Synthesis of three carbon homologated unsaturated aldehydes using regioselective Wittig olefination chemistry

Abstract

Unsaturated aldehydes are widely used in the synthesis of natural products and pharmaceutical molecules.18,19,20 Among various methods available in the literature, carbon homologation is a common reaction employed for the synthesis of unsaturated aldehydes. Wittig reaction has emerged as a very useful method for making homologated unsaturated aldehydes. The use of classical Wittig reaction is not desirable on a commercial scale due to the formation of the by-product triphenylphosphine oxide which is insoluble in water and generally difficult to remove. Use of alkyl phosphine reagents is one of the research interests in our group. Previously in our group, alkylphosphonium salts were successfully used in the Wittig reaction for the one and two carbon homologations.15 The trialkylphosphine oxide by-product is water soluble and can be easily removed. In this thesis, the three carbon homologation of aldehydes using (2-(1, 3-dioxolan-2-yl)ethyl)tripropylphosphonium bromide is described. The ylide formation is highly regioselective. A variety of aromatic and hetero aromatic aldehydes are homologated with good stereo selectivity. An attempt to synthesize the cytotoxic natural product (2R,3R,4R)-3,4-dihydro-3,4-dihydroxy-2-(3-methylbut-2-enyl)-1(2H)-naphthalenone using the homologated aldehyde is also illustrated.

Finally, the development of new synthetic routes for tricyclohexylphosphine is described. Tricyclohexylphosphine is used as a ligand in many important complexes which include the olefin metathesis Grubbs' catalyst and the homogeneous hydrogenation Crabtree's catalyst. It is synthesized generally from phosphorus trichloride and cyclohexylmagnesium bromide. It is also synthesized by hydrogenation of triphenyl phosphine with a niobium catalyst. Nevertheless, a new commercially viable synthesis possesses greatest advantage in the use of tricyclohexylphosphine.