Exploiting the reactivity of one functional group within a molecule to generate a reaction at a different position is an ongoing challenge in organic synthesis. Effective remote functionalization protocols have the potential to provide access to almost any derivatives but are difficult to achieve. The difficulty is more pronounced for acyclic systems where flexible alkyl chains are present between the initiating functional group and the desired reactive centres. In this Review, we discuss the concept of remote functionalization of alkenes using metal complexes, leading to a selective reaction at a position distal to the initial double bond. We aim to show the vast opportunity provided by this growing field through selected and representative examples. Our aim is to demonstrate that using a double bond as a chemical handle, metal-assisted long-distance activation could be used as a powerful synthetic strategy.

Combining functionalization at a distant position from a reactive site with the creation of several consecutive stereogenic centres, including the formation of a quaternary carbon stereocentre, in acyclic system represents a pinnacle in organic synthesis. Here we report the regioselective Heck arylation of terminal olefins as a distant trigger for the ring-opening of cyclopropanes. This Pd-catalysed unfolding of the strained cycle, driving force of the chain-walking process, remarkably proved its efficiency and versatility, as the reaction proceeded regardless of the molecular distance between the initiation (double bond) and termination (alcohol) sites. Moreover, employing stereodefined polysubstituted cyclopropane vaults allowed to access sophisticated stereoenriched acyclic scaffolds in good yields. Conceptually, we demonstrated that merging catalytically a chain walking process with a selective C–C bond cleavage represents a powerful approach to construct linear skeleton possessing two stereogenic centres.

Palladium(II)‐catalyzed procedures often use benzoquinone (BQ) to regenerate the catalyst. Besides its oxidation role, BQ can also promote various steps of the catalytic cycle. This review highlights the multifaceted properties of BQ and its analogues when involved in PdII‐catalyzed oxidative reactions and presents mechanisms proposed in the literature, in some cases with personal observations.

Remote functionalization of hydrocarbons could be achieved through successive zirconocene-mediated allylic C–H bond activations followed by a selective C–C bond cleavage.

4,5‐Diazafluorenone was found to promote the dehydrogenative Heck reaction of furans and thiophenes with hindered alkenes. High stereoselectivity was achieved in the synthesis of β,β‐diaryl α,β‐unsaturated alkenes. A mechanism, based on ESI‐MS studies, kinetic experiments, and competitive reactions, was proposed. The ligand influences C–H bond activation, insertion of the alkenes, the stereodetermining step, and the aerobic regeneration of the catalyst.

Electrospray ionization mass spectrometry, subsequent MS/MS, and high-resolution mass spectrometry were used to study the dehydrogenative Heck reaction of 2-alkylfurans 1 with acrylates 2, using [Pd(OAc)2]3 as the precatalyst, benzoquinone (BQ) as the stoichiometric oxidant, and a mixture of DMSO and AcOH as the solvent. Complexation of [Pd(OAc)2]3 by DMSO afforded mononuclear and dinuclear Pd(II) species, which proved to be active catalysts for the C–H activation of 1. Mononuclear and dinuclear Pd(II) species seem also to be involved in the insertion of 2 into the furyl–Pd bond. The C–H activation of 2 and DMSO by mononuclear complexes was observed. The reaction leads to 5,5′-dialkyl-2,2′-bifuran 4 as a byproduct. Bifuryl-palladium, which is an intermediate in the formation of 4, showing the coordination of BQ, was obtained and characterized.

In this study, the kinetics of the acid catalyzed hydrolysis of microcrystalline cellulose (Avicel PH101) to levulinic (LA) and formic (FA) acids was investigated in a batch reactor over the following range of conditions: 160–200°C, hydrochloric acid concentrations of 0.309–0.927 M (11.3–33.8 g/l), cellulose concentrations of 49.8–149 mM (8.06–24.1 g/l), and residence times of 0–50 min. The maximum LA yield of around 60% of theoretical was achieved for an initial cellulose concentration of 99.6 mM, acid concentration 0.927 M, and 180–200°C. A mathematical model and its analytical solution were developed to predict conversion of cellulose to LA and FA through glucose and hydroxymethyl‐2‐furfural based on an irreversible pseudo‐first order reaction. Rate analysis of each reaction indicated that the rate‐controlling step shifted from LA formation initially to HMF formation later. © 2011 American Institute of Chemical Engineers AIChE J, 2012

Several approaches using organozirconocene species for the remote cleavage of strained three-membered ring carbocycles are described. ω-Ene polysubstituted cyclopropanes, alkylidenecyclopropanes, ω-ene spiro[2.2]pentanes, and ω-ene cyclopropyl methyl ethers were successfully transformed into stereodefined organometallic intermediates, allowing an easy access to highly stereoenriched acyclic scaffolds in good yields and, in most cases, excellent selectivities. DFT calculations and isotopic labeling experiments were performed to delineate the origin of the obtained chemo- and stereoselectivities, demonstrating the importance of microreversibility.