Palladium assisted ring closures

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Virginia Polytechnic Institute and State University

The carbopalladation process has been extended to form carbocyclic systems. The intramolecular version of the carbopalladation process stereospecifically generates fused bicyclic palladium complexes upon treatment of cis and trans methyl-S-methyl-2-carbomethoxy-7-thio-hept-5-en-l-oate with lithium tetrachloropalladate and potassium tertbutoxide in moderate yield. The cyclization of the corresponding amines, cis and trans methyl-N,N-dimethyl-2-carhomethoxy-7-amino-hept-5-en-1-oate, proceeded more rapidly and stereospecifically generate stable fused bicyclic palladium complexes in excellent yield. NMR studies revealed the bicyclic complexes generated in this manner resulted from a trans addition of palladium and the carbon nucleophile. Direct reduction with sodium borohydride (for sulfides) or hydrogen (for amines) resulted in cyclopentyl sulfides and amines in good to excellent yields. The reaction was extended to ketoesters and homoallylic amines to give a variety of cyclopentanoids.

Extensions to larger ring systems yielded unstable palladium complexes. These complexes underwent oxidation at the amine functionality upon warming. Hydrolysis of the intermediate complexes yielded cyclohexyl and cycloheptyl aldehydes whereas reduction with hydrogen in the presence of molecular sieves gave cyclohexyl and cycloheptyl amines in excellent yields.

Attempts at utilizing olefin mid carbon monoxide insertions to form macrocycles proceeded poorly, if at all.