Radical cyclization of epoxy vinyl- and allylsulfones promoted by titanocene chloride.

A titanocene-mediated intramolecular radical addition of different epoxy vinyl- and allylsulfones has been achieved. Five- and six-membered ring products were obtained in good to excellent yields in the presence of both 2.2 and 0.2 equiv of Cp2TiCl. A novel double-activation strategy allowed us to achieve small-size rings such as cyclobutanes and cyclopropanes.

Synthesis of the BCDE molecular fragment of azadiradione mediated by titanocene(III).

A practical, short, and diastereoselective synthesis of the azadiradione BCDE fragment from a readily available starting material is described. The key step was the titanocene(III)-promoted tandem cyclization of unsaturated epoxy nitrile.

On the mechanism and kinetics of radical reactions of epoxyketones and epoxynitriles induced by titanocene chloride.

The reactions of a series of epoxynitriles and epoxyketones induced by titanocene chloride have been studied. The kinetics of the decyanogenation of beta,gamma-epoxynitriles with Ti(III) corresponds to a radical reaction (k25 approximately 106 s-1), as demonstrated by competition experiments with H-transfer from 1,4-cyclohexadiene (1,4-CHD) or PhSH or conjugate addition to acrylonitrile. The 5-exo cyclization onto nitrile induced by Ti(III) is a radical reaction (k25 approximately 107 s-1) as seen in competition experiments with H-transfer from PhSH or the titanocene-water complex. The iminyl or alkoxyl radicals generated by 5-exo cyclization onto nitriles or ketones only undergo a reduction with Ti(III). This reaction overwhelms any alternative process, such as tandem cyclization onto alkenes or beta-scission. Iminyl radicals generated by 4-exo cyclizations onto nitriles undergo reduction with Ti(III) and beta-scission reaction in a ratio of 96:4 when the alpha-substituent is CN. Alkoxyl radicals from 4-exo cyclizations onto ketone carbonyls undergo reduction with Ti(III) and beta-scission in a ratio of 60:40 when the alpha-substituent is COOR. In nearly all the reactions studied, the role of Ti(III) is triple: a radical initiator (homolytic cleavage of oxirane), a Lewis acid (coordination to CN or C=O), and a terminator (reduction of iminyl or alkoxyl radicals).