Modern drug discovery mandates the rapid and modular assembly of increasingly complex substances. Medicinally relevant molecules overwhelmingly bear nitrogen functionality with 179 of the top 200 brand name drugs containing at least one N-atom. Increasingly, the nitrogen atom is not merely a functional substituent, such as a pendant amine or linking amide, but is present in the form of a heterocycle, often bearing stereocenters. The development of methods to access these heterocycles from easily accessible precursors is an attractive goal. The resultant heterocycles will facilitate the pace of drug discovery, with the common motifs visible in biologically active agents ranging from antibiotics, antidepressants as well as agonists and antagonists of protein-protein interactions such as Hsp40-Hsp70. The specific goals of this research are as follows: 1) develop temporary tethering strategies for [2+2+2] cycloadditions;2) Investigate the oxidative coupling of amides and alkene/alkyne ? systems to assemble piperidines by a catalyzed/oxidative protocol;3) Exploit readily available aza-dienes in metal-catalyzed [4+2] reactions;and 4) Implement isocyanate cycloadditions to involve allenes and vinyl cyclopropanes. The long-term impact of this science is to enable chemists to rapidly assemble complex structures with high efficiency.
One of the most significant barriers to health-related research involving small molecules is the rapid assembly of therapeutic agents. This proposal seeks to develop new methods to synthesize complex frameworks using easily accessible precursors with high efficiency.
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|Neely, Jamie M; Rovis, Tomislav (2014) Rh(III)-catalyzed decarboxylative coupling of acrylic acids with unsaturated oxime esters: carboxylic acids serve as traceless activators. J Am Chem Soc 136:2735-8|
|Martin, Timothy J; Rovis, Tomislav (2013) A catalytic asymmetric synthesis of polysubstituted piperidines using a rhodium(I)-catalyzed [2+2+2] cycloaddition employing a cleavable tether. Angew Chem Int Ed Engl 52:5368-71|
|Dalton, Derek M; Rovis, Tomislav (2013) Catalytic, asymmetric indolizidinone aza-quaternary stereocenter synthesis: expedient synthesis of the cylindricine alkaloid core. Org Lett 15:2346-9|
|Neely, Jamie M; Rovis, Tomislav (2013) Rh(III)-catalyzed regioselective synthesis of pyridines from alkenes and ?,?-unsaturated oxime esters. J Am Chem Soc 135:66-9|
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|Hyster, Todd K; Ruhl, Kyle E; Rovis, Tomislav (2013) A coupling of benzamides and donor/acceptor diazo compounds to form ?-lactams via Rh(III)-catalyzed C-H activation. J Am Chem Soc 135:5364-7|
|Du, Ya; Hyster, Todd K; Rovis, Tomislav (2011) Rhodium(III)-catalyzed oxidative carbonylation of benzamides with carbon monoxide. Chem Commun (Camb) 47:12074-6|
|Hyster, Todd K; Rovis, Tomislav (2011) Pyridine synthesis from oximes and alkynes via rhodium(III) catalysis: Cp* and Cp(t) provide complementary selectivity. Chem Commun (Camb) 47:11846-8|
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