Ruthenium porphyrins and dirhodium(II, II) carboxylate-catalyzed carbene transfer and C-H insertion reactions and metal-free cross-coupling of diazo quinones with organoborons

Abstract

Both metal-carbenes and free carbenes are reactive and capable of undergoing numerous transformations to form C–C and C-X bonds in modern organic synthesis. The carbene entity bearing two functional groups (the two carbene substituents) is transferred into the product molecule, representing an attractive strategy to build up complex structures. Compared to traditional acceptor carbenes, α-perfluoroalkyl carbene and quinoid carbene, which have great potential in installing fluorinated groups and phenol moieties for the synthesis of bioactive and pharmaceutical compounds, remained underexplored. This thesis describes the catalytic α-perfluoroalkyl carbene and quinoid carbene transfer reactions as well as the synthesis of their corresponding metal-carbene complexes. In addition, boron-stabilized, free quinoid carbene-mediated C(sp2)–C(sp2) cross-coupling reactions are also described in this thesis. Chapter 2 presents an efficient synthesis of biaryls by a dirhodium(II)-catalyzed aromatic C-H arylation with diazo quinones. The new biaryl synthesis reaction can be performed under mild and neutral conditions and without the chelation assistance of directing group. The reaction tolerates various functionalities and is applicable to a broad range of aromatics. The regioselectivity of the C-H arylation was often high and predictable. The synthetic utility of the method was demonstrated by the late-stage modifications of a series of pharmaceuticals and functional materials as well as the short synthesis of a transthyretin amyloid inhibitor. Chapter 3 describes a new and efficient synthesis of multi-functionalized perfluoroalkyl aziridines via a ruthenium-perfluoroalkylcarbene intermediate. With Ru(p-Cl-TPP)CO as the catalyst, in situ-generated diazo compounds from fluorinated ammonium salt undergo a cascade reaction of nitrone formation/1,3-diploar cycloaddition/rearrangement with nitrosoarenes and alkynes to give a variety of multifunctionalized perfluoroalkyl aziridines in good to high yields and with moderate to high diastereoselectivity. The ruthenium-perfluoroalkylcarbene intermediates obtained through the stoichiometric reaction of ruthenium porphyrin and CnF2n+1CHN2 were spectroscopically characterized. The development of a transition-metal-free C(sp2)-C(sp2) bond formation reaction by the cross-coupling of diazo quinones with catechol boronic esters is presented in Chapter 4. With this protocol, a variety of biaryls and alkenyl phenols were obtained in good to high yields under mild conditions. The reaction tolerates various functionalities and is applicable to the derivatization of pharmaceuticals and natural products. The synthetic utility of the method was demonstrated by the short synthesis of multi-substituted triphenylenes and three bioactive natural products, honokiol, moracin M, and stemofuran A. Mechanistic studies and density functional theory (DFT) calculations revealed that the reaction involves attack of the boronic ester by a singlet quinone carbene followed by a 1,2-rearrangement via a stepwise mechanism.