Mike S. Anson

Radical cyclisations of methylenecyclopropyl azetidinones—synthesis of novel tricyclic β-lactams

Addition of lithium bis(methylenecyclopropyl)cuprates to acetoxy azetidinones gives methylenecyclopropyl azetidinones, which can be converted to various radical cyclisation precursors. Attempted 4- exo cyclisation of 3 led only to reduced product, while cyclisation of 5 , using CuCl/bipy, gave a carbacephem, via a 5- exo cyclisation, but in low yield. Cyclisation of 6 and 7 , however, gave novel tricyclic β-lactams, as the result of 7- endo cyclisation, in good yield, and a cyclisation of bromide 23 led to the tricyclic β-lactam 24 , via a radical cascade sequence.

A simple and effective synthetic approach to chiral 4-pyridinyl proline derivatives

A rapid approach has been developed to provide a novel series of 4-pyridinyl proline derivatives as potential stereoselective catalysts. Nucleophilic displacement at the 4-pyridinyl position proved straightforward using proline but required microwave heating to proceed when using the more bulky α-methyl proline. Total control of enantioselectivity was obtained for the synthesis of proline derivatives.

Radical cascade reactions of methylenecyclopropane derivatives - synthesis of cis-fused bicyclo-3.4.0-nonanes and bicyclo-4.4.0-decanes

Abstract 1,2 Disubstituted methylenecyclopropyl bromides, 6 and 11, undergo radical cascade reactions, involving cyclisation, ring-opening and further cyclisation, to give cis bicyclic products in 67% and 41% yields respectively.

Simultaneous high throughput assessment of thermodynamic and kinetic behaviour of chemical reactions: theory and experiment

There is an increasing requirement in the pharmaceutical industry to rapidly monitor reactions. High throughput screening (HTS) is typically achieved by performing experiments simultaneously in array format in microtitre plates. One method of monitoring reactions that has received particular attention recently is the use of thermal measurements. The change in temperature with time resulting from a reaction depends on both thermodynamics and kinetics. Temperature can be monitored in a number of ways, one of which suitable for HTS is thermographic imaging. Relating such thermal information to reaction parameters such as enthalpy and rate is complicated by issues such as heat loss to the surroundings and heat transfer to different parts of the apparatus. A method is presented whereby information obtained from thermal imaging of microtitre plates can be used, along with experimental data for heat transfer to the surroundings and the microtitre plate, to rank reaction enthalpy and time to completion of a set of reactions. Finally a comparison to enthalpies obtained by microcalorimetry is made.