Dotz benzannulation

The mild conditions and high chemoselectivity of the metathesis reaction ensures that a wide variety of temporary connection strategies are compatible, and it is envisaged that this strategy will find increasing use in the future. 

The benzannulation reaction is a versatile method for the formation of polysubstituted aromatic compounds such as naphthoquinones. This three-component coupling involves the reaction between an a. unsaturated Fischer carbene, an acetylene, and a CO ligand, and initially proceeds by cycloaddition of the alkyne with the carbene complex. The regioselectivity of this step is highly dependent on the substituents on the acetylene moiety and is usually low in the case of internal acetylenes. 

To overcome potential problems, Semmelhack et al. employed a tethered disubstitut-ed acetylene to control the regioselectivity of the synthesis of the internal six-membered ring in his synthesis of deoxyfrenolicin 393 [165]. Fischer carbene complex 394, bearing a pendant acetylene, was reacted in Et20 at 35 to 37 °C for 64 h, and after oxidative 

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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]. 

Merlic A, Xu D (1991) J Am Chem Soc 113 7418. For photo accelerated classical Dotz benzannulations see Choi YH, Rhee KS, Shin GP, Shin SC (1995) Tetrahedron Lett 36 1871 Weyershausen B, Dotz KH (1999) Synlett 231... 

A Dotz benzannulation reaction was utilized in the synthesis of the furo[2,3- >]furan core of aflatoxin B2 as illustrated below <06TL2299>. Synthesis of polynuclear aromatic compounds was achieved by using [5+5] cycloaddition of 2-alkynylarylcarbene complexes and enyne-aldehyde derivatives <06TL5303>. 

Scheme 6.79 Hydrosilylation of ketones [164], Dotz benzannulation chemistry [165], cobalt-mediated synthesis of angular [4]phenylenes [166], and nickel-mediated coupling polymerizations [167],...

Recent calculations [329] suggest that the first reaction step of the Dotz benzannulation reaction may not necessarily be the thermal cleavage of one carbonyl ligand. 

Fig. 2.24. Possible mechanism of the Dotz benzannulation reaction (R, R large, small substitutents H, alkyl, aryl).

Fig. 2.26. Synthesis of fredericamycin A utilizing a Dotz benzannulation reaction [268].

The Dotz benzannulation reaction yields either arene chromium tricarbonyl complexes or the decomplexed phenols, depending on the work-up conditions. Because of the instability of hydroxy-substituted arene chromium tricarbonyl complexes, yields of the latter tend to be low. High yields of arene complexes can, however, be obtained by in situ silylation of the crude product of the benzannulation reaction [336]. Oxidative work-up yields either decomplexed phenols or the corresponding quinones. Treatment of the benzannulation products with phosphines also leads to decomplexed phenols [272]. 

Despite the many limitations, the Dotz benzannulation remains a powerful tool for the preparation of substituted phenols. One example of the use of a Dotz benzannulation as the key step in a synthesis of the potent natural antibiotic fredericamycin A (as racemate) is sketched in Figure 2.26. 

Additional examples of Dotz benzannulation reactions are given in Table 2.17. Further examples have been reported (see, e.g., [269,270,340-344]). 

Table 2.17. Examples of the preparation of substituted phenols by use of the Dotz benzannulation reaction.

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. 

A new chromahexatriene (118) route has been proposed for the mechanism of the Dotz benzannulation reaction between vinylcarbene complexes (117) and ethynes (Scheme 46). ... 

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. 

An exceptionally mild Dotz benzannulation was used by W.J. Kerr and co-workers for the total synthesis of a natural insecticide, 2-(1,1-dimethyl-2-propenyl)-3-hydroxy-1,4-naphthalenedione, by utilizing dry adsorption (DSA) techniques. ... 

Related reactions Danheiser benzannulation, Dotz benzannulation reaction ... 

Caldwell, J. J., Colman, R., Kerr, W. J., Magennis, E. J. Novel use of a selenoalkyne within untraditionally mild Dotz benzannulation processes total synthesis of a Calceolaria andina L. natural hydroxylated naphthoquinone. S/rr/eff 2001,1428-1430. 

Divinylbenzene-hydrophilic methacrylate copolymer 944 DNOC 1350 Domesticine 1064 DOtz benzannulation 454-459 Double Fourier transform filtering 984, 985 DRD 953 Drinking water,... 

The Dotz benzannulation products involving propargyloxy derivatives are liable to eUmination, leading to o-quinonemethides whch can be trapped. ... 

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