Cyclohexadienones annulation

A comprehensive treatment of the benzannulation of Fischer carbene complexes with alkynes is not possible in this review, and thus instead the material presented here will hopefully serve to give the reader an overview of its scope and limitations. The first report of this reaction was in 1975 by Dotz in which he describes the formation of the naphthol chromium tricarbonyl complex (236) from the reaction of the phenyl chromium complex (la) with diphenylacetylene. In the intervening years over 100 papers have been published describing various aspects of this reaction.The reaction of the generic cartene complex (233 Scheme 34) with alkynes will serve to focus the organization of the scope and limitations of the benzaimulation reaction. The issues to be considered are (i) the regioselectivity with unsymmetri-cal alkynes (ii) possible mechanisms (iii) applications in natural product syntheses (iv) the effect of substitution on the aryl or alkenyl substituent of the carbene carbon (v) functionality on the alkyne (vi) effects of the solvent and the concentration of the alkyne (vii) tandem applications with other reactions of carbene complexes (viii) reactions where aromatization is blocked (cyclohexadienone annulation) (ix) annulation of aryl versus alkenyl carbene complexes (x) the effect of the ligands L on the metal (xi) the effect of the ancilliary substituent RX and (xii) reactions with —C X functionality. 

This method has been applied to the synthesis of taxodione and related diterpenes through cyclohexadienone annulations of a chromium-carbene complex which was prepared from a hindered vinyl triflate12lb (equation 99a). 

When 3-butyne-2-one 7 is used as a Michael acceptor component, a 2,5-cyclohexadienone, e.g. 8, is obtained as the annulation product ... 

As with Michael additions to activated alkenes, the initial adducts with activated alkynes can be trapped by various processes. An aldol reaction can occur if a carbonyl is properly situated in the starting material (Scheme 71).123 However, the use of methyl ethynyl ketone (509) and its homologs in the Robinson annulation process to give cyclohexadienones (510 equation 110) usually proceeds in poor... 

The tributyltin hydride mediated reaction of a (bromobutyl)cyclohexadienone affords the 6,6-m-annulated bicycle as the sole product32. The exclusive formation of the 6-cxo-product is caused by the rate-accelerating effect of the electron-withdrawing carbonyl group. A similar precursor with an unsubstituted cyclohexadiene gives a tricyclic product derived from 6-endo cyclization as a minor product. 

Spiro-annulated 2,5-cyclohexadienones have been obtained by the oxidation of 4-phenylphenols with phenyliodosodiacetate. Thus 1-(4-hydroxyphenyl)-2- 3-methoxyphenyl)ethane in acetonitrile afforded the 1-spirotetralin compound illustrated upon refluxing with the reagent during 4 hours (ref.32). Unsubstituted, 4-methoxy and 3,4-dimethoxyphenyl analogues have also been synthesised. 

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