Copper mediated atom transfer radical cyclisation reactions
The effect of different N-pentyl-2-pyridylmethanimine (NPMI) derivatives upon the rate of copper(I) mediated atom transfer radical cyclisation (ATRC) of mono-bromo- and trichloro-acetamides were investigated. 6-Functionalised NPMI derivatives retarded the rate of ATRC due to steric effects, while for the 5-substituted analogues, inductively increasing the electron density of the pyridine nitrogen increased the rate of ATRC. Multidentate amine derived copper(l) halide complexes were found to mediate the ATRC of I-halo-N-propargylacetamides. The cyclisation of trichloro- and dichloroacetamide precursors leads to a,B-unsaturated y-Iactams containing the gem-dihalide functional group, while monohaloacetamides gave rise to either cyclised atom transfer or reduction products depending upon the solvent and catalyst used. The tripyridyJamine (TPA) copper(I) halide complex facilitates the efficient ATRC of bromo-enamides to give plactams exclusively with no formation of y-Iactams. Initial products result from 4-exo bromine atom transfer and subesqucnt elimination can be readily achieved to furnish the corresponding alkenes. A range of fused bicyclic lactams were prepared via copper(l) mediated 5-endo ATRC of halo-N-(cycloalk-1-enyl)acetamides and the use of this methodology for the synthesis of the Iycorane and erythrinane alkaloid skeletons was investigated.