Cross-coupling of cobalt-complexed propargyl radicals : chemo-, regio-, and diastereoselective access to 3,4-diaryl-1,5-hexadiynes

The ability to control the chemo-, regio-, and stereoselectivity of radical reactions remains one of the main challenges of modern synthetic chemistry. Among innovative approaches is the coordination of organic moieties with transition metals that facilitates the generation of radical species and provides for their moderation. The very topology of metal complexes allows for altering the electronic, steric and conformational parameters of rt- and a-bonded ligands by varying the nature of the transition metal, its oxidation state, and attendant with it, the mode of interaction with an organic moiety. The chemistry of organometallic radicals, in particular those with an unpaired electron localized on the a-carbon atom in a rt-bonded ligand, has become an emerging interdisciplinary field. Intermolecular homo-coupling radical reactions constitute the bulk of the experimental material reported so far, while intermolecular radical cross-coupling reactions - with an unpaired electron localized in an a-position of a rt-bonded ligand - remains practically unknown. In this project, chemo- and diastereoselectivities of homo- and cross-coupling reactions of Co2(C0)6-complexed propargyl radicals were studied. The alternative radical generation methods - reduction of respective cations with Zn, or Cp2Co, and one-step mediation with THF, or Tf20 - were employed. In the case of cobalt complexes with terminal triple bonds, the product distribution is nearly statistical and dependent upon the reducing agent with the concentration of the cross-coupling product falling in the range of 3 8-49%. The diastereoselectivity varied widely (de 40- 92%) with the preponderant formation of D,L-diastereoisomers in both homo- and cross-coupling reactions. The highest level of stereocontrol was achieved in THF- and Tf20-mediated reactions (de up to 92%), while the reductions with Cp2Co were inferior in both homo- and cross-coupling processes (de 40-56% ). An introduction of a y-aromatic ring revealed a kinetic differentiation at the radical generation step that, in tum, resulted in a nonstatistical distribution of homo- and cross-dimers. The D,L-diastereoselectivity is found to be systematically lower for homo-dimers containing a y-phenyl substituent at the triple bond. The observed chemoselectivities are accounted for based on the computed values of charge distribution in the requisite cations. Two alternative procedures have been developed for decomplexation reactions. Ceric ammonium nitrate afforded D,L- and meso-3,4-diaryl-1 ,5-hexadiynes both with terminal triple bond and y-aryl substituents at the acetylenic termini, the potential aromatase inhibitors. Hydrogenation with Ni Raney unexpectedly triggers three different reactions - decomplexation, debenzylation, triple bond hydrogenation - affording, in a one-pot synthesis, the respective D,L- and meso-3,4-di(4- hydroxyphenyl)hexanes. The DDQ-induced dehydrogenation of C3-C4 bond in D,L-and meso-3,4-diaryl-1,5-hexadiynes allowed for incorporation of an unsaturation unit thus creating an extended organic chromophores of biological relevance.