Catalytic and tandem-catalytic routes to small molecules
thesisposted on 27.02.2017, 03:50 by Spiccia, Nicolas Daniel
A valuable PA-11 precursor, methyl 11-aminoundecanoate hydrochloride, was synthesised from methyl undec-9-enoate. This ester, obtained from renewable canola oil, was transformed in a three step, multi-catalytic sequence involving cross-metathesis, palladium-catalysed benzylic amine addition and concomitant hydrogenation/hydrogenolysis in 58% overall yield without the use of column chromatography. The corresponding unsaturated PA-11 precursor, methyl 11-aminoundec-9-enoate hydrochloride, was synthesised in a similar sequence of cross-metathesis, palladium-catalysed benzylamine addition and hydrolysis in 53% overall yield. Methods for the Brønsted masking of the amino group during metathesis reactions were also developed, and highlighted the importance of solvent and counterion selection. A collection of unsaturated diamine salts of various lengths, all useful for the production of copolymer polyamides, was synthesised in high yield. The corresponding saturated diamine salts were also synthesised in excellent yield by employing an addition assisted-tandem hydrogenation via the residual ruthenium emanating from the metathesis step. Similarly, cross-metathesis and tandem cross-metathesis/hydrogenation reactions of alkenyl ammonium salts with acrylates gave unsaturated and saturated amino carboxylate salts useful for homopolymer polyamides in excellent conversion. In closing, this new methodology was utilised to complete a formal synthesis of the biologically active alkaloid perhydrohistrionicotoxin. This new synthesis employs a cross-metathesis of an alkenyl ammonium salt as a key step and generates an advanced literature intermediate in a five step convergent synthesis with a total yield of 30%.