Fischer carbene complexes mechanisms

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 potential of Fischer carbene complexes in the construction of complex structures from simple starting materials is nicely reflected in the next example. Thus, the reaction of alkenylcarbene complexes of chromium and tungsten with cyclopentanone and cyclohexanone enamines allows the di-astereo- and enantioselective synthesis of functionalised bicyclo[3.2.1]octane and bicyclo[3.3.1]nonane derivatives [12] (Scheme 44). The mechanism of this transformation is initiated by a 1,4-addition of the C -enamine to the alkenylcarbene complex. Further 1,2-addition of the of the newly formed enamine to the carbene carbon leads to a metalate intermediate which can... 

S+3C] Heterocyclisations have been successfully effected starting from 4-amino-l-azadiene derivatives. The cycloaddition of reactive 4-amino-1-aza-1,3-butadienes towards alkenylcarbene complexes goes to completion in THF at a temperature as low as -40 °C to produce substituted 4,5-dihydro-3H-azepines in 52-91% yield [115] (Scheme 66). Monitoring the reaction by NMR allowed various intermediates to be determined and the reaction course outlined in Scheme 66 to be established. This mechanism features the following points in the chemistry of Fischer carbene complexes (i) the reaction is initiated at -78 °C by nucleophilic 1,2-addition and (ii) the key step cyclisation is triggered by a [l,2]-W(CO)5 shift. 

Scheme 4. Reaction mechanism of enyne with Fischer carbene complex...

Key words Dotz reaction, benzannulation, Fischer carbene complexes, reaction mechanism, density functional theory... 

Despite the undeniable synthetic value of the benzannulation reaction of aryl and alkenyl Fischer carbene complexes, the details of its mechanism at the molecular level remain to be ascertained. Indeed, although a relatively large number of theoretical studies have been directed to the study of the molecular and electronic structure of Fischer carbene complexes [22], few studies have been devoted to the analysis of the reaction mechanisms of processes involving this kind of complexes [23-30]. The aim of this work is to present a summary of our theoretical research on the reaction mechanism of the Dotz reaction between ethyne and vinyl-substituted hydroxycarbene species to yield p-hydroxyphenol. 

An enantiopure Fischer carbene complex was able to react with 2-methoxyfuran in an intriguing manner that led to the formation of trisubstituted cyclopropane molecules in excellent diastereoselectivities. The relevant mechanism for the formation of a cyclopropane is depicted in Scheme 88 <2007CEJ1326>. 

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. ... 

The reactions of both alkoxy and amino complexes are highly stereoselective and give the unnatural epimer at the C-6 position in the penicillin analogs, but methods are known for inversion at this center, llie mechanism of these reactions is thought to involve the intermediacy of a metal-4cetene complex whose formation is photo-induced.Early indications that this was the case came when it was found these reactions fail to give cyclic products of any kind under thermal conditions. More recently, vi-nylketene complexes have been trapped from these reactions.With the recent realization that metal-ketene intermediates are likely to be involved in these reactions further development of the photo-induced reactions of Fischer carbene complexes can be anticipated. 

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). ... 

For a recent, comprehensive discussion on the mechanism of reactions of Fischer carbene complexes, see C. F. Bemasconi, Adv. Phys. Org. Chem., 2002, 37, 137. 

Equations 10.47 to 10.51 demonstrate several examples of cyclopropanation reactions. As shown in equation 10.47, reaction of Group 6 Fischer carbene complexes with an electron-poor alkene—at a temperature high enough to promote CO dissociation—gives diastereomeric mixtures of cyclopropanes.71 Path a (Scheme 10.6) is the likely mechanism for this reaction, and the first of the two diastereomeric products tends to be favored. 

Although the use of Fischer carbene complexes for cyclopropanation is somewhat limited, there are other procedures that are more general. One such method is the use of cationic alkylidene complexes, with Fe complexes being perhaps the most thoroughly studied. These react at low temperature with a variety of alk-enes bearing alkyl and aryl substituents equation 10.50 shows a typical example with the cationic alkylidene precursor usually generated in situ.74 Path b (Scheme 10.6) has been shown to be the operative mechanism for these reactions.75... 

The early development of Mechanism 3 was bold for its day because Fischer carbene complexes had just been discovered a few years earlier, and alkylidenes were not yet known. The carbene complexes prepared before 1971 also did not catalyze olefin metathesis. With the discovery of Schrock carbene complexes and the demonstration that some alkylidenes could promote metathesis, the non-pairwise mechanism became more plausible (Section 11-1-2). It was, however, the elegant work of Katz and co-workers that provided early substantial support for the Herisson-Chauvin mechanism. 

Casey and Burkhardt reasoned that the metathesis mechanism influenced by Chauvin and Herisson s work was sufficient to explain their results. Complex 13 is interesting in that the pentacarbonyl substitution makes it similar to a traditional Fischer carbene complex, yet it also possesses Schrock character because both substituents at Ccarbene are hydrocarbon fragments. 

