Cobalt-catalyzed Markovnikov-selective hydrophosphonylation of unactivated alkenes enabled by phthalimidyl phosphite reagents.

Alkene hydrophosphonylation constitutes an indispensable tool for the synthesis of alkylphosphonates which have found widespread applications in pharmaceuticals, agrochemicals and materials science. Although numerous methods for alkene hydrophosphonylation have been reported, achieving Markovnikov selectivity with unactivated alkenes remains a formidable challenge. Herein we report the development of a class of phosphites featuring a unique N-O-P linkage, namely dialkyl phthalimidyl phosphites, which serve as efficient radical trapping reagents. Using dialkyl phthalimidyl phosphites as phosphonylating reagents and diphenylsilane as the hydrogen donor, the cobalt-catalyzed reaction of unactivated alkenes proceeds smoothly at room temperature, delivering exclusively Markovnikov hydrophosphonylation products in satisfactory yields. Notably, the transformation exhibits excellent functional group tolerance, enabling late-stage modification of drug derivatives. A mechanism involving cobalt hydride-mediated hydrogen atom transfer, alkyl radical addition to phosphites, β-scission of phosphoranyl radicals and oxidation of CoII to CoIII by phthalimidyl radicals, is proposed.