Efforts Toward a Unified Kainoid Family Synthesis Approach: Unexpected Sulfinamide‐Directed Conjugate Addition Results

Abstract

A short asymmetric synthesis of an all-syn and alltrans kainoid core is reported. The synthetic route relies on the application of a new asymmetric [3 + 2] annulation reaction followed by a conjugate addition reaction to install this kainoid's three stereocenters. A surprising intramolecular conjugate addition enabled by the chiral tert-butylsulfinyl group residing on the 3-pyrroline nitrogen atom surpassed its expected role as a steric spectator. Efforts to outcompete intramolecular 1,4-addition by further oxidizing the sulfoxide, or use of additives, and advancement of the all-syn addition product to the requisite kainoid common core are detailed. Results and DiscussionOur initial synthetic approach is presented in Scheme 2. Assembly of the targeted chiral 3-pyrroline product (3) with the desired stereochemistry at C2 was easily accomplished in one [a] Dr.

Gilman reagent toward the synthesis of natural products

“…106,107 In 2019, Chogii et al proposed an efficient and simple synthetic route towards the synthesis of (+)-α-allokainic acid 240 (Scheme 27). 108 In their synthetic scheme, the imine 234 and compound 235 were made to react in the presence of LDA and THF to provide pyrrolidine 236 (in 74% yield), which underwent further reaction with Gilman reagent via treatment with compound 237 in the presence of diethyl ether and TMSCl at −78 °C to furnish a mixture of compound 238 (in 79% yield) and compound 239 (dr = 1.5 : 1). The compound 238 was modified in a few steps to complete the synthesis of (+)-α-allokainic acid 240 .…”