Modified Bohlmann-Rahtz Pyridine Synthesis for Cyclic Ketones

Abstract

The Bohlmann-Rahtz pyridine synthesis, first reported in 1957, is a valuable technique for efficiently synthesizing trisubstituted pyridines by combining propargyl ketones and carbonyl compounds. However, this method typically requires heating highly reactive aminoacrylates or activated carbonyl compounds, such as β-ketoesters. In this study, we discovered that the addition of ammonium fluoride to various cyclic ketones enables the efficient synthesis of cycloalkane-fused pyridines under mild conditions. The optimal conditions established in this study exhibit a wide range of substrate generality. Furthermore, the reaction conditions were found to be selective for cyclic ketones in preference to aliphatic ketones. In addition, this reaction has been successfully applied to the synthesis of epiguaipyridine, a natural product, and aza[5]helicene, a functional molecule.

Keywords: azahelicene; epiguaipyridine; pyridine; total synthesis; Bohlmann–Rahtz pyridine synthesis.