Catalytic glycosylation for minimally protected donors and acceptors.

Oligosaccharides have myriad functions throughout biological processes1,2. Chemical synthesis of these structurally complex molecules facilitates investigation of their functions. With a dense concentration of stereocentres and hydroxyl groups, oligosaccharide assembly through O-glycosylation requires simultaneous control of site, stereo- and chemoselectivities3,4. Chemists have traditionally relied on protecting group manipulations for this purpose5-8, adding considerable synthetic work. Here we report a glycosylation platform that enables selective coupling between unprotected or minimally protected donor and acceptor sugars, producing 1,2-cis-O-glycosides in a catalyst-controlled, site-selective manner. Radical-based activation9 of allyl glycosyl sulfones forms glycosyl bromides. A designed aminoboronic acid catalyst brings this reactive intermediate close to an acceptor through a network of non-covalent hydrogen bonding and reversible covalent B-O bonding interactions, allowing precise glycosyl transfer. The site of glycosylation can be switched with different aminoboronic acid catalysts by affecting their interaction modes with substrates. The method accommodates a wide range of sugar types, amenable to the preparation of naturally occurring sugar chains and pentasaccharides containing 11 free hydroxyls. Experimental and computational studies provide insights into the origin of selectivity outcomes.

Doubly stereoconvergent construction of vicinal all-carbon quaternary and tertiary stereocenters by Cu/Mg-catalyzed propargylic substitution.

The construction of vicinal, congested stereocenters with high selectivities is of general utility in chemistry. To build two such stereocenters in one step from readily available starting materials is very desirable, but remains challenging. We report here a doubly stereoconvergent, Cu/Mg-catalyzed asymmetric propargylic substitution reaction to convert simple starting materials to products with vicinal tertiary and all-carbon quaternary stereocenters in high yields and excellent diastereo- and enantioselectivities. Both the nucleophiles and the electrophiles employed in this transformation are racemic. This reaction uses earth abundant metal catalysts, operates under ambient conditions, and demonstrates broad substrate scope. The products of this reaction are functional group rich and synthetically versatile. Key to the success of this development is the devise of a Cu/Mg dual catalytic system and the identification of a bulky tridentate pyridinebisimidazoline (PyBim) ligand.

Halogen-bond-assisted radical activation of glycosyl donors enables mild and stereoconvergent 1,2-cis-glycosylation.

The chemistry of carbohydrates has a history of over 100 years, but simple, stereoselective and efficient glycosylation methods remain highly needed to facilitate the studies of sugars in various disciplines. Here we report a strategy for 1,2-cis-glycosylation without using metals, strong (Lewis) acids, elaborate catalysts or labile substrates. Our method operates by a unique mechanism: it activates glycosyl donors through a radical cascade rather than the conventional acid-promoted, ionic process. As elucidated by computational and experimental studies, the allyl glycosyl sulfones (as donors) form halogen bond complexes with perfluoroalkyl iodides, which-merely by visible light irradiation-fragment via radical intermediates to give the electrophilic glycosyl iodides. In situ trapping by various nucleophiles affords, in a stereoconvergent manner, the challenging 1,2-cis-glycosides. This metal- and acid-free reaction shows remarkable tolerance to functional groups. The high stereoselectivity holds for a broad array of donors. This study suggests that the simple C2-alkoxy group can serve as an effective directing group for building 1,2-cis-glycosidic bonds.