Catalytic Multicomponent Synthesis ofC‐Acyl Glycosides by Consecutive Cross‐Electrophile Couplings

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(46)

Published: Sept. 27, 2022

C-Acyl glycosides are versatile intermediates to natural products and medicinally relevant entities. Conventional cross-coupling strategies secure these molecules often relied on two-component manifolds in which a glycosyl precursor is coupled with an acyl donor (pre-synthesized or generated situ) under transition metal dual catalysis forge C-C bond. Here, we disclose three-component Ni-catalyzed reductive regime that facilitates the chemoselective union of halides, organoiodides commercially available isobutyl chloroformate as CO surrogate. The method tolerates multiple functionalities resulting obtained high diastereoselectivities. Theoretical calculations provide mechanistic rationale for unexpectedly chemoselectivity sequential cross-electrophile couplings. This approach enables expeditious assembly difficult-to-synthesize C-acyl glycosides, well late-stage keto-glycosylation oligopeptides.

Language: Английский

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Remote C−H Glycosylation by Ruthenium(II) Catalysis: Modular Assembly ofmeta‐C‐Aryl Glycosides

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(42)

Published: July 25, 2022

Abstract The prevalence of C ‐aryl glycosides in biologically active natural products and approved drugs has long motivated the development efficient strategies for their selective synthesis. Cross‐couplings have been frequently used, but largely relied on palladium catalyst with prefunctionalized substrates, while ruthenium‐catalyzed glycoside preparation thus far proven elusive. Herein, we disclose a versatile ruthenium(II)‐catalyzed meta ‐C−H glycosylation to access ‐ from readily available glycosyl halide donors. robustness ruthenium catalysis was reflected by mild reaction conditions, outstanding levels anomeric selectivity exclusive ‐site‐selectivity.

Language: Английский

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Exploiting π and Chalcogen Interactions for the β‐Selective Glycosylation of Indoles through Glycal Conformational Distortion

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(7)

Published: Dec. 20, 2023

Harnessing unconventional noncovalent interactions (NCIs) is emerging as a formidable synthetic approach in difficult-to-access glycosidic chemical space. C-Glycosylation, particular, has gained flurry of recent attention. However, most reported methods are restricted to the relatively facile access α-C-glycosides. Herein, we disclose β-stereoselective glycosylation indoles by employing phosphonoselenide catalyst. The robustness this protocol exemplified its amenability for reaction at both indolyl C- and N- reactivity sites. In contrast previous reports, which chalcogens were solely involved Lewis acidic activation, our mechanistic investigation unraveled that often neglected flanking aromatic substituents phosphonoselenides can substantially contribute catalysis engaging π-interactions. Computations NMR spectroscopy indicated chalcogenic components catalyst be collectively exploited foster conformational distortion glycal away from usual half-chair boat conformation, liberates convex β-face nucleophilic attack.

Language: Английский

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Close‐Shell Reductive Elimination versus Open‐Shell Radical Coupling for Site‐Selective Ruthenium‐Catalyzed C−H Activations by Computation and Experiments

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(22)

Published: Feb. 27, 2023

Ruthenium-catalyzed σ-bond activation-assisted meta-C-H functionalization has emerged as a useful tool to forge distal C-C bonds. However, given the limited number of mechanistic studies, clear understanding origin site-selectivity and complete reaction pattern is not available. Here, we present systematic computational studies on ruthenium-catalyzed C-H with primary, secondary, tertiary alkyl bromides aryl bromides. The scission formation were carefully examined. Monocyclometalated ruthenium(II) complexes identified active species, which then underwent inner-sphere single electron transfer (ISET) activate organic results from competition between close-shell reductive elimination open-shell radical coupling. Based this understanding, multilinear regression model was built predict site-selectivity, further validated by experiments.

Language: Английский

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Ruthenium‐Catalyzed Remote Difunctionalization of Nonactivated Alkenes for Double meta‐C(sp²)−H/C‐6(sp³)−H Functionalization

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(26)

Published: April 22, 2023

Twofold distal C-H functionalization was accomplished by difunctionalization of nonactivated alkenes to provide rapid access multifunctionalized molecules. The multicomponent ruthenium-catalyzed remote 1,n-difunctionalization (n=6,7) with fluoroalkyl halides and heteroarenes in a modular manner is reported. meta-C(sp2 )-H/C-6(sp3 )-H featured mild conditions, unique selectivity, broad substrate scope domino process for twofold C(sp2 )-H/C(sp3 activation the sequential formation three different carbon-centered radicals. A plausible mechanism proposed based on detailed experimental computational studies.

