Development of Routes for the Stereoselective Preparation of β-Aryl-C-glycosides via C-1 Aryl Enones

Abstract

A wide range of enones derived from d-glucal, d-galactal, l-rhamnal, d-rhamnal, and l-arabinal underwent Heck-coupling with various arylboronic acids bearing electron-donating and -withdrawing groups in the presence of palladium acetate and 1,10-phenanthroline. These reactions provided synthetically useful C-1 aryl enones in good yields. Many sensitive functional groups as well as protecting groups present in arylboronic acids and enones, respectively, remained intact under optimized conditions. The stereoselective hydrogenation of C-1 aryl enones with Pd-C/H2 provides the β-isomer of 2-deoxy-aryl-C-glycosides in excellent yield. The C-1 aryl enones were also used as precursors for the synthesis of 2-hydroxy-β-aryl-C-glycosides. Regioselective C-2 halogenations and vinylations of C-1 aryl enones were achieved in excellent yields.

Synthesis of Hexenuloses and a Library of Disaccharides Possessing 3-oxo-glycal Unit

“…R f : 0.5 (10% EtOAc/hexane). 1 H NMR (500 MHz, CDCl 3 ): δ 7.17 (2R,3S,6S)-3,4-bis(Benzyloxy)-2-((benzyloxy)methyl)-6-methoxy-3,6-dihydro-2H-pyran (6). Compound 6 was synthesized from 5α (500 mg, 0.87 mmol) by following general procedure B.…”

“…Protected 3-oxoglycals have been used as substrates for the preparation of 2alkynyl 3-oxo-glycals via the 2-iodo derivative involving the Sonogashira coupling 5 as well as to synthesize 1-aryl hexenuloses through the Heck coupling with aryl boronic acids. 6 Moreover, due to the presence of a reactive α,β-unsaturated ketone system possessing an electron-donating endocyclic oxygen atom on the β-carbon, these glycals are prone to undergo stereoselective Michael/Hetero Michael addition reactions. Hence, 3-oxoglycals are excellent precursors for constructing O-, 7 S-, and Calkyl 8 /aryl 9 glycosides.…”

Recent Advances in Palladium-Catalyzed Oxidative Couplings in the Synthesis/Functionalization of Cyclic Scaffolds Using Molecular Oxygen as the Sole Oxidant

“…A straightforward method for the preparation of -aryl-C-glycosides was reported by Kandasamy and coworkers in 2019 via oxidative Heck coupling of sugar-derived enones and aryl boronic acids, presenting high yields and stereoselectivity towards the C1 carbon (Scheme 34). 60 The reaction presented broad substrate scope and good protecting group tolerance, in which a variety of enones derived from D-glucal, D-galactal, L-rhamnal, D-rhamnal, and L-arabinal could be functionalized, with the functional groups remaining intact at the end of the process. A plausible mechanism starts with coordination of 1,10-phenanthroline with palladium acetate, followed by transmetalation with the corresponding aryl boronic moiety.…”

Advances in Pd-catalyzed C–C bond formation in carbohydrates and their applications in the synthesis of natural products and medicinally relevant molecules

“…The two steps involved in this protocol include (i) the synthesis of C -1 aryl enones (53) via the regioselective Heck coupling from glycal enones (52) and (ii) synthesis of C- glycosides 54 and 55 through the stereoselective reduction of C -1 aryl enones (53) as depicted in Scheme 13 . 43 …”