Palladium-Catalyzed Markovnikov Hydroaminocarbonylation of 1,1-Disubstituted and 1,1,2-Trisubstituted Alkenes for Formation of Amides with Quaternary Carbon

Abstract

Hydroaminocarbonylation of alkenes is one of the most promising yet challenging methods for the synthesis of amides. Herein, we reported the development of a novel and effective Pd-catalyzed Markovnikov hydroaminocarbonylation of 1,1disubstituted or 1,1,2-trisubstituted alkenes with aniline hydrochloride salts to afford amides bearing an α quaternary carbon. The reaction makes use of readily available starting materials, tolerates a wide range of functional groups, and provides a facile and straightforward approach to a diverse array of amides bearing an α quaternary carbon. Mechanistic investigations suggested that the reaction proceeded through a palladium hydride pathway. The hydropalladation and CO insertion are reversible, and the aminolysis is probably the rate-limiting step.

Highly efficient Markovnikov hydroaminocarbonylation of alkenes and alkynes catalyzed by a “soluble” heterogeneous Pd catalyst

“…Our previous study has clearly indicated that the ultrafine Pd NPs confined in PPOC has a strong interaction with PPh 3 in the skeleton with the formation of Pd–P coordination bonds, 26 which makes this soluble heterogeneous Pd catalyst just like homogeneous phosphine-ligated Pd complexes. According to the above results and previous mechanistic investigation on the Pd-catalyzed hydroaminocarbonylation, 3,5–8 we propose that the reaction proceeds via the following pathways as shown in Scheme 2. First, the active [Pd–H] species A is formed in situ from the reaction of Pd@PPOC and HCl, which is similar to the homogeneous system.…”

“…1,2 Over the past decades, significant advances have been achieved on ligand-controlled Pd-catalyzed hydroaminocarbonylation of readily available alkenes and alkynes as starting materials, and a variety of valuable linear or branched amides and α,β-unsaturated amides have been constructed with strong dependence on phosphine ligands in either a Markovnikov or anti-Markovnikov manner (Scheme 1a). 3–13 However, their potential applications, particularly in the pharmaceutical industry, have been severely hampered by the difficulty of separation and recycling of expensive Pd complexes accompanied by purification of the target product. To date, only a few heterogeneous catalysts have been reported for hydroaminocarbonylation, and it remains a formidable challenge to achieve high efficiency and regioselectivity (Scheme 1b).…”

Recent Advances in Mono‐ and Difunctionalization of Unactivated Olefins

“…With regard to catalytic cycle (Scheme 57) first, complex 142 is formed by coordination of the amino pyridine to the ruthenium precatalyst Ru 1,1,2-trisubstituted alkenes with aniline hydrochloride salts for the synthesis of amides bearing an α-quaternary carbon 149 (Scheme 58). [54] The key features of this strategy include mild reaction conditions, wide availability of starting materials, tolerance of a broad range of functional groups and straight forward synthesis of amides bearing α-quaternary carbon. The initial reaction was performed using α-methyl styrene and aniline as model substrates and the optimized condition was identified includes the use of 3 mol% Pd(PPh 3 ) 2 Cl 2 as the catalyst and aniline hydrochloride as the substrate under CO atmosphere at 110 °C in THF.…”

Oxidative Cleavage and Ammoxidation of Unsaturated Hydrocarbons via Heterogeneous Auto-Tandem Catalysis

“…Among them, hydroaminocarbonylation of alkenes with amines including ammonia and CO represents an attractive strategy for amide synthesis from abundant feedstock chemicals (Figure a). Some key advances include the use of Co, Ni, Ru, and Pd complexes as the catalysts. − However, the formation of undesirable formamide byproducts, over-reliance on high-pressure toxic gaseous CO, and/or usage of expensive catalysts still limit most of these reaction classes. Therefore, novel catalytic technologies for efficient amidation of C–C double bonds are still needed to offer a viable pathway toward green, efficient, and economical unsaturated hydrocarbon utilization.…”