Indenes, reaction with carbenes

The reaction of dichlorocarbene with aromatic compounds, with a few exceptions, lacks preparative value the adducts rearrange undergoing addition of another molecule of carbene and the final yield of complex product mixture rarely exceeds more than a few percent. Of synthetic importance are the reactions with indenes, phenanthrene (its 9-substituted derivatives 9-ethoxy-,9-trimethylsilyl-, " 9-arylthio-, 9-arylseleno- ), pyrene and various alkyl-naphthalenes. 120 Reactions with aromatic compounds are discussed in Houben-Weyl, Vol. E19b, pp 1551-1553. 

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 unconventional structure of fulvenes with a unique C=C bond conjugation leads to unusual cycloaddition reactions with other unsaturated systems. For example, alkenylcarbene complexes react with fulvenes leading to indanone or indene derivatives which can be considered as derived from a [6S+3C] cycloaddition process [118] (Scheme 72). The reaction pathway is well explained by an initial 1,2-addition of the fulvene to the carbene carbon followed by [1,2]-Cr(CO)5-promoted cyclisation. 

The intermediate vinylketene complexes can undergo several other types or reaction, depending primarily on the substitution pattern, the metal and the solvent used (Figure 2.27). More than 15 different types of product have been obtained from the reaction of aryl(alkoxy)carbene chromium complexes with alkynes [333,334]. In addition to the formation of indenes [337], some arylcarbene complexes yield cyclobutenones [338], lactones, or furans [91] (e.g. Entry 4, Table 2.19) upon reaction with alkynes. Cyclobutenones can also be obtained by reaction of alkoxy(alkyl)carbene complexes with alkynes [339]. 

The ligand was then used to form a variety of transition metal carbene complexes [207] (see Figure 3.72). Interestingly, more than one method for the formation of transition metal carbene complexes was successfully employed presence of an inorganic base (IC COj) to deprotonate the imidazolium salt and the silver(I) oxide method with subsequent carbene transfer to rhodium(I), iridium(I) and copperfi), respectively. The silver(I) and copper(I) carbene complexes were used for the cyclopropanation of styrene and indene with 1,1-ethanediol diacetate (EDA) giving very poor conversion with silver (< 5%) and qnantitative yields with copper. The diastereomeric ratio (endolexo) was more favonrable with silver than with copper giving almost a pnre diastereomer for the silver catalysed reaction of indene. 

In certain substrates, addition of carbene involves ring expansion. Thus, the reaction of indene (2.83) with dichlorocarbene ( CCl2) gives 2-chloronaphthalene (2.84). 

Several reactions of metal-carbene complexes with alkynes leading to five-membered ring compounds have been described. The action of acetylenes on the chromium phenyl(pyrrolidino)carbene complex 472 results in mixtures of indanones 473 and indenes 474297 Terminal alkynes (pent-l-yne or hex-l-yne) react with the molybdenum carbene complex 475 to afford, after oxidative work-up, indanones 476 in contrast, trimethylsilylacetylene gave only the naphthoquinone 477. ... 

Chloroform-i4C added dropwise at 0° with vigorous stirring to a mixture of indene and K-/ rt-butoxide, after 1 hr. KOH and abs. alcohol added, then refluxed 2 hrs. 2-chloronaphthalene-2-i4C. Y 60-70%, P. J. van der Jagt, W. den Hollander, and B. van Zanten, R. 87, 1148 (1968) 2-fluoronaphthalenes, carbene generation with ethylene oxide (s. Synth. Meth. 21, 879) cf. F. Nerdel, G. Blume, and P. Weyerstahl, Tetrah. Let. 1969, 3867 reactions of w-dihalogenocyclo-propane compounds, review, s. R. Barlet and Y. Vo-Quang, Bl. 1969, 3729. 

Interest in this reaction was revived when the relevance of a carbene mechanism was realized, particularly following the demonstration (cf. SectionI,B) of a similar ring expansion of indene to 2-chloro-naphthalene by dichlorocarbene via the cyclopropane adduct. Indeed, at this time Nakazaki suggested that these reactions occurred by the addition of dichlorocarbene to the indolyl anion and subsequent rearrangement to the indolenine and, with loss of chloride ion, to the quinoline [Eq. (12)]. The preference of dichlorocarbene for... 

Alkenyl Fischer carbene complexes can serve as three-carbon components in the [6 + 3]-reactions of vinylchro-mium carbenes and fulvenes (Equations (23)—(25)), providing rapid access to indanone and indene structures.132 This reaction tolerates substitution of the fulvene, but the carbene complex requires extended conjugation to a carbonyl or aromatic ring. This reaction is proposed to be initiated by 1,2-addition of the electron-rich fulvene to the chromium carbene followed by a 1,2-shift of the chromium with simultaneous ring closure. Reductive elimination of the chromium metal and elimination/isomerization gives the products (Scheme 41). 

The cyclopentene annulations can also occur in the reactions of alkynyliodo-nium salts with nitrogen- and sulfur nucleophiles (Scheme 61). Specifically, azi-docyclopentene 155 is formed upon treatment of octynyliodonium tosylate 154 with sodium azide in dichloromethane [123]. The reaction of alkynyliodonium salt 156 with sodium toluenesulfinate results in the formation of substituted indene 157 via alkylidene carbene aromatic C-H bond insertion [124]. 

