Horner−Wadsworth−Emmons Reagents as Azomethine Ylide Analogues: Pyrrole Synthesis via (3 + 2) Cycloaddition

Abstract

Amido-substituted Horner-Wadsworth-Emmons reagents can serve as precursors to 1,3-dipoles for use in cycloaddition. These compounds are assembled in one pot via the TMSOTf-catalyzed Arbuzov reaction of imines, acid chlorides, and phosphites. The coupling of this synthesis with alkyne cycloaddition provides a three-component synthesis of pyrroles. The dipoles can be prepared with a diverse range of imines and acid chlorides, and (3 + 2) cycloaddition with unsymmetrical alkynes is highly regiospecific, providing a modular approach to form substituted pyrroles.

Recent advances in the synthesis of pyrroles by multicomponent reactions

“…In a refinement of their previous work on the synthesis of pyrroles by 1,3-dipolar cycloadditions of phosphorus-based 1,3-dipolar substrates, 88 the Arndtsen group has reported the preparation of pyrroles by reaction between imines, alkynes and acyl halides in the presence of phosphites (Scheme 67). 89 This transformation proceeds via the combination of a Lewis acid-catalyzed Arbuzov reaction with an alkyne 1,3-dipolar cycloaddition. Thus, the initial reaction between the imine and acyl halide components provides intermediate 53, which is transformed into the amido-substituted Horner-Wadsworth-Emmons reagent 54 by reaction with the phosphite followed by deprotonation.…”

Practical Synthesis of Phenanthrid­inones by Palladium‐Catalyzed One‐Pot C–C and C–N Coupling Reaction: Extending the Substrate Scope to o‐Chlorobenzamides

“…Arndtsen and co‐workers reported a series of excellent studies5 in which the acyliminium salt was used as an interesting intermediate with addition to various nucleophiles, involving palladium species,5a–g phosphine derivatives,5h–k copper acetylides,5l indium reagents,5m and isocyanides 5o. Enlightened by this knowledge and the strategy of electrophilic cyclizations via an acyliminium intermediate,6 we proposed an acyliminium/amidoallenylium species 1 which could be trapped by an intramolecular nucleophile to produce the highly substituted allene intermediate (Scheme ).…”

Cycloamination strategies for renewable N-heterocycles

“…[62][63][64][65][66][67][68] In view of the versatility of substituted pyrroles, many renewed synthetic methods have been developed to construct these types of unique N-heterocycles, such as metal-catalyzed cyclization, cycloaddition, rearrangement, aza-Wittig, multicomponent/ oxidative coupling, hydroamination/cyclization, and isocyanide-based reactions. [69][70][71][72][73][74][75][76][77][78][79] Instead of fossil-based resources, synthesis of pyrroles by full or partial use of renewable resources via newly-developed reaction routes is a highly desirable goal in sustainable chemistry. However, in these methods, leaching of metal species may cause serious environmental issues that should be taken into consideration for metal-mediated catalytic systems, especially with respect to the catalyst stability and reusability.…”