Silver(I) Triflate Catalysed PS Reactions

29 Feb
Published by KatB

Before I started on the triflic acid catalysed Pictet-Spengler reactions (see here), I was working on the silver(I) triflate catalysed reactions.

Initially started with small test reactions with copper(II) triflate and silver(I) triflate with the dimethoxy N-benzoyl PZQ analogue in attempts to isolate the enediamide intermediate (KAB11-1, KAB11-2 and KAB11-3). Instead, the Lewis acids cleanly and efficiently produced the completely cyclised product (R1 = OMe, R2 = Ph).
More attempts to give the dimethoxy N-benzoyl PZQ analogue (copper with KAB8-3, silver with KAB8-4). Attempts were made to produce PZQ using catalytic AgOTf and Cu(OTf)2, however only the enediamide intermediate was obtained (KAB3-9 and KAB3-10).
I'm currently focussing on obtaining yields and monitoring the reactions for the AgOTf catalysed (10 mol%) PS reactions to give PZQ and the 3 analogues (so far only KAB8-15).  Although, for the non-dimethoxy peptide acetal starting materials, it's expected that only the enediamides will be obtained.
I'm fairly confident that as long as the silver does not get reduced, the reactions to give the dimethoxy PZQ analogues will go to completion (possibly 100% conversion). So far, the silver survives for about 1-2 hours at most before it becomes a black solid in the bottom of the flask. I've tried doing the reaction in the dark under anhydrous conditions, but I think it's probably caused by something from my substrate.
Progress as of 06/03/12

  • Completed dimethoxy N-benzoyl PZQ analogue (KAB8-15)
  • Completed dimethoxy PZQ analogue (KAB1-6)
  • Incomplete: N-benzoyl PZQ analogue enamide (KAB17-2)
  • To do: PZQ enamide (to be named KAB13-3)

Table of yields for the AgOTf (10 mol%) catalysed PS reactions: