Carbenoids typical reactions

Whereas carbenoid character is definitely present in metalated alkyl vinyl ethers, lithiated alkyl and aryl vinyl sulfides and thioesters, which are easily available by hydrogen-lithium exchange, do not display carbenoid-typical reactions . They rather behave like nucleophilic reagents, so that their discussion is beyond the scope of this overview despite their utility in synthesis The same appiies to various derivatives of enamines, deprotonated in the vinyiic a-nitrogen position - . 

Another carbenoid-typical reaction of a-lithiated epoxides is the 1,2-hydrogen shift, illustrated in Scheme 14. Two mechanistic pathways offer an explanation for the formation of the lithium enolate 94 First, the route via the a-ring opening of the epoxide followed by an 1,2-hydride shift in the carbene 93, and second, the electrocyclic ring opening of an oxiranyl anion 95 to an enolate anion 94. Both mechanisms are in accordance with different experimental... 

Muller et al. have also examined the enantioselectivity and the stereochemical course of copper-catalyzed intramolecular CH insertions of phenyl-iodonium ylides [34]. The decomposition of diazo compounds in the presence of transition metals leads to typical reactions for metal-carbenoid intermediates, such as cyclopropanations, insertions into X - H bonds, and formation of ylides with heteroatoms that have available lone pairs. Since diazo compounds are potentially explosive, toxic, and carcinogenic, the number of industrial applications is limited. Phenyliodonium ylides are potential substitutes for diazo compounds in metal-carbenoid reactions. Their photochemical, thermal, and transition-metal-catalyzed decompositions exhibit some similarities to those of diazo compounds. 

Another feature of carbenoid-type reactivity is the cyclopropanation (reaction c). Again, this reaction does not only take place in vinylidene but also in alkyl carbenoids . On the other hand, the intramolecular shift of a /3-aryl, cyclopropyl or hydrogen substituent, known as the Fritsch-Buttenberg-Wiechell rearrangement, is a typical reaction of a-lithiated vinyl halides (reaction d) . A particular carbenoid-like reaction occurring in a-halo-a-lithiocyclopropanes is the formation of allenes and simultaneous liberation of the corresponding lithium halide (equation 3). ... 

No matter how they are generated, carbenes and carbenoids undergo four typical reactions. The most widely used reaction is cyclopropanation, or addition to... 

The second typical reaction of carbenes is insertion into a C H a bond. This three-centered reaction is similar to cyclopropanation, except that the carbene latches onto a a bond instead of a 77 bond. Again, both carbenes and carbenoids can undergo this reaction. It is most useful when it occurs in intramolecular fashion. If the C of the C-H bond is stereogenic, the reaction proceeds with retention of configuration. 

No matter how they are generated, carbenes and carbenoids undergo four typical reactions. The most widely used reaction is cyclopropanation, or addition to a TT bond. The mechanism is a concerted [2 + 1] cycloaddition (see Chapter 4). The carbenes derived from chloroform and bromoform can be used to add CX2 to a 7T bond to give a dihalocyclopropane, while the Simmons-Smith reagent adds CH2. Carbenoids generated from diazoalkanes with catalytic Rh(II) or Cu(II) also undergo cyclopropanations. 

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. 

Vinylidenecarbene or allenylidene3 (R)2C=C=C has a lance-shaped, unsubstituted and sp-hybridized carbene center and, therefore, will not be easily subject to steric hindrance in its insertion reactions. On this assumption, (2-methyljpropenylidenecarbene or its carbenoid was chosen as a prototype of typical vinylidenecarbenes and its insertion reaction with several different types of alkoxides was investigated by employing two methods (A and B, Scheme 10) for carbene generation.20 The insertion products 20 were obtained almost exclusively except lithium allyloxide (Table 4, entry 10).21 By-products such as propargyl ether and allenyl ether were not formed at all. To be noted here, in... 

The electrophilic reactivity of lithium carbenoids (reaction b) becomes evident from their reaction with alkyl lithium compounds. A, probably metal-supported, nucleophilic substitution occurs, and the leaving group X is replaced by the alkyl group R with inversion of the configuration . This reaction, typical of metal carbenoids, is not restricted to the vinylidene substitution pattern, but occurs in alkyl and cycloalkyl lithium carbenoids as well ". With respect to the a-heteroatom X, the carbenoid character is... 

