Cyclization Cascade of Allenyl Azides:  A Dual Mechanism

Abstract

A density functional theory based computational approach to describing the mechanistic course of the allene azide cycloaddition cascade sequence has been developed. The results of these calculations permit characterization of key reactive intermediates (diradicals and/or indolidenes), and explain the different behaviour observed in the experimental studies between conjugated and non-conjugated species. Furthermore, computational analysis of certain intermediates offer insight into issues of regioselectivity and stereoselectivity in cases where different reaction channels are in competition, suggesting suitable substitutions to achieve a single regioisomer in the indole synthesis via azideallene cyclization.

Cyclization Cascade of Allenyl Azides: Synergy Between Theory and Experiment

“…The electron delocalization is severed at the scissile C—N and N—N bonds, thus indicating that this is not a pericyclic type transition state, bound to satisfy the W-H rules, but an accidentally simultaneous cleavage of two bonds requiring no participation of the conjugated system. Further calculations aimed at quantifying the level of aromaticity at the cleaving bonds in this transition state also confirm the lack of aromaticity at the triazoline ring and the absence of ring currents typically associated with pericyclic transition states [24]. …”

“…11). This approach, while, offering improved regioselectivity [24], presents a number of disadvantages: the bulky substituents are not easily manipulated, yields are lower in some cases and the improved regioselectivity obtained is still very far from complete.…”

Theoretical investigations toward the tandem reactions of N-aziridinyl imine compounds forming triquinanes via trimethylenemethane diyls: mechanisms and stereoselectivity

“…In the present study, we theoretically investigated the tandem reactions in detail, and two representative N-aziridinyl imine compounds in which R 1 = R 2 = R 3 = R 4 = H (reaction 1 shown in Scheme 1) and R 1 = CH 3 , R 2 = R 3 = R 4 = H (reaction 2 shown in Scheme 4) were selected as our reactants. The wellknown UB3LYP density functional has been demonstrated to perform excellently well in other diradical systems, [27][28][29][30][31][32][33] and thus was selected as our calculation method. The following discussion will clarify the detailed reaction mechanisms for this tandem reaction process and disclose the factors responsible for the observed stereocontrol.…”

A stepwise retro‐imino‐ene as a key step in the mechanism of allene formation via the Crabbé acetylene homologation

“…[1] Allenes also play a relevant role in organic synthesis,[2] fullerene chemistry,[3] and show interesting chiroptical properties. [4] Our interest for these compounds is not only limited to the chiroptical properties of alleno‐acetylenic macrocycles[5] but also to explore the potential of allenyl azides as potential precursors of substituted indoles[6] and the peculiar stereoelectronic and reactive properties of allenes derivatives. [7] Following this line of work, we were exposed to the seminal contribution to allene formation by Crabbé et al[8] This procedure is often used to obtain allene compounds via homologation of acetylene precursors in the presence of diisopropylamine and formaldehyde (Fig.…”