Initial investigations focused on the reaction of 1a in the presence of con. HCl to generate 2a. We were pleased to find that with con. HCl as the solvent, this reaction provided isoquinoline 3a in 35% yield and 8% yield of desired product 2a after 16 h at room temperature (Table , entry 1). This initial experiment established the feasibility of the proposed sequence albeit in very low yield. We next examined the reaction in a variety of alternative solvents using organic acid as an additive. As shown in entries 2-8 of Table , these studies revealed that in the presence of acetic acid at reflux temperature, only enamine 4a was isolated in 61% yield suggesting that acetic acid was insufficiently acidic to deprotect the BOC group under this condition. Gratifyingly, the reaction proceeded efficiently with trifluoroacetic acid (TFA) as the solvent, yielding 67% of the desired product after 2 h at room temperature. Heating 1a at 50 ºC under TFA did not improve the yield (53% isolated). With further optimization, we found out that dichloromethane was the optimal cosolvent. In a dichloromethane/TFA mixture (1:1) at room temperature, the reaction proceeded efficiently giving the desired product in 58% yield. Finally, the best yields were obtained with a dichloromethane/TFA mixture (1v:1v) at 50 ºC. In this condition, the desired tetrahydro-3,4'-biisoquinoline is isolated in 73% yield. trace - [a] Conditions: 1a (0.2 mmol), in 1 mL solvent for 2 h at rt. [b] at 100°C. [c] solvent/TFA 1mL, (1v/1v). [d] at 50°C. [e] 20 equiv. [f] Isolated yields after chromatography