Cycloaddition reactions Chromium carbene complexes

Although most of the examples of [3S+2C] cycloaddition reactions with carbene complexes are referred to as 1,3-dipolar processes, we should include in this section another kind of non-dipolar transformation dealing with the reaction of pentacarbonyl(methoxymethylcarbene)chromium with a base followed by treatment with an epoxide in the presence of boron trifluoride. This reaction gives cyclic carbene complexes in a process that can be considered a [3S+2C] cycloaddition [44] (Scheme 14). 

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. 

Furthermore, the successful [3+2+1] cycloaddition of alkynes bearing a cyclopropane ring and a carbene complex unit has been reported. These benzannulations result in the formation of bimetallic naphthohydroquinone chromium tricarbonyl complexes [48]. Additionally, (non-strained) cyclic alkynes are potent reaction partners in the cycloaddition of chromium carbene complexes [49]. 

Silylketenes in formation of (3-lactones and (3-lactams 98JCS(P1)2105. Syntheses of (3-lactams, (3-lactones, and 1,3- and 1,4-diazetidinediones by pho-tochemically induced cycloaddition reactions of chromium carbene complexes with imines, aldehydes, and azo compounds 97T4105. 

By a photochemically induced elimination of CO, a chromium carbene complex with a free coordination site is generated. That species can coordinate to an alkyne, to give the alkyne-chromium carbonyl complex 4. The next step is likely to be a cycloaddition reaction leading to a four-membered ring compound 5. A subsequent electrocyclic ring opening and the insertion of CO leads to the vinylketene complex 6 ... 

The [3S+1C] cycloaddition reaction with Fischer carbene complexes is a very unusual reaction pathway. In fact, only one example has been reported. This process involves the insertion of alkyl-derived chromium carbene complexes into the carbon-carbon a-bond of diphenylcyclopropenone to generate cyclobutenone derivatives [41] (Scheme 13). The mechanism of this transformation involves a CO dissociation followed by oxidative addition into the cyclopropenone carbon-carbon a-bond, affording a metalacyclopentenone derivative which undergoes reductive elimination to produce the final cyclobutenone derivatives. 

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]. 

At this point the catalytic process developed by Dotz et al. using diazoalkanes and electron-rich dienes in the presence of catalytic amounts of pentacar-bonyl(r]2-ds-cyclooctene)chromium should be mentioned. This reaction leads to cyclopentene derivatives in a process which can be considered as a formal [4S+1C] cycloaddition reaction. A Fischer-type non-heteroatom-stabilised chromium carbene complex has been observed as an intermediate in this reaction [23a]. 

Table 2.15. Cycloaddition reactions of photochemically activated chromium carbene complexes.

Initial [2 + 2] cycloaddition of the alkyne to the saturated chromium carbene complex followed by [2 + 2] cycloreversion to yield a l-chroma-l,3,5-hexatriene may be an energetically more favorable reaction pathway (Figure 2.25). However, no energy minima could be located on the path from the starting carbene complex to the chromahexatriene. Hence, the metallacyclobutene shown in Figure 2.25 does not represent an intermediate but only a transition state. 

Extensive studies on diastereoselectivity in the reactions of 1,3-dipoles such as nitrile oxides and nitrones have been carried out over the last 10 years. In contrast, very little work was done on the reactions of nitrile imines with chiral alkenes until the end of the 1990s and very few enantiomerically pure nitrile imines were generated. The greatest degree of selectivity so far has been achieved in cycloadditions to the Fischer chromium carbene complexes (201) to give, initially, the pyrazohne complexes 202 and 203 (111,112). These products proved to be rather unstable and were oxidized in situ with pyridine N-oxide to give predominantly the (4R,5S) product 204 in moderate yield (35-73%). 

Another more versatile method involves the photocycloaddition of chromium carbene complexes to alkenes. These transformations can be formally regarded as [2 + 1 + 1] cycloadditions since these carbene complexes are derived from [1 + 1] carbanion insertion reactions to hexacarbonylchromium. 

