Diversification of Glycosyl Compounds via Glycosyl Radicals

Jiang, Yi; Zhang, Yijun; Lee, Boon Chong; Koh, Ming Joo

doi:10.1002/anie.202305138

Cited by 39 publications

(19 citation statements)

References 103 publications

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“…Unlike phosphine-based ligands, nitrogen-based ligands and N -heterocyclic carbene ligands we tried were less effective (see SM, section 4). Addition of a stoichiometric amount of TEMPO was fully tolerated, essentially excluding a radical-based mechanism (entry 14) ( 22 , 37 ).…”

Section: Reaction Validation and Condition Optimizationmentioning

confidence: 99%

Palladium catalysis enables cross-coupling–like S _N 2-glycosylation of phenols

Deng,

Wang,

et al. 2023

Science

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Despite their importance in life and material sciences, the efficient construction of stereo-defined glycosides remains a challenge. Studies of carbohydrate functions would be advanced if glycosylation methods were as reliable and modular as palladium (Pd)-catalyzed cross-coupling. However, Pd-catalysis excels in forming sp 2 -hybridized carbon centers whereas glycosylation mostly builds sp 3 -hybridized C–O linkages. We report a glycosylation platform through Pd-catalyzed S N 2 displacement from phenols toward bench-stable, aryl-iodide–containing glycosyl sulfides. The key Pd(II) oxidative addition intermediate diverges from an arylating agent (Csp 2 electrophile) to a glycosylating agent (Csp 3 electrophile). This method inherits many merits of cross-coupling reactions, including operational simplicity and functional group tolerance. It preserves the S N 2 mechanism for various substrates and is amenable to late-stage glycosylation of commercial drugs and natural products.

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Section: Reaction Validation and Condition Optimizationmentioning

confidence: 99%

Palladium catalysis enables cross-coupling–like S _N 2-glycosylation of phenols

Deng,

Wang,

et al. 2023

Science

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“…The major topics covered are photocatalytic glycosylations, generation of radicals at the anomeric position, transformations involving radical formation at non-anomeric positions, additions to glycals, processes initiated by photocatalytic hydrogen atom transfer from sugars, and functional group interconversions at OH and SH groups. We anticipate that this relatively broad coverage will provide a distinct type of perspective from more specialized reviews discussing photochemical glycosylations, 11 the chemistry of anomeric radicals, 12 biomimetic radical reactions of sugars 13 and photocatalytic C–H and C–C bond activation of carbohydrate derivatives. 14 While a representative carbohydrate derivative may be included among a panel of structurally diverse substrates to explore the scope and limitations of a method, the focus here is on studies that have examined the reactivity of carbohydrate-derived substrates in depth.…”

Section: Introductionmentioning

confidence: 99%

Transformations of carbohydrate derivatives enabled by photocatalysis and visible light photochemistry

Gorelik,

Desai,

Jdanova

et al. 2024

Chem. Sci.

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“…However, the power of reactions employing glycosyl radicals to make glycosidic bonds has yet to be fully explored. This may be attributable in part to the difficulty associated with generating glycosyl radicals (Figure B). Owing to the presence of an adjacent oxygen atom, some classical glycosyl radical precursors, such as glycosyl bromides and epoxides, tend to undergo facile heterolytic cleavage.…”

Section: Introductionmentioning

confidence: 99%

Radical Pathway Glycosylation Empowered by Bench-Stable Glycosyl Donors

Shang,

Niu

2023

Acc. Chem. Res.

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Conspectus The study of carbohydrates has emerged as a crucial research area in various disciplines due to their pivotal roles in cellular processes. To facilitate in-depth exploration of their biological functions, chemical glycosylation reactions that allow facile access of glycoconjugates to a broad research community are highly needed. In classical glycosylation reactions, a glycosyl donor is activated by an acid to generate a reactive electrophilic intermediate, which subsequently forms a glycosidic bond upon reaction with a nucleophilic acceptor. Such an ionic pathway glycosylation has been the mainstay technique for glycoconjugate synthesis and allowed the synthesis of numerous intricate structures. Nevertheless, limitations still exist. For instance, when labile glycosyl donors or harsh activating conditions are required, these methods show limited tolerance to hydroxyl groups that are abundant on sugar rings. In addition, achieving good stereocontrol represents another longstanding obstacle. In recent years, new modes of donor activation have been sought to tackle the above challenges. We noted that glycosylation methods passing through the intermediacy of glycosyl radicals via a cascade of single-electron transfer steps possess significant but underexplored potential. Progress in this area has been slow due in large part to a dearth of handy methods to generate and maneuver glycosyl radicals. Most existing methods call for either forcing conditions or unstable/inconvenient starting materials. In order to better exploit the power of the radical pathway glycosylation, we have developed a range of glycosyl donorsnamely, glycosyl sulfoxides, glycosyl sulfones, and glycosyl sulfinatesthat are bench stable and can be readily prepared from simple starting materials. These donors can be activated to form glycosyl radicals under mild conditions. Enabled by the use of these donors, we have developed a series of glycosylation methods that could be used for making O-, S-, or C-glycosides, some of which were previously difficult to access. In many cases, no protecting group on glycosyl donors is required. As an illustration of their potential utility, our methods have been adopted in the preparation of sugar–drug conjugates, sugar–DNA conjugates, glycopeptides, and even glycoproteins. While in most cases the intrinsic reactivity of glycosyl radical intermediates can be explored to access axially configured products, some of the methods also allow the utilization of external, delicate reagents, or catalysts to override such innate preference and achieve catalyst-controlled stereoselectivity. We believe that radical pathway glycosylation has enormous potential and can inspire the development of novel methods for glycoside synthesis. In this Account, we highlight the design principles for the development of our glycosyl donors, summarize our recent advancements in radical pathway glycosylation enabled by their use, and provide an outlook on the future directions of this field.

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Diversification of Glycosyl Compounds via Glycosyl Radicals

Cited by 39 publications

References 103 publications

Palladium catalysis enables cross-coupling–like S _N 2-glycosylation of phenols

Palladium catalysis enables cross-coupling–like S _N 2-glycosylation of phenols

Transformations of carbohydrate derivatives enabled by photocatalysis and visible light photochemistry

Radical Pathway Glycosylation Empowered by Bench-Stable Glycosyl Donors

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Diversification of Glycosyl Compounds via Glycosyl Radicals

Cited by 39 publications

References 103 publications

Palladium catalysis enables cross-coupling–like S N 2-glycosylation of phenols

Palladium catalysis enables cross-coupling–like S N 2-glycosylation of phenols

Transformations of carbohydrate derivatives enabled by photocatalysis and visible light photochemistry

Radical Pathway Glycosylation Empowered by Bench-Stable Glycosyl Donors

Contact Info

Product

Resources

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Palladium catalysis enables cross-coupling–like S _N 2-glycosylation of phenols

Palladium catalysis enables cross-coupling–like S _N 2-glycosylation of phenols