1 research outputs found
Intramolecular additions of various π-nucleophiles to chemoselectively activated amides and application to the synthesis of (±)-tashiromine
Abstract: Vilsmeier-Haack type cyclizations proved to be particularly efficient for generating parts of the polycyclic
cores of many alkaloids, although only monocyclizations have so far been reported. With the goal of
rapidly and efficiently constructing polycyclic alkaloids, we decided to exploit the Vilsmeier-Haack
reaction by utilizing iminium ions successively generated and trapped with tethered nucleophiles. To
develop such a strategy, we had to set the first cyclization. This constitutes a great challenge in itself
because amide activation conditions are usually not compatible with tethered nucleophiles, except for
indoles and aromatic rings which have already been reported. This paper describes the comprehensive
study of intramolecular addition of silyl enol ethers, allylsilanes, and enamines to chemoselectively activated
formamides, aliphatic amides, and lactams. Good to excellent yields were obtained for the 5-exo, 6-exo,
and 6-endo modes of cyclization. Moreover, we demonstrated that the species in solution after the
cyclization are iminium ions. This is highly encouraging for the development of bis-cyclization strategies.
An expeditious total synthesis of (()-tashiromine is also reported