Mild and Catalyst-Free Petasis/Decarboxylative Domino Reaction: Chemoselective Synthesis of N-Benzyl Propargylamines

Abstract

Multicomponent domino reactions are attractive for assembling functionalized compounds. To this end, a one-pot catalyst-free chemoselective synthesis of N-benzyl propargylamines is reported with good functional group compatibility. This mild process involves in situ formation of an active amine through Petasis reaction of primary amines, formaldehyde solution, and boronic acids, which reacts with propiolic acids to give product in up to 94% yield via decarboxylative coupling reaction.

Reactivity and Synthetic Applications of Multicomponent Petasis Reactions

“…This type of metal-free four-component PR was independently reported by two groups for the synthesis of N -benzyl propargylamines 108 – 111 . 130,131 It is noteworthy that two components of formaldehyde are involved in this transformation to form the initial benzyl hemiaminal intermediate 107 , and thus it can also be classified as a five-component reaction (Scheme 34). Substituted propargylamines are versatile substrates for the synthesis of diverse heterocycles via a variety of synthetic transformations, such as RCM, ROM, and enyne cyclization reactions.…”

Metal‐Free Decarboxylation of α,β‐Unsaturated Carboxylic Acids for Carbon–Carbon and Carbon–Heteroatom Coupling Reactions

“…In 2014, Feng and Sun disclosed a catalyst‐free Petasis/decarboxylative domino reaction for the chemoselective synthesis of N ‐benzyl propargylamines with good functional group compatibility (Scheme 4a). [17] A one‐pot four‐component coupling of a primary amine, formaldehyde, a boronic acid and a propiolic acid was carried out to yield the target products (34 examples) in up to 94% yield.…”

CuBr–ZnI2 Combo-Catalysis for Mild CuI–CuIII Switching and sp2 C–H Activated Rapid Cyclization to Quinolines and Their Sugar-Based Chiral Analogues: A UV–Vis and XPS Study

“…Thus, activating an sp 2 C–H bond, especially in electron-rich arenes such as anilines, − under mild conditions is desirable and will open up new opportunities toward the selective construction of ubiquitous heterocycles such as quinolines and their valuable chiral analogues through multicomponent − domino cyclization − reactions. In this regard, we envisaged the development and exploitation of a new Cu I –Cu III switching catalysis − under mild conditions, which would efficiently deliver C–H-activated C–C/C–X bonds to form functional groups with tandem cyclization toward an unprecedented general synthesis of quinolones, with an improved reaction rate, selectivity, and substrate scope. The mechanisms of the widely used catalysis with Cu I -compounds − that pass through a Cu I –Cu III transition have not been thoroughly investigated.…”