The formation of side products depends on the choice of substituents and solvent [21]. The role of the solvent is illustrated by the reaction of phenyl carbene complex 1 with diphenylethyne (Scheme 7). An ethereal solvent such as THF leads exclusively to the benzannulation product isolated as quinone 7 after oxidative work-up, while use of the noncoordinating solvent hexane results in comparable amounts of cyclobenzannulation and cyclopentannulation products 7 and 8a. Strongly coordinating acetonitrile suppresses benzannulation product 7 in favor of the cyclobutenone 9, which is accompanied by minor amounts of cyclopentannulation products 8a and 8b. Indene 8a is obtained exclusively if the polar solvent DMF is employed. 

Many reactions afford, in addition to the naphthalene derivatives, mixtures of products. One of the major side reactions is the formation of indene derivatives directly from the metathesis intermediate without insertion of carbon monoxide. Other products frequently isolated as minor components are furans, cyclobutanones, and cyclopentenediones. The product distribution is dependent on numerous factors, including solvent, reaction temperature, concentration of the alkyne, and the nature of the aryl substituent. Molybdenum carbenes give, depending on the alkyne, either naphthols or indenes exclusively. The molybdenum Fischer carbenes can be tuned to give naphthoquinones by replacing one of the carbon monoxide ligands with a phosphine (Scheme 45). 

In almost all situations the reactions of Fischer carbene complexes of chromium with alkynes lead to the formation of six-membered ring products, but on several occasions five-membered ring annulated products have been observed as minor products or as major products if the formation of six-membered rings is blocked. In an early report by Ddtz, the reaction of the 2,6-dimethylphenyl complex (209) was observed to react with diphenylacetylene to give the complexed and uncomplexed indenes (210) and... 

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. 

In his initial paper in 1975, D6tz reported that the thermal cycloaddition of pentacar-bonyl(methoxyphenylcarbene)chromium with diphenylacetylene in di-n-butyl ether yielded a chromium-complexed 4-methoxy-l-naphthol [2]. Soon thereafter, he related that the same reactants in w-heptane produced not only naphthol product, but also indene, furan, and cyclobutenone products [4]. As it turned out, these results foreshadowed the extraordinary richness of organic structural types that may be derived from cycloadditions of alkynes with Fischer carbenes, as well as very recent contributions to reaction chemoselectivity through control of reaction conditions. Indeed, in the years since, the field has seen the introduction of a number of newly discovered cycloaddition types and, maybe more importantly, has... 

Indenes, like cyclobutenones and furans, are common side-products in the reaction of chromium arylalkoxycarbene complexes with alkynes, especially internal alkynes [9]. The in-dene structure comes about by a process that is very similar to naphthol formation annula-tion to the aryl ring still occurs, but without carbon monoxide insertion, and, instead, bond formation takes place directly between an alkyne carbon and the aryl carbon ortho to the metal carbene substituent [Eq. (18)] [4]. Scheme 5-1 shows two pathways that have been suggested for this transformation beginning from the vinylcarbene intermediate 3, naphthol formation can be diverted to intermediate 8, either by direct cyclization (3 -+ 8) or through the chromacyclohexadiene (3->6- 8). Aromatization and decomplexation yield the indene [7 b, d, 43], More detailed mechanistic analyses consider the roles of the stereochemistry of 3, as an ( )- or (Z)-vinylcarbene, as well as the coordination of external ligands, in the production of indenes, naphthols, furans, cyclobutenones, and other common side-products [8 a, 9, 13, 44],... 

Certain alkyne and carbene substitution patterns divert the reaction toward predominant indene formation. For example, ynamines and ynediamines both react with chromium arylalkoxycarbenes to give isolable vinyl carbenes, which proceed on to indenes thermally [21 a, b]. Chromium aryla/nmocarbenes also lead to good to excellent yields of indanones after hydrolysis of the enamine [Eq. (19)] [45]. In this latter case, the increased electron-donating... 

Cyclobutenones are fairly common side-products in the reaction of chromium arylalkoxy-carbenes with internal alkynes. As indicated in Scheme 5-1, the branch point in the formation of cyclobutenone versus naphthol products is believed to be vinylketene intermediate 4, which may undergo electrocyclic ring closure to 9, followed by reductive elimination to the product [7 a]. Cyclobutenone formation occurs only in the presence of internal or external ligands that can coordinate to unsaturated chromium species sufficiently well to prevent complexation to an internal n-system and thus divert the system toward 9. Depending on the alkyne and aryl substitution patterns and the reaction conditions, cyclobutenone formation can be made to predominate. Thus, solvents of good coordinating ability such as acetonitrile, o-OMe aryl substitution (which allows internal coordination to chromium), and bulky alkynyl substituents all favor cyclobutenone formation [Eq. (23)] [13]. In fact, the effect of solvent alone can be even more dramatic for the reaction partners in Eq. (21), a 0.5 M concentration of the carbene complex in acetonitrile gives instead a 78 % yield of cyclobutenone and only a combined 17 yield of quinone and indene products [9]. 

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... 

The products of diaminoacetylene insertions into metal-carbene carbon bonds have been further examined. After initial insertion at room temperature, warming causes a subsequent displacement of carbon monoxide with formation of a new, cyclic carbene complex. The carbene-C of this species, on further heating, attacks the nr/Ao-carbon of the phenyl ring forming a substituted indene. This sequence, in which the chromium atom behaves essentially as a template, is shown in Scheme 39. A different reaction path is, however, taken when the carbene... 

Acetylenes generally react with carbenes to form cyclopropenes. Whether this is a reaction via a singlet carbene or a two-step process via a biradical cannot be determined from the product, as is the case in the trapping with olefins. Isolation of indenes (116) from the reaction of acetylenes with di-phenylcarbene generated photochemically from the diazo-compound, however, was considered to be evidence for the intermediacy of a triplet carbene. 

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