed as a side product on TLC, dformation of multiple spots observed on TLC.