The Importance of 1,5‐Oxygen⋅⋅⋅Chalcogen Interactions in Enantioselective Isochalcogenourea Catalysis

Abstract

The importance of 1,5‐O⋅⋅⋅chalcogen (Ch) interactions in isochalcogenourea catalysis (Ch=O, S, Se) is investigated. Conformational analyses of N‐acyl isochalcogenouronium species and comparison with kinetic data demonstrate the significance of 1,5‐O⋅⋅⋅Ch interactions in enantioselective catalysis. Importantly, the selenium analogue demonstrates enhanced rate and selectivity profiles across a range of reaction processes including nitronate conjugate addition and formal [4+2] cycloadditions. A gram‐scale synthesis of the most active selenium analogue was developed using a previously unreported seleno‐Hugerschoff reaction, allowing the challenging kinetic resolutions of tertiary alcohols to be performed at 500 ppm catalyst loading. Density functional theory (DFT) and natural bond orbital (NBO) calculations support the role of orbital delocalization (occurring by intramolecular chalcogen bonding) in determining the conformation, equilibrium population, and reactivity of N‐acylated intermediates.

Chemistry Evolves, Terms Evolve, but Phenomena Do Not Evolve: From Chalcogen–Chalcogen Interactions to Chalcogen Bonding

“…[29] Extensive structural investigations,b oth in solution using nuclear Overhauser effect spectroscopy and in the crystal using X-ray structural analyses,w ere able to demonstrate the importance of these oxygen-sulfur interactions for this catalysis. [30] Kinetic studies showed asignificantly higher catalytic activity for the analogous isoselenourea derivatives.C omputational studies,s uch as the first theoretical investigation on chalcogen-chalcogen interactions in 2006, [7,8] demonstrated the electron delocalization as n Ch !s* Ch-C interactions.…”

Quantifying Interactions and Solvent Effects Using Molecular Balances and Model Complexes

“…61 Chalcogen bonding interactions have been implicated in the mechanism of isochalcogenureacatalyzed kinetic resolutions of secondary benzylic alcohols. 62 These reactions proceed via an acylated intermediate containing a carbonyl-chalcogen contact (Figure 10C). Indeed, the molecular orbitals and NBOs of these intermediates bear a striking resemblance to those observed in molecular balances (Figure 10C cf.…”

Substituent-Controlled Tailoring of Chalcogen-Bonded Supramolecular Nanoribbons in the Solid State

“… 19 When the central polarizable E atom belongs to Group VI of the periodic table, the term chalcogen bonding (EB, known also as ChB) is used to describe the interaction between a positively polarized chalcogen atom and a Lewis base. 20 − 22 Despite recent developments in catalysis 23 − 28 and sensing, 25 , 30 EB interactions have been mainly exploited in crystal engineering, 31 , 32 providing a distinctive series of persistent recognition motifs. 33 − 36 The structure of the most part of these chalcogen-bonding synthons builds on a heterocyclic scaffold, in which the chalcogen bond donors and acceptors are proximal to each other, 37 − 39 thus effectively developing macrocyclic 40 − 42 and wire-like 43 , 44 supramolecular architectures.…”