Generation of Aryl Carbenes

21 kJ mol. A brief review of this and related work with 2-aminophenylcarbene has been published.  

Photolysis of a 1 1 complex of copper(II) with 5-trimethylsilyl-l,3-phenylene-bis[diazo(4-pyridyl)methane] produces a ferromagnetic chain with an alternating array of the 3d spins of Cu(II) and the 2p spins of the quintet dicarbenes. The diazirine radioligand (34) has been synthesized as a photoaflinity probe for NADHrubiquinone oxidoreductase, to help define the structure of the pyridaben-inhibition site.  

2 Generation of Aryl Carbenes - A review has been published of studies of the fluorescence spectroscopy and the determination of zero-field splitting 

Laser flash-photolysis investigations have been carried out for benzylchloro-carbene, phenylchlorocarbene, methoxyphenylcarbene and fluorenylidene, and some other carbenes, generated from diazirine, diazo and other precursors, in the presence of oxiranes and thiiranes. These carbenes abstract oxygen or sulfur atoms with bimolecular rate constants in the range 10 to 10 s  

The carbenes (23 R = H, Me) have been generated in Ar matrices at 10 K, by visible light irradiation of the diazoanthrone precursors. The carbenes were identified by trapping with O2, comparison of IR and UV-visible spectra with those of the parent anthronylidene, and by comparison of the IR spectra with spectra calculated by DFT methods. Further irradiation of the carbenes with visible or UV light induces hydrogen migration and rearrangement to the quinone methides (24 R = H, Me). 

In a laser flash-photolysis study, 2-phenyladamantene was generated in benzene at room temperature from 3-noradamantyl(phenyl)diazomethane. This strained cycloalkene decays with second-order kinetics to give a dimer, and reacts much faster with O2 and Bu3SnH than with methanol, thus revealing a substantial radical character. Diphenyldiazomethanes possessing stable /er -butylaminoxyl and Ullman s nitronyl nitroxide radicals, e.g. (25), have been prepared by photolysis of the parent diazomethanes. Analysis of ESR fine structures showed that the carbene and radical centres couple ferromagnetically in these molecules, as expected. 

A range of (phosphino)(aryl)carbenes (20 R = i-Pr, c-hexyl V, W, X, Y, Z = various combinations of H, F, Me, CF3, NMe2) have been generated by photolysis of their diazo precursors. The substituent effects on carbene stability were investigated both experimentally and theoretically. The presence of an acceptor and also a spectator aryl substituent resulted in stable or at least persistent carbenes, which could be characterized by standard spectroscopic techniques, whereas a donor aryl ring produced a very fleeting carbene. 

Triplet sensitization of two 1,2-diaryIdiazoethanes in methanol solution gave rise to stilbenes, by intramolecular 1,2-H shifts, and ethers, by reaction of the corresponding carbenes with methanol.This method of generating the intermediate carbenes bypasses the singlet excited diazo compounds, and thus eliminates the possibility that the products arise by direct reaction of these excited species. The results go some way towards establishing that 1,2-H and 1,2-C shifts can compete with alcohol trapping of a spin-equilibrated carbene. 

A study of aryl(acyloxy)carbenes, generated photolytically from diazirine 

A number of biochemical probes containing diazirine moieties as arylcarbene precursors have been synthesized. These include a photolabile oligodeoxyribonu-cleotide, a photoactivatable antagonist for the binding site of the tachykinin NK2 receptor, and a biotinylated lactose derivative as a photoprobe for GM3 synthase.  

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The photochemical generation of aryl carbenes for potential use as organic ferromagnets has been reported. 

An interesting class of covalent tnflates are vinyl and aryl or heteroaryl triflates Vinyl tnflates are used for the direct solvolytic generation of vinyl cations and for the generation of unsaturated carbenes via the a-elimination process [66] A triflate ester of 2-hydroxypyndine can be used as a catalyst for the acylation of aromatic compounds with carboxylic acids [109] (equation 55)... 

Cycloaddition of aryl imines 155 with diazomethane followed by oxidation of the intermediate triazoline with potassium permanganate afforded l-(4-methylsulfonylphenyl)-5-ary 1-1,2,3-triazoles 156 <05JHC33>. l,2,3-Triazolo-3 -deoxycarbanucleosides and their analogs were prepared efficiently by palladium(0)-catalyzed reactions <05T11744>. Base-induced generation of aryl(l,2,3-triazol-lyl)carbenes from l-[(7V-phenylsulfonyl)benzohydrazonoyl)-... 

Generation of gold carbene was also shown to proceed via internal redox processes involving homopropargylic sulfoxides (Scheme 11.10). The carbenoid can then be trapped by insertion into an aryl C-H bond or alkyl 1,2-... 

F. Nawaz, K. Mohanan, L. Charles, M. Rajzmann, D. Boime, O. Chuzel, J. Rodriguez, Y. Coquerel, Temporary intramolecular generation of pyridine carbenes in metal-free three-component C-H bond functionalization/aryl-transfer reactions, Chem. Eur. J. 19 (2013) 17578-17583. 

