Controlling Regioseletivity and Enantioselectivity in C–H activation

Abstract

Abstract The direct functionalisation of C–H bonds has emerged in recent years as an efficient and atom-economic alternative to the traditional cross coupling reaction. One of the challenges towards this goal is the selective transformation of a particular C–H bond amongst many other C–H bonds. This thesis describes studies on the use of CO2 as a traceless promoter for controlling meta-regioselective arylation of phenols and a separate investigation into an enantioselective arylation of pre-chiral η6-arene tricarbonyl chromium complexes. The introduction provides a general review of recent advances in the use of coordinating moieties as directing groups for selective activation of aromatic C–H bonds. The challenge of meta-selective C–H activation and the direct functionalisation of phenols is assessed and discussed. To overcome the scarce methods for accessing meta-arylated phenols, our objective was to develop an efficient methodology for the meta-arylation of phenols. Our strategy includes an ortho-carboxylation of the phenol followed by ortho-arylation of the salicylic acids and the subsequent protodecarboxylation to afford meta-arylphenols is proposed. A step-wise approach towards our aim is applied. First, a convenient and efficient method for the carboxylation of phenols is presented in Chapter 2. Then, a tandem arylation/decarboxylation reaction of salicylic acids is described in Chapter 3. Last, an efficient methodology for the meta-arylation of phenols via carboxylation/arylation/ decarboxylation processes in one-pot is presented in the following section in Chapter 3. To demonstrate the utility of this powerful methodology, an efficient synthesis of ϒ-secretase inhibitor and the further transformation of the meta-arylphenols are shown. Furthermore, an alternative method is described for the synthesis of meta-arylphenols via a tandem oxidation/arylation/decarboxylation reaction of salicylaldehydes. In Chapter 4, an approach towards the development of enantioselective C–H arylation leading to planar chirality is stated. Preliminary results are presented for this ongoing project.