Aryl complexes benzannulation

As stated above, cyclopentanones, cyclobutenones, and indenes have been observed as by-products in the DBR. Wulff has studied the effect of solvent, chelation, concentration, and alkyne substitution on the product distribution. He reported that simple a,(3-unsaturated chromium carbene complexes typically show excellent selectivity for the benzannulated product. This selectivity is not sensitive to changes in solvent or substituents on the acetylene. However, the reactions of aryl complexes with acetylenes are very sensitive to the nature of both the solvent and the acetylene. For aryl chromium complexes, the highest selectivities and yields for the benzannulated product arise with solvents of low coordinating ability hexane and benzene. Solvents with intermediate coordinating ability and small size... 

Irradition has been used to initiate the DBR. Ultraviolet irradiation allows reactions to occur at temperatures as low as -78 C. High selectivity for the benzannulated product is seen with simple aryl complexes, but high selectivity for indene products for complexes having a chelating o-methoxy on the aryl ring. 

Aryl- and alkenylcarbene complexes are known to react with alkynes through a [3C+2S+1C0] cycloaddition reaction to produce benzannulated compounds. This reaction, known as the Dotz reaction , is widely reviewed in Chap. Chromium-Templated Benzannulation Reactions , p. 123 of this book. However, simple alkyl-substituted carbene complexes react with excess of an alkyne (or with diynes) to produce a different benzannulated product which incorporates in its structure two molecules of the alkyne, a carbon monoxide ligand and the carbene carbon [128]. As referred to before, this [2S+2SH-1C+1C0] cycloaddition reaction can be carried out with diyne derivatives, showing these reactions give better yields than the corresponding intermolecular version (Scheme 80). 

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

The superior donor properties of amino groups over alkoxy substituents causes a higher electron density at the metal centre resulting in an increased M-CO bond strength in aminocarbene complexes. Therefore, the primary decarbo-nylation step requires harsher conditions moreover, the CO insertion generating the ketene intermediate cannot compete successfully with a direct electro-cyclisation of the alkyne insertion product, as shown in Scheme 9 for the formation of indenes. Due to that experience amino(aryl)carbene complexes are prone to undergo cyclopentannulation. If, however, the donor capacity of the aminocarbene ligand is reduced by N-acylation, benzannulation becomes feasible [22]. 

Mikami M, Hatano M, Akiyama K (2005) Active Pd(II) Complexes as Either Lewis Acid Catalysts or Transition Metal Catalysts. 14 279-322 Minatti A, DOtz KH (2004) Chromium-Templated Benzannulation Reactions. 13 123-156 Miura M, Satoh T (2005) Catalytic Processes Involving b-Carbon Elimination. 14 1-20 Miura M, Satoh T (2005) Arylation Reactions via C-H Bond Cleavage. 14 55-84 Mizobe Y, see Hidai M (1999) 3 227-241... 

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. 

Aryl(dialkylamino)carbene chromium complexes do not yield aminonaphthols upon treatment with alkynes, but form indene derivatives. Vinyl(dialkylamino)car-bene complexes, however, react with alkynes to yield aminophenols as the main products if solvents of low nucleophilicity are used [335]. (2-Amino-1-vinyl)carbene complexes do not undergo benzannulation when treated with alkynes, but form cyclopentadienes or heterocycles instead [251]. 

If the Ddtz benzannulation reaction is conducted with ori/zo-disubstituted aryl-carbene complexes, the final aromatization step is blocked and cyclohexadienones can be isolated (Figure 2.34) [356,378,379]. 

The facile decarbonylation of pentacarbonyl complexes 23a and 23b results in tetra-carbonyl carbene complex intermediates 24a and 24b, respectively. Their annulation can produce benzene and/or cyclopentadiene derivatives 25 and/or 26. In the case of aryl acyla-mino complex 23a, the reaction course is shifted towards the benzannulation reaction (25a 26a = 84 16). With the vinyl carbene complex 23b, the benzannulation product 25b (25b 26b = 100 0) is produced exclusively. 

In contrast to aryl carbene complexes, vinyl carbene complexes are known to yield only the benzannulation products [37]. For instance, carbohydrates [38], tetramethyl ketals of qui-nones [39], heterocycles, and oxacycloalkenylidene carbene complexes [40] have been used as part of a (cyclic) vinyl carbene complex. For example, complex 29 and diphenylethyne were converted to the acyl hydroquinone 30. Thus, 29 serves as a synthon for the (electron-poor) benzoyl vinyl carbene complex (Scheme 14) [40]. 

One of the main features of the benzannulation reaction of Fischer carbene complexes is the regiochemistry of the incorporation of alkynes into the assembled hydroquinone [53]. While terminal alkynes are incorporated with high regioselectivity (regardless of alkyl and aryl substituents), internal alkynes are prone to much poorer regioselectivity. Regioselectivity is virtually lost in the case of diarylacetylenes. 

Apart from the construction of phenanthrenes, carbene complexes have also been used for the synthesis of more extended polycyclic arenes. An unusual dimerization of chromium coordinated ortbo-ethynyl aryl carbenes results in the formation of chrysenes (Scheme 37) [81]. This unusual reaction course is presumably due to the rigid C2 bridge that links the carbene and alkyne moieties, and thus prevents a subsequent intramolecular alkyne insertion into the metal-carbene bond. Instead, a double intermolecular alkyne insertion favored by the weak chromium-alkyne bond is believed to occur forming a central ten-membered ring that may then rearrange to the fused arene system. For example, under typical benzannulation conditions, carbene complex 97 affords an equimolar mixture of chrysene 98a and its monochromium complex 98b. The peri-interactions between the former alkyne substituent (in the 5- and 11-positions) and the aryl hydrogen induce helicity in the chrysene skeleton. 

Pulley, S. R., Carey, J. P. C-Aryl Glycosides via a Benzannulation Mediated by Fischer Chromium Carbene Complexes. J. Org. Chem. 

Generally, arene(alkoxy)carbene chromium complexes react with aryl-, alkyl-, terminal or internal alkynes in ethers or acetonitrile to yield 4-alkoxy-l-naphthols, with the more hindered substituent ortho to the hydroxyl group . Upon treatment with alkynes, aryl(dialkylamino)carbene chromium complexes do not yield aminonaphthols, but they form indene derivatives . Vinyl(dialkylamino)carbene complexes, however, react with alkynes to yield aminophenols as the main products The solvent is one of the many factors that affects this type of reaction, for which the most important is the polarity and/or coordinating ability of the solvent. The Dotz benzannulation reaction yields either arene chromium tricarbonyl complexes or the decomplexed phenols, depending on the work-up conditions. Oxidative work-up yields either decomplexed phenols or the corresponding quinones. 

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. 

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