The Claisen Rearrangement Mechanism And Kinetics PDF Download

"Part AWhile several catalytic methods of the Claisen rearrangement using Lewis acids and transition metals have been developed in the past years, only one example of an organocatalytic Claisen rearrangement using a hydrogen-bond donor catalyst has been reported. Recently, our research group published the first example of an iminium-catalyzed Cope rearrangement using a diazepane carboxylate catalyst, which was shown to be efficient in forming [alpha]-substituted iminium ions. Inspired by our success with the Cope rearrangement, we investigated the application of the diazepane carboxylate catalyst in the iminium-catalyzed Claisen rearrangement. Our research efforts focused on identifying the appropriate substrates that can undergo Claisen rearrangement under our iminium catalysis conditions. In our studies, the aromatic Claisen substrates were shown to be robust under acidic conditions, and the diazepane carboxylate catalyst was efficient in forming iminium ions with these substrates. However, an unexpected decomposition pathway was identified under our iminium catalysis conditions, and further investigations led us to conclude that the aromatic Claisen substrates are not compatible with our iminium catalysis, potentially due to the formation of highly reactive intermediates or products which are prone to other decomposition pathways.Part BIn our iminium-catalyzed Cope rearrangement, we found that the larger ring sized hydrazide catalyst, particularly the 7-membered ring, was most efficient in catalyzing the Cope rearrangement of a variety of 2-formyl-1,5-hexadienes. We hypothesized the higher reactivity of the 7-membered hydrazide catalyst was from the reduced proton affinity of the amine, facilitating the proton transfer steps in the iminium ion formation, and we proposed that the iminium ion formation should be the rate-limiting step of our Cope rearrangement. Our density functional theory calculations suggested a stepwise mechanism for this rearrangement, proceeding through an intermediate carbocation. However, Houk’s group proposed that the observed reactivity trend has to do with the relative rigidity/flexibility of the cyclic hydrazide catalyst, and the rate-limiting step is the Cope rearrangement. This part of the thesis describes our mechanistic experiments performed in collaboration with the Houk research group to determine the mechanism and the origin of rate acceleration by the cyclic hydrazide catalysts. The reaction kinetics for different ring sized hydrazide catalysts have been measured, and the carbon kinetic isotope effect for a model reaction has been experimentally determined to elucidate the reaction mechanism of our Cope rearrangement. Current results suggest that our model reaction proceeds through a concerted mechanism with the Cope rearrangement as the rate-limiting step, but the reaction may also proceed through a stepwise mechanism depending on the substituents.Part CThe synergistic combination of photoredox catalysis and organocatalysts has enabled the activation of inert substrates towards useful chemical transformations. From our previous investigations, we found that the 7-membered hydrazide catalyst was highly efficient in forming iminium ions compared to other secondary amines. The purpose of this investigation was to merge photoredox catalysis with iminium catalysis, by taking advantage of the high reactivity of the hydrazide catalyst. The two studied reactions were the reductive radical cyclization and the decarboxylative radical cyclization of [alpha], [beta]-unsaturated aldehydes. For the reductive cyclization, current results suggest that the [beta]-enaminyl radicals generated from our hydrazide catalyst may be electron-poor and not nucleophilic enough to undergo the anticipated radical addition pathway. For the decarboxylative radical cyclization, current results suggest that the reactivity is highly dependent on the stability of the alkyl radicals, as well as the reaction solvent used"--