Silver(I)‐Catalyzed Tandem Approach to β‐Oxo Amides

Abstract

A facile and efficient AgI‐catalytic approach is reported for the first time to synthesize β‐oxo amides from β‐oxo esters a with broad substrate scope in good to excellent yields. Crossover and in situ NMR studies confirmed that the reaction occurred through a new pathway and not by the traditional condensation reaction. The key advantages of this method are the readily available starting materials, the air‐stable reaction, the simple protocol, and the environmental friendliness.

β‐Keto Amides: A Jack‐of‐All‐Trades Building Block in Organic Chemistry

“…Woodward and co‐workers [43] used air‐stable AlMe 3 and DABCO adduct (DABAL‐Me 3 , 29 ), to promote the aminolysis of methyl 3‐oxohexanoate to β ‐keto amide 30 in 89 % yield (Scheme 6d). Besides, AgOTf‐catalyzed, [44] microwave‐assisted, [45] and hexafluoroisopropanol‐promoted [46] procedures have also been developed.…”

Route exploration and synthesis of the reported pyridone-based PDI inhibitor STK076545

“…Starting from b-keto ester 3, we first tested a Ag(I)-catalyzed aminolysis (Scheme 4). 18 Rather than observing conversion to the desired b-keto amide, reaction monitoring via LC-MS when using condition A showed masses associated with ester 21 and amide 24 (Scheme 5). Similarly, when heating ester 3 with N,N-diethyethylenediamine in toluene at 80 ºC with or without DMAP, the same decomposition peaks were present.…”

“…12 Direct aminolysis of b-keto esters 13 or b-keto thioesters 14 at high temperature is possible (approach 'd'), but can be compromised by competing enamine formation. Aminolysis reactions catalyzed with DMAP, 15 enzymes, 16 or transition metals [17][18] have also been reported. Alternatively, addition of a ketone or enamine to an isocyanate have also been reported (approach 'e').…”

Aza-Riley Oxidation of Ugi-Azide and Ugi-3CR Products toward Vicinal Tricarbonyl Amides: Two-Step MCR-Oxidation Methodology Accessing Functionalized α,β-Diketoamides and α,β-Diketotetrazoles

“…The former are readily prepared by the Claisen reaction . However, diverse sets of β-ketoamides are difficult to prepare, with recent methodology offering some improvement . Unfortunately, in both cases β-diketone syntheses require catalysts or metal reagents and are restricted by a lack of diversity elements.…”