Additive-Free Gold(III)-Catalyzed Stereoselective Synthesis of 2-Deoxyglycosides Using Phenylpropiolate Glycosides as Donors.

Stereoselective synthesis of deoxyglycosides has been achieved from benchtop stable and easily synthesizable deoxy-phenylpropiolate glycosides (D-PPGs) using gold(III) salt as catalyst under external additive-free conditions. Under a simple catalytic system, D-PPGs reacted with a variety of sugar and non-sugar acceptors to produce majorly α-stereoselective O/N-deoxyglycosides in good to excellent yields and regenerate easily separable and reusable phenylpropiolic acid. Deoxy-PPGs containing armed and disarmed groups survived well under the optimized reaction conditions. In addition, the orthogonal nature of D-PPGs was showcased, and 1,1'-linked trehalose-type sugar was also synthesized.

Visible-Light-Mediated ß-C(sp3)-H Amination of Glycosylimidates: En Route to Oxazoline-Fused/Spiro Nonclassical Bicyclic Sugars.

A straightforward route has been developed for the diastereoselective synthesis of nonclassical conformationally constrained oxazoline-fused and spiro bicyclic sugars bearing a quaternary center via selective ß-C-H amination of appropriately positioned glycosylimidates. The desired transformation proceeds via the generation of imidate N-radicals under visible-light conditions followed regioselective intramolecular N-C bond formation. The reactions tolerate broad functional groups under the optimized conditions. Furthermore, the synthetic utility of oxazoline-fused bicyclic sugar moiety is demonstrated through the glycosylation reactions.

Gold(III)-Catalyzed Glycosylation using Phenylpropiolate Glycosides: Phenylpropiolic Acid, An Easily Separable and Reusable Leaving Group.

An efficient and operationally simple gold(III)-catalyzed glycosylation protocol was developed using newly synthesized benchtop stable phenylpropiolate glycosyl (PPG) donors. Gold(III)-catalyzed activation of PPGs proceeds well with various carbohydrate and noncarbohydrate-based glycosyl acceptors and leads to their corresponding O/ N-glycosides in good to excellent yields with regeneration of reusable and easily separable phenylpropiolic acid. Differentially protected PPGs reacted well under the optimized reaction conditions. In particular, good anomeric selectivity was observed with mannosyl and rhamnosyl PPG donors. A preliminary mechanistic study reveals that the presence of a triple bond adjacent to the ester group is essential for activation, and PPG-based donor shows higher reactivity than analogous acetate and benzoate donors.

Electron-deficient pyridinium salts/thiourea cooperative catalyzed O-glycosylation via activation of O-glycosyl trichloroacetimidate donors.

The glycosylation of O-glycosyl trichloroacetimidate donors using a synergistic catalytic system of electron-deficient pyridinium salts/aryl thiourea derivatives at room temperature is demonstrated. The acidity of the adduct formed by the 1,2-addition of alcohol to the electron-deficient pyridinium salt is increased in the presence of an aryl thiourea derivative as an hydrogen-bonding cocatalyst. This transformation occurs under mild reaction conditions with a wide range of O-glycosyl trichloroacetimidate donors and glycosyl acceptors to afford the corresponding O-glycosides in moderate to good yields with predictable selectivity. In addition, the optimized method is also utilized for the regioselective O-glycosylation by using a partially protected acceptor.

Copper(II)-Mediated Aerobic Oxidation of Benzylimidates: Synthesis of Primary α-Ketoamides.

A simple and straightforward method for the synthesis of primary α-ketoamides has been discovered. The reaction represents the first example of benzylimidates directly converting to primary α-ketoamides by using sustainable molecular oxygen as an oxidant. This reaction proceeds in the presence of copper(II) salt via cleavage of benzylic C-H and C-O bonds of the benzylimidates with liberation of alcohols as the only byproduct. A wide substrate scope, operationally mild conditions, the use of single substrates, and a reaction scaled up to grams make this strategy very attractive and practical. Furthermore, mechanistic studies illustrate that the imidate group adjacent to the benzylic position plays crucial role in facilitating this chemical process.