Chiral Chalcogen Bond Donors Based on the 4,4'-Bipyridine Scaffold.

Robin Weiss,Sergio Cossu,Patrick Pale,Paola Peluso,Emmanuel Aubert,Victor Mamane

doi:10.3390/molecules24244484

Abstract

Organocatalysis through chalcogen bonding (ChB) is in its infancy, as its proof-of-principle was only reported in 2016. Herein, we report the design and synthesis of new chiral ChB donors, as well as the catalytic activity evaluation of the 5,5′-dibromo-2,2′-dichloro-3-((perfluorophenyl)selanyl)-4,4′-bipyridine as organocatalyst. The latter is based on the use of two electron-withdrawing groups, a pentafluorophenyl ring and a tetrahalo-4,4′-bipyridine skeleton, as substituents at the selenium center. Atropisomery of the tetrahalo-4,4′-bipyridine motif provides a chiral environment to these new ChB donors. Their synthesis was achieved through either selective lithium exchange and trapping or a site-selective copper-mediated reaction. Pure enantiomers of the 3-selanyl-4,4′-bipyridine were obtained by high performance liquid chromatography enantioseparation on specific chiral stationary phase, and their absolute configuration was assigned by comparison of the measured and calculated electronic circular dichroism spectra. The capability of the selenium compound to participate in σ-hole-based interactions in solution was studied by 19F NMR. Even if no asymmetric induction has been observed so far, the new selenium motif proved to be catalytically active in the reduction of 2-phenylquinoline by Hantzsch ester.

Highlights

The term chalcogen bond (ChB) describes the intermolecular interaction occurring between a Lewis base (BL ) and a group 16 atom (S, Se, Te) which behaves like Lewis acid, according to the recommendations of the International Union of Pure and Applied Chemistry (IUPAC) [1,2,3]
The tetrahalo-4,40 -bipyridine skeleton contributes to increase the electrophilic character of the Ch atom and makes the new motif chiral, due to its atropisomeric geometry
Donors are characterized by a charged heterocyclic structure, which provides sufficient polarization to the Ch atom [2,3,14]. Another peculiarity of the new motif described here is the possibility of rotation around the C–Ch bond, which offers conformational adjustments/tuning during catalysis

Summary

Introduction

The term chalcogen bond (ChB) describes the intermolecular interaction occurring between a Lewis base (BL ) and a group 16 atom (S, Se, Te) which behaves like Lewis acid, according to the recommendations of the International Union of Pure and Applied Chemistry (IUPAC) (net attractive interaction between an electrophilic region associated with a chalcogen atom in a molecular entity and a nucleophilic region in another, or the same, molecular entity) [1,2,3]. ChB belongs to the family of σ-hole-based interactions [4], among which the most prominent and most studied is halogen bonding (XB) [5,6,7]. Molecules 2019, 24, 4484 the past decade [10], it is only recently that a few applications involving ChB in solid state [11]. Among the applications based on σ-hole interactions in solution, catalysis represents an active research area. While several catalysts acting as XB donor have been described during the last decade [6,13,14], the first examples of ChB-based catalysis have been very recently reported by the groups of Matile [15,16,17,18], Huber [19,20,21], and Wang [22]. Other recent applications of ChB concern anion binding [23,24] and transport [25,26,27]

Methods

Results

Conclusion