Mechanistic studies using kinetic isotope effects

Abstract

Understanding reaction mechanisms is an important aspect of chemistry. A now convenient way to study reaction mechanisms is kinetic isotope effects at natural abundance. This technique circumvents the cumbersome methods of traditional isotope effect studies. This technique was used to determine the carbon KIEs for the palladium trimethylenemethane cycloaddition of an electron deficient alkene. Substantial intermolecular KIEs were observed for the olefinic carbons of the acceptor alkene. This data would seem to indicate that a concerted mechanism is at work. However, this is in direct contrast to the mechanistic pathway suggested by Trost. Further studies were conducted to insure correct interpretation of the intermolecular KIEs. One study included a Michael reaction that exhibited a large KIE only at the β carbon of the acceptor olefin. Another study used novel methodology to determine intramolecular KIEs for the product-determining step of the reaction pathway. To fit the experimental data, the stepwise mechanism required a surprising isotope-dependent selection between diastereomeric ring closures. The experimental results can not be reconciled with a stepwise cycloaddition.