Lewis Acid Catalysed Pictet-Spengler Reaction Model

12 Mar
Published by KatB

Over the next 12 weeks I will be working on a model system for the Lewis Acid catalysed Pictet-Spengler formation of substitued tetrahydroisoquinolines (e.g. 4).

After making the starting materials (3, R1 = H, OMe and R2 = H, NO2, OMe) I'll work on screening various Lewis Acids with a focus on silver(I) triflate, given recent results - see AgOTf post here.
If all goes reasonably well, the next stage will be to screen the reactions with added enantiopure bisoxazoline (BOX) ligands (5).[ref]

So far, I've started the preparation of the N-benzylidene-N-phenethylamine (R1=H, R2=H) starting material (KAB18-1) and will be making the dimethoxy substitued analogue (R1=OMe, R2=H), to be named KAB19-1, sometime this week.

Comments

MatTodd's picture

Right - you're making S/M and are going to develop a good protocol for screening this reaction, i.e. work through any handling issues of S/M and products, get a good TLC system in place, work out the HPLC conditions for examining the product. You're then going to use some BOX ligands for this reaction. But clearly it would be more efficient if you could hook up with others interested in doing this reaction, who might have ligands for Lewis acid-catalyzed reactions of this type. Kat, try to think of groups we could ask to join the campaign. If you're reading this and have BOX, or equivalent, ligands in the fridge you're interested in screening, let us know and we can work on the problem together. There are a lot of ligands in the world, and we don't want to have to make them all...