Synthesis of non-classical heteroaryl C-glycosides via Minisci-type alkylation of N -heteroarenes with 4-glycosyl-dihydr
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nthesis of non-classical heteroaryl C-glycosides via Minisci-type alkylation of N-heteroarenes with 4-glycosyl-dihydropyridines *
Qingbing Wang, Juan Duan, Pingping Tang, Gong Chen & Gang He
*
State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China Received May 29, 2020; accepted July 2, 2020; published online August 25, 2020
A radical-mediated method was reported for diastereoselective synthesis of non-classical heteroaryl C-glycosides via Miniscitype alkylation of N-heteroarenes with 4-glycosyl-1,4-dihydropyridine (DHP) reagents. These DHP reagents serve as convenient precursors for various glycosyl radicals under the activation of single electron transfer (SET) oxidation by persulfate and visible light irradiation with or without photocatalyst. non-classical C-glycoside, Minisci reaction, 4-glycosyl-dihydropyridine Citation:
Wang Q, Duan J, Tang P, Chen G, He G. Synthesis of non-classical heteroaryl C-glycosides via Minisci-type alkylation of N-heteroarenes with 4glycosyl-dihydropyridines. Sci China Chem, 2020, 63, https://doi.org/10.1007/s11426-020-9813-5
Aryl C-glycosides are frequently found in natural products and synthetic drugs [1]. While the classical aryl C-glycosides bear aryl substituents on the anomeric C-1 position, nonclassical (Nc) aryl C-glycosides, sometimes referred as “reverse C-glycoside”, feature aryl substituents on the other side of O atom in pyranose or furanose rings and have also been used in the design of glycomimetic drugs (Scheme 1 (a)). For example, antidiabetic drug Sotagliflozin acts as a dual inhibitor of SGLT1 (sodium-dependent glucose transporter 1) and SGLT2 [2]. The synthesis of non-classical aryl or heteroaryl C-glycosides is still challenging. The conventional synthetic strategies often rely on the reactions of organometallic reagents such as aryl-zinc or Grignard reagents with suitable glycosyl precursors to introduce the aryl or heteroaryl groups [2c,3]. [4+2] cycloaddition reaction has also been applied to construct the core structure of nonclassical C-glycosides [4]. The groups of Vismara and Inoue demonstrated that Minisci type C–H alkylation reaction of N-heteroarenes with glycosyl radical intermediates, generated from uronic acids or α-alkoxyacyl tellurides, can provide a more streamlined access to these structures (Scheme 1
(b)) [5–8]. Recently, Molander group reported the synthesis of non-classical aryl C-glycosides by radical-mediated coupling 4-“Nc-glycosyl”-1,4-dihydropyridine (4-Nc-glycosylDHP) reagents with aryl- and heteroaryl-bromides under the co-catalysis of Ni(II) and organic photocatalyst (Scheme 1 (c)) [9]. Herein, we report a new radical-mediated method for the synthesis of non-classical heteroaryl C-glycosides via Minisci-type alkylation of N-heteroarenes with various 4Nc-glycosyl-DHPs under photo irradiation (Scheme 1(d)). While DHPs (Hantzsch esters) have long been used as organic hydride donors, recent studies showed that 4-alkylDHPs can serve as excellent donors of alkyl
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