Rhodium(III)-Catalyzed Anti-Markovnikov Hydroamidation of Unactivated Alkenes Using Dioxazolones as Amidating Reagents

Abstract

The amide is one of the most prevalent functional groups in all of pharmaceuticals, and for this reason, reactions that introduce the amide moiety are of particular value. Intermolecular hydroamidation of alkenes remains an underexplored method for the synthesis of amide-containing compounds. The majority of hydroamidation procedures exhibit Markovnikov regioselectivity, while current methods for anti-Markovnikov hydroamidation are somewhat limited to activated alkene substrates or radical processes. Herein, we report a general method for the intermolecular anti-Markovnikov hydroamidation of unactivated alkenes under mild conditions, utilizing Rh(III) catalysis in conjunction with dioxazolone amidating reagents and isopropanol as an environmentally friendly hydride source. The reaction tolerates a wide range of functional groups and efficiently converts electrondeficient alkenes, styrenes, and 1,1-disubstituted alkenes, in addition to unactivated alkenes, to their corresponding linear amides. Mechanistic studies reveal a reversible rhodium hydride migratory insertion step, leading to exquisite selectivity for the anti-Markovnikov product.

The Indenyl Effect: Accelerated C−H Amidation of Arenes via Ind*RhIII Nitrene Transfer Catalysis**

“…Such structural modifications have led to the development of new Cp x M(III) complexes that catalyse innovative chemical transformations including the amination of phenols [14] . In particular, the use of Cp x Rh(III) complexes containing electron deficient cyclopentadienyl ligands can increase reaction rates, yield and selectivity as reported by Tanaka, [14a–c] Zhang, [14d] Miura [14e] and Rovis [14f–h] …”

Progression of Hydroamination Catalyzed by Late Transition-Metal Complexes from Activated to Unactivated Alkenes

“…Consequently, reports of direct N–H additions to unactivated alkenes are uncommon, and these reactions often required a large excess of alkene and occurred with limited tolerance of functional groups . Several alternative strategies for the hydroamination of unactivated alkenes also have been developed, including the reactions of alkenes bearing a directing group, formal hydroaminations with silanes and esters of hydroxylamines or dioxazolones as the source of an amino group, and hydroamination under photocatalytic conditions . Our group has sought to achieve the hydroamination of unactivated alkenes by the oxidative addition or deprotonation of the N–H bond to generate metal amido complexes that can form the C–N bond by insertion of the alkene.…”

Copper-catalyzed [1,3]-nitrogen rearrangement ofO-aryl ketoximesviaoxidative addition of N–O bond in inverse electron flow

“…Catalytic transformations involving the cleavage of an N–O bond have recently gathered much attention as a unique method to synthesize nitrogenous compounds, 1 because the starting materials are readily accessible and storable despite the weak N–O bond (bond dissociation energy: 55–65 kcal mol −1 ). 2 The N–O bond cleavage, which is the driving force of the catalytic cycle, occurs via various mechanisms, including the oxidative addition to low-valent metal catalysts, homolytic cleavage, single electron transfer, and ionic cleavage, to generate unique reactive intermediates, such as aminyl radicals, 3 nitrenes, 4 and nitreniums. 5 In contrast to the catalytic transformations in which the oxygen atom of the N–O bond is typically cleaved off as a leaving group, rearrangement reactions yield molecules with both nitrogen and oxygen functional groups in an atom-efficient manner, 6,7 by using metal catalysts 8 and organocatalysts 9 under mild reaction conditions.…”