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Date of Award

2001

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

Supervisor

Professor M.A. Brook

Abstract

The enolate Claisen rearrangements of (E )-1-(alkylsilyl)-1-propen-3-ol-[ N -PG]-glycinate and (E )-1-(alkylsilyl)-l-buten-3-ol-[ N -PG]-glycinate esters were investigated (PG = protecting group). Several different variants of the Claisen rearrangement were evaluated; the formation of the syn stereoisomer was favored in all cases. The product was obtained in good to excellent yield (85-92%). The diastereoselectivity of the reaction varied from 2:1 to 29:1 (syn:anti ) depending on reaction conditions. In the case of the Ireland-Claisen variant, the relationship between enolate trap (R3 SiCl, R2 SiCl2 and Cl3 SiH) and diastereoselectivity was investigated, showing that chlorotrimethylsilane gave the best results in both selectivity and product yield. The size of the silyl group on the ester was also found to affect the diastereoselectivity slightly, in the sense that bulkier silanes improved reaction selectivity except in the case of aryl-substituted silanes. The Claisen rearrangement of 1-(alkylsilyl)-1-propyn-3-ol-[N -Boc]-glycinate ester and 1-(alkylsilyl)-1-butyn-3-ol-[N -Boc]-glycinate ester led to the formation of the unusual α-(3,5-bis(silyl)allenyl)-amino acid derivatives in moderate to good yield (30 to 85%) and high stereoselectivity (9:1 to 22:1). The amount of base (3.5 eq.) and enolate trap (3.5 eq.) employed in this reaction was found to be crucial for a high yield of the product. Diastereoselective additions of methyl-2-(N -PG)-3-(trimethylsilyl)-( E )-pent-4-enoate and methyl-2-(N -PG)-3-(trimethylsilyl)-( E )-hex-4-enoate to aromatic acetals in the presence of Lewis acids were investigated. Reaction conditions were examined in detail. TiCl 4 was found to be most effective in promoting the addition. Among the aromatic acetals examined, 2-bromo-benzaldehyde dimethyl acetal gave the best selectivity (>99% d.e.) and the best product yield (89%). The reaction of benzaldehyde dimethyl acetal resulted in modest selectivity (6:1) and yield (77%). BF3 .OEt2 promoted the addition reaction to give moderate yield and selectivity. The reaction of BF3 .OEt2 was found to be slower and required longer reaction times, to achieve high yield, than TiCl4 .

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