Experimental Studies on the Selective β-C-H Halogenation of Enones

Here we describe the realization of a one-pot protocol for the β-C-H halogenation of cyclic enones via umpolung of the β-carbon. The developed method includes hydrazone formation and selective β-halogenation (bromination, chlorination) with N-bromosuccinimide and Palau'chlor (2-chloro-1,3-bis(methoxycarbonyl)guanidine) followed by hydrolysis of the hydrazone moiety. Using the optimized conditions, we were able to effectively β-brominate and β-chlorinate for the first time cyclic enones with different substitution patterns and various functional groups in one flask, whereas previous methods for this transformation required several steps. Additionally, the utility of the method was demonstrated in a short synthesis of the core structure of the Aspidosperma alkaloid jerantinine E.