Alkyne/Fischer carbene cycloaddition

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). 

Vinyl Fischer carbenes can be used as three-carbon components in Ni(0)-mediated and Rh(l)-catalyzed [3 + 2 + 21-reactions with alkynes (Schemes 48 and 49)142 and with allenes (Schemes 50 and 51).143 All three of the proposed mechanisms for the [3 + 2 + 2]-cycloadditions involve an initial carbene transfer from chromium to nickel or rhodium (Schemes 49, 52, and 53). As is seen from the products of the two [3 + 2 + 2]-reactions with 1,1-dimethylallene, although the nickel and rhodium carbenes 147G and 147K appear similar, the initial insertion of the allene occurs with opposite regioselectivity. 

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. 

The nickel-catalysed 3 + 1 + 1-cycloaddition of alkenyl Fischer carbene complexes with methylenecyclopropanes produced the methylenecyclopentanone in high yields.169 The nickel-catalysed three-component 3 + 2 + 2-cocyclization of ethyl cyclopropylide-neacetate with two alkynes gave cycloheptadienes in good yields and high chemo- and regio-selectivity.170... 

Thermal reactions of Fischer carbenes with alkynes afford a variety of prodncts depending on the snbstrates. The reactions can be visnalized mechanistically as a [2 -F 2]cycloaddition... 

The first carbene compound to be well characterized was prepared in 1966 and was one of many Fischer-Type Carbene Complexes io be reported (see equation 7). Fischer carbenes are characterized by heteroatom substituents at the carbene carbon, stabilization by a low-valent metal center, and a partial positive charge at the carbene carbon. In contrast, Schrock Type Carbene Complexes, or alkylidenes, that have alkyl substituents, are found on metal centers in higher oxidation states, and are nucleophilic at carbon. Many Fischer carbenes are known for chromium, whereas chromium alkylidenes are much less common. Monohalocarbenes of chromium, for example, (OC)5Cr=C(F)NEt2, have also been extensively investigated. Two carbene reactions of note for their application to organic synthesis are the cycloaddition of alkenes with carbene complexes and the reaction of aromatic carbenes with alkynes to yield complexed naphthols (the Dotz reaction ). ... 

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... 

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. 

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. 

Moreover, the carbene may be constructed directly in the metal coordination sphere, much like Fischer carbene complex synthesis. For example, the cycloaddition of alkynes to amino-functionalised Fischer carbene chromium... 

The Wulff-Ddtz reaction is another approach to the synthesis of the cyclophane system by formal [2 + 2 + 2] cycloaddition. The intramolecular benzannulation of the Fischer carbene complex, which has an alkyne tethered to the a-position of the alkenyl substituent, gave a para-cyclophane in moderate yield under highly diluted conditions (Scheme 8.6) [6]. 

Closely related to the ring-closing metathesis of enynes (Section 3.2.5.6), catalyzed by non-heteroatom-substituted carbene complexes, is the reaction of stoichiometric amounts of Fischer-type carbene complexes with enynes [266,308 -315] (for catalytic reactions, see [316]). In this reaction [2 + 2] cycloaddition of the carbene complex and the alkyne followed by [2 -t- 2] cycloreversion leads to the intermediate formation of a non-heteroatom-substituted, electrophilic carbene complex. This intermediate, unlike the corresponding nucleophilic carbene... 

Particularly interesting is the reaction of enynes with catalytic amounts of carbene complexes (Figure 3.50). If the chain-length between olefin and alkyne enables the formation of a five-membered or larger ring, then RCM can lead to the formation of vinyl-substituted cycloalkenes [866] or heterocycles. Examples of such reactions are given in Tables 3.18-3.20. It should, though, be taken into account that this reaction can also proceed by non-carbene-mediated pathways. Also Fischer-type carbene complexes and other complexes [867] can catalyze enyne cyclizations [267]. Trost [868] proposed that palladium-catalyzed enyne cyclizations proceed via metallacyclopentenes, which upon reductive elimination yield an intermediate cyclobutene. Also a Lewis acid-catalyzed, intramolecular [2 + 2] cycloaddition of, e.g., acceptor-substituted alkynes to an alkene to yield a cyclobutene can be considered as a possible mechanism of enyne cyclization. 

However, the reaction was shown to be catalyzed by a methylidene tungsten-carbene complex rather than the Fischer tungsten carbene complex. They proposed that the reaction would proceed by [2 + 2] cycloaddition of the tungsten carbene complex with the alkyne in Equation (3), ring opening, and another [2 + 2] cycloaddition with the alkene moiety to finally give the cyclized product. 

Whereas Fischer-type chromium carbenes react with alkenes, dienes, and alkynes to afford cyclopropanes, vinylcyclopropanes, and aromatic compounds, the iron Fischer-type carbene (47, e.g. R = Ph) reacts with alkenes and dienes to afford primarily coupled products (58) and (59) (Scheme 21). The mechanism proposed involves a [2 -F 2] cycloaddition of the alkene the carbene to form a metallacyclobutane see Metallacycle) (60). This intermediate undergoes jS-hydride elimination followed by reductive elimination to generate the coupled products. Carbenes (47) also react with alkynes under CO pressure (ca. 3.7 atm) to afford 6-ethoxy-o -pyrone complexes (61). The unstable metallacyclobutene (62) is produced by the reaction of (47) with 2-butyne in the absence of CO. Complex (62) decomposes to the pyrone complex (61). It has been suggested that the intermediate (62) is transformed into the vinylketene complex... 

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 vinylcarbene complexes Cr(CX))5 =C(OEt)C=CXR) (X = NMe2, OEt R = alkyl, aryl) react with alkynes R OCH to form various cyclopenta[b]pyrans.30S In a two step process, addition of the alkynes NEt20Chfe u> the l-metalla-l,3-diene W(CX))s =C(OEt)CHsCHHi) results in metallatriene species that cyclise U) fwm cyclopentadiene complexes 40. Chromium Fischer type alkoxyalkenyl carbene complexes react with ketoalkynes to fcxm bicyclic lactones in a number of different processes involving 8 and 10-e cyclizations. Various dienyl carbene complexes whose parent in Crortho-substituted aromatic alcohols through a variation upon the more usual benzannulation reaction involving alkyne cycloaddition with carbene complexes. ... 

The first ene-yne metathesis was reported by Katz etal. [3], who used a Fischer tungsten-carhene complex. Then, Mori et al. reported a chromium-catalyzed ene-yne metathesis [4]. It was later found that the ruthenium-carhene complexes [Ru]-IV and [Ru]-I were very effective for ene-yne metathesis [5]. The reaction would proceed via a [2 -T 2]-cycloaddition of a ruthenium-carhene complex 3 with an alkyne part to produce ruthenacyclobutene 4, and ring opening of this latter species affords a ruthenium carbene complex 5, which reacts with an alkene part to produce ruthenacyclobutane 6. Subsequent ring opening of 6 gives a cychzed compound 2, and a ruthenium-carbene complex is regenerated (Scheme 6.1, Route 1). The other mechanism considered also involves at first reaction of the... 

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