α-Arylation of Amides from α-Halo Amides Using Metal-Catalyzed Cross-Coupling Reactions

Abstract

Metal-catalyzed α-arylation of amides from α-halo amides with organometallic reagents is reviewed. The article includes Suzuki–Miyaura, Kumada–Corriu, Negishi, and Hiyama cross-coupling reactions.1 Introduction2 Suzuki–Miyaura Cross-Coupling2.1 Palladium Catalysis2.2 Nickel Catalysis3 Kumada–Corriu Cross-Coupling3.1 Nickel Catalysis3.2 Iron Catalysis3.3 Cobalt Catalysis4 Negishi Cross-Coupling5 Hiyama Cross-Coupling6 Conclusion

The Fascinating Chemistry of α‐Haloamides

“…The scope of amide arylation by reaction of aryl halides has been greatly expanded using zinc enolates generated from α‐bromoamides instead of alkali metal enolates . On the other hand, a polarity reversal by using a metal‐catalyzed cross‐coupling between α‐haloamides and aryl organometallics showed to be a valuable synthetic alternative.…”

“…The scope of amide arylation by reaction of aryl halides has been greatly expanded using zinc enolates generated from αbromoamides instead of alkali metal enolates. [225] On the other hand, a polarity reversal by using a metal-catalyzed crosscoupling between α-haloamides and aryl organometallics showed to be a valuable synthetic alternative. Within this context, efforts to individuate asymmetric cross-couplings requiring low catalyst loading is a worthwhile goal for making valuable building blocks for medicinal chemistry.…”

Modular synthesis of α-arylated carboxylic acids, esters and amides via photocatalyzed triple C–F bond cleavage of methyltrifluorides

“… 4 Later, metal-catalyzed cross-coupling of α-halo carbonyl electrophiles with aryl nucleophiles has also been described. 5 However, these methods are typically not applicable to direct arylation of aliphatic carboxylic acids and amides with acidic N–H bonds. 6 To address this issue, Hartwig a reported an elegant Pd-catalyzed α-arylation of carboxylic acids and secondary amides through the in situ formation of the corresponding disilyl intermediates in the presence of a base and TMSCl ( Scheme 1B ).…”

Catalytic α-Hydroarylation of Acrylates and Acrylamides via an Interrupted Hydrodehalogenation Reaction

“…α-Arylated carbonyl compounds are ubiquitous substructures in organic synthesis, and the diverse bioactivity of such molecules is exemplified by familiar blockbuster drugs, such as Naproxen and Ibuprofen. Traditionally, this structural motif can be prepared using Pd(0)-catalyzed α-arylation of enolates, as pioneered by Buchwald and Hartwig (Figure A). , In these systems the reactive nucleophile is generated via in situ deprotonation of carbonyl compounds with strong base or via preformation of the corresponding silyl enol ether. Alternatively, cross-coupling-based methods from the corresponding α-halocarbonyl electrophiles have also been described under nickel or palladium catalysis (Figure B). , …”