Radical reactions of epoxy esters induced by titanocene chloride

[EN]The reductive radical cyclizations of several epoxy esters have been achieved using titanocene chloride. The tether length from the initial radical to the carbonyl acceptor is the key of the reactions. We obtained products from radical cyclization onto carbonyl formate and products from formate and hydrogen elimination. The stereochemical outcome of the 5-exo radical cyclization of two diastereomers is reported. A radical cascade cyclization of an unsaturated epoxy formate is also described

On the Mechanism and Kinetics of Radical Reactions of Epoxyketones and Epoxynitriles Induced by Titanocene Chloride

[EN]The reactions of a series of epoxynitriles and epoxyketones induced by titanocene chloride have been studied. The kinetics of the decyanogenation of β,γ-epoxynitriles with Ti(III) corresponds to a radical reaction (k25 ≈ 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 ≈ 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 β-scission. Iminyl radicals generated by 4-exo cyclizations onto nitriles undergo reduction with Ti(III) and β-scission reaction in a ratio of 96:4 when the R-substituent is CN. Alkoxyl radicals from 4-exo cyclizations onto ketone carbonyls undergo reduction with Ti(III) and β-scission in a ratio of 60:40 when the R-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 CdO), and a terminator (reduction of iminyl or alkoxyl radicals)

Synthesis of the BCDE Molecular Fragment of Azadiradione Mediated by Titanocene(III)

[EN]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

A Radical Clock for Reactions of Epoxy Derivatives Induced by Titanocene Chloride

[EN]A new radical clock based on pinene derivatives has been designed to measure the radical cyclization rate onto cyano and carbonyl groups and the radical elimination rate of OR and CN. In this system, the known rate constant of cyclobutylcarbinyl radical cleavage is used as the internal clock. At room temperature, the cyclization rate constants for 4-exo and 5-exo processes onto nitrile and aldehyde carbonyl groups are in the order of 107 to 108 s-¹. The radical elimination rate constants for CN, OH, OCHO, and OAc are in the order of 105 to 108 s-¹

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