Carbenes nucleophilic, reactions

In a significant series of reports describing the formation of metathesislike products from cyclopropanes via a carbene retroaddition reaction, Gassman (68) also presented results that were interpreted to mean that carbenes which normally participate in conventional metatheses are negatively polarized (nucleophilic). 

All synthetic methods described up to now (ligand displacement, acac or halo-methyl precursors, metal-bonded carbene + nucleophile, metal-bonded nucleophile + carbene) result in a metal-bonded ylide through the Ca atom. The reactivity of ylides toward metallic systems is, however, greater than anticipated and other reaction pathways could compete with simple C-bonding. 

Keywords Absolute configuration, Amines, Amino acids, Carbenes, Cascade reactions, 2-chloro-2-cyclopropylideneacetates. Combinatorial libraries. Cycloadditions, Cyclobutenes, Cyclopropanes, Diels-Alder reactions. Heterocycles, Michael additions. Nitrones, Nucleophilic substitutions, Peptidomimetics, Palladium catalysis. Polycycles, Solid phase synthesis, Spiro compounds. Thiols... 

Benzene derivatives such as m-methylanisole (40) can be converted to distonic carbene ions. Reaction of 40 with O occurs with loss of H2, generating the conventional carbene anion 41 this anion reacts with molecular fluorine by dissociative ET, followed by nucleophilic attack of F on the methyl group, forming 42. In contrast to phenyhnethylene, 42 has a singlet ground state however, upon protonation it gives rise to the triplet state of m-hydroxyphenyl-methylene. This interesting reaction can be viewed as a spin-forbidden proton-transfer reaction. 

The computed values of Aee and Aen also predict that dimethoxycarbene should be a nucleophilic carbene. Experimentally, dimethoxycarbene does not add at all to electron-rich alkenes (preferring to dimerize instead), but does add readily to electron-poor methyl acrylate and acrylonitrile." Many other nucleophilic reactions of (CH30)2C and related dialkoxycarbenes have been investigated and reviewed by Warkentin." ... 

Butenyl)-, (2,3-dimethyl-3-butenyl)- and (4-pentenyl)-dimethylsilyl)]carbene have been generated by treatment of the corresponding chloromethylsilanes with sodium. Intramolecular [1 + 2] cycloaddition of the carbenic carbon atom to the double bond leads to l-silabicyclo[3.1.0]hexanes and l-silabicyclo[4.1.0]heptanes, respectively, usually in competition with intramolecular C,H insertion (equation 24)56. In contrast, no carbene-derived product could be obtained from (allyldimethylsilyl)carbene. Finally, reaction of chloromethyldimethylvinylsilane with sodium provided, besides the typical products of a Wurtz reaction (103 and 104), a small amount of cyclopropane 106 (equation 26)56. It has been suggested that (dimethylvinylsilyl)carbene (102) isomerizes to silabicyclo[1.1.0]butane 105 by intramolecular cyclopropanation, and nucleophilic ringopening finally leads to 106. 

Other reactions for which a discussion of their structure-reactivity behavior in terms of the PNS has provided valuable insights include nucleophilic addition and substitution reactions on electrophilic alkenes, vinylic compounds, and Fischer carbene complexes reactions involving carbocations and some radical reactions. 

An attempt to generate an amino-aryl carbene 154 from the alkylated phenanthridinium salt 153 (Equation 78) <2006TL531> was unsuccessful due to steric interactions. The actual reaction with a variety of strong, sterically hindered bases/nucleophiles is shown (Equations 79-81). The mesityllithium products proved that a carbene intermediate is not possible. Unlike /-butyl alcohol and hexamethyldisilazane, trimethylbenzene, the conjugate acid of mesityllithium, is not prone to carbene insertion reactions. Electronically this is explained by the planar nature of 153 which serves to lower the lowest unoccupied molecular orbital (LUMO) energy of the iminium moiety. 

Substituted bicyclo[ . 1.0]alkanes may also be obtained by condensation of secondary amines with 2-haloketones. A variety of nucleophilic reactions can be carried out on the intermediate cyclopropaniminium salt 116251 (Scheme 108). Competing alkene scission and cyclopropanation occurs on reaction of enamines with pentacarbonyl-chromium carbene complexes252 (Scheme 109). N-Silylated allylamines and their derived N-silylated enamines undergo rhodium or copper catalysed cyclopropanation by methyl diazoacetate253 (Scheme 110). 

Bis(trifluoromethyl)diazomethane is a reactive, electrophilic compound. It forms adducts with nucleophiles such as amines and phosphines5 and adds to olefins, acetylenes,5 and thiocar-bonyl compounds6 to form heterocycles. It has been used as a source of bis(trifluoromethyl) carbene in reactions with benzene,5 saturated hydrocarbons,7 carbon disulfide,8 and transition metal compounds,8 and it undergoes a unique radical chain reaction with saturated hydrocarbons to form adducts that are hydrazoncs and azines.7... 

Several heteroatom nucleophiles, for example, amines, alcohols, thiols, carboxylates, and dialkylphosphines, undergo Michael addition reactions with alkene- and alkyne-substituted carbene complexes. Reaction of alkyne-substituted chromium carbenes with urea affords products derived from Michael... 

