Transition‐Metal‐Free Alkoxycarbonylation of Aryl Halides

Abstract

Transition-metal-catalyzed carbonylation involving CO gas is a very important and fundamental chemical transformation, which not only extends the carbon chain length, but also introduces a synthetically versatile carbonyl group. Since the pioneering work of Heck and co-workers, [1,2] transition-metalcatalyzed alkoxycarbonylation of organic halides with CO to afford esters has shown synthetic potential, and been applied in some chemical syntheses during the past several decades (Scheme 1). [3][4][5][6][7] Besides, transition metals, especially palladium-and manganese-catalyzed radical alkoxycarbonylation of alkyl iodides under photoirradiation conditions have also been developed to be an efficient approach towards the synthesis of carboxylic acid esters. [8][9][10][11][12][13] However, there are still some challenges such as the turnover numbers and turnover frequencies, which hinder its wide industrial application. Generally, low-valent-metal catalysts such as palladium(0) are required to activate the CÀX bond, whereas the strong binding ability of CO towards low-valent metals deactivate the catalyst, which present a challenge in this transformation. Therefore, discovering a practical alternative to transitionmetal-catalyzed carbonylation and opening a new avenue for the carbonylation by utilizing CO gas is highly desirable.Transition-metal-free processes have recently attracted more and more attention from the synthetic community, and we thought that it might serve as an alternative route to addressing the above-mentioned challenge (Scheme 1). The key challenge of this idea is to determine how to activate CÀX without the help of transition-metal catalysts. Radical activation could be an option. Recently, transition-metal-free coupling reactions of aryl halides with arenes and alkenes have been developed, and the combination of MOtBu and bidentate nitrogen ligands was employed to initiate the aryl radical by single-electron transfer (SET). [14][15][16][17][18][19][20][21][22] Obviously, if aryl radicals were formed, the insertion of CO would produce the acyl radical and further generate a carboxylic derivative. Although known since the 1950s, [23] the potential of radical carbonylation in chemical synthesis has not received a great deal of attention, and in fact, only a few nice results have been reported to date. These results usually involve a xenon photolytic system or AIBN/tin hydride mediated radicalchain reaction employing alkyl iodides as substrates. [24][25][26][27][28][29][30] To the best of our knowledge, there is no example of employing a transition-metal-free process in alkoxycarbonylation of aryl halides. Herein, we disclose a protocol for accessing tert-butyl benzoates through the transition-metal-free alkoxycarbonylation of aryl halides.Our experiment was initiated by treating 4-iodotoluene (1 a) with KOtBu in the presence of a high pressure CO (Table 1). By optimizing various reaction parameters, the best results were obtained with the combination of 40 mol % 1,10

The Chemistry of CO: Carbonylation

“…95 Treatment of a solution of hexane and alcohols (or amides) with di-tert-butylperoxide (DTBP) in the presence of CO at 120 C afforded the In 2012, Lei and co-workers developed a transition-metal-free alkoxycarbonylation of aryl halides (Scheme 30). 96 A range of aromatic carboxylic tert-butyl esters was prepared under thermodynamic conditions in good yields. The organocatalyst 1,10-phenoanthroline was used to facilitate the generation of aryl radicals from their parent halides.…”

Manganese-Mediated C–C Bond Formation: Alkoxycarbonylation of Organoboranes

“… 1 , 5 , 7 , 8 Ever since its initial discovery, the substrate scope of alkoxycarbonylations has rapidly expanded to include aryl and alkyl halides, 9 − 12 alternative leaving groups, 13 − 16 as well as epoxides, 17 allyl phosphates and acetates, 18 and amines 19 ( Figure 1 c). Further improvements to the methodology have come from metal-free strategies, 14 , 20 and efforts to eliminate the need for an external CO pressure. Although CO is relatively cheap and abundant in industry, it can be difficult or undesirable to work with at smaller scale because many laboratories are not set up for handling hazardous gases.…”

Solvent‐Controlled Copper‐Catalyzed Oxidation of Benzylic Alcohols to Aldehydes and Esters

“…[1] Traditionally, esters are prepared by the reaction of activated carboxylic acid derivatives (acyl chlorides and anhydrides) with alcohols. [3,4] The oxidative esterification of aldehydes with alcohols is also reported for the synthesis of esters. [3,4] The oxidative esterification of aldehydes with alcohols is also reported for the synthesis of esters.…”