Abstract
Chlorine substituents on the alkene control the regioselectivity of the cyclization of 5-hexenyl or 6-heptenyl radicals generated by oxidation of an acetoacetate ester or 1,3-diketone with Mn(0Ac)3-2H20. 6-Exo-cyclization of the radicals obtained by oxidation of benzoylacetone derivatives 10 and 13, containing a chlorine on the terminal
double bond carbon, gives -chloroalkyl radicals that add to the aromatic ring to give 11 and 16, respectively. Loss of HC1 leads to naphthols 8 and 17 indicating that this reaction may be useful for aureolic acid synthesis. Exo-cyclization is the exclusive process with acetoacetates 28b, 44,55b, and 59 containing a chlorine on the terminal double bond carbon. 6-Endo-cyclization is the exclusive process with acetoacetates 18c and 51b containing a chlorine on the internal double bond carbon. Intra- and intermolecular competition experiments indicate that these effects are primarily steric. The chlorine substituent controls the regioselectivity of the cyclization by sterically hindering attack of the radical on the chlorine bearing double bond carbon thereby retarding formation of the 5-chloroalkyl radical. The chlorine substituent does not electronically accelerate attack on the other end of the double bond to give the -chloroalkyl radical.