Remote carboxylation of halogenated aliphatic hydrocarbons with carbon dioxide

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From: Nature(Vol. 545, Issue 7652)
Publisher: Nature Publishing Group
Document Type: Report
Length: 3,137 words
Lexile Measure: 1720L

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Author(s): Francisco Juli-Hernndez [1]; Toni Moragas [1]; Josep Cornella [1]; Ruben Martin (corresponding author) [1, 2]

Catalytic carboncarbon bond formation has enabled the streamlining of synthetic routes when assembling complex molecules [1]. It is particularly important when incorporating saturated hydrocarbons, which are common motifs in petrochemicals and biologically relevant molecules. However, cross-coupling methods that involve alkyl electrophiles result in catalytic bond formation only at specific and previously functionalized sites [2]. Here we describe a catalytic method that is capable of promoting carboxylation reactions at remote and unfunctionalized aliphatic sites with carbon dioxide at atmospheric pressure. The reaction occurs via selective migration of the catalyst along the hydrocarbon side-chain [3] with excellent regio- and chemoselectivity, representing a remarkable reactivity relay when compared with classical cross-coupling reactions. Our results demonstrate that site-selectivity can be switched and controlled, enabling the functionalization of less-reactive positions in the presence of a priori more reactive ones. Furthermore, we show that raw materials obtained in bulk from petroleum processing, such as alkanes and unrefined mixtures of olefins, can be used as substrates. This offers an opportunity to integrate a catalytic platform en route to valuable fatty acids by transforming petroleum-derived feedstocks directly [4].

Methods that incorporate saturated hydrocarbon chains have traditionally been problematic using palladium catalysts [2]. Pioneering work [5, 6] demonstrated that nickel catalysts markedly improved the efficiency of alkyl cross-coupling reactions by minimizing the rate of unproductive -hydride elimination that leads to alkene by-products. These reports prompted the design of nickel-catalysed reactions of unactivated alkyl electrophiles occurring at the initial reaction site, ranging from classical nucleophilic/electrophilic regimes to the coupling of two distinct electrophiles [7], and culminating in stereoconvergent reactions [8] or visible-light photochemical techniques [9] (Fig. 1a, left). An emerging strategy has been the design of catalytic bond formation at remote reaction sites [3, 10]. However, carboncarbon bond formation in hydrocarbons is problematic, owing to the presence of multiple, yet similar, sp 3 CH positions. Several methodologies have tackled this issue by activating weak sp 3 CH bonds [11] or by using directing groups at a specific location within the side-chain [12, 13, 14, 15]. As part of our interest in nickel-catalysed carboxylations [16, 17], we sought to develop a protocol for incorporating carbon dioxide (CO2 ) at remote sp 3 CH sites en route to fatty acids (Fig. 1a, right), which are relevant in the manufacture of soaps, detergents, rubber, plastics and dyes [4, 18]. Indeed, the global market for carboxylic acids is anticipated to reach approximately $20 billion by 2023, expanding at an annual growth rate of 5% from 2017 to 2023 [4].

A detailed description of our design principle is outlined in Fig. 1b. Although retarding -hydride elimination has long been the goal of organometallic chemists when using alkyl (pseudo)halides as coupling partners (Fig. 1a, left), we questioned whether we could turn a to-be-avoided event into a desirable process. Specifically, we envisioned that fine-tuning of the ligand on the nickel catalyst could accelerate the rate of -hydride elimination from I before...

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Gale Document Number: GALE|A491085635