The Growing Synthetic Utility of Weinreb′s Amide

Chemoenzymatic synthesis of the chiral side-chain of statins: application of an alcohol dehydrogenase catalysed ketone reduction on a large scale

“…1 Synthetic HMG-CoA reductase inhibitors rosuvastatin and atorvastatin method turned out to be unreliable in our hands, a finding confirmed by others as well [21][22][23]. 1 Improved yields in the C-acylation of enolates have been reported for the application of Weinreb amides as acylating reagents [26][27][28]. Indeed, we obtained diketo ester 10 in a 58% yield after purification by column chromatography on acidwashed silica gel when we employed commercially available 2-chloro-N-methoxy-N-methyl acetamide for the acylation of bisenolate 12 [15][16][17].…”

“…Presumably, the a-chloro substituent of methyl chloroacetate 14 can stabilise the primary tetrahedral addition intermediate which prevents the harmful liberation of the newly formed keto group prior to hydrolytic work-up. The same protective effect is assigned to the N-methoxy group of Weinreb amides in this kind of ketone synthesis[26][27][28].…”

Enantioselective Construction of Quaternary Stereocenters

“…[22a] This diphosphane, bearing planar as well as central stereogenic elements, forms trans chelate complexes with rhodium. Cyanoacetamides such as 26 (Weinreb amide) [23] which acted as Michael donors were reported to be alkylated in the a-position by vinyl ketones or acrolein under the reaction conditions used.…”

Synthesis of Indole‐Derived Allocolchicine Congeners through Pd‐Catalyzed Intramolecular C‐H Arylation Reaction

“…Thus, we envisaged that the tetracyclic scaffold of both rac-9 and rac-10 could be formed by direct intramolecular C-H arylation reaction [12] of aryl iodides 11 and 12, respectively (Scheme 1). Precursor 11 might be accessible through a Weinreb ketone synthesis [13] by starting from commercial acid 13 and 1-methyl-1H-indole (14). Substrate 12 could be formed through Friedel-Crafts acylation reaction of 14 [14] with a suitably functionalized acylation reagent, again derived from 13.…”