Reactive intermediates : model substrate studies
Degree GrantorUniversity of Canterbury
Degree NameDoctor of Philosophy
The reactions of cinnamyl chloride and crotyl chloride with various aldehydes, RCHO; R=Me, Et, iPr, CH₃(CH₂)₅, PhCH₂, Ph, p-MeOPh, p-NCPh, to form homoallylic alcohols under the control of Sn-Al, Cr(II), Zn and Mg were examined and the stereochemistry of the products determined. Stereoselectivity and regioselectivity of these reactions are compared and explained with reference to cyclic and linear mechanisms and the metal involved, frontier molecular orbital energies and molecular modelling experiments. An attempt was made to extend control of the relative stereochemistry of the Sn-Al reaction to systems with more than two contiguous carbon centers. The aldehydes, RCH(CH₃)CHO; R=Me, Ph, tBu, reacting with cinnamyl chloride under control of Sn-Al resulted in moderate Cram selectivity, this diastereofacial selectivity increasing with the bulk of the aldehydes' R group. Glyceraldehyde gave very poor diastereofacial selectivity. Dialdehydes terephthaldecarboxaldehyde and glyoxal were reacted with cinnamyl chloride mediated by Sn-Al and the relative stereochemistries of the major products deduced. Competition experiments of crotyl bromide and cinnamyl chloride with aryl aldehydes, p-R-C₆H₄CHO; R=H, Me, MeO, NC, O₂N, under the control of tin mediated conditions (Sn-Al) and of crotyl organotin and cinnamyl organotin (allylic-SnL₃; L=Ph, nBu) catalysed by either BF₃.OEt₂ or heat were carried out and the results of these experiments discussed in the light of frontier molecular orbital theory. Molecular mechanics calculations were performed to evaluate the steric stability of rotamers of threo and erythro homoallylic alcohols and these used in association with electronic effects to explain the diastereoselectivity of the linear mechanism. Conformational analysis using MM calculations were undertaken in an attempt to rationalize the stereoselectivity at the cyclic transition state. Synthetic pathways to β,γ-epoxy ketones were explored and the synthesis of 38, 44, and 50 effected by a number of different paths to maximize yields; the diastereoselectivities of the epoxidations of intermediate hydroxy and acetoxy alkenes was investigated.