Overman rearrangement mechanism

Similarly to the mechanism of the Claisen rearrangement, the Overman rearrangement is a suprafacial, concerted, nonsynchronous / 3,37-sigmatropic rearrangement. The reaction is irreversible, which is the result of the significant driving force associated with the formation of the amide functionality. The mechanism of the metal catalyzed reaction is believed to proceed via an iminomercuration-deoxymercuration sequence and it is only formally a [3,3]-sigmatropic shift. 

As a preliminary mechanistic proposal, we hypothesize that the palladimn(ll)-phosphoramidite catalyst acts as a chiral n-acid to activate the amine iV-oxide substrate (Scheme 1S.291. similar to the mechanism proposed for the Overman rearrangement of allylic trichloroacetimidates. While it is not clear whether the reactive species is oxide-bound complex 119a or olefin-bound complex 119b, we propose heterocycle 120 as an intermediate in this cyclization-induced mechanism Grob-type fragmentation eventually reveals O-allylhydroxylamine 117 and the palladium(n)-phosphoramidite catalyst, which can reenter the catalytic cycle. 

The mechanism has been shown to involve a cyclization step followed by a pinacol rearrangement (Hopkins, M. H. Overman, L. E. Rishton, G. M., J. Am. Chem. Soc., 1991, 113, 5354 see also Bach et al., p. 5365, and Woods et al., p. 5378, mentioned in questions 4 and 5, respectively). Provide a detailed mechanism for the reaction and discuss features of the steps and intermediates from the point of view of orbital interactions. 

Jacobsen, E. J., Levin, J., Overman, L. E. Synthesis applications of cationic aza-Cope rearrangements. Part 18. Scope and mechanism of tandem cationic aza-Cope rearrangement-Mannich cyclization reactions. J. Am. Chem. Soc. 1988, 110, 4329-4336. 

Several mechanisms have been proposed for palladium catalysis of Cope rearrangements. Overman, who has examined metal ion catalysis of a number of 3,3-sigmatropic rearrangements, considers this an... 

Treatment of the alcohol (282, Scheme 3.178) with paraformaldehyde follows the mechanism given in Scheme 3.176. First, the iminium ion is formed by condensation of the secondary amine and the aldehyde. [3,3]-Sigmatropic rearrangement gives an intermediate enol, shown below, which cyclizes onto the new iminium ion to give the ketone product. See S. G. Knight, L. E. Overman and G. Pairaudeau, J. Am. Chem. Soc., 117 (1995), 5776. 

Overman and co-workers carried out extensive studies on Pd(II)-catalyzed asymmetric allylic rearrangement of allylic imidates to form enantioenriched allylic amides. They achieved 97 % ee as the best result by the reaction of the allylic imidate 612 using the cyclopalladated ferrocenyl oxazoline 613 having elements of planar chirality as a catalyst precursor, and discussed the mechanism of the reaction [220]. 

As a final exercise, the Overman group exposed their synthetic sample of quadrigemine C (1) to a solution of AcOH (0.1 n) at 100°C for 36 hours in order to convert it into psycholeine (2). In line with literature precedent, these conditions provided this intriguing alkaloid (2) in 38 % yield. Scheme 7 provides a mechanism that can account for this impressive rearrangement based simply on a series of equilibria in which the six-membered rings of the central core of psycholeine (2) provide a thermodynamic sink. ... 

In 1987, when rationalizing the formation of 24 from 21, one mechanistic pathway suggested by Overman and coworkers involved the formation of intermediate 22 which might undergo a concerted 2-oxonia[3,3]sigmatropic rearrangement followed by an intramolecular aldol reaction/ While other evidence in these studies favors an alternate mechanism, the oxonia-Cope mechanism suggested here has in fact been identified as a competitive, and sometimes favored pathway " in a number of transformations. 

---