An Expedient Formal Total Synthesis of (-)-Diazonamide A via a Powerful Stereoselective O-Aryl to C-Aryl Migration to form the C10 Quaternary Center

摘要

During the course of studies on the synthesis of diazonamide A >1 an unusual O-aryl into C-aryl rearrangement was discovered that allows partial control of the absolute stereochemistry of the C-10 quaternary stereogenic center. Treatment of >30 with TBAF/THF gave the O-tyrosine ethers >31 and >32 (1:1), which on heating each separately in chloroform at reflux rearranged to >33 and >34 in ratios of (84:16) and (56:44) respectively. This corresponds to a 70% yield of the correct C-10 stereoisomer >33 and a 30% yield of the wrong C-10 stereoisomer >34. Attempts to convert >34 into >33 by ipso-protonation and equilibriation were unsuccessful. Confirmation of the stereochemical outcome of the rearrangement was obtained by converting >33 into >37, an advanced intermediate in the first synthesis of diazonamide A by Nicolaou et al. It was also found that the success of the above rearrangement is sensitive to the protecting group on both the tryptophan nitrogen atom and the tyrosine nitrogen atom.