Cope rearrangements catalysis

Recent structural papers have highlighted several examples of antibody-catalyzed reactions for which a small catalytic effect was already present in a germline antibody, one that originated from the original library of 109 structures present in the unimmunized animal. In the case of an oxy-Cope rearrangement, catalysis was more efficient in the germline antibody compared with its improved ... 

Oxy-Cope rearrangement of 56 to form the cyclic ketone 57 can be carried out at room temperature with catalysis by PdCl2(PhCN)2(47]. 

Fiedler, D., Bergman, R.G. and Raymond, K.N. (2004) Supramolecular catalysis of a unimolecular transformation Aza-Cope rearrangement within a self-assembled host. Angew. Chem., Int. Ed., 43 (48), 6748-6751. 

The X-ray crystal structure for AZ-28 has a variety of structural features that are consistent with the proposed mechanism operative for the oxy-Cope rearrangement. The antibody binds the transition stage analog in a chair-like conformation, consistent with the preferred chair transition state for this pericyclic reaction (Doering and Roth, 1962). The positions of the C-2 and C-5 atoms are fixed in the antibody-bound hapten molecule in a similar fashion, the C-2 and C-5 positions in the hexadiene substrate should be held in a fixed position by conserved van der Waals interactions locking in the two phenyl substituents in the antibody combining site. This bound conformation of the acyclic (47T + 2er) system of the hexadiene substrate should enforce a molecular conformation close to the transition state for the rearrangement reaction, consistent with the catalysis observed for AZ-28. 

Brown CJ, Bergman RG, Raymond KN (2009) Enantioselective catalysis of the aza-cope rearrangement by a chiral supramolecular assembly. J Am Chem Soc 131 17530-17531... 

Dioxolanone 33 is obtained when the unsaturated silyldiazoester 30 is decomposed by Rh2(pfb)4 in the presence of an aldehyde or of acetone (Scheme 11) [21]. The reaction sequence is likely to include formation and (probably reversible) 1,5-cyclization of carbonyl ylide 31, and Cope rearrangement of the allylvinylether 32. In analogy to carbonyl ylide 21, the SiMe3 should occupy the exo-position in 31, thereby bringing the ester carbonyl in a geometry that is favorable to the cyclization step. Again, the choice of catalyst determines the product pattern, since CuOTf catalysis affords not only 33, but also oxirane 22 and the intramolecular cyclopropanation product 34. 

An experimental aspect of the Cope rearrangement particularly important in synthesis is the feature that it is frequently subject to catalysis. We have already seen that in the anionic oxy-Cope rearrangement enormous rate enhancements are realized by the incorporation of an alkoxide ion in the substrate. In many Cope rearrangements similar rate enhancements are achieved by the addition of catalysts, particularly acids and metals. ... 

The aza-Cope rearrangement generally requires higher temperatures than the corresponding oxa analog, but quatemization or catalysis may allow milder conditions to be used. 

---