| Amides have long been recognized as a valuable fundamental structural motif in a variety of pharmacologically active compounds,agrochemicals,natural products and function materials.Branched amides,such as napropamide,carbetamide,naproanilide and flutamide,are a particularly important subclass of amides that often exhibite useful biological activities.The rapid synthesis of this structural motif is thus of outmost important to the drug discovery process.Over the past decades,many approaches to construct amides from a variety of simple starting materials had been established.Among possible approaches for the construction of amides,the catalytic hydroaminocarbonylation of alkenes with amines is one of the most straightforward and atom-efficient method.Extensive studies on the hydroaminocarbonylation of alkenes have already been reported,but mostly focused on the use of aromatic amines as coupling partners.Furthermore,the formation of branched amides from Pd-catalyzed hydroaminocarbonylation is more challenge.This is often attributed to the reluctance of formation of the more sterichindered secondary alkylpalladium species and the tendency of the aliphatic amines with strong basic to retard the generation of the active palladium hydride species,which is crucial for the catalysis.The hydroaminocarbonylation reactions were conducted in the presence of 20 atm of CO at 120 °C.Pd(t-Bu3P)2 has been identified as catalyst(5 mol%)and hydroxylamine hydrochloride was used as cocatalyst(5 mol%).The yields of desired products can be up to 95% with excellent regioselectivity(B:L >20:1).Compared to previous methods,there is a good adaptability for substrate under relative mild reaction conditions,thus it has a good prospect of application.The herbicide naproanilide could be obtained in 93% yield with excellent regioselectivity when 2-(vinyloxy)naphthalene and aniline were utilized as raw material in the presence of CO. |
