Heteroatom[1,3]-Migratory Studies In The Claisen And Benzidine Rearrangements

To date, the types of organic reactions involving heteroatoms are very rich, and increasingly attract people’s attention. Furthermore, the reaction mechanism of the heteroatom [1,3]-migration needs to be thoroughly studied. It is of important significance to organic reactions and synthesis. My thesis work is devoted to making new advances in the Claisen and Benzidine Rearrangements. The reaction mechanisms were studied via experiments and density functional theory (DFT) calculations, toward the formal [l,3]-migration in thermal Claisen Rearrangement and the formation of diphenyline and semidines in Benzidine Rearrangement.The Claisen Rearrangement, well-known as the [3,3]-sigmatropic shift of vinyl allyl or allyl aryl ethers, which construct unsaturated carbonyl compounds or allyl substituted phenols with a new C-C formation, is among the most important reactions and widely used in organic synthesis. The [3,3]-rearrangement product emerges as the major, accompanied with the formal [1,3]-byproduct in the Claisen Rearrangement. So far, the mechanism of [3,3]-rearrangement have been widely studied from both the mechanistic and synthetic viewpoints. However, the mechanism of the formal [1,3]-rearrangement process is still a riddle, and also limit the potential application of these reactions in total synthesis and other disciplines. Chemists have revealed some other methods to promote the formal [1,3]-rearrangement for over100years. The Lewis acid catalyzed [1,3]-migration proceeds via an ionic pair mechanism, while in the presence of radical initiator [1,3]-shift proceeds through a radical pair mechanism. But the mechanism of the thermal formal [1,3]-rearrangement is still puzzled, and three mechanistic possibilities, referred to as the radical, ionic, and concerted carbon [1,3]-shift with the inversion of configuration mechanisms, were put forward. Herein, we describe he detailed experiment and the DFT calculations studies on the formal 1,3]-migration in the thermal Claisen Rearrangement, aiming to ciariry tnis process. The former two of mechanistic possibilities had been excluded via in solvent and solvent-free intercrossing experiments and the radical trapping experiments, as well as the third had been withstood in experimental scrutiny. Thus, we propose three possible concerted mechanisms:1) a tandem O[1,3]-and [3,3]-rearrangement process,2) a concerted C[1,3]-sigmatropic shift,3) a cascade [3,3]-and C[1,3]-sigmatropic shifts process. DFT calculations indicates that the tandem O[1,3]-and [3,3]-rearrangement is more favored over the other two pathways. Further intermediate trapping experiments and the rearrangement experiments with an optically active substrate verify our proposed cascade mechanism. In addition, DFT calculations indicate that the isomerization of ketone into enol proceed through H2O assists proton shift rather than the intramolecular [1,3] proton shift.The name Benzidine rearrangement refers to a class of acid-catalyzed, intramolecular rearrangements of hydrazobenzene giving rise to benzidine and diphenyline, and some other products such as obenzidine, osemidine and p-semidine. The synthetic application of benzidine is widely, and it has been used in different fields. Through over150years’history and extensive mechanistic studies, it seems to be clear that the benzidine rearrangement is a concerted [5,5]-sigmatropic shift, and the obenzidine rearrangement is a concerted [3,3]-sigmatropic shift. However, the mechanisms of the diphenyline and semidine rearrangements process are still riddles, and also limit the potential application of these reactions in total synthesis and other disciplines. Shine and co-workers reported nitrogen and carbon KIE (kinetic isotope effects) of some substrates. Their results demonstrated that diphenyline should be formed via a multi-step mechanism, and p-semidine should be formed through a [1,5]-shift, whereas the presence of slight carbon KIE in the formation of o-semidine. In order to disclose their reaction mechanism, we present the results of experiments and DFT calculations in which the rearrangement of substituent hydrazobenzene is fully described. The results of intercrossing experiments indicate that the rearrangement is intramolecular. Thus, we propose possible mechanisms for the formation of o-semidine:1) a concerted N[1,3]-sigmatropic shift with inversion of configuration,2) a tandem [3,3]-and C[1,3]-sigmatropic shifts process. DFT calculations indicate that N[1,3]-sigmatropic shift is more favorable. Possible mechanisms for the formation of diphenyline:1) a tandem N[1,3]-and [3,3]-sigmatropic shifts process,2) a cascade [3,3]-and C[1,3]-sigmatropic shifts process. Whereas possible mechanisms for the formation of p-semidine:1) a tandem N[1,3]-and N[1,3]-sigmatropic shifts process,2) a cascade [3,3]-and [3,3]-sigmatropic shifts process. DFT calculations demonstrate that the p-semidine rearrangement prefers a cascade N[1,3]-and N[1,3]-sigmatropic shifts process, while the diphenyline rearrangement occurred predominantly through a tandem N[1,3]-and [3,3]-sigmatropic migration. Meanwhile, it is consistent with the results of KIE reported by shine and his co-workers.In conclusion, the mechanisms of Claisen and Benzidine rearrangements have been studied experimentally and theoretically. The results indicate that the formation of the formal [1,3]-rearrangement products is a novel O[1,3]-sigmatropic shift process with a configuration inversion of the oxygen atom in Claisen Rearrangement, the formation of diphenyline and semidine products are a novel N[1,3]-sigmatropic process with a configuration inversion of the nitrogen atom as a key process in Benzidine rearrangement. In this thesis, all our investigation proves our new insight into the mechanism of Claisen and Benzidine rearrangements.