Stereoselective C(sp²)–H Alkylation of Enamides with Unactivated Aliphatic Carboxylic Acids via Decarboxylative Cross-Coupling Reactions

Abstract

An efficient and straightforward stereoselective alkylation reaction of enamides using commercially available and easily accessible unactivated alkyl carboxylic acids as alkylating agents is described, giving rise to a diverse array of synthetically important and geometrically defined β-alkylated enamides bearing primary, secondary, or tertiary alkyl moieties. This transformation also shows excellent functional group tolerance, satisfying atom economy, and operational simplicity.

Rh(I)-Catalyzed C6-Selective Decarbonylative Alkylation of 2-Pyridones with Alkyl Carboxylic Acids and Anhydrides

“…The availability, stability, diversity, and low cost of alkyl carboxylic acids has resulted in their widespread use . Since the pioneering work of Minisci, the decarboxylative alkylation of heteroarene C–H bonds with alkyl carboxylic acids has been a topic of sustained interest. , These reactions exhibit substrate-controlled site selectivity. Transition-metal catalysis with directing groups, however, enable greater C–H selectivity and functionalization .…”

Rhodium(III)-Catalyzed Direct C–H Arylation of Various Acyclic Enamides with Arylsilanes

“…Recently, the direct functionalization of enamides via olefinic β-C­(sp 2 )–H bond activation has attracted immense attention. A variety of direct C–H functionalization reactions such as alkylation, allylation, alkynylation, trifluoromethylation, acylation, arylation, and sulfonylation have been successively realized. Despite the significant advances achieved in the β-C­(sp 2 )–H arylation of enamides, these reactions are usually limited to cyclic enamides.…”

Tertiary Enamides as Versatile and Valuable Substrates to Reach Chemical Diversity

“…In addition to their previous results, the same authors reported a similar stereoselective alkylation reaction of enamides via decarboxylative cross-coupling using carboxylic acids. 47 The alkylation of tertiary enamides 165 with carboxylic acids 166 proceeds smoothly using a catalytic amount of silver carbonate in combination with potassium persulfate and sodium bicarbonate to afford exclusively (E)configured alkylated enamides 167 in moderate to good yields (Scheme 30).…”