Phenols react with chloroform in the presence of hydroxide ion in water to give o- and jp-hydroxybenzaldehydes. The steps of the reaction are (1) the formation of dichlorocarbene, as shown in Example 4.22 (2) nucleophilic reaction of the phenoxide with the electrophilic carbene and (3) hydrolysis. 

Reactivity (General Topics, Reactions with Electrophiles and Oxidants, Reactions with Nucleophiles and Reducing Agents, Reactions toward Free Radicals, Carbenes, etc., Reactions with Cyclic Transition State, Reactivity of Substituents, Heterocycles as Intermediates in Organic Synthesis). 

Interestingly, cobalt porphyrin catalysts tend to prevent carbene dimerization reactions, and allow cyclopropanation reactions with electron-deficient alkenes. This feature illustrates the more nucleophilic behavior of the carbenoid species formed as compared to typical electrophilic Fischer carbenes. The enhanced nucleophilic character of the carbene reduces its tendency to dimerize and allows reactions with more electron-deficient olefins. 

The carbene 163 exists in resonance with the species 163a. The nucleophilic reaction of 163a with an aldehyde, as shown, forms the 1,4-zwitterion 166. Now, proton transfer from carbon to oxygen generates the 1,3-zwitterion 167, which collapses to 164 after electron reorganization. 

Nucleophilic reactions. 2-Lithio-l,3-dithianes are found to add to styrenes and stilbenes. Access to mononuclear Fischer carbene complexes is realized by the reaction of organolithiums to the CO ligand followed by O-alkylation." ... 

Substitution of CO by phosphines 145 The Dotz reaction 149 Rearrangement reactions with loss of CO 151 Photochemical reactions 153 Reactions at the carbene carbon 158 General features 158 Amine nucleophiles 159 Phospine and phosphite nucleophiles 167 Alcohols and alkoxide ion nucleophiles 171 Thiol and thiolate ion nucleophiles 179 Intramolecular nucleophilic reactions 191 Hydroxide ion and water as nucleophiles 194 Insertion reactions initiated by nucleophilic attack Acid-base reactions at the a-carbon 207 General features and methods 207 Kinetic and thermodynamic acidities 209 Effect of structure on pKa values 210 Intrinsic rate constants for proton transfer 219 Thermodynamic acidities in organic solvents 223 Hydrolysis of ionizable carbene complexes 228 Acknowledgments 232 References 233... 

The reaction of carbenes with CO2 under the conditions of matrix isolation allows to qualitatively estimate the philicity of carbenes. [36] The initial step of this reaction is the nucleophilic attack of the carbene at the CO2 carbon atom. The primary adduct subsequently rearranges to give an a-lactone which is easily identified by IR spectroscopy. [36] Since carbenes act as a nucleophile in this reaction, the reactivity increases with increasing carbene nucleophilicity, and electrophilic carbenes like 2a (R = H), despite being of very high reactivity towards a variety of reactants (see below), can not be carboxylated. We thus... 

Nevertheless, the use of relative reactivities to characterize carbenic philicity is restrictive the apparent philicity is related to the alkenes selected for the relative reactivity measurements. What if the set of alkenes were expanded by the addition of an even more electron-deficient alkene Such a test was applied in 1987 [65], using a-chloroacrylonitrile, 26, which is more 7t-electron deficient than acrylonitrile, 27. We found that PhCF or PhCCl added 15 or 13 times, respectively, more rapidly to 26 than to 27. In preferring the more electron-deficient olefin, the carbenes exhibited nucleophilic character. However, because they also behave as electrophiles toward other alkenes (Table 4), they must in reality be ambiphiles. In fact, we now realize that all carbenes have the potential for nucleophilic reactions with olefins the crucial factor is whether the carbene s filled a orbital (HOMO)/alkene vacant Ji orbital (LUMO) interaction is stronger than the carbene s vacant p orbital (LUMO)/aIkene filled k orbital (HOMO) interaction in the transition state of the addition reaction. [63]... 

The rearrangement of 308b to 311 involves initial nucleophilic attack of the thioxo sulfur to the acetic a carbon atom (species 313). Analogies with the first formal intermediate of the carbene cyclization reaction (species 314) are striking. 

Remarkably, mononitrosyl iron(—II) complexes displayed great potential in the activation of diazo compormds and carbene-transfer reactions [102]. Generally, the activation of diazo compound can be realized by electrophilic transition metal complexes. However, according to the concept of Umpoirmg [103], the electron-rich, nucleophilic iron(—II) compound 31 is expected to react with diazo compounds of electron-poor carbenes, such as ethyl diazoacetate (Scheme 42). At first the iron center would add the C=N bond of the diazo compound followed by release of N2 and formation of the electrophilic iron carbene moiety. The nitrosyl group in such transformations is assumed to support as an ancillary ligand the N2 release by pulling electron density to the iron center. 

The mechanism operating in A-heterocyclic carbene-mediated reactions was proposed initially by Breslow in 1958 for the thiazolium salt-catalyzed benzoin condensation (Scheme 6.1). This proposal involves the formation of a carbene as the catalytically active species by deprotonation of the thiazolium cation, which subsequently adds to one molecule of the aldehyde, generating a nucleophilic intermediate known as the Breslow intermediate. Next, this... 

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