A Stoichiometric Haloform Coupling for Ester Synthesis with Secondary Alcohols

Alastair Lennox describes a stoichiometric haloform houpling for the synthesis of esters.

The haloform reaction, first reported in 1822 by Georges Simon Serullas, is a staple of undergraduate organic chemistry courses taught in universities. It takes methyl ketones to carboxylic acids through the triple α-halogenation of the methyl group to form a good nucleofuge, which is replaced by hydroxide. This reaction has been widely applied in the pharmaceutical and fragrance industries. It has since evolved to form methyl or ethyl esters when the reaction is performed in methanol or ethanol, respectively. Dr. Alastair Lennox from the University of Bristol (UK) mentioned that “undergraduate textbooks tell you this is all that is possible.” Together with his group, he wondered why it was not possible to use more complicated and extravagant alcohols to make more interesting esters. After repeated in-depth literature search, no previous examples of complicated alcohols were found. Even secondary alcohols had hardly been attempted, except for one example of the use of isopropanol. Based on these surprisingly limited publications, the group were inspired to explore whether it was possible to derive conditions with one equivalent of a complex primary or secondary alcohol.

Read the full article A Stoichiometric Haloform Coupling for Ester Synthesis with Secondary Alcohols