As a young pup, I cut my teeth in a few guest posts over at Paul's place. Since I saw a sexy, streamlined version of one molecule go by in Org. Lett. last week, I decided to do a (memorial? celebratory?) post in true Tot Syn style.
Folks who've read the other syntheses might agree with me that the trigonoliimines, as drawn by Tambar, resemble a terrifying pterodactyl:
|Respectfully stolen from Tot Syn|
Hao aims to use two fairly well-known reactions to join his tryptamines: a modified Strecker, followed by a Houben-Hoesch cyclization. First, the group pops open a methoxylated, phthalamide-protected Trp precursor using CuCl under oxidative conditions (the 'cool' kids use blue LEDs now). Now they've set the stage for the really short racemic synthesis:
Initial TMS-promoted imine condensation with the aryl ketone sets up a CN alkylation, which cyclizes on the nearby formamide (probably through an isonitrile). Now here comes a 7-membered Houben-Hoesch ring closure, which they perform in a one-pot prep due to instability of the methoxy-Strecker intermediate. Basic workup, followed by hydrazine deprotection / cyclization, produces Trigonoliimine A, in a respectable 35% yield (4 steps, 3 pots).
Godspeed Dr. Docherty, wherever you are...
Update: Neil posits that Paul is still alive and well, and writing for Chemistry World.