Belluš-Claisen Rearrangement

What is Belluš-Claisen rearrangement?

Malherbe and Belluš initially discovered, in the pursuit of investigating the [2+2] cycloaddition, this chemical transformation in 1978. It is a variation of the Claisen rearrangement that involves the reaction of an allylic ether 2, thioether, or amine with a ketene 1.

The product formed is a γ,δ-unsaturated ester 6, thioester, or amide with a trans configuration of the double bond.

Belluš-Claisen rearrangement
Belluš-Claisen rearrangement

During the reaction, both the anticipated product 4 and γ,δ-unsaturated ester 6 were detected in the product mixture. This observation led to the proposal of the zwitterionic intermediate 5, which is formed by the trapping of ketene with the ether oxygen, as illustrated in the figure.

This reaction has been called the Belluš-Claisen rearrangement, Belluš-Claisen reaction, or simply the Belluš reaction. Other names for this reaction include acyl-Claisen rearrangement, ketene-Claisen reaction, and ketene Claisen rearrangement, which do not acknowledge Belluš’s contribution.

When allylic amine is used, the corresponding rearrangement is also called the aza-Claisen rearrangement or zwitterionic aza-Claisen reaction.

The Bellus-Claisen rearrangement can result in a four carbon ring expansion that is frequently employed in the synthesis of medium-sized lactams, lactones, and thiolactones, particularly when the heteroatom of the allyl component is integrated into a carbocycle.

References

Malherbe, R. and Belluš, D. (1978), A New Type of Claisen Rearrangement Involving 1,3-Dipolar Intermediates. Preliminary communication. Helvetica Chimica Acta, 61: 3096-3099
DOI: 10.1002/hlca.19780610836

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