Intermolecular Stetter Reactions on Morita-Baylis-Hillman Adducts: an Approach to Highly Functionalized 1,4-Dicarbonyl Compounds

We reported herein an N-heterocyclic carbene (NHC)-mediated intermolecular Stetter reaction between oxidized Morita-Baylis-Hillman (MBH) adducts and a variety of aldehydes. This protocol allows the synthesis of highly functionalized 1,4-dicarbonyl compounds. The reaction is an alternative approach to these compounds using commercially available starting materials. This metal-free process exhibits a wide substrate scope, excellent atom economy, compatibility with functionalized substrates and mild reaction conditions. The 1,4-dicarbonyl compounds were prepared in two steps via MBH reactions with overall yields up to 99%. This protocol is easily scalable. The synthetic usefulness of this method was demonstrated in a high yield synthesis of a tri-substituted pyrrole used as an advanced intermediate in the total synthesis of kinase inhibitors as well as in the synthesis of another heterocycles.