Enhanced Selectivity of Chalcogen Bonding over Halogen Bonding Catalyzed C-glycosylation Through Differentiated
1College of Chemistry and Materials Science, Guangdong Provincial Key Laboratory of Functional Supramolecular Coordination Materials and Applications, Jinan University, Guangzhou, 510632, P.R. China.
Abstract:
σ-hole-based noncovalent interactions are gaining intense attention as robust tools in stereoselective carbohydrate synthesis. However, the mechanistic understanding behind the differing performance between chalcogen bonding (ChB) catalysis versus halogen bonding (XB) catalysis in chemical glycosylations still remains unresolved. Herein, we disclose a remarkable instance whereby phosphonochalcogenide (PCH) catalysis displays pronounced selectivity and reactivity elevation in aryl-C-glycosylations compared to XB catalysis. Mechanistic studies revealed that the enhanced stereocontrol can be attributed to the differentiated downstream activation of a key bicyclic intermediate. Hammett analysis supported that ChB catalysis shifted the C-glycosylation toward the SN1 domain, while the XB catalysis proceeded with SN2 characteristics. DFT calculations further illuminated that the downstream ChB catalytic engagement involved all four selenium σ-holes engaging in two bifurcated ChB modes. This study thus sheds new light that the selectivity benefits of ChB catalysis could be accounted for by privileged mechanistic access into an otherwise inaccessible stereoselective pathway.
Related Concept Videos
02:17Regioselectivity of Electrophilic Additions to Alkenes: Markovnikov's Rule
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...
01:24Oligosaccharide Assembly
Multiple sugar molecules that may or may...
02:34Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration
02:17Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
01:21Acid-Catalyzed α-Halogenation of Aldehydes and Ketones
In the first step of the mechanism, the acid protonates the carbonyl oxygen resulting in a resonance-stabilized cation, which subsequently loses an α-hydrogen to form an enol tautomer. The C=C bond in an enol is highly nucleophilic because of the electron-donating nature of the –OH group. Consequently, the double bond attacks an electrophilic halogen to form a...
02:36Regioselectivity and Stereochemistry of Hydroboration
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.