Carbenoids, metal-stabilized, reaction

Reactions of metal-stabilized carbenoids with pyrroles 95M12. 

CONTENTS Reaction of Metal Stabilized Carbenoids with ... 

A select number of transition metal compounds are effective as catalysts for carbenoid reactions of diazo compounds (1-3). Their catalytic activity depends on coordination unsaturation at their metal center which allows them to react as electrophiles with diazo compounds. Electrophilic addition to diazo compounds, which is the rate limiting step, causes the loss of dinitrogen and production of a metal stabilized carbene. Transfer of the electrophilic carbene to an electron rich substrate (S ) in a subsequent fast step completes the catalytic cycle (Scheme I). Lewis bases (B ) such as nitriles compete with the diazo compound for the coordinatively unsaturated metal center and are effective inhibitors of catalytic activity. Although carbene complexes with catalytically active transition metal compounds have not been observed as yet, sufficient indirect evidence from reactivity and selectivity correlations with stable metal carbenes (4,5) exist to justify their involvement in catalytic transformations. 

The understanding of this catalysis started in 1952, shortly after the concept of carbenes was introduced (see Sect. 8.1). Yates postulated that transition-metal catalysts react with diazo compounds by formation of transient electrophilic metal carbenes, because that complex can be depicted as a metal-stabilized carbocation (8.104). Doyle (1986 a) proposed the catalytic cycle (8-46) for the formation of the carbenoid 8.104 and its reaction with an electron-rich substrate S . The reagent S is, first of all, an alkene in cyclopropanation, but can also belong to other groups of compounds, to be discussed later in this section. 

Arenes suffer dearomatization via cyclopropanation upon reaction with a-diazocarbonyl compounds (Btlchner reaction) [76]. Initially formed norcaradiene products are usually present in equilibrium with cycloheptatrienes formed via electrocyclic cyclopropane ring opening. The reaction is dramatically promoted by transition metal catalysts (usually Cu(I) or Rh(II) complexes) that give metal-stabilized carbenoids upon reaction with diazo compounds. Inter- and intramolecular manifolds are known, and asymmetric variants employing substrate control and chiral transition metal catalysts have been developed [77]. Effective chiral catalysts for intramolecular Buchner reactions include Rh Cmandelate), rhodium carboxamidates, and Cu(I)-bis(oxazolines). While enantioselectivities as high as 95% have been reported, more modest levels of asymmetric induction are typically observed. 

Interaction of an electrophilic carbene or carbenoid with R—S—R compounds often results in the formation of sulfonium ylides. If the carbene substituents are suited to effectively stabilize a negative charge, these ylides are likely to be isolable otherwiese, their intermediary occurence may become evident from products of further transformation. Ando 152 b) has given an informative review on sulfonium ylide chemistry, including their formation by photochemical or copper-catalyzed decomposition of diazocarbonyl compounds. More recent examples, including the generation and reactions of ylides obtained by metal-catalyzed decomposition of diazo compounds in the presence of thiophenes (Sect. 4.2), allyl sulfides and allyl dithioketals (Sect. 2.3.4) have already been presented. 

Insertion of phenyl, trimethylsilyl, and nitrile-stabilized metalated epoxides into zircona-cyclcs gives the product 160, generally in good yield (Scheme 3.37). With trimethylsilyl-substituted epoxides, the insertion/elimination has been shown to be stereospecific, whereas with nitrile-substituted epoxides it is not, presumably due to isomerization of the lithiated epoxide prior to insertion [86]. With lithiated trimethylsilyl-substituted epoxides, up to 25 % of a double insertion product, e. g. 161, is formed in the reaction with zirconacyclopentanes. Surprisingly, the ratio of mono- to bis-inserted products is little affected by the quantity of the carbenoid used. In the case of insertion of trimethylsilyl-substituted epoxides into zirconacydopentenes, no double insertion product is formed, but product 162, derived from elimination of Me3SiO , is formed to an extent of up to 26%. 

Carbene complexes can be prepared by reaction of stabilized carbenes or carbenoids (e.g. a-haloorganolithium compounds) with transition metal complexes [610]. This method is particularly useful for the preparation of donor-substituted... 

