Palladium-Catalyzed Alkoxycarbonylation of Unactivated Secondary Alkyl Bromides at Low Pressure

Abstract

Catalytic carbonylations of organohalides are important C–C bond formations in chemical synthesis. Carbonylations of unactivated alkyl halides remain a challenge, and currently require the use of alkyl iodides under harsh conditions and high pressures of CO. Herein, we report a palladium-catalyzed alkoxycarbonylation of secondary alkyl bromides that proceeds at low pressure (2 atm CO) under mild conditions. Preliminary mechanistic studies are consistent with a hybrid organometallic-radical process. These reactions efficiently deliver esters from unactivated alkyl bromides across a diverse range of substrates and represent the first catalytic carbonylations of alkyl bromides with carbon monoxide.

Cobalt-Catalyzed Silylcarbonylation of Unactivated Secondary Alkyl Tosylates at Low Pressure

“…6 As this system involved carbon-centered radical intermediates formed from single-electron processes, it was ineffective with alkyl sulfonates. We therefore became interested in developing an alternative system for low pressure, carbonylative transformations of alkyl sulfonates.…”

Carbonylative Suzuki coupling and alkoxycarbonylation of aryl halides using palladium supported on phosphorus‐doped porous organic polymer as an active and robust catalyst

“…Carbon monoxide, an inexpensive and readily available C 1 building block, is widely used as a carbonyl source for palladium‐catalyzed carbonylation of aryl halides . On the other hand, CO could also act as a strong π‐acidic ligand for the palladium metal, thus resulting in a decrease of electron density for the palladium center and making the oxidative addition of aryl halide difficult . Meanwhile, under a CO atmosphere, palladium atom is easily aggregated to form the catalytically inactive species .…”

“…[1][2][3][4] On the other hand, CO could also act as a strong π-acidic ligand for the palladium metal, thus resulting in a decrease of electron density for the palladium center and making the oxidative addition of aryl halide difficult. [9,10] Meanwhile, under a CO atmosphere, palladium atom is easily aggregated to form the catalytically inactive species. [11,12] To address these problems, electronrich ligands were usually added to the catalytic systems, thus increasing electron density of the palladium center and preventing the aggregation of palladium atoms.…”

“…Phenol, as a representative example of phenols, could also react with iodobenzene smoothly (Table 4, entry 8). With ethanol as a nucleophile, aryl iodides bearing different functional groups at the para position could react smoothly, affording the corresponding aryl esters in excellent yields in 4 hr(Table 4, entries[9][10][11][12][13][14]. Moderately hindered aryl iodides, such as 3-OMe, 2-OMe substituted iodobenzene, could also react readily, although prolonged reaction times were needed (Table 4, entries 15 and 16).…”

Cobalt-Catalyzed Carbonylative Cross-Coupling of Alkyl Tosylates and Dienes: Stereospecific Synthesis of Dienones at Low Pressure

“…A palladium-based catalytic system we previously used in the esterification of unactivated secondary alkyl bromides provided no product (entry 4). 8 Lowering the catalyst loading to 5 mol % (entry 5) had a minor effect on chemical yield. Decreasing the CO pressure to 1 atm (entry 6) led to decreased reaction conversion and enantiospecificity.…”