ALPHA-Bromination of linear enals and cyclic enones.

Abstract

In a prior report, -iodination of cyclic and linear enones was found to be effected by pyridine and stoichiometric iodine. However, with the same combination of iodine and pyridine, refluxing was necessary for reactions of linear enones. For example, (Z)-4-iodo-4-hexen-3-one was obtained from trans- 4-hexen-3-one in 62% yield in boiling acetonitrile. Other -iodinations of cyclic and linear enones include the use iodine and excess quantities of pyridine, iodine and morpholine, pyridinium dichromate (PDC) with iodine and IN3, prepared in situ from ICl and NaN3. Extending the aforementioned reactions to the bromination of enones is not practical due to the handling difficulties of bromine, and its oxidative nature. Thus milder conditions are required that will tolerate sensitive groups such as an aldehyde in - bromination reactions. Previous examples of -bromination involve synthesis of -bromo analogues of flavones using a combination of iodobenzene diacetate and tetrabutylammonium bromide. Another bromination method involves the use of a rhodium (III) complex and acid halides or benzyl halides, via halogenation of diazodicarbonyl analogues. The same combination was also effective for -chloroenones. Herein we report a methodology for the formation of cyclic -bromo enones and linear enals, which are useful templates for synthesis. Enones or enals are converted directly to their respective -bromoenones or -bromoenals using a combination of pyridine-N-oxide and N-bromosuccinimide (NBS) by stirring in typical organic solvents at room temperature.1 Unlike the previously reported iodination methodology, which gave excellent yields with pyridine as catalyst, -bromination is more effective with pyridine-N-oxide. -Halogenations of linear enals were found to proceed with double bond geometry retention.