Nonsymmetrical 1,1'-disaccharides and related derivatives constitute structural components in various glycolipids and natural products. Some of these compounds have been shown to exhibit appealing biological properties. We report a direct yet stereoselective 1,1'-glycosylation strategy for the synthesis of nonsymmetrical 1,1'-disaccharides with diverse configurations and sugar components. The strategy is based on the joined forces of a new class of configurationally stable glycoside acceptors and stereodirecting thioglycoside donors. The new glycoside acceptors feature a picoloyl (Pico) protecting group at the remote C4/C3 position that confers unusual stability on TMS glycosides under acidic conditions.

β- and γ-fluorinated ketones are desirable moieties in building blocks for bioactive molecules. Recent progress in installing this functionality has centered around ring-opening carbon–carbon bond cleavage/fluorination of strained cycloalkanols, either using precious silver catalysis or superstoichiometric ceric ammonium nitrate (CAN). Careful study of these methods has allowed us to design and develop a general Earth-abundant-element-catalyzed method for remotely fluorinated ketone synthesis via C–C bond cleavage. Critically, the use of manganese as a catalyst allows for the system to turnover with Selectfluor, permitting low catalyst loadings and high reaction efficiencies. This method allows the efficient synthesis of a wide variety of β- and γ-fluoroketones and is highly scalable, proceeding with no loss of efficiency on gram scale. Preliminary mechanistic experiments implicate a radical pathway. Together, we introduce a robust and simple approach to the remote fluorination of ketones using Earth-abundant-element catalysis with wide substrate tolerance and scalability.

A general strategy for the diverse synthesis of ten disaccharide aminoglycosides, including natural 2‐trehalosamine (1), 3‐trehalosamine (2), 4‐trehalosamine (3), and neotrehalosyl 3,3′‐diamine (8) and synthetic aminoglycosides 4–7, 9, and 10, has been developed. The aminoglycoside compounds feature different anomeric configurations and numbers of amino groups. The key step for the synthesis was the glycosylation coupling of a stereodirecting donor with a configuration‐stable TMS glycoside acceptor. Either the donor or acceptor could be substituted with an azido group. The aminoglycosides prepared in the present study were characterized by 1D and 2D NMR spectroscopy.

Decarboxylative protonation is a general deletion tactic to replace polar carboxylic acid groups with hydrogen or its isotope. Current methods rely on the pre-activation of acids, non-sustainable hydrogen sources, and/or expensive/highly oxidizing photocatalysts, presenting challenges to their wide adoption. Here we show that a cooperative iron/thiol catalyst system can readily achieve this transformation, hydrodecarboxylating a wide range of activated and unactivated carboxylic acids and overcoming scope limitations in previous direct methods. The reaction is readily scaled in batch configuration and can be directly performed in deuterated solvent to afford high yields of d-incorporated products with excellent isotope incorporation efficiency; characteristics not attainable in previous photocatalyzed approaches. Preliminary mechanistic studies indicate a radical mechanism and kinetic results of unactivated acids (KIE = 1) are consistent with a light-limited reaction.

Ceric ammonium nitrate allows the rapid and scalable synthesis of fluoroketones from cyclobutanols.