Synthetic methods for the installation of nitrogen- containing quaternary centers in complex bioactive natural products
Nitrogen-containing quaternary centers are a common moiety found in alkaloid natural products. However, synthetic chemists lack many options for their efficient construction. Four methods for the installation of nitrogen-containing quaternary centers and their application toward natural product synthesis are described. (1) The synthesis of indolin-3-ones via a novel multi-oxidation of indoles to indolones is described. (2) The Ugi 4-component-3-center reaction of levulinic acids to generate pyroglutamic acid analogues is explored, including the development of a new convertible isocyanide. (3) An improved version of the Ugi 4C-3C reaction of cyclic ketimines is introduced and the increased scope of the reaction is discussed. (4) The Ugi 4C-3C reaction of \[delta\]-ketoacids is used to complete a model system of natural product marcfortine A.