Excited-State Palladium-Catalyzed 1,2-Spin-Center Shift Enables Selective C-2 Reduction, Deuteration, and Iodination of Carbohydrates

Abstract

Excited-state catalysis, a process that involves one or more excited catalytic species, has emerged as a powerful tool in organic synthesis because it allows access to the excited-state reaction landscape for the discovery of novel chemical reactivity. Herein, we report the first excited-state palladium-catalyzed 1,2-spin-center shift reaction that enables site-selective functionalization of carbohydrates. The strategy features mild reaction conditions with high levels of regio-and stereoselectivity that tolerate a wide range of functional groups and complex molecular architectures. Mechanistic studies suggest a radical mechanism involving the formation of hybrid palladium species that undergoes a 1,2-spin-center shift followed by the reduction, deuteration, and iodination to afford functionalized 2-deoxy sugars. The new reactivity will provide a general approach for the rapid generation of natural and unnatural carbohydrates.

Deoxy sugars. General methods for carbohydrate deoxygenation and glycosidation

“…More recently, other methods were reported, for example visible light promoted dehalogenations involving a 1,2-spin-center shift. 23 This rearrangement is detailed in section 2.7.…”

“…7F). 23 A similar 1,2-acyloxy migration was proposed as a key step of this procedure, through the radical oxidative addition of a photoexcited Pd(0) catalyst [(Pd(PPh) 3 ) 4 ] to the 1-halosugar, generating the hybrid 1-glycosyl-Pd-X complex, which weakens the C-2–OAc bond by hyperconjugation and induces the 1,2-spin-center shift in a concerted way, forming the deoxypyranosan-2-yl radical. No oxidation is produced in this case, and by adapting the conditions, other C-modifications can be achieved (2-iodo-, or 2-aryl-pyranosyl esters).…”

“…No oxidation is produced in this case, and by adapting the conditions, other C-modifications can be achieved (2-iodo-, or 2-aryl-pyranosyl esters). 23…”

Radical Deoxyfunctionalisation Strategies

“…Ngai and co-workers published a novel and creative strategy for the C2-selective deoxyfunctionalisation of carbohydrates (Scheme 32). [55] This versatile methodology can be applied to C2-selective reduction, deuteration and iodination of 1halosugars, using Pd(PPh3)4 as catalyst under blue light irradiation. In addition to regio-and stereoselectivity, the mild reaction conditions tolerate a wide range of functional groups.…”

“…Saccharide and nucleosides are fundamental biomolecules possessing several hydroxy groups, thus representing ideal targets for the application of late-stage deoxyfunctionalisation strategies. Although some advancements have been made in this area, [55][56]69] there is still a lack of general methodologies that can be applied for selective nucleoside derivatisations. We believe that at the current pace of innovation, these challenges will be tackled in the not-so-distant future.…”