Phenols Chromium carbene complexes

The convergent approach comprises, among other reaction steps, a regio-specific intermolecular benzannulation reaction between the alkyne 88 and the chromium carbene complex 89 for AB ring construction (Scheme 43). It is noteworthy that the regioselectivity of this reaction is attributed to the bulky TBDMS ether in the alkyne a-substituent, that dictates the incorporation of the large substituent ortho to the phenol. Another curiosity is the fact that the reaction failed to provide 90 in the absence of acetic anhydride. 

Alkynyl complexes. These complexes, which are readily available by reaction of an alkynyllithium with chromium carbonyl followed by methylation with CH3OSO2F, undergo facile Diels-Alder reactions with dienes to provide a general route to ,p-un-saturated chromium carbene complexes. The latter undergo benzannelation or cyclo-hexadienone annelation on reaction with an alkyne. A (trimethylsilyl)ethynyl complex is useful because benzannelation results in migration of silicon from carbon to oxygen to provide a protected phenol. 

Sugar acetylene reacted with a Fisher chromium carbene complex to give a phenol derivative, a possible intermediate for naturally occurring aryl-C-glycoside antibiotics (O Scheme 34) [55]. 

In the Dotz reaction, an unsaturated chromium carbene complex is combined with an alkyne to give a substituted phenol. The unsaturated group may be an alkenyl, cycloalkenyl, or aryl group. There is almost always a methoxy or other alkoxy group attached to the carbene. 

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. ... 

C. A. Merlic made use of this procedure in a benzannulation reaction leading to ortho-substituted phenols. Note that the photochemical method perfectly complements the Dotz-reaction which gives p-alkoxyphenols from chromium carbene complexes and alkynes. 

Three component cyclization of an aromatic or vinylic alkoxy pentacarbonyl chromium carbene complex, an alkyne, and carbon monoxide, generating a Cr(CO)3 coordinated phenol ... 

Seperately Wulff has described the effect on selectivity and yield of substitution on the aryl ring of chromium carbene complexes. It was shown that electron-withdrawing groups para- to the chromium carbene increase the chemoselectivity for benzannulation. Substituents in the ortho position are detrimental to phenol formation irrespective of the substituent s electronic nature. Finally, it was shown that large alkoxy groups on the earbene earbon (1, X = OR) give increased yields of the desired phenol product. 

Organometallic reagents were used for the synthesis of bicyclic aromatic compounds via Moore-type cyclization. Rahm and Wulff described the new synthesis of 5-hydroxyindolines with the use of a chromium carbene complex bearing alkynyl substituent 22." The amino-tethered bis-alkynyl carbene complex 22 was transformed into indoline 23 by thermolysis in the presence of a hydrogen source. The low yield of product 23 was improved when the reaction was carried out in the presence of the electrophile, added to protect the phenol function. This process involves the insertion of one carbon monoxide group from the chromium complex into the skeleton of an eneyne compound 24. The resulting enyne-ketene 25 undergoes a cycloaromatization reaction to afford the 1,4-diradical intermediate 26. Subsequent demetalation yields product 23."... 

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. 

Structural analogues of the /]4-vinylketene E were isolated by Wulff, Rudler and Moser [15]. The enaminoketene complex 11 was obtained from an intramolecular reaction of the chromium pentacarbonyl carbene complex 10. The silyl vinylketene 13 was isolated from the reaction of the methoxy(phenyl)-carbene chromium complex 1 and a silyl-substituted phenylacetylene 12, and -in contrast to alkene carbene complex 7 - gave the benzannulation product 14 after heating to 165 °C in acetonitrile (Scheme 6). The last step of the benzannulation reaction is the tautomerisation of the /]4-cyclohexadienone F to afford the phenol product G. The existence of such an intermediate and its capacity to undergo a subsequent step was validated by Wulff, who synthesised an... 

Density functional calculations on the Dotz reaction leading from chromium carbene (75) with acetylene to give the phenol (78) suggested a new mechanism involving the formation of a chromahexatriene complex (77) from the initially formed vinylallyl-idene complex (76). " Complex (77) then collapses to the phenol complex (78). 

The stepwise coupling of two cis ligands as depicted in Scheme 3 has been verified as involving a sequence of three discrete steps at low temperatures, allowing the isolation of the relevant intermediates as individual compounds [18]. When a chelated tetracarbonyl amino-vinyl carbene complex (chelated analogue of intermediate B in Scheme 3) was reacted with an electron-deficient alkyne under controlled conditions, a l,4,5- 3-dienylcarbene tetracarbonyl chromium complex (corresponding to intermediate D in Scheme 3) was formed. It underwent thermal decomposition to give phenol derivatives as the final products. 

