Direct Experimental Evidence for the Priority of Flexible Ligand Skeleton in Asymmetric Friedel-Crafts Alkylation of Indole with Nitroalkenes

Abstract

Abstract: Direct experimental evidence for the priority of flexible ligand skeleton in asymmetric Friedel-Crafts alkylation was obtained through XRD analysis of flexible ligand/ZnCl 2 complex, as well as synthesis of dihydroacridine-linked bis(oxazoline) ligands with planar rigid scaffold. A transition state model without NH …  interaction was proposed for the rigid ligands to interpret the inversion of absolute configuration. Keywords: Rigid scaffold, flexible scaffold, diphenylamine, dihydroacridine, bis(oxazoline), Friedel-Crafts alkylation. INTRODUCTION Since the pioneering reports on oxazolines [1], chiral bis(oxazoline) ligands have been extensively developed by chemists in the fields of coordination chemistry, synthetic chemistry, and catalysis [2]. Large number of ligands with diverse scaffolds have been synthesized from commercially available amino alcohols and carboxylic acids/aldehydes through facile procedures, which illustrates their great potency in application. Some ligand scaffolds stand out from vast reports and gain broad applications in different asymmetric transformations [3], while most ligand scaffolds give satisfying results only in specific cases. Such a situation makes the design of novel ligands for designated reactions a difficult and unprofitable work. In recent years, some groups dedicated to the research on the relationship of ligand structure and enantioselectivity, especially the tuning of electronic effect and rigidity of ligand scaffold. Compared with the encouraging results achieved in the former case [4], much less attention has been paid on the tuning of rigidity [5]. Herein, we would like to document our recent progress on this subject. Diphenylamine-linked bis(oxazoline) ligands