The Generation of Chiral Centres at Heterogeneous Surfaces

Prochiral substrates may undergo enantioselective hydrogenation when a chirally modified metal catalyst is used. This involves the chemisorption of a chiral source, natural or synthetic, which creates a chiral environment on which the substrate may be reduced. Historically, prochiral beta-ketoesters and alpha-ketoesters (notably ethyl pyruvate) in conjunction with a cinchona modified platinum surface has led to the most efficient system known, furnishing products with enantiomeric excesses as high as 95%. The original purpose of this work was to examine the possibility of obtaining a modifier which is effective across a range of substrates. However, these preliminary studies strongly suggest that the substrate and modifier must be thought of as a matched pair. It is now widely accepted that the substrate and modifier interact via a diastereomeric intermediate at which juncture chirality is conferred. Hydrogenation of prochiral alkenes using modified heterogeneous catalysis has yet to lead to significant induction. As part of this speculative project, two alkenes of specific industrial interest were selected and prepared. A variety of modifiers were then synthesised, many of which were axially chiral. Such molecules are often particularly efficient with regard to the transmission of chirality. Preparation of molecules with 'conventional' C-centred chirality was also undertaken. Resolution of several potential modifiers was achieved using a variety of methods including fractional crystallisation of diastereomers and enantioselective enzymic hydrolysis of a target compound derivative. Certain structural attributes are believed to be necessary in order to facilitate induction. Therefore, these characteristics were incorporated by design into the molecules under consideration. It is important that the modifier is able to adsorb onto the metal surface by way of a polar grouping or an aromatic moiety. In addition, a pendant polar grouping is now considered to be essential. This enables the formation of a transient hydrogen bond, which acts as a 'conduit' for enantioselectivity. This thesis describes the search for an efficient substrate-modifier complementary pair and contributes to the overall understanding of the concepts involved in the generation of chiral centres at heterogeneous surfaces