Picolinamides and Iodoalkynes Enable Palladium‐Catalyzed syn‐Aminoalkynylation of Di‐ and Trisubstituted Alkenes to Give Pyrrolidines

Abstract

Palladium‐catalyzed aminoalkynylation of electronically unbiased olefins with iodoalkynes is reported. The picolinamide auxiliary enables for the first time the syn‐selective aminoalkynylation of mono‐, di‐ and trisubstituted alkenes to afford the corresponding pyrrolidines in up to 97 % yield and as single diastereomers. Furthermore, through a C−H activation approach, the picolinamide allows the rapid synthesis of functionalized olefins, which are suitable cyclization precursors. Facile and orthogonal deprotection of the amides and SiiPr3‐acetylenes in the products, and a subsequent Pictet–Spengler reaction is demonstrated.

Catalytic Arylalkylation of Alkenyl Amines at Remote Sites via Directed Nickel Catalysis

“…Among the various synthetic methods, metal‐catalyzed difunctionalization of alkenyl amines has emerged as a powerful strategy for the efficient construction of value‐added complex alkylamines from easily accessible starting materials. [ 3‐11 ] Considering that the structure of alkyl groups appended to the nitrogen atom would influence the physical properties and control the biological interactions, [ 12‐13 ] difunctionalization of alkenyl amines at various sites would be highly desirable to prepare new aliphatic amines, especially those that are difficult to access using traditional methods.…”

The Alkynylative Difunctionalization of Alkenes

“…[32][33][34][35][36] Very recently, Carreira reported a Pd-catalyzed aminoalkynylation of alkenes with alkynyl halides as alkynylating reagents (Scheme 10f). [37] The key feature of this protocol is the use of picolinamide as a directing group (DG), which plays an essential role in the further CÀ H functionalization of complex alkene substrates, and in the subsequent aminoalkynylation reaction. In addition, the picolinamide auxiliary of the alkynylating products can be easily removed under simple conditions to afford amines, which can be further derivatized.…”

“…Very recently, Carreira reported a Pd‐catalyzed amino‐alkynylation of alkenes with alkynyl halides as alkynylating reagents (Scheme 10f) [37] . The key feature of this protocol is the use of picolinamide as a directing group (DG), which plays an essential role in the further C−H functionalization of complex alkene substrates, and in the subsequent amino‐alkynylation reaction.…”

The cobalt(ii)-catalyzed acyloxylation of picolinamides with bifunctional silver carboxylateviaC–H bond activation

“…Transition-metal-catalyzed direct C–H bond functionalization is one of the most dynamic synthetic chemistry methods available for constructing multifunctional polysubstituted aromatic hydrocarbons and other useful heterocyclic compounds with great step efficiency and low waste. Due to good reactivity in terms of C–H bond activation, powerful and versatile strategies involving picolinamide and 8-aminoquinoline have been developed for the installation of alkoxy/aryloxy, 1 alkylamino/arylamino, 2 alkyl, 3 aryl, 4 fluoroalkyl, 5 alkenyl, 6 alkynyl, 7 carbonyl, 8 carboxyl, 9 acyloxy, 10 alkylthiol/alkaneselenyl/sulfonyl, 11 halogen, 12 acyl, 13 alkanesilicyl, 14 and nitro 15 groups. For the above important methods, which access multifunctional 8/4-substituted 1-naphthalene amides, picolinamide remains a meaningful choice as a C–H bond activation acceptor.…”