The use of alkenes with chiral auxiliary groups leads to chiral cyclobutanones 4. Reaction yields of 50 67% and diastereomeric excesses of 86-97% were obtained for the 3-amidocy-clobutanones which were obtained from cycloaddition of the chromium carbene complexes with chiral ene carbamates (see also Section 1.3.4.3.3.).11... 

The advantage of using the photocycloaddition of pentacarbonylcarbenechromium complexes over the ketene cycloaddition method is the absence of ketene dimerization and the avoidance of use of excess alkene in the former method. Also, the mild reaction conditions associated with the use of chromium carbene complexes avoids epimerization and thermodynamic equilibration of 2-monosubstituted cyclobutanones. 

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... 

Chromium carbene complexes undergo other reactions, too. The mechanisms of these reactions consist of steps ([2 + 2] cycloadditions, electrocyclic reactions) that are similar to those seen in the mechanism of the Dotz reaction. 

However, yields in the intermolecular cycloaddition reactions of vinylcarbene complexes, formed by intramolecular insertion of an alkynyl tethered metal carbene complex, are higher when molybdenum rather than chromium or tungsten carbene complexes are employed. Mild thermolysis (THF, 65 °C, 1 h) in the presence of ten equivalents of an electronically undemanding alkene directly leads to the 2-alkyl-2-(2-methoxycyclopentenyl)cyclopropanes 31. ... 

Fischer-type chromium carbene complexes with 1-ethoxycyclopropylalkynyl substituents at the carbene carbon, e.g. 25, on reaction with dimethylamine and subsequent conversion of the resulting vinylcarbene with alkynes surprisingly did not give phenol derivatives, as would be expected from the known Dotz reaction, but gave cyclopenta[ )]pyrans, e.g. 26. The reaction is interpreted as a double alkyne-insertion/CO-insertion sequence with formation of a trienylketene intermediate, which undergoes intramolecular hetero-Diels-Alder cycloaddition and dimethylamine elimination. ... 

The preparation of cyclobutanone (123) via the [2 + 2] cycloaddition of ketene (121), and the photolytic reaction of chromium carbene complex (122) with 2,3-dihydro-1,4-dioxin (10 has also been described <92TL927>. 

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. 

Harrity and co-workers described the application of 2-substituted 1-alkynylboronic esters in the Dotz cycloaddition of Fisher chromium carbene complexes, affording in a highly regioselective fashion a novel class of hydroxy-naphthyl boron pinacolates (entry 18, Table 1.3) [217]. These reaction products also provided, upon treatment with ceric ammonium nitrate, the corresponding quinone boronic esters. 

The insertion of alkynes into a chromium-carbon double bond is not restricted to Fischer alkenylcarbene complexes. Numerous transformations of this kind have been performed with simple alkylcarbene complexes, from which unstable a,/J-unsaturated carbene complexes were formed in situ, and in turn underwent further reactions in several different ways. For example, reaction of the 1-me-thoxyethylidene complex 6a with the conjugated enyne-ketimines and -ketones 131 afforded pyrrole [92] and furan 134 derivatives [93], respectively. The alkyne-inserted intermediate 132 apparently undergoes 671-electrocyclization and reductive elimination to afford enol ether 133, which yields the cycloaddition product 134 via a subsequent hydrolysis (Scheme 28). This transformation also demonstrates that Fischer carbene complexes are highly selective in their reactivity toward alkynes in the presence of other multiple bonds (Table 6). 

Catalytic cyclopropanation of alkenes has been reported by the use of diazoalkanes and electron-rich olefins in the presence of catalytic amounts of pentacarbonyl(rj2-ris-cyclooctene)chromium [23a,b] (Scheme 6) and by treatment of conjugated ene-yne ketone derivatives with different alkyl- and donor-substituted alkenes in the presence of a catalytic amount of pentacarbon-ylchromium tetrahydrofuran complex [23c]. These [2S+1C] cycloaddition reactions catalysed by a Cr(0) complex proceed at room temperature and involve the formation of a non-heteroatom-stabilised carbene complex as intermediate. 

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