The reactions of Fischer carbene complexes with alkynes can under certain conditions lead to products that result from the incorporation of two alkynes, the carbene ligand and a carbon monoxide. In inter-molecular reactions, this is most commonly observed for acetylene itself or for sterically unhindered al-kynes. °2 As can be anticipated by the mechanism in Scheme 36, two-alkyne incorporated products of the type (258) are also favored for high alkyne concentration. Synthetically, the two-alkyne reactions are most useful in intramolecular reactions, two of which have been reported and are exemplified by the reactions in Scheme 43. The typical product from the reaction of a Fischer carbene complex with a diyne, such as (308), is a bicyclic phenol of the type (309). ° These products are apparently the result of the assembly of pieces indicated by (311). Under some conditions, dienones of the type (310) and (314) can be isolated, and it is thought they are the immediate precursors of the phenol products via an in situ reduction by a chromium(O) species. This reaction is completely regioselective with diyne (308) and the phenol (309) results from incorporation of the terminal alkyne of (308) before the disubstituted alkyne. Phenols of the type (309) have also been observed from the reaction of diynes with carbyne complexes. ... 

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. 

The reactivity of carbene-metal complexes, amongst others the reactivity with respect to alkenes and alkynes, has been reviewed by Dotz Just like free carbenes the coordinated carbenes add to triple bonds to give cyclopropene derivatives. Other reaction products, however, are also possible. For instance, the carbene ligand of chromium complex 23 reacts with diphenylacetylene to a mixture of products, including naphthalene derivative 24 and furan derivative 25 (equation 18). A carbonyl ligand has participated. Molecular orbital calculations by Hofmann and Hammerle " on this system reveal that the reaction would pass through an y-vinylcarbene type of complex (26) instead of through a planar chromacyclobutene 27. The subsequent steps to yield either phenol or furan could involve vinylketene 28, but this still is a matter of debate. Similar, but more selective, furan syntheses have been observed for carbene complexes based on iron and cobalt. ... 

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 currently accepted mechanism of the DBR is shown above. The rate-determining step is thought to be loss of a carbon monoxide ligand to form a coordinatively unsaturated intermediate II. This process can be facilitated thermally or photolytically. An alkyne can then coordinate to form 12. The alkyne inserts into the carbene heteroatom bond to give a new chromium carbene 13. At this point there are at least two possible pathways. In the first pathway, carbon monoxide can insert to provide chromium complexed ketene 14, which undergoes electrocyclization to give the hexadienone 15. Tautomerization completes the reaction to provide the phenol 2. Alternatively, metallacycle 16 can form prior to carbon monoxide insertion. Reductive elimination before carbon monoxide insertion leads to pentadiene 5, a commonly observed by-products of the DBR. Cyclopentanones 6, cyclobutenones 7, and indenes have also been observed as by-products in the... 

Transition-metal carbene complexes have proven especially useful in the construction of six-membered rings, primarily in the synthesis of naphthalenes and higher aromatic ring systems. The major method employed is the Dbtz benzannulation reaction (depicted in Scheme 17.12), where an a,p-unsaturated or aryl carbene complex of chromium (78) couples with an alkyne to afford a phenol derivative (76). This reaction has been demonstrated for a vast array of molecular architectures and functionalities and has proven to be a very reliable and efificient process. Perhaps the major limitation on the synthetic utility is the construction of the carbene complex for systems that require structural complexity in the carbene complex. In addition to the Dotz reaction itself, several efforts to develop alternative procedures have been inspired by a detailed understanding of the mechanism of the Dotz reaction. 

A [5+1] carbonylative cycloaddition of chromium Fischer carbene complexes having /ra j,/ra 5-dienyl substituents at the carbene carbon atom with nonacarbonyldiiron gives ri -2-alkoxycyclohexa-2,4-dienone(tricarbonyl)iron complexes and 2-alkoxyphenols (Scheme 4-13). Without the addition of the carbonyliron complex, this reaction works only for substrates that have a cw-disposition at the a,P-double bond. The ri -2-alkoxycyclohexa-2,4-dienone(tricarbonyl)iron complexes can be converted to the corresponding phenols by treatment with base or by stirring with silica gel in the presence of air. 

A plausible pathway is that the aromatisation of the cyclohexadienone 92 by a proton shift is accelerated in the presence of Ac20 under formation of acetate 93. The simultaneously generated acetic acid then cleaves the acetate to form the free phenol 94 (Scheme 44). This effect was observed for the first time during studies towards the total synthesis of the lipid-alternating and anti-atherosclerotic furochromone khellin 99 [64].The furanyl carbene chromium complex 96 was supposed to react with alkoxyalkyne 95 in a benzannulation reaction to give the densely substituted benzofuran derivative 97 (Scheme 45). Upon warming the reaction mixture in tetrahydrofuran to 65 °C the reaction was completed in 4 h, but only a dimerisation product could be isolated. This... 

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