Hydrazones cyclizations onto

Radical reactions are not restricted to cyclizations onto alkenes or alkynes. Increasingly popular is the use of an imine or imine derivative, such as an oxime or hydrazone. ° Most examples involve 5- or 6-exo-trig cyclization to give cyclopentane or cyclohexane ring systems. Thus, treatment of the bromide 77 withtributyltin hydride gave the cyclopentane 78 (4.66). The stereoselectivity of the cyclization is in line with that expected on the basis of a chair-like transition state (compare with Scheme 4.53). 

A useful variant of this chemistry involves the radical cyclization onto an A-aziridinyl hydrazone. Fragmentation of the intermediate nitrogen-centred radical to release nitrogen gas and an alkene (typically styrene or stilbene) results in the formation of a new carbon radical at the original hydrazone carbon atom. Thus, in a synthesis of the sesquiterpene a-cedrene, the radical species 80, formed from the thiocarbonyl compound 79, cychzes onto the hydrazone to give the nitrogen-centred... 

The ability of the intermediate aminyl radicals to rearrange was exploited by several authors. For instance, macrocyclic lactams are obtained in excellent yields via a ring expansion process developed by Kim (Scheme 8.41, top)." Preparation of cychc imines via a tin hydride promoted radical cyclization onto an hydrazone is also possible (Scheme... 

Furthermore, we also performed kinetic studies for alkyl radical additions onto different types of C=N bonds such as imines and oxime ethers. The kinetic data are summarized in Figure S. Kinetic analysis of the intramolecular addition of alkyl radicals to C=N bonds provides several experimentally important results. First, alkyl radical additions to C=N bonds are much faster than the corresponding additions to C=C bonds, indicating that C=N bonds are much better radical acceptors than C=C bonds. Furthermore, 5-exo cyclization is faster than 6-exo cyclization. Second, the intramolecular additions of alkyl radicals to C=N bonds are essentially irreversible. Third, alkyl radical additions to oxime ethers and hydrazones are faster than alkyl radical additions to imines, suggesting the possibility of a dependence of the cyclization rate on the electron density at the carbon atom of the radical acceptor. 

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