Natalie M. Williamson

New procedures for the Juliá–Colonna asymmetric epoxidation: synthesis of (+)-clausenamide

The oxidation of chalcone 1 to optically active epoxide 2 [a precursor of (+)-clausenamide (+)-3] may be effected using a 15-mer or 20-mer of L-leucine bound to a PEG based support; poly-L-leucines of this type may be used as immobilised catalysts in a fixed-bed reactor.

Preparation and Cyclization of Some N-(2,2-Dimethylpropargyl) Homo- and Heteroaromatic Amines and the Synthesis of Some Pyrido[2,3-d]pyrimidines

The Cu(i) catalyzed cyclization of o-substituted N-(2,2-dimethylpropargyl)anilines yields 8-substituted 2,2-dimethyl-1,2-dihydroquinolines, while m-substituted analogues provide a mixture of 5- and 7-substituted dihydroquinoline systems. This reaction can be extended to 2-amino-N-(2,2-dimethylpropargyl)anthracene, yielding a dihydronaphtho[2,3-f]quinoline product, and to aminoquinoline derivatives, which yield substituted phenanthroline products. Pyridine analogues did not cyclize, apparently because of complexation with the copper reagent. An alternative synthetic approach to these cyclized products, when complexation may be a problem, is illustrated by the following example. 2-Chloro-4-N-(2,2-dimethylpropargyl)pyrimidine was reduced using a Lindlar catalyst to the corresponding alkene which did not undergo an amino-Claisen rearrangement. However, the 5-bromopyrimidine alkene analogue underwent addition with phenylselanyl bromide to give a product that cyclized, using butyllithium, to a pyrido[2,3-d]pyrimidine selenium-containing product from which the selenium moiety could be removed to yield either a dihydro- or a tetrahydro-pyrido[2,3-d]pyrimidine system. A Heck reaction on the 5-bromopyrimidine alkene gave a 5-methylene-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine.

Juliá–Colonna asymmetric epoxidation reactions under non-aqueous conditions: rapid, highly regio- and stereo-selective transformations using a cheap, recyclable catalyst

The asymmetric oxidation of some enones (Table 1), selected dienones 3–5, and a trienone 13 is accomplished using poly-L-leucine or poly-D-leucine and urea hydrogen peroxide under non-aqueous conditions. One of the resultant epoxy ketones 6 has been converted into the δ-lactones 19 and 22.

Stereoselective epoxidation of electron poor dienes using poly(L-leucine)

Poly(L-leucine) catalysed oxidation of dienes 2, 3, 10, 16 and 18 and the triene 17 furnishes the corresponding epoxides 4, 5, 11, 19, 21 and 20 respectively in good to excellent yield and in states of high optical purity. Some regioselective reactions of the saturated epoxy ketones 5 and 11 are described.

Polyamino Acids as Man-Made Catalysts

Polyamino acids are easy to prepare by nucleophile-initiated polymerisation of amino acid N-carboxyanhydrides. Polymers such as poly-(l)-leucine act as robust catalysts for the epoxidation of a wide range of electron-poor alkenes, such as γ-substituted α,β-unsaturated ketones. The optically active epoxides so formed may be transformed into heterocyclic compounds, polyhydroxylated materials and biologically active compounds such as diltiazem and taxol side chain.