A comprehensive treatment of the benzannulation of Fischer carbene complexes with alkynes is not possible in this review, and thus instead the material presented here will hopefully serve to give the reader an overview of its scope and limitations. The first report of this reaction was in 1975 by Dotz in which he describes the formation of the naphthol chromium tricarbonyl complex (236) from the reaction of the phenyl chromium complex (la) with diphenylacetylene. In the intervening years over 100 papers have been published describing various aspects of this reaction.The reaction of the generic cartene complex (233 Scheme 34) with alkynes will serve to focus the organization of the scope and limitations of the benzaimulation reaction. The issues to be considered are (i) the regioselectivity with unsymmetri-cal alkynes (ii) possible mechanisms (iii) applications in natural product syntheses (iv) the effect of substitution on the aryl or alkenyl substituent of the carbene carbon (v) functionality on the alkyne (vi) effects of the solvent and the concentration of the alkyne (vii) tandem applications with other reactions of carbene complexes (viii) reactions where aromatization is blocked (cyclohexadienone annulation) (ix) annulation of aryl versus alkenyl carbene complexes (x) the effect of the ligands L on the metal (xi) the effect of the ancilliary substituent RX and (xii) reactions with —C X functionality. 

The aminolysis of carboxylic esters to which the reaction of Fischer carbene complexes with amines has frequently been compared, typically proceeds by a similar mechanism with rate-limiting deprotonation of the corresponding zwitter-ionic tetrahedral intermediate (59) and so do many SnAt reactions where the deprotonation of the zwitterionic Meisenheimer complex (e.g., 60) is rate... 

The hydrolysis of Fischer carbene complexes such as 11,13,42,87 and 112 has been discussed in the section Hydroxide ion and water as nucleophiles and proceeds by a standard nucleophilic addition-elimination mechanism (equation 74). On the other hand, carbene complexes with ionizable a-carbons are hydrolyzed by a different mechanism which involves the deprotonated carbene complex as the key intermediate. This conclusion is based on a detailed kinetic investigation of the hydrolysis of 66, 68, 144 and 8 in 50% MeCN-50%... 

P-Lactams finm Fischer carbene complexes Scope, limitations, and reaction mechanism 13THC(30)65. 

WuLEF, W. D. Korthals, K. A. Martinez-Alvarez, R. G6mez-Gallego, M. Fernandez, L Sierra, M. A. Study of the ESI-mass spectrometry ionization mechanism of Fischer carbene complexes. J. Org. Chem. 2005, 70, 5269-5211. 

The first report of using RCM to synthesize aromatic compounds seems to be the 1976 report by Katz and Rothchild, who investigated the mechanism of olefin metathesis [3], They synthesized phenanthrene (7) from a 1 1 mixture of 2,2 -divinylbiphenyl (5) and the deuterated derivative 6 by RCM using a Fischer carbene complex (molybdenum catalyst or tungsten catalyst) in one of the experiments to reveal whether metathesis occurred by a pairwise or a nonpairwise mechanism [4] (Scheme 26.1). Although the yield of 7 was only 1 to 2% [5], this experiment clearly demonstrated the possibility of using RCM to synthesize aromatic compounds. 

The mechanism of addition of oxime derivatives to alkynyl Fischer carbene complexes has been studied experimentally and by DFT methods. ... 

The kinetic and thermodynamic properties of Fischer-type carbene complexes have also been addressed by Bernasconi, who relates the strength of the 7r-donor substituent to the thermodynamic acidity [95-101] and the kinetics and mechanism of hydrolysis and reversible cyclization to differences in the ligand X [96,102]. 

Fischer alkenylcarbene complexes undergo cyclopentannulation to alkenyl AT,AT-dimethylhydrazones (1-amino-1-azadienes) to furnish [3C+2S] substituted cyclopentenes in a regio- and diastereoselective way along with minor amounts of [4S+1C] pyrrole derivatives. Enantiopure carbene complexes derived from (-)-8-(2-naphthyl)menthol afford mixtures of trans,trans-cycloipentenes and ds,ds-cyclopentenes with excellent face selectivity [75]. The mechanism proposed for the formation of these cyclopentene derivatives is outlined in Scheme 28. The process is initiated by nucleophilic 1,2-attack of the carbon... 

The regioselective preparation of 2-substltuted naphthalenediol derivatives having the diols differentially protected in a predictable and straightforward manner, previously not directly attainable, is readily accomplished using chromium carbene complexes. First prepared by E. O. Fischer, chromium carbene complexes react readily with alkynes (extensively investigated by K. H. D6tz, and others).3 Steric effects dictate the substitution pattern observed2-4 and the reaction mechanism has been widely studied.2... 

E.O. Fischer s discovery of (CO)sW[C(Ph)(OMe)D in 1964 marks the beginning of the development of the chemistry of metal-carbon double bonds (1). At about this same time the olefin metathesis reaction was discovered (2), but It was not until about five years later that Chauvln proposed (3) that the catalyst contained an alkylidene ligand and that the mechanism consisted of the random reversible formation of all possible metallacyclobutane rings. Yet low oxidation state Fischer-type carbene complexes were found not to be catalysts for the metathesis of simple olefins. It is now... 

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