Carbene Dotz benzannulation

The reaction of alkoxyarylcarbene complexes with alkynes mainly affords Dotz benzannulated [3C+2S+1C0] cycloadducts. However, uncommon reaction pathways of some alkoxyarylcarbene complexes in their reaction with alkynes leading to indene derivatives in a formal [3C+2S] cycloaddition process have been reported. For example, the reaction of methoxy(2,6-dimethylphenyl)chromium carbene complex with 1,2-diphenylacetylene at 100 °C gives rise to an unusual indene derivative where a sigmatropic 1,5-methyl shift is observed [60]. Moreover, a related (4-hydroxy-2,6-dimethylphenyl)carbene complex reacts in benzene at 100 °C with 3-hexyne to produce an indene derivative. However, the expected Dotz cycloadduct is obtained when the solvent is changed to acetonitrile [61] (Scheme 19). Also, Dotz et al. have shown that the introduction of an isocyanide ligand into the coordination sphere of the metal induces the preferential formation of indene derivatives [62]. 

The Dotz Reaction A Chromium Fischer Carbene-Mediated Benzannulation Reaction... 

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). 

Depending on the types of substituents and the precise reaction conditions (l,3-butadien-l-yl)carbene complexes can undergo direct cyclization to yield cyclo-pentadienes [337,350]. As mentioned in Section 2.2.5.1, cyclopentadiene formation occurs particularly easily with aminocarbene complexes [351]. Alternatively, in particular at higher reaction temperatures, CO-insertion can lead to the formation of a vinylketene complex, which, again depending on the electronic properties of the substituents and the reaction conditions, can cyclize to yield cyclobutenones, furans [91,352], cyclopentenones, furanones [91], or phenols (Dotz benzannulation) [207,251,353]. 

The formation of cycloheptadienones from alkoxy(cyclopropyl)carbene complexes and alkynes (Entry 5, Table 2.24) [388,389] proceeds essentially by the same mechanism as the Dotz benzannulation reaction (see Figure 2.32). The cyclopropyl group participates in the electrocyclic rearrangement as the equivalent of a vinyl group. 

Sola, M. Duran, M. Torrent, M. The Dotz reaction A chromium Eischer carbene-mediated benzannulation reaction. In Computational Modeling of Homogeneous Catalysis Maseras, E. Lledos, A. eds. Kluwer Academic Boston 2002, 269—287. (Review). 

The Dotz benzannulation reaction, based on the alkyne cycloaddition to chromium carbene complexes, is the most important application of Fischer carbene complexes. Among the various Fischer carbene complexes, alkoxy and aminocarbene complexes of chromium undergo a novel inter- and intramolecular tandem alkyne insertion/ carbene annotation sequence to give 9H-carbazoles and nf/-benzo[fl]carbazoles. 

Fischer-type chromium carbene complexes of furans underwent Dotz benzannulation with alkynes to provide trisubstituted benzo [, ]furan derivatives. An example used in the synthesis of isodityrosine is depicted in Equation (39) <2005JOC7422>. The efficiency of the reaction could be improved by ultrasound sonication <19990L1721>. 

The stereoselectivity of the Buchi-Paterno reaction between 3-hydroxy-2,3-dihydrofuran and benzophenone was found to be influenced by solvent, temperature and steric effect <06TL2527>. A Dotz benzannulation involving a dihydrofuran chromium carbene complex and an alkyne was employed to form the aflatoxin skeleton, providing the annulated product as the only regioisomer <06TL2299>. Cycloaddition involving 2,3-dihydrofuran, 1-aminoanthraquinone and salicy aldehyde was catalyzed by... 

The mechanism of the Dotz benzannulation reaction has not been fully elucidated. The first step is the ratedetermining dissociation of one carbonyl ligand from the Fischer carbene complex, which is cis to the carbene moiety. Subsequently, the alkyne component coordinates to the coordinatively unsaturated carbene complex, and then it inserts into the metal-carbon bond. After the alkyne insertion, a vinylcarbene is formed that can lead to the product by two different pathways (Path A or Path b). ... 

P. Quayle and co-workers utilized the Dotz benzannulation reaction for the synthesis of diterpenoid quinones." The authors developed a novel synthetic approach to 12-O-methyl royleanone using a simple vinyl chromium carbene complex along with a disubstituted oxygenated acetylene. The bicyclic hydrazone was converted to the corresponding vinyllithium derivative by the Shapiro reaction and then functionalized to give the desired crude Fischer chromium carbene complex. The benzannulation took place in refluxing THF with excellent regioselectivity, and the natural product was obtained in 37% overall yield from the hydrazone. 

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. 

Also known as the Dotz benzannulation, the Dotz reaction is the Cr(CO)3-coordinated hydroquinone from vinyhc alkoxy pentacaiboityl chromium caibene (Fischer carbene) complex and alkynes. 