In view of the limited stability of the "carbenoid" LiCsCCb Cl, functionalization reactions have to be carried out a temperatures that are as low as possible Silylations of metallated acetylenes are usually rather slow in E12O at temperatures below -20 C. A small amount of HMPT appears to cause a considerable enhancement of the rates of silvlation with trimethylchlorosilane. It is not known whether this effect is only due to the typical properties of HMPT as a dipolar aprorir solvent (also shown in alkylation with alkyl halides) or whether it is a result of active participation of this solvent in the reaction as depicted in the following equations ... 

Chiral rhodium(II) oxazolidinones 5-7 were not as effective as Rh2(MEPY)4 for enantioseleetive intramolecular cyclopropanation, even though the sterie bulk of their chiral ligand attachments (COOMe versus /-Pr or C Ph) are similar. Significantly lower yields and lower enantiomeric excesses resulted from the decomposition of 11 catalyzed by either Rh2(4S-IPOX)4, Rh2(4S-BNOX)4, or Rh2(4R-BNOX)4 (Table 3). In addition, butenolide 12, the product from carbenium ion addition of the rhodium-stabilized carbenoid to the double bond followed by 1,2-hydrogen migration and dissociation of RI12L4 (Scheme II), was of considerable importance in reactions performed with 5-7 but was only a minor constituent ( 1%) from reactions catalyzed by Rh2(5S-MEPY)4. This difference can be attributed to the ability of the carboxylate substituents to stabilize the earboeation form of the intermediate metal carbene. 

The halogen-metal exchange of one of a geminal pair of bromine atoms is readily achieved -a carbenoid is formed which may have sufficient stability to react as an organolithium before decomposing to a carbene by a-elimination.. m in cyclic systems, diastereoselectivity in this process has long been known,114116 though the outcome of reactions such as that of 137 is under a mixture of kinetic and thermodynamic control.117... 

The series 6 diphosphiranes are stabilized by transition metal complexes and are prepared by [2 + l]-cycloaddition reactions of carbenoids to diphosphene complexes. 

In view of the remarkable stability of metal homoenolates of esters, the existence of homoenolate species containing a 3-halo substituent, i.e. zinc carbenoid moiety connected to an ester group, appeared to be possible. Indeed, when a silyl ketene acetal is treated with a carbenoid generated from CHBrj and Et2Zn, two types of highly intriguing reactions ensue [58]. With a purely aliphatic substrate, Eq. (61), an alkyl cyclopropylcarboxylate due to intramolecular p-CH-insertion of the intermediate zinc carbenoid formed. When the substrate contained an olefmic double bond in the vicinity of the carbenoid function, Eq. (62), in particular an intermediate derived from an a,P-unsaturated ester, internal cyclo-propanation occurred to give bicyclic or tricyclic product (Table 15). 

The carbenes produced by the means described in Sections 5.3.1-5.3.4 are initially in the singlet state, but they can relax to the triplet ground state if reaction does not occur first The Simmons-Smith reaction produces a carbenoid, in which a carbene is stabilized by association with a metal, which reacts as a singlet carbene. It is possible to produce a triplet carbene directly through a process known as sensitization, in which a photoexcited triplet molecule S transfers energy to a carbene precursor and returns to its ground (singlet) electronic state. Conservation of electron spin requires that the carbene be produced in its triplet state (Scheme 5.18). 

It is well established that the reaction of carbenoids with At-alkylindoles delivers zwitterionic intermediates. The reason why this scenario is favored can be ascribed to the fact that the positive charge of the intermediate is stabilized by the electron-rich indole while the negative charge is stabilized by the carbenoid component. In other words, the site of C3 is highly reactive in metal carbenoid insertion reactions. In 2010, Lian and Davies described such a process in their seminal work on Rh-catalyzed [3 + 2] annulation of indoles. In the presence of 1,2-dimethylindole 53, Rh2(S-DOSP)4 induced the decomposition of methyl a-phenyl-a-diazoacetate la and C—H bond insertion of indole, providing the C3 functionalization product 54 in 95% yield but negligible asymmetric induction (<5% ee). It is proposed that the poor chiral induction in the formation of C—H bond insertion product 54 can be attributed to the rapid proton transfer from the zwitterionic intermediate A to the achiral enol B, which can further tautomerize into the observed C—H bond insertion product 54 (Scheme 1.18). 

Generation of carbenoids. The Simmons-Smith reaction produces a carbene equivalent that is stabilized by association with a metal and that reacts as a singlet carbene. ... 

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