Hydrazones, addition onto

Scheme 31 Enantioselective radical additions onto hydrazones...

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. 

As expected from kinetic data [2, 3], imines as radical traps are somewhat less efficient than oxime ethers and hydrazones. An intramolecular radical addition onto... 

Furthermore, iminyl radicals have been used in intramolecular homolytic aromatic substitutions. The iminyl radicals can be generated in situ by C-radical addition onto nitriles [55] or they may be generated directly from the corresponding oximes [56] and hydrazones [57]. 

Once a molecule is modified with a hydrazine reagent and another molecule is modified with the benzaldehyde compound, they may be combined to form the final conjugate, which will result in a hydrazone linkage between the two molecules. In addition, chemoselective ligation using aldehyde/hydrazine reactions may be done to immobilize biomolecules. In this regard, one modified component may be a surface and the other one an antibody, protein, or oligonucleotide destined for immobilization onto the surface. 

Finally, Friestad designed the radical addition of BMDMS-derived radicals onto chiral hydrazones. Implementation of this methodology gave him entry to chiral amino alcohols with high diastereoselectivities (eq 15). The silicon tether is an essential tool for the stereochemical outcome, as it allows the reaction to proceed through a temporary cyclic transition state, but eventually leads to formal acyclic control. 

---