Atropisomeric Diaryl Ethers and other Non-Biaryl Atropisomers

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Abstract

Atropisomerism is a property exhibited by molecules where rotation about one or more bonds is restricted. Along with biaryls, which are widely utilised in asymmetric catalysis, several other classes of compounds display atropisomerism. These molecules have applications in enantioselective synthesis, asymmetric catalysis and have been used to relay stereochemical information. There are, however, a number of challenges associated with their asymmetric synthesis (Chapter 1).This thesis describes research carried out on the synthesis and asymmetric synthesis of atropisomeric diaryl ethers. Chapter 2.1 explains how these ethers are synthesised in multi-gram quantities and to allow the incorporation of large ortho substituents.Having a number of diaryl ethers with suitable substitution patterns to achieveatropisomerism, Chapter 2.2 goes on to report two novel and complimentarybiocatalytic approaches to the enantioselective synthesis of diaryl ethers bydesymmetrisation. This chapter also describes a possible route towards the synthesis of a diaryl ether based ligand.Chapter 2.3 reports the lateral lithiation of meso diaryl ethers to yield diastereomeric atropisomers stereoselectively. Our attempts to use (–)-sparteine in lateral lithiations to desymmetrise a diaryl ether enantioselectively is also described. We go on to determine the configurational integrity of our organolithiums and the reaction pathway that exists in lithium substitution.Finally, the diastereoselective synthesis of both a diaryl ether (via a stereoselective reduction of a pro-chiral ketone) and a diaryl sulfide (via an addition reaction) is described in chapter 2.4. This chapter also reports the conformational behaviour of a diaryl amide in solution.

Keyword(s)

Atropisomer; enantioselective synthesis

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