Cooperative Bifurcated Chalcogen Bonding and Hydrogen Bonding as Stereocontrolling Elements for Selective Strain-Release Septanosylation

Harnessing Multistep Chalcogen Bonding Activation in the α-Stereoselective Synthesis of Iminoglycosides

“…Concurrent measurement of this titration set using 1 H NMR also revealed a downfield shift of the hydroxyl proton as the catalyst concentration increased (with reference to the hydroxyl resonance of pure 2n , see SI Supporting Figure S20). These observations are in line with a selenium-hydroxyl activation in the presence of the catalyst. , Subsequently, 77 Se and 13 C NMR titrations between catalyst J and intermediate 5 (see SI Supporting Figures S21 and S23) revealed a 77 Se NMR downfield shift (0.028 ppm downfield with reference to pure J ) when the concentration of 5 was increased (see SI Supporting Figure S21), and a concomitant downfield shift of the carbamate carbonyl 13 C resonance (1.70 ppm downfield with reference to pure 5 , see SI Supporting Figure S23). This suggests that catalyst J may engage both intermediate 5 and the acceptor’s hydroxyl oxygen through bifunctional activation in the downstream mechanistic step.…”

“…Using PCH catalysts, the core scaffold electronics could be fine-tuned using easily commercially available bis-phosphine precursors. While a wide variety of activation modes ranging from bidentate, bifunctional, chalcogen-π, bifurcation, and even synergistic ChB, π–π, and CH-π were reported by Wang, Huber, and our group, all of the currently known ChB-catalyzed reactions are predominantly based on a single activation event within a single elementary step (Figure B). Hence, the potential to harness the temporal catalyst–substrate engaging/disengaging nature of NCIs in the ChB activation manifold in numerous activation events within a multielementary step manifold could offer untapped opportunities for synthesis.…”

“…By virtue of our enriching journey in uncovering unusual sigma-hole based catalytic manifolds in carbohydrate chemistry, particularly demonstrated in our recent reports on the stereoselective access of 7-membered ring sugars, and β-indolyl glycosides, we are curious if further exploration of new mechanistic avenues using ChB catalysis in carbohydrate synthesis could address difficult carbohydrate classes that are considerably understudied.…”

Efficient O- and S-glycosylation with ortho-2,2-dimethoxycarbonylcyclopropylbenzyl thioglycoside donors by catalytic strain-release

“…1C). 10–12 While these methodologies have predominantly led to the generation of non-natural oligosaccharides or glycoconjugates, the realm of chemical glycosylation encompassing strain-driven reactions to access naturally occurring glycoarchitectures remains underexplored, with sporadic protocols having been reported.…”

Stereoselective Entry into α,α’‐C‐Oxepane Scaffolds through a Chalcogen Bonding Catalyzed Strain‐Release C‐Septanosylation Strategy

“…Our research group has on this front lately reported seminal work in the usage of the highly modular Wang's phosphonochalcogenide (PCH) catalyst [11] to access hitherto difficult-to-access, but biologically relevant glycosides via unprecedented catalytic mechanisms (Figure 1A, right). This include the α-stereoselective synthesis O,S-septanosides, [12] the β-selective synthesis of C,N-indolyl glycosides, [13] as well as the α-stereoselective synthesis of iminoglycosides. [14] During these studies, we were particularly intrigued by the biologically interesting 7-membered ring septanosides [15] as they are endowed with a central oxepane [16] core which is recognized as a privileged scaffold [17] in contemporary chemical biology.…”