Research On Palladium-catalyzed Oxidative Allylic C-H Functionalization Of Alkenes

Over the past10years, transition metal catalyzed direct C–H bond functionalization hassince emerged as a powerful tool in organic synthesis, playing vital roles in the syntheses ofnatural and unnatural compounds. Prominent among these processes are thepalladium-catalyzed C–H bond functionalization. Because the historical, mechanistic,theoretical, and practical aspects of these processes have been amply discussed. In particular,the development of alternative methodologies that could be advantageous in terms of theselectivity and the availability of starting materials prior to the C–H bond functionalizationevent are of extraordinary interest.Palladium-catalyzed direct functionalization of allylic C-H bonds leading to oxygenation,alkylation, amination, silylation or dehydrogenation is a valuable complement to thewell-known Trost-Tsuji reaction. The new procedure shows that unnecessary functional groupmanipulations (FGMs) can be bypassed which presents a highly efficient approach for thesynthesis of functionalized alkenes, reducing synthetic steps and increasing overall yield.Clearly a catalytic version of the allylic C-H activation would be highly desirable from anatom-economic and environmental perspective.In this context, we have studied the palladium-catalyzed allylic functionalization ofterminal alkenes with water, carbon monoxide, N-tosylhydrazones or sodium azides forstreamlining the synthesis of functionalized alkenes. The details are summarized as following:(1) Palladium-catalyzed oxidative allylic C-H oxygenation of terminal alkenes. Alkenylaldehydes and allylic alcohols as versatile building blocks have been widely used in organicsynthesis. Their importance in chemistry and biology has stimulated considerable attentionfrom organic chemists and encouraged the development of new synthetic strategies to preparethese compounds. We developed a facile synthesis of (E)-alkenyl aldehydes or (E)-allylicalcohols from alkenes via Pd(II)-catalyzed allylic C-H oxygenation. In this process, water wasused as a nucleophilic reagent and an oxygen source for direct oxygenation of an allylic C-Hbond. By controlling temperature or oxidant, the reaction can be made selective for(E)-alkenyl aldehydes or (E)-allylic alcohols.(2) Palladium-catalyzed oxidative allylic C-H carbonylation of terminal alkenes. Generally, afunctional group at the allylic position is required in Tsuji–Trost carbonylation to serve as areacting and leaving group for the synthesis of synthetically useful β-enoic acid esters.Therefore, the development of new allylic carbonylation in synthetic efficiency throughavoiding unnecessary functional group manipulations is attracting increasing attention. We developed palladium-catalyzed direct oxidative carbonylation of allylic C–H bonds withcarbon monoxide. These observations provides novel routes for accessing β-enoic acid estersand synthetically important1,4-dicarbonyl scaffolds with high regioselectivity, whichabolishes the need for a leaving group, will lead to this becoming a popular synthetic tool.(3) Palladium-catalyzed oxidative allylic C-H alkylation of terminal alkenes usingN-tosylhydrazones as allylating agents. Over the past few decades, the development ofpalladium-catalyzed carbon–carbon bond-forming reactions has dramatically advanced“state-of-the-art” organic synthesis. Recently, Pd-catalyzed cross-coupling reactions ofdiazo compounds have emerged as a new type of cross-coupling reaction for the constructionof carbon-carbon bonds. An alternative route that makes use of N-tosylhydrazones asnucleophiles, which are an in situ source of diazo compounds for this transformation, hasattracted much attention. The required N-tosylhydrazones are easily generated from carbonylcompounds, and the reaction can be seen as a cross-coupling of carbonyl groups, a process ofhigh synthetic relevance that involves several steps and other methodologies. We developedpalladium-catalyzed direct oxidative alkylation of allylic C–H bonds with N-tosylhydrazones.The reaction proceeds with readily available starting materials and affords1,4-dienes and4-en-1-ones in a highly stereoselective manner.(4) Palladium-catalyzed oxidative allylic C-H azidation of terminal alkenes with sodium azide.The azide functional group has been used as an important moiety for the formation ofnitrogen-containing compounds in fields ranging from synthetic organic chemistry to totalsynthesis, pharmaceutical chemistry, materials science, supramolecular chemistry, polymerchemistry, and biotechnology. Generally, Azides are typically prepared from the substitutionof organic halides with sodium azide, but this approach requires the prior synthesis of theorganic halides. We developed palladium-catalyzed direct oxidative azidation of alkenes withsodium azide under atmospheric pressure of dioxygen. This methodology provides a newefficient and green route for accessing allylic azides. Furthermore, the one-pot processconsisting of Pd-catalyzed allylic azidation of alkenes and Cu-catalyzed [3+2] cycloadditionled directly to the triazole from alkene. The formed allylic azide can be also in situ reduced toallylic amino or oxidized to alkenyl nitrile.