Addition of Nucleophilic Carbenes

Sufficiently derivatized nanotubes were soluble in DMSO, allowing the separation of insoluble, unreacted and insufficiently functionalized SWCNTs [148], The n-doping of the tubes surface offers a new way to modify the tube properties and control the electronic properties. 

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Nucleophilic carbenes, such as dimethoxycarbenes (Section 5.2.1) or N-heterocyclic carbenes (NHCs) (Section 5.2.2), are used as reagents in the synthesis of heterocycles, becoming part of the final molecule. These MCRs involve zwitterionic species generated by the addition of nucleophilic carbenes to multiple bonds and subsequent reactions with electrophilic compounds. 

Although formally the product of 1,4-addition of the carbene to the ADC 4n unit, 1,3,4-oxadiazolines probably arise via initial nucleophilic attack of the diazo compound to give, after loss of N2, a dipolar intermediate. This intermediate azomethine imine can collapse directly to give the oxadiazoline,... 

Closely related to the a-addition of nucleophiles is the P-deprotonation of electrophilic carbyne complexes. In many of the examples reported [143,530,531] the resulting vinylidene complexes could not be isolated but were generated in situ and either oxidized to yield stable carbene complexes [532] or used as intermediates for the preparation of other carbyne complexes [527]. Cationic carbyne complexes can be rather strong acids and undergo quick deprotonation to vinylidene complexes with weak bases [143]. An interesting example of the use of anionic vinylidene complexes as synthetic intermediates is sketched in Figure 3.24. 

Ylide formation, and hence X-H bond insertion, generally proceeds faster than C-H bond insertion or cyclopropanation [1176], 1,2-C-H insertion can, however, compete efficiently with X-H bond insertion [1177]. One problem occasionally encountered in transition metal-catalyzed X-H bond insertion is the deactivation of the (electrophilic) catalyst L M by the substrate RXH. The formation of the intermediate carbene complex requires nucleophilic addition of a carbene precursor (e.g. a diazocarbonyl compound) to the complex Lj,M. Other nucleophiles present in the reaction mixture can compete efficiently with the carbene precursor, or even lead to stable, catalytically inactive adducts L M-XR. For this reason carbene X-H bond insertion with substrates which might form a stable complex with the catalyst (e.g. amines, imidazole derivatives, thiols) often require larger amounts of catalyst and high reaction temperatures. 

The use of methanol or ethanol as solvent (or sometimes the molecule of water resulting from the spontaneous dehydration) often leads to the isolation of a Fischer-type alkoxy- or hydroxy-carbene [M]=C(OR)CH=CR R instead of the desired allenylidene. Addition of nucleophiles to allenylidenes dominates the reactivity of these electrophilic groups (see below). Nevertheless, in some cases, the use of silver (I) salts Ag[X] (X = PFg, TfO, BF4 ) results in a more practical and flexible synthetic method since the use of nucleophilic polar solvents can be avoided. 

In contrast, the As values for CH3OCCH3 in Table 7.4 reveal that Aen < Aee, so that interaction 7b should dominate additions of this carbene. It should be nucleophilic, and Table 7.3 demonstrates that CH3OCCH3 does indeed exhibit pronounced reactivity toward electron-poor alkenes. 

Until 1998, only gold(III) was believed to be effective for catalyzing these processes because, as mentioned previously, only the gold(I) compound K[Au (CN)2] was tested and it was inert to catalysis. Fortunately, Teles et al. reported very strong activity in the addition of alcohols to alkynes when they used cationic gold( I) -phosphane complexes [14]. In this study, the aforementioned authors tested for the first time the suitability of nucleophilic carbenes that displayed even greater activity than other gold complexes, but they were unable to synthesize the subsequent cationic derivatives. 

In 1986, we found that alkynyl-A3-iodanes serve as good Michael acceptors toward soft nucleophiles, because of the highly electron-deficient nature of the /3-acetylenic carbon atom. This conjugate addition of nucleophiles constitutes a key step of a highly versatile cyclopentene annulation of alkynyl-A3-iodanes via the tandem Michael-carbene insertion (MCI) reaction [Eq. (103)] [185]. 

C60 chemically behaves as an electron-deficient polyalkene, with rather localized double bonds. Thus, the reactions that mainly take place involve cycloadditions, additions of nucleophiles, free radicals, and carbenes, as well as rp-complexation with various transition metal elements. 

In cooperation with Teles and colleagues, our research group has studied the triazole heterocycle as an alternative core structure of nucleophilic carbenes. First, the triazol-5-ylidene 12 (Fig. 9.3 see also Scheme 9.2) was synthesized and shown to be stable at temperatures up to 150 °C in the absence of air and moisture [22]. Compound 12 exhibited the typical behavior of a nucleophilic N-heterocyclic car-bene, and was found to be sufficiently stable to become the first commercially available carbene [23]. As shown in Scheme 9.2, the crystalline carbene was obtained from the corresponding triazolium salt precursor 13 by the addition of methanolate and subsequent thermal decomposition of the adduct 14 in vacuo via a-elimination of methanol [24]. 

Besides by these epoxidations, oxaspiropentanes have been prepared through the nucleophilic addition of 1-lithio- 1-bromocyclopropanes to ketones at low temperature. Thus for example, the dibromocyclopropane 96 prepared by addition of dibromo-carbene to cyclohexene 52) underwent metalation with butyllithium to give the lithio-bromocyclopropane 97 which was converted into the oxaspiropentane 98 upon simple addition to cyclohexanone, Eq. (28) 53,54). 

The dichloride 17, R = H is dehydrohalogenated to a cyclopropene by addition of nucleophiles such as phenylthiolate but, in the absence of a trap, it ring-opens to a carbene which in turn is intercepted by insertion into the solvent36,37,85. In the case of related cyclopropanes e.g. 17, R = CH2CH2Ph, the carbene may be trapped in intramolecular reactions38 ... 

Alkylidenes have been prepared by reduction of alkyli-dynes, by C H oxidative addition from alkyls, and by treatment of unsaturated metal clusters with diazoalkanes. In most instances, the alkylidene adopts a /r2-h coordination mode. However, alkylidenes with heteroatom substituents may also be found in terminal coordination modes. The latter are typically prepared by the Fischer-type carbene route (see Fischer-type Carbene Complexes) (sequential addition of nucleophilic and electrophilic alkylating agents to carbonyl or isocyanide ligands), by condensation of metal fragments with mono- or dimetallic carbene complexes, or by C-H activation of alkylamines. These heteroatom substituted carbenes may also bind in a p3-ri mode, as in (12). 

The formation of bonds c and b can take a couple of forms, either a Darzens-type approach (i.e., addition of a nucleophile bearing a leaving group) or addition of a carbene. Both of these routes have been used in the synthesis of fused-ring aziridines as well as monocyclic aziridines. The addition of a carbene or nucleophile such as an ylide to an imine can provide a nice route to fused-ring aziridines. The necessary cyclic imines are sometimes more readily obtained and used than the acyclic imines. These methods have largely been used on pyridine and quinoline derivatives. 

Pericyclic reactions, such as the addition of a carbene to an alkene and the Diels-Alder cycloaddition (Review Table 1, reactions Ih and li), involve neither radicals nor nucleophile-electrophile interactions. Rather, these processes take place in a single step by a reorganization of bonding electrons through a cyclic transition state. We ll look at these reactions mate closely in Chapter 30. 

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