Guanidinium Claisen rearrangement

In a follow-up paper, Jacobsen showed that the chiral guanidinium 80 provides catalytic power and enantioselectivity in the Claisen rearrangement systems such as Reaction 6.36. Here the reaction proceeded in 81 percent yield with an ee of 84 percent. The reaction is also diasteroselective for Reaction 6.37, the diastere-oselectivity increases from 11 1 without catalyst to 16 1 with 80. 

Uyeda, C. Jacobsen, E. N. Transition-state charge stabilization through multiple non-covalent interactions in the guanidinium-catalyzed enantioselective claisen rearrangement, 7 Am. Chem. Soc. 2011,133, 5062-5075. 

Scheme 13.28 Claisen rearrangement catalysed by a guanidinium salt.

Jacobsen and co-workers [79] reported on an elegant asymmetric catalytic Claisen rearrangements (Scheme 6.30). They found that guanidinium ions efficiently... 

Scheme 35 Asymmetric guanidinium-ion-promoted Claisen rearrangements.

Scheme 10.57 Enantioselective Claisen rearrangement catalyzed by guanidinium salt 60.

Figure 40.4 Transition state model for the guanidinium-catalyzed Claisen rearrangement.

This mechanistic analysis suggested that enhancement of the electron density at the phenyl substituents of the guanidinium ion would be beneficial for the reaction, and led to the development of a new p-(dimethylamino)phenyl-substituted catalyst 25, which afforded better yields and stereoselectivities than the parent guanidinium 24 in a subset of substrates (Scheme 40.37) [45]. Catalyst 24 was also tested in the Claisen rearrangement of substituted 0-allyl (i-ketoesters, with excellent results (Scheme 40.38) [46]. Again, di- and tri-substituted compounds rearranged with high selectivity (from 5 1 dr to >20 1 dr) for the major diastereomer predicted by a six-membered chair-like transition state. 

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