Light-mediated synthesis of aliphatic anhydrides by Cu-catalyzed carbonylation of alkyl halides

Abstract

Acid anhydrides are valuable in the chemical industry for their role in synthesizing polymers, pharmaceuticals, and other commodities, but their syntheses often involve multiple steps with precious metal catalysts. The simplest anhydride, acetic anhydride, is currently produced by two Rh-catalyzed carbonylation reactions on bulk scale for its use in synthesizing products ranging from aspirin to cellulose acetate. Here, we report a light-mediated, Cu-catalyzed process for producing aliphatic, symmetric acid anhydrides directly by carbonylation of alkyl (pseudo-)halides in a single step without any precious metal additives. The transformation requires only simple Cu salts and abundant bases to proceed, maintains high efficiency and selectivity upon scale up, and operates by radical mechanism with several beneficial features. This discovery will enable engineering of bulk processes for producing commodity anhydrides efficiently and sustainably.

Photochemical synthesis of acyl fluorides using copper-catalyzed fluorocarbonylation of alkyl iodides

“…Having established a diverse substrate scope, we next examined the mechanism for the transformation. Based on related reactions in the literature, [18][19][20] we propose the mechanistic scenario in Figure 3a Several experimental results support this proposal. The requirement of copper(I) catalyst and photoexcitation were established through appropriate control experiments (Table 1, entries 1 and 8), providing support for intermediates A and A*.…”

“…[14][15][16][17][18] We recently reported that, under photochemical conditions, Cu-catalyzed carbonylation of alkyl halides can proceed even with weak nucleophiles like K2CO3 to form carboxylate derivatives. 19 Here, we report Cucatalyzed, photochemical fluorocarbonylation of alkyl iodides using KF as the fluoride source (Figure 1c). Benefits of this new method include short reaction times (4-6 h); the use of a commercially available, non-precious metal catalyst with an inexpensive, benign fluoride source; and chemoselective alkyl halide activation even in the presence of aryl halides.…”

“…We initially screened reaction conditions using the model substrate, 3-phenyl-1iodopropane (1a), starting with standard carbonylation conditions inspired by our recent anhydride-forming reaction 19 (6 atm CO, 3 equiv. KF, 10 mol% CuBr•SMe2, CH3CN).…”

Photochemical Synthesis of Acyl Fluorides Using Copper-Catalyzed Fluorocarbonylation of Alkyl Iodides

“…17−22 We recently reported that, under photochemical conditions, Cucatalyzed carbonylation of alkyl halides can proceed even with weak nucleophiles like K 2 CO 3 to form carboxylate derivatives. 23 Here, we report Cu-catalyzed, photochemical fluorocarbonylation of alkyl iodides using KF as the fluoride source (Figure 1c). 24 Benefits of this new method include short reaction times (4−6 h); the use of a commercially available, non-precious metal precatalyst with an inexpensive fluoride source; and chemoselective alkyl halide activation even in the presence of aryl halides.…”

Recent Advances in Base‐Metal‐Catalyzed Carbonylation of Unactivated Alkyl Electrophiles†

“…Very recently, the Mankad group elegantly developed a light‐ mediated, Cu‐catalyzed process for the synthesis of aliphatic, symmetric acid anhydrides by direct carbonylation of alkyl (pseudo)halides (Scheme 19). [ 41 ] The reaction took place under photoexcitation by blue LED light in the presence of the CuBr·SMe 2 without any ligands and K 2 CO 3 as the base. Besides alkyl iodides, alkyl bromides and alkyl tosylates were also suitable substrates when NaI was used as an additive to generate the corresponding anhydrides in moderate to excellent yields.…”