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

• Published in: Journal of organic chemistry Vol. 72; no. 26; pp. 9973 - 9982
• Main Authors: Fernández-Mateos, A, Herrero Teijón, P, Mateos Burón, L, Rabanedo Clemente, R, Rubio González, R
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 21.12.2007; Amer Chemical Soc
• Subjects: Alicyclic compounds; Alicyclic compounds, terpenoids, prostaglandins, steroids; Alkenes - chemical synthesis; Alkenes - chemistry; Chemistry; Chemistry, Organic; Coordination compounds; Cyclization; Epoxy Compounds - chemistry; Exact sciences and technology; Free Radicals - chemical synthesis; Free Radicals - chemistry; Inorganic chemistry and origins of life; Ketones - chemistry; Kinetics; Kinetics and mechanisms; Molecular Structure; Nitriles - chemistry; Organic chemistry; Organometallic Compounds - chemistry; Physical Sciences; Preparations and properties; Reactivity and mechanisms; Science & Technology; Stereoisomerism; ALKYL; CYANO; RATE CONSTANTS; STEREOCHEMISTRY; CHEMISTRY; IMINYL RADICALS; TERT-BUTOXYL; GENERATION; INTRAMOLECULAR ADDITION; CYCLIZATION; Water; Nitrile; Acrylonitrile; Oxygen heterocycle; Metallocene; Free radical reaction; Scission; Chemical reduction; Titanium Complexes; Alkene; Titanium Organic compounds; Oxirane derivatives; Reaction mechanism; Lewis acid; Complexation; Alkoxyl; Exo stereoisomer; Transition metal Complexes; Experimental study; Tandem reaction; Organic chlorine compounds; Ketone; Titanium III; Thiophenols; Cyclization; Organic free radical; Epoxide; Addition reaction; Homolysis; Kinetics; Ethylenic compound; Iminyl
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo701497e

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 (k 2 5 ≈ 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 (k 2 5 ≈ 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 α-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 α-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).