The Growing Synthetic Utility of Weinreb′s Amide

Abstract

Since the original discovery of Weinreb [1], that N-methoxy-N-methyl amides 1, now popularly called as Weinreb amides (WA), cleanly reacted with Grignard reagents and organolithium to produce ketones, these amides have gained wide importance as very effective acylating agents for various organometallic reagents The esters and lactones have been invariably converted [5a -g] to Weinreb amides (Scheme 2) by using a combination of trimethyl aluminium and

Investigation of the reaction of α-thioamides, α-esters and α-nitriles with N-halosuccinimides

“…[17][18][19] The Weinreb amide 20 was prepared as reported, 17 however triethylamine was used in place of pyridine to give the amide as a clear oil in 76% yield. The -thioamide was then prepared as described previously 1 using thiophenol and sodium in ethanol for 18 hours.…”

Direct Acylation of C(sp3)−H Bonds Enabled by Nickel and Photoredox Catalysis

“…Classic approaches to the synthesis of this valuable motif require multistep processes and prefunctionalized reagents. [9, 10] An α-amino C(sp 3 )–H carbonylation has been previously reported by Murai and co-workers utilizing a rhodium catalyst, CO, and ethylene. However, this reaction requires a 2-pyridyl directing group on the amine substrate, temperatures exceeding 100°C, and only generates ethyl ketones.…”

Merging Photoredox and Nickel Catalysis: The Direct Synthesis of Ketones by the Decarboxylative Arylation of α‐Oxo Acids

“…Moreover, ketones are a common structural element found in a wide range of agrochemicals, bioactive natural products, pharmaceuticals, and electronic materials (including photovoltaics). [5] Common protocols for ketone synthesis currently include (i) organometallic additions to Weinreb amides, [6] (ii) Stille couplings between acyl chlorides and stannanes, [7] (iii) metal-catalyzed carbonylations between aryl halides and prefunctionalized transmetallation reagents (e.g. boronic acids), [8] and (iv) alkene hydroacylations.…”