Vinyl epoxides radical cyclization

Most of the recent synthetic developments in the field of radical cyclization have involved the reactions of carbon-centered radicals with alkenes and alkynes. Other useful acceptors include allenes,31 dienes30 and vinyl epoxides.32 The same methods are used for cyclizations to these acceptors as for radical additions, and the preceding chapter should be consulted for specific details on an individual method (the organization of this section parallels that of Section 4.1.6). Selection of a particular method to conduct a proposed cyclization is based on a variety of criteria, including the availability of the requisite pre-... 

The mechanism of titanocene (TiCp2Cl2)-mediated 3-exo cyclization of vinyl epoxides containing carbonyl, phenyl, and vinyl groups has been determined by DFT calculations and experimental studies (Scheme 52).86 The reaction is exothermic and reversible, in contradiction to an earlier mechanistic proposal. The energies of activation for ring closure are among the lowest known for radical reactions. The crucial step for a successful completion of the reaction is rapid trapping of the cyclopropylcarbinyl... 

Fig (22) 2-isopropylphenol (183) is converted to allylic alcohol (185). Its bromide derivative reacts with methyl acetoacetate. The resulting compound undergoes radical cyclization yields ketoester (186) whose vinyl triflate on reduction and carbonylation furnishes lactone (187). Diol (188) obtained from (187), is converted to monoepoxide (189) which on further epoxidation produces triptonide (148). Its conversion to triptolide (149) is accomplished by reduction. 

GansSuer et al. studied the tandem titanocene-mediated cyclization/inter-molecular addition to Michael acceptors [132]. After treatment with t-butyl acrylate in the presence of Zn, collidine hydrochloride and catalytic amounts of titanocene [133], epoxide 143 yielded the desired bicycUc product 144 in reasonable yield and high diastereoselectivity (Scheme 46). Remarkably, alkyne 145 led to the first example of an intermolecular addition involving a vinylic radical. The success of this reaction was attributed by the authors... 

This titanocene-catalyzed procedure was immediately extended by Gansauer et al. to the enantioselective opening of meso-epoxides by employing substoichiometric quantities of titanocene complexes with chiral hgands [58-60]. It has also been applied by this group in racemic form not only for reductive epoxide openings and intermolecular additions to a,P-unsaturated carbonyl compounds, but also to achieve 3-exo, 4-exo, and 5-exo cycliza-tions, as well as tandem cyclization addition reactions featuring vinyl radicals (Scheme 9) [8,9,44,46,57,61-65]. 

---