Language: Английский

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Ruthenium-Catalyzed Difunctionalization of Vinyl Cyclopropanes for Double m-C(sp²)–H/C-5(sp³)–H Functionalization

Organic Letters, Journal Year: 2024, Volume and Issue: 26(15), P. 3213 - 3217

Published: April 4, 2024

With in-depth research on 1,2-difunctionalization, remote difunctionalization has garnered widespread attention for achieving multifunctionality. Herein, we report a strategy under mild conditions. This exhibited good substrate suitability and functional group tolerance. In addition, the significance of this method is further evidenced by its successful application in scaling up conducting additional transformations target compounds. Mechanistic studies showed that radical might be involved process.

Language: Английский

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Electrochemical Glycosylation via Halogen-Atom-Transfer for C-Glycoside Assembly

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(15), P. 11532 - 11544

Published: July 19, 2024

Glycosyl donor activation emerged as an enabling technology for anomeric functionalization, but aimed primarily at O-glycosylation. In contrast, we herein disclose mechanistically distinct electrochemical glycosyl bromide activations via halogen-atom transfer and C-glycosylation. The radical addition to alkenes led C-alkyl glycoside synthesis under precious metal-free reaction conditions from readily available bromides. robustness of our e-XAT strategy was further mirrored by C-aryl C-acyl glycosides assembly through nickela-electrocatalysis. Our approach provides orthogonal with expedient scope, hence representing a general method direct C-glycosides assembly.

Language: Английский

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Direct Construction of C‐Alkyl Glycosides from Non‐Activated Olefins via Nickel‐Catalyzed C(sp³)─C(sp³) Coupling Reaction

Advanced Science, Journal Year: 2024, Volume and Issue: 11(12)

Published: Jan. 18, 2024

Among C-glycosides, C-alkyl glycosides are significant building blocks for natural products and glycopeptides. However, research on efficient construction methods remains relatively limited. Compared with Michael acceptors, non-activated olefins more challenging substrates have rarely been employed in the of C-glycosides. Here, a highly convenient approach synthesis through nickel-catalyzed C(sp

Language: Английский

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Pd-Catalyzed Stereospecific Glycosyl Cross-Coupling of Reversed Anomeric Stannanes for Modular Synthesis of Nonclassical C-Glycosides

Precision Chemistry, Journal Year: 2024, Volume and Issue: 2(11), P. 587 - 599

Published: July 21, 2024

Nonclassical C-glycosides, distinguished by their unique glycosidic bond connection mode, represent a promising avenue for the development of carbohydrate-based drugs. However, accessibility nonclassical C-glycosides hinders broader investigations into structural features and modes action. Herein, we present first example Pd-catalyzed stereospecific glycosylation anomeric stannanes with aryl or vinyl halides. This method furnishes desired in good to excellent yields, while allowing exclusive control configuration. Of significant note is demonstration generality practicality this C-glycosylation approach across more than 50 examples, encompassing various protected unprotected saccharides, deoxy sugars, oligopeptides, complex molecules. Furthermore, biological evaluation indicates that modifications drug molecules can positively impact activity. Additionally, extensive computational studies are conducted elucidate rationale behind differences reaction reactivity, unveiling transmetalation transition state containing silver (Ag) within six-membered ring. Given its remarkable controllability, predictability, consistently high chemical selectivity stereospecificity regarding carbon Z/E configuration, outlined study offers solution longstanding challenge accessing stereocontrol.

Language: Английский

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Ruthenium-Catalyzed Remote Trifunctionalization of Non-Activated Alkenes via Cyano Migration and meta-C(sp²)–H Functionalization

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

A novel Ru-catalyzed radical-triggered trifunctionalization of hexenenitriles is presented, employing a strategy remote cyano group migration and meta-C(sp2)-H functionalization. Through migration, the alkenyl moiety undergoes difunctionalization to formation benzylic radical intermediate. This intermediate facilitates para-selective C-H bond addition relative C-Ru within Ru(III) complex, ultimately enabling trifunctionalization. methodology provides an efficient route diverse array nitrile-containing compounds with broad functional compatibility.

Language: Английский

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