Carbenes isolation

The reactivity of carbenes is strongly influenced by the electronic properties of their substituents. If an atom with a lone pair (e.g. O, N, or S) is directly bound to the carbene carbon atom, the electronic deficit at the carbene will be compensated to some extent by electron delocalization, resulting in stabilization of the reactive species. If both substituents are capable of donating electrons into the empty p orbital of the carbene, isolable carbenes, as e.g. diaminocarbenes (Section 2.1.6), can result. The second way in which carbenes can be stabilized consists in complexation. The shape of the molecular orbitals of carbenes enable them to act towards transition metals as a-donors and 71-acceptors. The chemical properties of the resulting complexes will also depend on the electronic properties of the metallic fragment to which the carbene is bound. Particularly relevant for the reactivity of carbene complexes are the ability of the metal to accept a-electrons from the carbene, and its capacity for back-donation into the empty p orbital of the carbene. 

Note that the other type of aromatic carbene isolated by Enders et al.," namely, the l,2,4-triazol-5-ylidene (Vila) is stable enough to be prepared by thermal elimination at 80 °C, and it became the first carbene to be commercially available. 

Burling S, Mahon MF, PoweU B-E, Whittlesey MK, WUhams JMJ. Ruthenium induced C—N bond activation of an N-heterocyclic carbene isolation of C- and N-bound tautomers. J Am Chem Soc. 2006 128 13702-13703. 

Chiefly in an hydrophobic medium, a base can extract the proton on position 2 leading to a reactive intermediate (able to give subsequent condensation) that could be an ylid (35, 36) or a carbene (37), though no dimer has ever been isolated as is the case with benzothiazolium (32, 38). Two mechanisms have been proposed for explaining the particular reactivity of thiazolium ... 

Carbenes are too reactive to be isolated and stored but have been trapped m frozen argon for spectroscopic study at very low temperatures... 

Hydrogen atoms in azolium ions can be removed easily as protons (e.g. 230—>232) exchange with deuterium occurs in heavy water. The intermediate zwitterion (e.g. 231) can also be written as a carbene, and in some cases this carbenoid form can be trapped or isolated as a dimer. 

Several years ago, there was much debate concerning the mechanism of the Darzens condensation.2.3 The debate concerned whether the reaction employed an enolate or a carbene intermediate. In recent years, significant evidence that supports the enolate mechanism has been obtained, wherein the stabilized carbanion (11) of the halide (10) is condensed with the electrophile (12) to give diastereomeric aldolate products (13,14), which subsequently cyclize via an internal Sn2 reaction to give the corresponding oxirane (15 or 16). The intermediate aldolates have been isolated for both a-fluoro- and a-chloroesters 10. 

Ciamician and Dennstedt reacted the potassium salt of pyrrole with chloroform in ether and isolated, after much purification, 3-chloropyridine, which was confirmed by crystallization with platinum. While the pyrrole salt can be used as the base, the chloroform carbene is typically formed with an alkali alcohol. Forty years later, Robinson and co-workers made 3-chloroquinolines from indoles using the Ciamician-Dennstedt reaction. ... 

The only known reaction of a furan with a dihalocarbene is that recently reported between benzofuran and dichlorocarbene in hexane at 0°. The initial adduct (7) could not be isolated but on hydrolysis gave the ring-expanded product 8, possibly via 9, in 15% yield. Benzothiophene was recovered in 92% yield under the same conditions. 2,5-Dihydrofuran reacted with dichloro- and dibromo-carbene to give the products of allylic insertion, 2-dihalogenomethyl-2,5-dihydrofuran, as well as the normal addition products. ... 

Isothiazole forms the carbenes upon treatment of its lithium salt with [CfiF5Au(THT)] and methyl triflate while the C-coordinated complex formed before methylation was not isolated. When [Ph3PAuCl] is used as the precursor, both C-coordinated complex and then carbene can be prepared (95JCS(D)2067). 

The first reaction pathway for the in situ formation of a metal-carbene complex in an imidazolium ionic liquid is based on the well loiown, relatively high acidity of the H atom in the 2-position of the imidazolium ion [29]. This can be removed (by basic ligands of the metal complex, for example) to form a metal-carbene complex (see Scheme 5.2-2, route a)). Xiao and co-workers demonstrated that a Pd imida-zolylidene complex was formed when Pd(OAc)2 was heated in the presence of [BMIMjBr [30]. The isolated Pd carbene complex was found to be active and stable in Heck coupling reactions (for more details see Section 5.2.4.4). Welton et al. were later able to characterize an isolated Pd-carbene complex obtained in this way by X-ray spectroscopy [31]. The reaction pathway to the complex is displayed in Scheme 5.2-3. 

