Hauser-Kraus Annulation

Hauser-Kraus Annulation

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The synthesis of naphthalene hydroquinones from phthalide anions and α,β–undaturated carbonyl compounds through the Michael addition-then-Dieckmann condensation is known as the Hauser-Kraus annulation. It is used frequently to synthesize polyketide compounds.

Technically, the Hauser cyclization uses a sulfone group and the Kraus cyclization uses a cyano group at the benzylic position. The latter tends to be higher yielding because of the less steric hindrance.

When o-methyl benzoate esters are used instead of phthalides, the reaction is called the Staunton-Weinreb cyclization. Naphthols are the products in this case.

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The reaction of homophthalide.[1]


Total synthesis of fused pentacyclic tetracyclin derivative.[2]


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  1. Tamura, Y.; Sasho, M.; Nakagawa, K.; Tsugoshi, T.; Kita, Y. J. Org. Chem. 1984, 49, 473. DOI: 10.1021/jo00177a017
  2. Charest, M. G.; Lerner, C. D.; Brubaker, J. D.; Siegel, D.; Myers, A. G. Science 2005, 308, 395. DOI:10.1126/science.1109755
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