Nucleophilic carbenes stability

Investigating thermal stabilities of compounds 23-28 revealed that when heated to 80 C the compounds containing PPh,i i.e., 23,25, and 27, were less stable than their PCyy bearing analogues (24, 26, and 28, respectively). The least stable was (PPhy)2Cl2Ru(3-phenylindenylid-l-ene) (23) which decomposed after 2 h at 80 C (Table IX, entry 1) and the most stable was (lPr)(PPhy)Cl2Ru(3-phenylindenylid-1 -ene) (27) (Table IX, entry 4) which showed decomposition after 42 h at the same temperature. It can be concluded that the presence of the nucleophilic carbene... 

In 1991 Arduengo and co-workers42 reported the isolation and characterization of the first stable carbene, l,3-di(l-adamantyl)-2,3-dihydroimidazol-2-ylidene. Since that time many substituted nucleophilic carbenes have been prepared.43 From ab initio studies it can be shown that cyclic electron delocalization is partly responsible for the extraordinary stability of 2,3-dihydroimidazol-2-ylidenes.44... 

If the resonance stabilization of singlet carbenes is increased even more, for example, by replacing the CH3O substituents of (CH30)2C by amino groups [as in (R2N)2C] or phosphorus substiments (13), stable, isolable, nucleophilic carbenes can be obtained. These species are considered in Chapter 8 in this volume. 

I have been pursuing enzyme mimics, artificial enzymes that perform biomimetic chemistry, since starting my independent career in 1956. In the first work [52-59] my co-workers and I studied models for the function of thiamine pyrophosphate 1 as a coenzyme in enzymes such as carboxylase. We discovered the mechanism by which it acts, by forming an anion 2 that we also described as a stabilized carbene, one of its resonance forms. We examined the related anions from imidazolium cations and oxazolium cations, which produce anions 3 and 4 that can also be described as nucleophilic carbenes. We were able to explain the structure-activity relationships in this series, and the reasons why the thiazolium ring is best suited to act as a biological... 

The basic nature of N-heterocyclic carbenes, stabilized by the presence of two adjacent N atoms, has been emphasized by several authors [38], Therefore, the yield and the selectivity of any organic synthesis (driven by the reactivity of a substrate vs. appropriate bases and carried out in imidazohum salts as solvents) can be affected by side reactions related to the acidity of C2-H unit in 1,3-dialkylimidazo-lium cation and to the basicity and nucleophilicity of the resulting N-heterocychc carbene. On this subject, noticeable work (related to the Baylis-Hillman, Knoevenagel and Claisen condensation, Homer reaction, etc.) carried out in RTlLs has been reported and discussed [37]. 

These results may be understood in the context of soft-hard acid-base theory.As mentioned earlier, the Fischer carbene complexes can be regarded as soft electrophiles, especially the alkylthio complexes. Hence, the adducts 99 formed by the reaction of 98b with a thiolate ion nucleophile enjoy enhanced stability due to the symbiotic effect of adding a soft nucleophile. This stabilization apparently reduces the need for additional stabilization by the phenyl substituent, which translates to a reduced p(Ki) value. 

The results with dimethoxyearbene highlight an inherent deficiency of Eq. 4 it is an empirical correlation of parameters normalized to the electrophilic car-bene, CCI2. Its electrophilic heritage means that although the equation can predict values for highly resonance stabilized, nucleophilic carbenes such as (MeO)2C or Me2NCOMe, these are virtual selectivity indexes. The nucleophilic carbenes simply do not add to the aUcenes of the standard set. However, the equation helps us define the Wcxy regions in which electrophilic and nucleophilic carbenes reside. The electrophilic species, which react appropriately with the standard alkenes of Table 1, exhibit w xy values between 0.29 (BrCCOOEt) and... 

What about a nucleophilic carbene, for which negative charge should build up on the olefinic carbon atoms during the carbene addition cf. 5 With ArCH=CH2 substrates, electron-withdrawing aryl substituents would stabilize such a transition state and the p value should be positive. There are several examples of this phenomenon. For example, cycloheptatrienylidene, 10, adds to / -substituted styrenes with p = -t-1.02 - 1.05 (vs. a) consistent with a nucleophilic selectivity that seems to implicate the aromatic resonance form 10a as an important feature of the carbene. [45] It is satisfying to compare this result with p = -0.76 (vs. a) or -0.46 (vs. a" ") for additions to styrenes of cyclopentadienylidene, 11, where contributions of the cyclopentadienide form (11a) would render the carbene electrophilic. [46] However, these conclusions are too facile. There is reason to believe that the chemistry attributed to 10 might in fact be due to its allenic isomer 12. [47] And the electronic structure of 11 is also more complicated than the simple depiction above. [48]... 

In contrast to the electrophilic nature of most carbenes, highly resonance-stabilized carbenes can be nucleophilic, as suggested by the right-hand resonance structure in the margin. Dimethoxycarbene is a good example of a nucleophilic carbene. Intermediate cases such as methoxychlorocarbene can be ambiphilic, showing increased reactivity to both electron rich and electron deficient olefins. 

The philicity of a carbene directly depends on the structure of the transition state of an addition reaction. The rules of orbital symmetry conservation forbid the least-motion C2v-symmetry reaction path [41]. For electrophilic carbenes, characterized by predominance of the n — p interaction, preferable is the so-called 7r-approach (Fig. 8.3). In the case of nucleophilic carbenes, optimum conditions for the overlap between the (Tcxy 7r -orbitals are provided by the asymmetrical cr-approach (Fig. 8.3b). By making use of certain assumptions, Rondan, Houk, and Moss [44, 45] calculated the overlap integrals Sjj between the corresponding frontier orbitals of carbene and alkene for the n- and the (7-approaches. Then, having computed the energies of those orbitals, they obtained the energies of stabilization of the composite system arising in two... 

Carbenes can be heteroatom stabilized (Fischer) or not (Schrock). Fischer carbenes have an electrophilic carbene carbon and Schrock carbenes have a nucleophilic carbene carbon. 

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