Exploring Skeletal Diversity via Ring Contraction of Glycal-Derived Scaffolds

Abstract

Aryl ether C-glycoside scaffolds have been prepared from tri-O-acetyl-D-glucal by C-glycosylation followed by allylic substitution with phenols mediated by Pd(0). The aryl ethers were subjected to either [3,3]-sigmatropic rearrangement to produce 3-pyranyl-phenols or Au(III)-mediated ring contraction to create highly substituted tetrahydrofurans. [structure: see text]

(R,R)-1,2-Bis(aminocarbonylphenyl-2′-diphenylphosphino)cyclohexane

“…103 A range of phenols were added to C-glycosides to produce an array of aryl ethers (eq 49). 105 The same regio-and stereochemistry were achieved using either the (R,R)-or (S,S)-ligand; however, the reaction was unsuccessful using achiral ligands such as dppb or dppp. (49) Morita-Baylis-Hillman diene adducts underwent palladiumcatalyzed allylic alkylation with phenol nucleophiles with good regio-and enantioselectivities (eq 50).…”

Ferrier–Nicholas pyranosidic cations: application to diversity-oriented synthesis

“…Glycals, i.e., Δ 1,2 -unsaturated carbohydrate derivatives, have already shown its usefulness in DOS. For instance, Schreiber and co-workers reported the combination of Ferrier [27,28] and Pauson-Khand [29,30] reactions to gain access to a library of tricyclic compounds [31], whereas Porco and co-workers employed a glycal-derived scaffold to produce a collection of highly substituted tetrahydrofurans [32]. In line with our previous approach to appendage diversity based in polyfunctionalized carbohydrate derivatives, we have studied the behavior of, previously unknown, Ferrier-Nicholas cations, e.g., 4 [33].…”

Skeletal and appendage diversity as design elements in the synthesis of a discovery library of nonaromatic polycyclic 5-iminooxazolidin-2-ones, hydantoins, and acylureas

“…10 Recently, skeletal diversity has evolved as the most powerful element in the design of small molecule discovery libraries. 11 It can be generated through branching strategies 12 or through rearrangement and fragmentation processes 13 in the library design. Polymorphic scaffolds 14 and sigma-elements that contain appendages with pre-encoded skeletal information as defined by Schreiber 15 have been described as alternative strategies to obtain skeletal diversity.…”