As with phenylcarbene (35) (c/. Scheme 5), the ring expansion of phenylnitrene (75) could occur directly on the singlet potential energy surface or via a bicycHc intermediate, in this case azirine 92. Such azirines were first detected in the matrix photolysis of 1- and 2-azidonaphthalene. For example, photolysis of 93 generated a photoproduct with an IR absorption at 1730 cm, which in turn gave a cyclic ketenimine [v(C=C=N) at 1926 cm ] on further photolysis. It was proposed that the intermediate with the 1730 cm IRband was the tricyclic azirine 94, which subsequently rearranged to 95. At the time of these experiments, however, reliable computations of IR transitions were not available, so a definitive identification of the azirines was scarcely possible. Nevertheless, a clear parallel was found here with the behavior of aryl carbenes, which give detectable cyclopropenes in the naphthalene series (c/. 44 and 45) but not with the monocyclic carbenes (see the brief discussion of this point in Section 14.4). 

The superior donor properties of amino groups over alkoxy substituents causes a higher electron density at the metal centre resulting in an increased M-CO bond strength in aminocarbene complexes. Therefore, the primary decarbo-nylation step requires harsher conditions moreover, the CO insertion generating the ketene intermediate cannot compete successfully with a direct electro-cyclisation of the alkyne insertion product, as shown in Scheme 9 for the formation of indenes. Due to that experience amino(aryl)carbene complexes are prone to undergo cyclopentannulation. If, however, the donor capacity of the aminocarbene ligand is reduced by N-acylation, benzannulation becomes feasible [22]. 

Another successful approach to catalyst immobilisation involves attachment of the carbene precursor to a peptide on solid support. Treatment with base generates the corresponding carbenes that undergo in situ complexation to Pd(ll) centres (Scheme 6.33). Again, the main drawback of this approach was the low reactivity of the catalytic system that only allowed the coupling of aryl iodides and bromides [116], The reasons for this outcome are in need of further studies. 

The first examples of microwave-assisted cross-couplings with organozinc compounds were recently reported [47]. In addition, the first high-speed synthesis of aryl boronates (Suzuki coupling reactants) has been performed under the action of single-mode irradiation with an in-situ-generated palladium carbene catalyst [48],... 

Aryl(trimethylsiloxy)carbenes. Acylsilanes (153) undergo a photoinduced C —> O silyl shift leading to aryl(trimethylsiloxy)carbenes (154).73,74 The carbenes 154 can be captured by alcohols to form acetals (157) 73 or by pyridine to give transient ylides (Scheme 29).75 LFP of 153 in TFE produced transient absorptions of the carbocations 155 which were characterized by their reactions with nucleophiles.76 The cations 155 are more reactive than ArPhCH+, but only by factors < 10. Comparison of 154 and 155 with Ar(RO)C and Ar(RO)CH+, respectively, would be of interest. Although LFP was applied to generate methoxy(phenyl)carbene and to monitor its reaction with alcohols,77 no attempt was made to detect the analogous carbocation. 

As mentioned in Sections 3.1.6 and 4.1.3, cyclopropenes can also be suitable starting materials for the generation of carbene complexes. Cyclopropenone di-methylacetal [678] and 3-alkyl- or 3-aryl-disubstituted cyclopropenes [679] have been shown to react, upon catalysis by Ni(COD)2, with acceptor-substituted olefins to yield the products of formal, non-concerted vinylcarbene [2-1-1] cycloaddition (Table 3.6). It has been proposed that nucleophilic nickel carbene complexes are formed as intermediates. Similarly, bicyclo[1.1.0]butane also reacts with Ni(COD)2 to yield a nucleophilic homoallylcarbene nickel complex [680]. This intermediate is capable of cyclopropanating electron-poor alkenes (Table 3.6). 

Thermolysis of aryl chloro diazirine (18) in the presence of acetone and a trapping agent such as A -phenylmaleimide gave rise to cycloadducts such as 41. The unstable adduct hydrolyzed during purification resulting in synthesis of bicyclic hemiacetals 42 and 43 as a mixture of endo and exo adducts in 37 and 8% yield, respectively. The exclusive generation of the singlet carbene was confirmed by low-temperature electron spin resonance (ESR) study of the irradiated diazirine. 

Saito et al. <1995S87> described a new method for the synthesis of heterocycle-fused[c]thiophenes via reaction of aryl heteroaryl thioketones with the carbene precursors. Heteroaromatic thioketones A react with carbenoids generated from bis(arylsulfonyl)diazomethanes or phenyliodonium bis(phenylsulfonyl)methylides to give heterocycle-fused[f]thiophenes B. The reaction involves the ring closure of the intermediary thiocarbonyl ylides, followed by restorative aromatization via the elimination of a sulfenic acid (Equation 11). 

The carbonyl ylide generated from metal carbene can also add to C=0 or C=N bonds. The [2 + 3]-cycloaddition of carbonyl ylide with G=0 bond has been used by Hodgson and co-workers in their study toward the synthesis of zaragozic acid as shown in Scheme n 27a,27d Recently, a three-component reaction approach to syn-a-hydroxy-f3-amino ester based on the trapping of the carbonyl ylide by imine has been reported.The reaction of carbonyl ylide with aldehyde or ketone generally gives l,3-dioxolanes. Hu and co-workers have reported a remarkable chemoselective Rh2(OAc)4-catalyzed reaction of phenyl diazoacetate with a mixture of electron-rich and electron-deficient aryl aldehydes. The Rh(ii) carbene intermediate reacts selectively with electron-rich aldehyde 95 to give a carbonyl ylide, which was chemospecifically trapped by the electron-deficient aldehyde 96 to afford 1,3-dioxolane in a one-pot reaction (Equation (12)). 

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