Ligand-Controlled Monoselective C-Aryl Glycoside Synthesis via Palladium-Catalyzed C–H Functionalization of N-Quinolyl Benzamides with 1-Iodoglycals

Abstract

A monoselective synthesis of aryl-C-Δ(1,2)-glycosides from 1-iodoglycals via palladium-catalyzed ortho-C-H activation of N-quinolyl benzamides has been developed. An amino acid derivative was used as a crucial ligand to improve the yield and monoselectivity of the coupling reaction. The utility of this protocol was demonstrated by a concise synthesis of key moieties of some natural products.

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…A Pd-based catalytic system was used by Wu and Ye to achieve the functionalisation of arenecarboxamides with 1-iodoglycals. 423 An additional ligand derived from l -proline was required to obtain good to high yields (51–91%) and mono-selectivity ( Scheme 69D ), even if traces of diglycosylated compounds were generally detected. Various substituents on the amide partner were tolerated, such as a bromine atom particularly useful for further post-modifications.…”

Palladium‐Catalysed C(sp3)−H Glycosylation for the Synthesis of C‐Alkyl Glycoamino Acids

“…However, many existing methods resort to pre-functionalized coupling partners of high reactivity (such as metallated arenes/alkanes for nucleophilic substitution and metal-catalysed cross-coupling), [4] lack general regiochemical control (such as Friedel-Crafts-type glycosylation), [5] and often require a multistep reaction sequence and delicate operating conditions. [6] Recently, several groups have reported elegant methods for the synthesis of C-aryl glycosides via C À H functionalization [6,7] by applying metal-catalyzed activation of aryl C À H bond and avoiding pre-activation of the acceptors in the glycosylation. These methods offer a mild, straightforward, efficient, and general strategy for the synthesis of a series of C-aryl glycosides.…”

Glycosylation via Transition‐Metal Catalysis: Challenges and Opportunities

“…Most recently, Wu, Ye and co‐workers discovered a new approach for the synthesis of diverse C ‐aryl glycals (aryl‐ C ‐Δ 1,2 ‐glycosides, cf. 256 – 263 , Table ) from various 1‐iodoglycals 254 and N ‐quinolyl benzamides 253 via palladium‐catalyzed ortho ‐C–H activation . As shown in Table , various C ‐aryl glycals 256 – 263 were obtained in good to excellent yields under optimal condition {10 mol‐% Pd(OAc) 2 , 30 mol‐% ligand ( 255 ), 2 equiv.…”