Why Do Some Fischer Indolizations Fail?

Abstract

The mechanisms of the Fischer indole synthesis and competing cleavage pathways were explored with SCS-MP2/6-31G(d) and aqueous solvation calculations. Electron-donating substituents divert the reaction pathway to heterolytic N–N bond cleavage and preclude the acid-promoted [3,3]-sigmatropic rearrangement.

Fischer Indolizations as a Strategic Platform for the Total Synthesis of Picrinine

“…23,31 Finally, the viability of the Fischer indolization reaction was a notable concern considering the substrate's complexity, its differences compared to ketolactone 19 used in the synthesis of aspidophylline A, 23 and our prior experiences with challenging Fischer indolizations of related substrates. 32 ■ RESULTS AND DISCUSSION Initial Forays and First-Generation Retrosynthetic Analysis. Based on the synthetic plan mentioned above, we tested the Fischer indolization of ketone 24, a known intermediate from our prior synthesis of aspidophylline A ( Figure 5).…”

Pardon the Interruption: A Modification of Fischer’s Venerable ­Reaction for the Synthesis of Heterocycles and Natural Products

“…We pursued the natural product psychotrimine, which led to mechanistic insight pertaining to the Fischer indolization and an exciting collaboration with my colleague Professor Ken Houk. 22 We used the interrupted Fischer indolization to construct the core of the communesins. 23 Moreover, we completed a concise synthesis of phenserine, 24 a compound undergoing clinical trials for the treatment of Alzheimer’s disease.…”

An asymmetric pericyclic cascade approach to 3-alkyl-3-aryloxindoles: generality, applications and mechanistic investigations

“…12), which provided the best results in an equivalent key [3,3]-sigmatropic rearrangement step of the acid-promoted Fischer indole reaction, where B3LYP optimizations were shown to yield highly asynchronous and dissociative transition states. 40 In the first step of the pericyclic cascade mechanism, the 3 + 2 cycloaddition between nitrone and ketene across the CvO bond forms the substituted 1,2,4-dioxazolidine. The 3 + 2 cycloaddition transition structure, TS-(3 + 2), is predicted to be 16.7 kcal mol −1 uphill from the starting nitrone and ketene (Fig.…”