Radical couplings of epoxides and nitriles mediated by Cp(2)TiCl provide a diastereoselective route to the synthesis of beta-hydroxyketones. The conditions of this "aldol-like" reaction are mild enough to avoid the dehydration of the beta-hydroxyketone. The scope of the coupling reaction with functionalized and tetrasubstituted epoxides has been studied. The radical character of the coupling reactions is demonstrated.

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The reaction of a series of 2,3‐epoxy alcohols and the corresponding formates, acetates, and benzoates promoted by Cp2TiCl has been studied. The different outcome of the reaction of epoxy derivatives has been rationalized in terms of mechanistically biased processes. After homolytic oxirane cleavage, four main types of reaction were found: dehydroxylation, decarboxylation, dehydrogenation, and deoxygenation. The reaction products varied according to the substitution pattern. The radical nature of these eliminations is demonstrated.

Radical cascade cyclizations of unsaturated epoxynitriles induced by titanocene chloride proceed in good yields and with excellent diastereoselectivities. From three to seven stereocenters were created by the reaction and a single isomeric product was obtained from most of the substrates examined. The relative configuration of the products is consistent with cyclization occurring via a chair-like transition state. The termination of the radical cascade reaction by 4-exo, 5-exo or 6-exo cyclization onto nitrile is remarkable.Radical cyclizations in cascades have been devised as a method of considerable synthetic potential for the construction of polycyclic structures starting from acyclic precursors. 1 Thus, many functionalized polyenes containing 1,5-dienes or similar units have been cyclized into terpenoids. In most examples of intramolecular radical cyclizations of polyenes reported, the starting point for the generation of the primary radical is a double bond, halide, acyl selenide, or keto ester. 2 Recently, the polyene reaction cascade has been started by homolytic cleavage of an oxirane with titanocene chloride. 3 In many of the reported examples the termination step in the radical cascade of polyenes is onto a C=C double bond or a CC triple bond, and very few onto other functional groups.In this context, we undertook a study of radical cascade cyclizations, employing as substrates a series of monoand polyunsaturated epoxynitriles with the aim to develop a straightforward procedure for the synthesis of polycyclic terpenoids. In general, our cascade started with the known homolytic cleavage of the oxirane with titanocene chloride, 4 followed by a radical 6-endo cyclization onto C=C and finishing on a nitrile group. The novelty of this cascade is the termination step. Radical cyclization onto nitrile is a slow process and has been considered enigmatic, since both success and failures have been reported. 5 However, in a previous work we demonstrated the reliability of epoxynitrile cyclizations with titanocene chloride by synthesizing cyclic compounds from cyclobutanones to cycloheptanones in good yields (Scheme 1). 6 Epoxynitriles 1-4 (Scheme 2) formed the first series of compounds whose radical cascade cyclizations were studied. Scheme 2 Radical cascade cyclization of 1-4To the best of our knowledge there are few reports of radical cascade reactions that incorporate 5-exo or 6-exo radical cyclization onto nitrile. 7 No reports were found for a radical cascade terminated on the nitrile through a 4-exo cyclization process. Scheme 1 Radical cyclization of epoxynitriles O HO 1. Ti(III) 2. H 3 O + CN ( ) n ( ) n O n = 1-4 O CN HO CN HO CN 1 1a (62%) 1b (16%) + 1. Ti(III) O CN HO O H 2 2a OH β (57%) 2b OH α (7%) + 1. Ti(III) HO CN 2c (12%) O CN O CN HO O H HO CN HO CN HO O H 3 4 4 b (25%) 4a (50%) 3b (38%) 3a (38%) + + 1. Ti(III) 1. Ti(III) 2.

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