Approaches to antibody-catalyzed cationic cyclizations: Chemical studies of leaving groups and cyclization modes

Article abstract of DOI:10.1002/ijch.199600022

The solvolysis of a range of esters of 2-methylbenzyl alcohol 10 has been studied. It was found that sulphonate esters are solvolyzed very rapidly in aqueous solution (t_1/2 ≈ 35 s), whereas sulphinates react slowly (t_1/2 ≈ 35 h) and a phosphonate diester is stable. The fluorescent 5-dimethylaminonaphthalene-1-sulphinate (dansinate) esters (e.g. 22) held the most promise as substrates for antibody-catalyzed cationic cyclizations. It was shown by ¹⁸O-labeling studies that ester 13 is hydrolyzed predominantly (but not exclusively) by S_NI reaction at the benzylic position. A number of conditions were tried to effect cationic cyclizations of an unsaturated benzylic alcohol 26, whose ester is intended as the substrate for the antibody-catalyzed reaction. The products obtained were the result of attack of the non-benzylic alcohol on either the benzylic cation, to give 31 and 32, or on the protonated alkene, to give 29. No cyclization of the alkene onto the benzylic cation, to give 4, was observed, suggesting that this is a disfavored reaction in solution.