Submitted to: Organic Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/2/2008
Publication Date: 10/24/2008
Citation: Petroski, R.J. 2008. Improved Preparation of Halopropyl Bridged Carboxylic Ortho Esters. Organic Communications. 1(3):46-53.
Interpretive Summary: There is a continuing need to develop more efficient and selective pest and weed control strategies. Insect pheromones can be used to monitor pest populations and to track dispersal of certain insects used for the biological control of invasive weeds. Difficulties occur when the chemical synthesis of the pheromone substances is lengthy or expensive. This paper describes how to prepare a useful molecular building block for application in synthetic organic chemistry. These results are important to scientists, stakeholders, and chemists working for small companies who would actually do the preparation of synthetic pheromones using this reaction as part of the process, because synthetic pathways must be capable of scale-up in order to be viable for commercial production.
Technical Abstract: Protection of a carboxylic acid function as a bridged ortho ester derivative enables the use of strongly basic conditions in the synthetic strategy because the protons, alpha to the previous carbonyl carbon, are less acidic. Protected 3-halopropionic acid can behave like an alkyl halide making them useful three-carbon homologating agents. This enables the chemistry of alkyl halides, includng Wittig reactions, Williamson ether synthesis, and lithiation at the 3-position. Bridged ortho esters of 3-haolpropyl carboxylic acids were prepared by esterification of 3-methyl-3-hydroxyoxetane with 3-bromopropionyl chloride and pyridine in dry tetrahydrofuran, followed by rearrangement with boron trifluoroetherate, to afford 1-(2-bromoethyl)-4-methyl-2,6,7-triazabicyclo[2,2,2]-octane. The 1-(2-iodoethyl)-4-methyl-2,6,7-triazabicyclo[2,2,2]-octane analogue could not be prepared directly by halogen exchange of 1-(2-bromoethyl)-4-methyl-2,6,7-triazabicyclo[2,2,2]-octane but could be prepared by halogen exchange of the 3-bromopropionate ester of 3-methyl-3-hydroxyoxetane with a mixture of sodium iodide and anhydrous sodium sulfate in acetone, followed by rearrangement with boron trifluoroetherate.