Dötz benzannulation

What is Dötz benzannulation?

In 1975, K.H. Dötz reported the discovery of the formal [3+2+1] cycloaddition between a chromium phenylmethoxycarbene complex and diphenylethyne, which resulted in the formation of a chromium tricarbonyl-complexed 4-methoxy-1-naphthol when heated in dibutyl ether at 45 ºC. This reaction is now known as the Dötz benzannulation, which involves the reaction of an α,β-unsaturated pentacarbonyl chromium carbene complex (also known as a Fischer-type carbene) with an alkyne to produce a substituted hydroquinone (1,4-dihydroxybenzene) derivative. Since its initial discovery, the Dötz benzannulation has become one of the most extensively studied reactions of chromium complexes, with the products largely dependent on the carbene substituents and reaction conditions such as solvents, temperature, and concentration.

Dötz benzannulation - general reaction scheme - preparation of α,β−unsaturated Fischer-type carbenes
Dötz benzannulation (preparation of α,β−unsaturated Fischer-type carbenes)
Dötz benzannulation - general reaction scheme
Dötz benzannulation

The Fischer chromium carbenes required for the Dötz benzannulation can be easily prepared by treating Cr(CO)6 with an organolithium nucleophile, followed by the O-alkylation of the resulting acyl metalate with a strong alkylating agent such as Meerwein’s salt or alkyl triflates. This process allows for the synthesis of a wide range of unsaturated chromium-carbenes, with the only limitation being the availability of the organolithium reagent.

Advantages of the Dötz benzannulation include the access to densely functionalized aromatic compounds with excellent chemo- and regioselectivity, the compatibility with a variety of substituents on both the alkyne and unsaturated carbene side chain, the ability of aryl carbene complexes with electron-withdrawing or electron-donating substituents to work as well as unsubstituted aryl- or heteroaryl carbenes, and the fact that hydroquinone products can be oxidized to give highly substituted quinones. Additionally, the reaction can also occur intramolecularly with a reversal of the regioselectivity. However, there are also several disadvantages to the Dötz benzannulation, including the toxicity of chromium complexes, the poor reactivity or low yields obtained with alkynes bearing electron-withdrawing or heterosubstituents, and the tendency for the reaction to form indenes and cyclobutenones.

References

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