Dataset Information

Stereoretentive Intramolecular Glycosyl Cross-Coupling: Development, Scope, and Kinetic Isotope Effect Study.

ABSTRACT: A series of cyclic C-glycosides were synthesized using the palladium-catalyzed stereoretentive intramolecular glycosylation of aryl iodides by employing a bulky phosphine ligand. A variety of functional groups are tolerated in the reaction, and enantioenriched anomeric nucleophiles could be coupled without erosion of optical purity. This study offers a unified method to access both cis- and trans-fused rings by capitalizing on the stereoretentive nature of the Stille reaction. In addition, competition experiments for intermolecular and intramolecular cross-couplings revealed secondary KIEs of 1.43 and 0.81, respectively, suggesting a profoundly different steric congestion at the transition state.

SUBMITTER: Yi D

PROVIDER: S-EPMC9637396 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Stereoretentive Intramolecular Glycosyl Cross-Coupling: Development, Scope, and Kinetic Isotope Effect Study.

Yi Duk D Zhu Feng F Walczak Maciej A MA

Organic letters 20180717 15

A series of cyclic C-glycosides were synthesized using the palladium-catalyzed stereoretentive intramolecular glycosylation of aryl iodides by employing a bulky phosphine ligand. A variety of functional groups are tolerated in the reaction, and enantioenriched anomeric nucleophiles could be coupled without erosion of optical purity. This study offers a unified method to access both cis- and trans-fused rings by capitalizing on the stereoretentive nature of the Stille reaction. In addition, compe ...[more]

PMID: 30015497

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Project description:Stereoselective manipulations at the C1 anomeric position of saccharides are one of the central goals of preparative carbohydrate chemistry. Historically, the majority of reactions forming a bond with anomeric carbon has focused on reactions of nucleophiles with saccharide donors equipped with a leaving group. Here, we describe a novel approach to stereoselective synthesis of C-aryl glycosides capitalizing on the highly stereospecific reaction of anomeric nucleophiles. First, methods for the preparation of anomeric stannanes have been developed and optimized to afford both anomers of common saccharides in high anomeric selectivities. We established that oligosaccharide stannanes could be prepared from monosaccharide stannanes via O-glycosylation with Schmidt-type donors, glycal epoxides, or under dehydrative conditions with C1 alcohols. Second, we identified a general set of catalytic conditions with Pd2(dba)3 (2.5 mol%) and a bulky ligand (JackiePhos, 10 mol%) controlling the ?-elimination pathway. We demonstrated that the glycosyl cross-coupling resulted in consistently high anomeric selectivities for both anomers with mono- and oligosaccharides, deoxysugars, saccharides with free hydroxyl groups, pyranose, and furanose substrates. The versatility of the glycosyl cross-coupling reaction was probed in the total synthesis of salmochelins (siderophores) and commercial anti-diabetic drugs (gliflozins). Combined experimental and computational studies revealed that the ?-elimination pathway is suppressed for biphenyl-type ligands due to the shielding of Pd(II) by sterically demanding JackiePhos, whereas smaller ligands, which allow for the formation of a Pd-F complex, predominantly result in a glycal product. Similar steric effects account for the diminished rates of cross-couplings of 1,2-cis C1-stannanes with aryl halides. DFT calculations also revealed that the transmetalation occurs via a cyclic transition state with retention of configuration at the anomeric position. Taken together, facile access to both anomers of various glycoside nucleophiles, a broad reaction scope, and uniformly high transfer of anomeric configuration make the glycosyl cross-coupling reaction a practical tool for the synthesis of bioactive natural products, drug candidates, allowing for late-stage glycodiversification studies with small molecules and biologics.

Dataset Information

Stereoretentive Intramolecular Glycosyl Cross-Coupling: Development, Scope, and Kinetic Isotope Effect Study.

Publications

Stereoretentive Intramolecular Glycosyl Cross-Coupling: Development, Scope, and Kinetic Isotope Effect Study.

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