Development of catalysts derived from chiral amines

In this thesis we report the development of biaryl azepinium salts (e.g. 83, Figure i) and their application in the enantioselective epoxidation of tri-substituted alkenes. These iminium salts appear to exist as a mixture of two conformers at room temperature. The observed enantiocontrol in the epoxidation reactions investigated appears to result from the chiral amine biasing the reactivity of one biaryl azepine conformation over the other towards attack of a nucleophilic oxidant. This leads to the epoxidation proceeding preferentially via one diastereoisomer of the oxaziridinium intermediate. t-Bu t-Bu Figure i. We also report the development of biaryl azepinium salts (e.g. 112, Figure ii) and their application in the highly enantioselective alkylation and Michael addition of glycine imines. It would appear that these salts exist in a single biaryl azepine conformation. Favourable ion- pair interaction between the quaternary ammonium and the glycine imine enolate in the transition state of the reactions result in the high enantioselectivities observed. t-Bu t-Bu Figure ii. We report preliminary studies into the application of biaryl azepines as part of bifunctional catalysts, for application in conjugate addition reactions (142) and in direct aldol reactions (152) (Figure iii). Figure iii. These results idicate that the novel tertiary amine salt 152 is capable of delivering both high diastereo- and enantioselectivity in the direct aldol reaction of 4-nitrobenzaldehyde 134 with 2-cyciohexanone 133 (Scheme i). 133 Scheme i. 134 o OH N02 138: 95%, 98% de, 98% ee The synthesis of a range of biaryl azepines with a chiral centre in the azepine ring is reported (Figure iv). Figure iv. These amines all appear to exist in a single biaryl azepine conformation. They were synthesised via a highly atropodiastereoselective direct arylation, as their corresponding trifluoroacetamide derivatives. Azepines (+)-155 and (+)-185, act as chiral relays and switch their conformation on removal of the trifluoroacetamide protecting group. Azepine (-)-211 can only exist in one conformation, and as such has the same conformation as its corresponding trifluoroacetamide derivative. Preliminary investigations into the potential of these chiral amines as precursors to asymmetric catalysts are reported. In this thesis, we also report the development of quaternary ammonium salts formed form combining a chiral amine with complex fragments that do not exhibit axial chirality. This study identified a novel quaternary ammonium salt 257, which is capable of delivering moderate levels of enantioselectivity in the Michael addition of glycine imine 10 to MVK (Scheme ii). Scheme ii. 10 K2C03, PhMe, 5h, MVK x.o, 92%, 52% ee Finally, we report the development of tetra-butyl ammonium borates (e.g. 283, Scheme iii) and their application in Suzuki-Miyaura cross-coupling reactions involving no additional water or base. Scheme iii. CI-Q-N02 280 Pd(OAch (3 mol%), IPA, 85 cc, 0.17 h ) < }-N02 282: 96% The quaternary ammonium borate reagents are capable of transferring a range of aryl groups and can react with a range of aryl halides in excellent yields. No additional base is required and reactions proceed with sub-stoichiometric quantities of water. These represent very useful reagents, particularly if one of the substrates is either water or base sensitive.EThOS - Electronic Theses Online ServiceGBUnited Kingdo