The activation of dihapto-coordinated trifluorotoluene towards hydroamination type reactions was investigated with the tungsten dearomatization agent, {TpW(NO)(PMe3)}. The [TpW(NO)(PMe3)(η2-trifluorotoluene)] complex has been shown to undergo stereo- and regioselective addition reactions with an electrophile (proton) followed by a nucleophile (hydride, enolate), across an uncoordinated double bond of the dearomatized ring. The range of nucleophiles accessible for the first tandem electrophilic/nucleophilic addition to η2-trifluorotoluene was expanded to include a variety of primary and secondary amines. Conditions were found to isolate these unstable amine addition products, which yielded η2-1,3-diene complexes with high regioselectively (&gt;20:1) in high yields (&gt;70%). This reactivity was shown with amines containing additional functional groups, such as alcohol and ester groups, as well as, benzylic amines. The tandem addition of a proton and cyclic amines was also demonstrated with amines such as piperidine, imidazole, and azetidine derivatives. The ability to add a range of amines, including cyclic amines, to an activated aromatic ligand with functional group tolerance is particularly exciting given the prevalence of nitrogen heterocycles in pharmaceuticals. Further metal-mediated functionalization of these delicate amine dienes was investigated to probe the effect of the reversible nature of the first nucleophilic addition on the ability to undergo a second addition reaction. Typically, the second tandem addition resulted in the adjacent installation of nucleophiles with high regio- and stereocontrol. This reactivity was demonstrated with a proton as the electrophile and nucleophiles including enolates, cyanide, and amines. Furthermore, investigation into the chemistry of these η2-1,3-diene complexes led to a number of intramolecular cyclization reactions with the amine substituent and incoming nucleophiles. Expanding the scope of this reactivity with a variety of amines enabled the synthesis of a diverse set of cis-fused tetrahydrobenzimidazole and hexahydroindole derivatives. Subsequent oxidation of the metal complex releases the free trifluoromethylated cyclohexene, tetrahydrobenzimidazole and hexahydroindole derivatives.

Activation of trifluorotoluene towards hydroamination type reactions by a tungsten dearomatization agent

2019 Fall National Meeting

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