Many of bioactive natural products or synthetic drugs contain pyrrole moiety as a key skeleton. Pyrrole is one of the well known classes of heterocycle that display remarkable biological activities such as antibacterial, antiviral, anti-inflammatory, antitumor, and antioxidative. Especially lots of tetra- or penta-substituted pyrroles have been identified as anti-inflammatory and anticancer potent drug moiety. As representative example, atorvastatin (Lipitor?) is top-selling drug applied as an antihyperlipidemic agent. Therefore, highly substituted pyrrole has been one of the major targets in synthetic chemistry community. Many synthetic methods have been reported for the novel synthetic protocol exploration of the pyrrole structure, which can be categorized by following; classical Paal–Knorr synthesis, Hantzsch procedure, metal mediated cyclization and various cycloaddition strategies. Whereas these methods have been proven to be useful for the synthesis of pyrrole derivatives, the desired products are associated with regioisomers, especially in the case of cycloaddition strategies, which limits the scope of synthetic modification. However, there are a quite limited number of synthetic reports which can partly control the regioselectivity of pyrrole. Most of the cycloaddition approaches in the literature used symmetric alkynes to bypass the regioselectivity issue or has low regioselectivity with unsymmetrical alkyne or alkene.
We designed and synthesized α,β-unsaturated cyclic ketone(1) as a non-symmetric dipolarophile and various Münchnones (1,3-oxazolium-5-olates, 2) as 1,3-dipole for a [3+2] cycloaddition. This system can control the regiochemistry of resulting pyrroles, and the efficiency of this transformation was enhanced by the introduction of microwave-assisted reaction condition. Substituents on pyrrole are derived from aldehydes, amino acids and acylating agents, which means that we can achieve a huge molecular diversity based on pyrrole core skeleton.