Alkenyl complexes benzannulation

The annulations of alkenyl complexes of the type (233 Scheme 34) have been examined mainly with alkyl substituents and in a few cases with oxygen - ° and silicon - substituents in a variety of cyclic and noncyclic systems. It is notable that the benzannulations of the parent vinyl complex of (233) (42a Scheme 7) fail, which is apparently due to competing polymerization of (42a). ° Annulations of complexes of the type (233) are successful if at least one of the three substituents is nonhydrogen. Benzannulations of alkenyl complexes have been employed in the synthesis of 7-ethoxyprecocene, ° vitamin E - and daunomycinone. " ... 

Amino(aryl)carbene complexes prefer cyclopentannulation over benzannulation. Amino(alkenyl)carbene complexes may react in a benzannulation reaction. 

Wulff et al. examined the necessary reaction conditions for a,fi-unsaturated aminocarbene complexes to react in a benzannulation reaction [23]. The reaction of dimethylamino(alkenyl)carbene complexes 18 with terminal alkynes in non-coordinating and non-polar solvents afforded phenol products in acceptable yields (Scheme 12). 

Scheme 12 Benzannulation of alkenyl(dimethylamino)carbene complexes...

Among the synthetically useful reactions of Fischer carbenes, the benzannulations are certainly the most prominent. In particular, the so-called Dotz reaction, first reported by Dotz in 1975 [3], is an efficient synthetic method that starting from aryl- or alkenyl-substituted alkoxycarbene complexes of chromium affords p-alkoxyphcnol derivatives by successive insertion of the alkyne and one CO ligand in an a,/Tunsaturated carbene, and subsequent electrocyclic ring closure (see Figure 1). 

Despite the undeniable synthetic value of the benzannulation reaction of aryl and alkenyl Fischer carbene complexes, the details of its mechanism at the molecular level remain to be ascertained. Indeed, although a relatively large number of theoretical studies have been directed to the study of the molecular and electronic structure of Fischer carbene complexes [22], few studies have been devoted to the analysis of the reaction mechanisms of processes involving this kind of complexes [23-30]. The aim of this work is to present a summary of our theoretical research on the reaction mechanism of the Dotz reaction between ethyne and vinyl-substituted hydroxycarbene species to yield p-hydroxyphenol. 

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. 

The mechanism proposed by Ddtz involves the insertion of a carbon monoxide into the vinyl carbene complex intermediate with the formation of the vinyl ketene complex (255). °° Electrocyclic ring closure of (255) leads to the cyclohexadienone complex (252), which is related to the final benzannulation product by a tautomerization when R is hydrogen. The mechanism proposed by Casey differs from that of Ddtz in that the order of the steps involving carbon monoxide insertion and cyclization to the aryl or alkenyl substituent is reversed.Specifically, the vinyl carbene complex intermediate (248) first undergoes cyclization to the metallacyclohexadiene (249), followed by carbon monoxide insertion to give the intermediate (251), and finally reductive elimination to give cyclohexadienone intermediate (252). At this time the circumstantial evidence favors the intermediacy of vinyl ketene intermediates since they can be trapped from these reactions and isolated where the metal is dispaced from the vinyl ketene functionality however, there is not any evidence which can rule out the alternative mechanism. 

The chromium-templated coupling of alkenyl- or arylcarbene, aUcyne and carbonyl ligands generates arene tricarbonylchromium complexes as primary benzannulation products which - based on their unsymmetric substitution pattern - bear a plane of chirality. Chiral arene complexes are powerful reagents in stereoselective synthesis however, the preparation of pure enantiomers is a lengthy and often tedious procedure, and thus diastereoselective benzannulation appears to be an attractive alternative. In order to lure the chromium fragment to one or the other face of the arene formed, chiral information may be incorporated in the carbene complex or the aUcyne. 

The Wulff-Ddtz reaction is another approach to the synthesis of the cyclophane system by formal [2 + 2 + 2] cycloaddition. The intramolecular benzannulation of the Fischer carbene complex, which has an alkyne tethered to the a-position of the alkenyl substituent, gave a para-cyclophane in moderate yield under highly diluted conditions (Scheme 8.6) [6]. 

The thermal [3-i-2-i-l]benzannulation reaction of a,/3-unsaturated alkenyl- or aryl-carbene complexes with alkynes represents the unique and most synthetically valuable reaction of chromium carbenes [20]. A variety of densely substituted benze-noid compounds is accessible by this Cr(CO)3-templated one-pot cyclization reaction. Experimental and theoretical studies support a stepwise C-C bond formation according to a mechanism (Scheme 11.6) that starts with a reversible decarbonyla-... 

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