aza-Wittig Reaction with Nitriles: How Carbonyl Function Switches from Reacting to Activating

Abstract

Transformations of α-EWG-substituted (electron-withdrawing group, EWG) γ-azidobutyronitriles proceeding via unusual aza-Wittig reactions between the phosphazene and nitrile functions and affording pyrrole-derived iminophosphazenes were developed. α-EWGs were found to control chemoselectivity and, depending on their nature, act as CN group activators (e.g., ester, amide, or nitrile) or competitors (e.g., ketone) in aza-Wittig reactions. To demonstrate the synthetic utility of the obtained iminophosphazenes as N,N-binucleophiles, their transformations into pyrrole-fused systems, pyrrolo­[1,2-a]­imidazoles and pyrrolo­[1,2-a]­[1,3]­diazepines, were carried out.

Time‐Dependent Diastereodivergent Michael Addition Enabled by Phosphazenes Acting as Catalysts and Reactants

“…Recently, we reported an interesting and rare example of an aza ‐Wittig reaction taking place between phosphazenes and nitriles [5d,11] . Treating azides 1 , wherein the CN group is activated by α ‐EWG, with PPh 3 triggered a cascade of Staudinger and aza ‐Wittig reactions leading to phosphazene‐substituted pyrrolidines 3 via acyclic phosphazenes 2 as intermediates (Scheme 2).…”

High Nitrile Yields of Aerobic Ammoxidation of Alcohols Achieved by Generating •O2– and Br• Radicals over Iron-Modified TiO2 Photocatalysts

“…Nitriles are important intermediates in organic synthesis and a crucial moiety with a wide application in medicinal, organic, and polymer chemistry. , General methods for synthesizing nitriles mainly include the nucleophilic cyanation of alkyl halides, Wittig reactions, and transition-metal-catalyzed cyanation of arenes. , However, these methods demonstrate the drawbacks associated with using high-cost starting materials, the generation of toxic wastes, and the poor atomic efficiency. Therefore, much effort has been devoted to developing novel catalytic methods for the environmentally friendly synthesis of nitriles.…”

One-Pot Synthesis of Core Structure of Shewanelline C Using an Azidoindoline

“…To verify our initial concept (plan A), we tried a condensation of amine 6a with isatoic anhydride 3a ; unfortunately, the desired product 2aa was obtained in 1% yield and undesired uncyclized product 7aa was obtained in 55% yield (Scheme b). To avoid this undesired reaction, iminophosphorane 4a generated in situ from 5a and PPh 3 , a less nucleophilic nitrogen nucleophile, was selected (Scheme c; plan B). , The second approach through the iminophosphorane led to the formation of the desired product 2aa in 45% yield. The one-pot formation of 2aa represented our key step and highlighted the fine-tunable nucleophile approach to afford an unprecedented indole-quinazoline-2,4-dione framework which is difficult to make by other methods.…”

“…Based on the above-mentioned experimental results and the reported literature, , a possible reaction mechanism is proposed (Scheme ). Initially, the reaction proceeds via a chemo-selective aza-Wittig reaction between the iminophosphorane 4a generated in situ and isatoic anhydride 3a to afford the intermediate 12 under the neutral anhydrous reaction conditions.…”