A conversion typical of a-halo-a-lithioaUcanes is the formation of epoxides that results from their reaction with aldehydes or ketones. As illustrated in equation 61, the bromo-lithium carbenoid is usually generated by halogen-lithium exchange. The intermediate lithium aUcoxide 113 undergoes an in situ ring closure to give the oxirane 114 . 

The introduction of umpoled synthons 177 into aldehydes or prochiral ketones leads to the formation of a new stereogenic center. In contrast to the pendant of a-bromo-a-lithio alkenes, an efficient chiral a-lithiated vinyl ether has not been developed so far. Nevertheless, substantial diastereoselectivity is observed in the addition of lithiated vinyl ethers to several chiral carbonyl compounds, in particular cyclic ketones. In these cases, stereocontrol is exhibited by the chirality of the aldehyde or ketone in the sense of substrate-induced stereoselectivity. This is illustrated by the reaction of 1-methoxy-l-lithio ethene 56 with estrone methyl ether, which is attacked by the nucleophilic carbenoid exclusively from the a-face —the typical stereochemical outcome of the nucleophilic addition to H-ketosteroids . Representative examples of various acyclic and cyclic a-lithiated vinyl ethers, generated by deprotonation, and their reactions with electrophiles are given in Table 6. 

In view of the limited stability of the "carbenoid" LiCsCCP Cl, functionalization reactions have to be carried out a temperatures Lhat are as low as possible. Silylations of meiallated acetylenes are usually rather slow in Et20 at temperatures below -20 C. A small amount of HMPT appears to cause a considerable enhancement of the rates of silylatton with tri-methylchlorosilane. It is not known whether this effect is only due 10 the typical properties of HMPT as a dipolar aprotic 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 ... 

Bis(dialkylamino)cyclopropenylium magnesium halides, like their lithium counterparts, react as nucleophiles in various reactions, but their use is much less extensive. Like typical Grignard reagents they undergo hydrolysis, alkylation and reactions with carbonyl compounds at the carbenoid carbon (equation 292)357. 

The cyclopropanation of alkenes, alkynes, and aromatic compounds by carbenoids generated in the metal-catalyzed decomposition of diazo ketones has found widespread use as a method for carbon-carbon bond construction for many years, and intramolecular applications of these reactions have provided a useful cyclization strategy. Historically, copper metal, cuprous chloride, cupric sulfate, and other copper salts were used most commonly as catalysts for such reactions however, the superior catalytic activity of rhodium(ll) acetate dimer has recently become well-established.3 This commercially available rhodium salt exhibits high catalytic activity for the decomposition of diazo ketones even at very low catalyst substrate ratios (< 1%) and is less capricious than the old copper catalysts. We recommend the use of rhodium(ll) acetate dimer in preference to copper catalysts in all diazo ketone decomposition reactions. The present synthesis describes a typical cyclization procedure. 

A related allylic C-H insertion that has considerable promise for strategic organic synthesis is the reaction with enol silyl ethers [23]. The resulting silyl-protected 1,5-dicarbonyls would otherwise typically be formed by means of a Michael addition. Even though with ethyl diazoacetates vinyl ethers are readily cyclopropanated [l],such reactions are generally disfavored in trisubstituted vinyl ethers with the sterically crowded donor/acceptor carbenoids [23]. Instead, C-H insertion predominates. Again, if sufficient size differentiation exists at the C-H activation site, highly diastereoselective and enantioselective reactions can be achieved as illustrated in the reaction of 20 with 17 to form 21 [23]. 

The Cu(I)-catalyzed decomposition of (alkynyloxysilyl)diazoacetates 119 furnishes the silaheterocycles 120 and/or 121 (equation 30) in modest yield63. In these cases, the photochemical extrusion of nitrogen from 119 does not lead to defined products and the thermal reaction is dominated by the 1,3-dipolar cycloaddition ability of these diazo compounds. In mechanistic terms, carbene 122 or more likely a derived copper carbene complex, is transformed into cyclopropene 123 by an intramolecular [1 + 2] cycloaddition to the triple bond. The strained cyclopropene rearranges to a vinylcarbene either with an exo-cyclic (124) or an endocyclic (125) carbene center, and typical carbene reactions then lead to the observed products. Analogous carbene-to-carbene rearrangements are involved in carbenoid transformations of other alkynylcarbenes64. 

While there can be no doubt that dihalomethylenes are readily formed by the action of bases on haloforms such as bromodichloro-methane (equation 7), relatively minor structural changes can make carbene formation unfavourable relative to other modes of decomposition, even though the reaction products are those typical of carbenoid reactions. 

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