Chiral Catalyst-Directed Dynamic Kinetic Diastereoselective Acylation of Lactols for De Novo Synthesis of Carbohydrate

Abstract

The control of the stereochemistry at the anomeric position is still one of the major challenges of synthetic carbohydrate chemistry. We have developed a new strategy consisting of a chiral catalyst-directed acylation followed by a palladium-catalyzed glycosidation to achieve high α- and β-stereoselectivity on the anomeric position. The former process involves a dynamic kinetic diastereoselective acylation of lactols derived from Achmatowicz rearrangement, while the latter is a stereospecific palladium-catalyzed allylic alkylation.

Site-Divergent Delivery of Terminal Propargyls to Carbohydrates by Synergistic Catalysis

“…Considering that the axial hydroxyls in a carbohydrate scaffold are in general less reactive than the equatorial ones, it is remarkable this reaction could override such reactivity bias and modify the axial 2-OH of 4 selectively. In 2017, the Tang group 47,50,51 reported a catalyst-controlled, site-divergent acylation of carbohydrates with benzotetramisole-based catalysts 52,53 (11 to 12 or 12 0 via 14; Figure 1D). It is proposed that the favorable interaction between the lone pair electrons on OR 0 of the nucleophile and the cationic center in the electrophile (cf.…”

De Novo Synthesis of Mono‐ and Oligosaccharides via Dihydropyran Intermediates

“…The group of Ta ng developed ac hiralo rganocatalyst-directed DKDA with high diastereoselectivity for both matched and mismatched substrates (Scheme 11). [30] The (R)-and (S)-BTM catalysts used in this acylation reaction were first introduced by Birman's group for the kinetic resolution of alcohols. [31] The mixed anhydride protocold eveloped by the group of Shiino is also applicable to the DKDA reactiona nd introduces many different acyl groups to both matched and mismatched substrates.…”

“…[65] Essentially,a ll possible stereoisomers of rhodinoand amicetopyranosides were systematicallys ynthesized,i ncluding both a and b anomers. The combination of this strategy and previously discussed chiral-catalyst-directed DKDA reaction [30] allows the generation of all eight stereoisomers by three pairs of chiral catalysts. The method was then extended to the synthesis of both a-a nd b-narbosine Bd isaccharides (Scheme 27).…”

Synthesis of D-manno-heptulose via a cascade aldol/hemiketalization reaction

“…However, the synthesis of D- manno -heptulose and its derivatives from the common differentially protected ketoheptose building block is still attractive due to the versatile functionalization possibilities of the building block into various derivatives of D- manno -heptulose. A de novo synthesis has proved to be an attractive strategy to produce orthogonally protected carbohydrate building blocks from simple precursors [28–39]. Here, we report a [4 + 3] approach to access differentially protected ketoheptose building blocks, which enables the synthesis of D- manno -heptulose.…”