Yet another kind of alkene addition is the reaction of a carbene with an alkene to yield a cyclopropane. A carbene, R2C , is a neutral molecule containing a divalent carbon with only six electrons in its valence shell. It is therefore highly reactive and is generated only as a reaction intermediate, rather than as an isolable molecule. Because they re electron-deficient, carbenes behave as electrophiles and react with nucieophiiic C=C bonds. The reaction occurs in a single step without intermediates. 

The preparative value of this compound lies in the surprising fact that bis(l,3-diphenylimidazolidinylidenc-2) behaves in many reactions ie.g., with aromatic aldehydes,2,7 and with carbon acids 2 7-fJ) as if it dissociated to form a nucleophilic carbene. The hydrolytic cleavage of these derived imidazolidine derivatives makes possible the preparation of formyl compounds, so that the amino olefin can be considered as a potential carbonyla-tion reagent. In many reactions it is not necessary to isolate... 

Dichlorocarbene, generated by the action of 50 % potassium hydroxide on chloroform, adds to ethyl 1 W-azepine-l-carboxylate to furnish the all /rntu-trishomoazepine 12 in 35% yield280 (see Houben-Weyl, Vol. E 19b, p 1523). Subsequently, and as a result of a careful and detailed study of the addition of dichlorocarbene generated by the thermal decomposition of phenyl(trichloromethyl)mercury, it was deduced that carbene addition takes place sequentially in the order C4 —C5, C2—C3 and C6 — Cl. The intermediary mono- 10 and bis(dichlorocar-bene) 11 adducts have been isolated and characterized. 

Does a Silylene-Complex exist This rhetorical question is the title of a theoretical paper published in 1983 [84], As a result of an ab-initio calculation, the authors came to the conclusion that a moderately positive answer can be given. However, silylene complexes are thermodynamically less stable than carbene complexes (the MSi bond energy for the hypothetical complex (OC)5Cr = Si(OH)H is 29.6 kcal/mol, the bond energy of the MC bond in (OC)5Cr = C(OH)H is 44.4 kcal/mol) [85], and therefore silylene complexes should be difficult to isolate. 

NITRILE OXIDES. Nitrile oxides are a well known class of compds represented by R.C N- 0, and are usually prepd by treating hydroxamic acid chlorides with a mild alkali, thus eliminating HQ (Ref 2). Wieland (Refs 1 3) was responsible for the first isolation of free nitrile oxides. These compds are somewhat unstable, showing a marked tendency to dimerize to (he corresponding furoxanes (1,3-dipolar addition) (Refs 2 3). The nitrile oxides add to a considerable number of carbenes, as benzonitrUe oxide (for example) to a large number of olefins in ether at 20° (Ref 3)... 

Carbenes - molecules with a neutral dicoordinate carbon atom - play an important role in all fields of chemistry today. They were introduced to organic chemists by Doering and Hoffmann in the 1950s [1] and to organometallic chemists by Fischer and Maasbol about 10 years later [2,3]. But it took another 25 years until the first carbenes could be isolated [4-8] examples are given in Scheme 1. 

The report of the successful isolation of a stable carbene by Arduengo in 1991 [6,7] (Scheme 1,1) and the realization of the extraordinary properties of these... 

Other examples of [2C+2S+1C0] cycloaddition reactions have been described by Herndon et al. by the use of chromium cyclopropyl(methoxy)carbenes. These complexes react with alkynes releasing ethene and forming cyclopenta-dienone derivatives, which evolve to cyclopentenone derivatives in the presence of chromium(O) and water [122] (Scheme 76). This reaction has been extended to intramolecular processes and also to the synthesis of some natural products [123]. These authors have also described another process involving a formal [2C+2S+1C0] cycloaddition reaction. Thus, the reaction of methyl and cyclo-propylcarbene complexes with phenylacetylene derivatives does not afford the expected benzannulated products, and several regioisomers of cyclopentenone derivatives are the only products isolated [124] (Scheme 76). 

J-Oxygen-functionalised sp3 organolithium compounds react with alkenyl-carbene complexes to generate the corresponding cyclic carbene complexes in a formal [3+3] process (see Sect. 2.8.1). In those cases where the organolithium derivative contains a double bond in an appropriate position, tricyclic ether derivatives are the only products isolated. These compounds derive from an intramolecular cyclopropanation of the corresponding cyclic carbene complex intermediate [89] (Scheme 83). 

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