Arylsulfonyl based compounds for the synthesis and functionalization of nitrogen containing heterocycles

The research described in this PhD thesis has been carried out mainly at the Department of Chemistry, University of Camerino, under the supervision of Prof. Marino Petrini and Prof. Alessandro Palmieri, following their ongoing research interest in the chemistry of sulfonyl azoles and α-amidosulfones for the synthesis and functionalization of nitrogen-heterocycles. A convenient and easy method for the synthesis of unsymmetrical 3, 3'-bisindolyl and 3, 3'-bisbenzazolyl structures was developed. The presence of the p-toluenesulfonyl moiety at the benzylic position enables further functionalization of these framework: elimination of the sulfonyl group, in fact, occurs under basic conditions affording a reactive indolenine intermediate that can undergo nucleophilic addition of a variety of nucleophiles. In particular, addition of hydride, Grignard and Reformatsky reagents affords the corresponding addition products. Functionalization at C-3 of pyrrole was achieved by base-promoted addition of nitrocompounds to sulfonylalkylpyrroles; this procedure allows the synthesis of 3-(2-nitroalkyl)pyrroles, challenging targets by mean of a regioselective Friedel-Crafts alkylation. The obtained addition products can be easily converted into functionalized 6-azaindoles through a three-step procedure involving reduction of the nitro group, Pictet-Spengler reaction and final oxidation on Pd/C. Reaction conditions for the synthesis of α-acryloylamidoalkysulfones were optimized in order to minimize the competitive conjugate addition to the acryloyl moiety. Various allyl bromides can be added under Barbier-like reaction conditions affording in good yields N-acryloyl homoallyl derivatives; the latter can undergo ring-closing metathesis to afford useful 6-substituted tetrahydropyridinones in good yields. When a substrate with a substituted double bond is submitted to reaction in presence of Grubb's II catalyst cross metathesis occurs, affording selectively N-substituted fumaramides. The last chapter, instead, deals with the research performed under the guidance of Prof J. N. Johnston as a visiting student at Vanderbilt University, Tennesse. Following their research line on umpolung amide synthesis, an analogue strategy leading to thioamides was envisaged. Preparation of opportune substrates and preliminary results for umpolung thioamides synthesis are herein reported.