The Dotz benzannulation reaction (DBR) is the reaction of an a,P unsaturated Fischer carbene with an alkyne to produce a highly substituted phenol. Alternatively, the DBR can be considered a metal templated 3 + 1 + 2 cycloaddition of an allylic carbine (3 carbon unit), carbon monoxide (1 carbon unit), and an alkyne (2 carbon unit). The initial product of the reaction is the arene chromium tricarbonyl complex of the phenol as in 4. These complexes are typically unstable in air such that workup and purification of the product lead to the complete loss of the metal. Chromium is the most often used metal for the benzannulation. Molybdinum, tungsten, and manganese have been used but usually give mixtures of products and require harsh reaction conditions. 

The [3+2+1] cycloaddition of an a, 3-unsaturated or aryl carbene complex of chromium, an alkyne, and carbon monoxide, that is named the Dotz benzannulation, is a useful method for the synthesis of a phenol or naphthol derivative, although this reaction requires a stoichiometric amount of the chromium carbene complex of chromium [35]. A mechanism of this reaction is shown in Scheme 21.31. When unsymmetrical alleynes are used, the regioselectivity is determined in the alkyne insertion step by the steric effect. 

Dbtz Benzannulation Reactions. The Dotz benzannulation involves the reaction of a vinylic or aryl chromium Fischer carbene with an alkyne to afford substituted... 

Miscellaneous Triple Bond Additions. An example has been published in which a Fischer carbene chromium complex adds to 3-trimethylsilyl-1-propyne, to give the Dotz benzannulation product in 62% yield (eq 44). ... 

In some cases, the coupling of carbene complexes and alkynes leads to furan derivatives in a process that incorporates a CO molecule (Scheme 17.11). Although this pathway is usually a minor undesired competing process in the Dotz benzannulation... 

One of the major applications of Fischer carbene complexes is the formation of substituted phenols, known as Dotz benzannulation. The first example of this reaction on solid phase was reported by the group of Martinez [35]. The Fischer carbene complex 16 was obtained with a loading of 95% (Scheme 10), and the reaction could be monitored by colorimetric analysis. Microwave-assisted D5tz benzannulation allowed a sixfold decrease in the reaction time. Investigations into various reaction conditions showed that the reaction was almost independent of solvent, and that elevated temperature and prolonged reaction time did not have a major influence on the yield. 

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). 

The first and rate-determining step involves carbon monoxide dissociation from the initial pentacarbonyl carbene complex A to yield the coordinatively unsaturated tetracarbonyl carbene complex B (Scheme 3). The decarbonyla-tion and consequently the benzannulation reaction may be induced thermally, photochemically [2], sonochemically [3], or even under microwave-assisted conditions [4]. A detailed kinetic study by Dotz et al. proved that the initial reaction step proceeds via a reversible dissociative mechanism [5]. More recently, density functional studies on the preactivation scenario by Sola et al. tried to propose alkyne addition as the first step [6],but it was shown that this... 

A similar tandem Dotz-Mitsunobu reaction has been reported starting from a l,6-methano[10]annulene carbene complex, but no conclusion could be reached on the influence of the chiral information regarding the stereoselective course of the reaction since the chromium fragment could not be kept coordinated to the benzannulation product [47]. 

The thermal benzannulation of Group 6 carbene complexes with alkynes (the Dotz reaction) is highly developed and has been used extensively in synthesis [90,91]. It is thought to proceed through a chromium vinylketene intermediate generated by sequential insertion of the alkyne followed by carbon monoxide into the chromium-carbene-carbon double bond [92]. The realization that photodriven CO insertion into Z-dienylcarbene complexes should generate the same vinylketene intermediate led to the development of a photochemical variant of the Dotz reaction (Table 14). 

Key words Dotz reaction, benzannulation, Fischer carbene complexes, reaction mechanism, density functional theory... 

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. 

The Dotz reaction was first reported2 for an aryl carbene of the type 8, and the resulting benzannulation may be summarized conveniently as shown in Scheme 3. The major product of the reaction is usually the naphthol 9, the result of a formal [3 + 2 + 1] cycloaddition.10 In cases where CO insertion does not take place, five-membered rings (10) may also be formed. 

Heinrich Dotz, from the Kekule-Institut (a predestined name ) of the University of Bonn, is another famous chemist who has given his name to a reaction. Coming from E. O. Fischer s school, he advantageously exploited his serendipitous discovery of the very rich reactivity of Fischer-type carbene complexes in synthesizing polycydic arene derivatives. This chromium-templated carbene benzannulation approach to densely functionalized arenes (Dotz reaction) is the subject of the chapter (No. 8) that he has co-authored with J. Stendel Jr. 

The Chromium-Templated Carbene Benzannulation Approach to Densely Functionalized Arenes (Dotz Reaction)... 

Dotz, K. H., Stendel, J., Jr. The chromium-templated carbene benzannulation approach to densely functionalized arenas (Dotz reaction). Modern Arene Chemistry 2002, 250-296. 

Gleichmann, M. M., Dotz, K. H., Hess, B. A. Intermediates and Transition Structures of the Benzannulation of Heteroatom-Stabilized Chromium Carbene Complexes with Ethyne A Density Functional Study. J. Am. Chem. Soc. 1996, 118, 10551-10560. 

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