Carbenes philicity

Carbene protonation has been amply demonstrated by product studies, time-resolved spectroscopy, and kinetic measurements. The ability of singlet carbenes to accept a proton is not adequately described by the traditional scale of carbene philicities, which is based on addition reactions with alkenes. In particular, aryl- and diarylcarbenes excel as proton acceptors but would traditionally be classified as electrophiles. 

A deeper understanding of carbenic philicity requires a more detailed representation of the addition reaction transition state than that afforded by structure 4. Early MO calculations furnished structure 6 as representative of the transition state for addition of a singlet carbene to an alkene (Fig. 7.6). " ... 

Sander applied DFT (B3LYP) theory to carbenic philicity, computing the electron affinities (EA) and ionization potentials (IP) of the carbenes." " The EA tracks the carbene s electrophilicity (its ability to accept electron density), whereas the IP represents the carbene s nucleophilicity (its ability to donate electron density). This approach parallels the differential orbital energy treatment. Both EA and IP can be calculated for any carbene, so Sander was able to analyze the reactivity of super electrophilic carbenes such as difluorovinylidene (9)" which is sufficiently electrophilic to insert into the C—H bond of methane. It even reacts with the H—H bond of dihydrogen at temperamres as low as 40 K, Scheme 7.2) ... 

Fluorodiazirines have also been used extensively as carbene photoprecursors for cryogenic matrix isolation " and laser flash photolysis studies. Photolysis of fluorophenoxydiazirine has made observation of the corresponding carbene directly observable in yet another fashion encapsulated in a hemicarcer-and. Diazirines have been used for studies in solution of carbene philicities as well as for synthesis of cyclopropanes and cyclopropenes.Of course, diazo compounds can also serve as carbene photoprecursors, but for carbenes such as difluorocarbene, the diazo precursor is either nonexistent or extremely unstable. 

The philicity of singlet carbenes is an important concept to classify carbenes that was systematically studied by Moss. [9-11] The relative reactivity (selectivity) of a series of singlet carbenes in cyclopropanation reactions with electron rich and electron poor carbenes was used to quantify the carbene philicity. An empirical carbene philicity scale with a parameter niQ- (where X and Y are the substituents at the carbene center) was defined (Figure 1). Electrophilic carbenes show Wqxy values below 1, nucleophilic carbenes above 2, and ambiphiles are between. [10] Ambiphilic carbenes act as an electrophile towards electron-rich alkenes and as a nucleophile towards electron-poor alkenes. The niQ- Y values obey an empirical linear free energy relationship with the Taft substituent parameters and Oj. This allows to estimate the niQ- Y values of unknown carbenes. 

Figure 1. Carbene philicity spectrum as defined by Moss [10].

To overcome this problem we recently suggested to correlate the ionization potential (IP) and the electron affinities (EA) of carbenes with the carbene philicity. [14] IP and EA of carbenes can in principle be measured by negative ion photoelectron spectroscopy (NIPES), and data of a series of simple carbenes and vinylidenes were published by Lineberger et al. [15-23] The experimental data allow to evaluate the reliability of theoretical methods for the calculation of IP and EA. As shown in Table 1, there is a decent agreement between the experimental EA and calculations of the vertical EA of carbenes. The calculated adiabatic EAs are systematically too large by ca. 0.3 eV. However, if the adiabatic EAs are corrected by this value the agreement with the experiment is even better. 

A particularly interesting use of the Hammett relation to examine carbenic philicity was proved by Tomioka, et. al. [40] These scientists determined for the additions of carbenes 19 and 20 to a series of substituted styrenes. Although these carbenes possess triplet ground states, their additions to styrene... 

Thus, the regiochemistries of the CCI2, MeOCCl, or (MeO)2C additions to dimethylfulvene reflect the carbenes philicities, and can be understood in terms of molecular orbital theory. [56]... 

By about 1980, a reasonable empirical understanding of carbenic philicity seemed to be at hand electrophiles, ambiphiles, and nucleophiles had been identified and could be assigned m xy or p xv values that reflected the magnitude and character of their selectivity during their additions to alkenes. And yet, our rationalization of these reactions only in terms of relative reactivities and linear free energy relations was surely incomplete. 

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]... 

It was clear that we needed a better theoretical Iramework to parallel and permit interpretation of carbenic philicity. Two crucial developments occurred around 1980 the application of ab initio computational methods and frontier molecular orbital (FMO) theory to carbene/alkene addition reactions, and the measurement of absolute rate constants for these reactions by laser flash photolysis (LFP). Together, these approaches greatly clarified our understanding of carbenic selectivity and philicity, and defined the current state of the art. ... 

FMO theory [67] was successfully applied to the rationalization of electrophilic, nucleophilic, and ambiphilic behavior in 1,3-dipolar cycloaddition and Diels-Alder reactions. [68] The availability of orbital energies computed for a variety of CXY, [69] enables a similar rationalization of carbenic reactivity and philicity. It was from my colleagues Ken Houk (then of Louisiana State University, now of UCLA) and Karsten Krogh-Jespersen (of Rutgers University) that 1 learned how incisively FMO theory could help us to understand carbenic philicity. My collaborations with each of these excellent scientists have greatly enriched my understanding of carbenic reactivity. 

Finally, Sander has analyzed carbenic philicity in terms of DFT (B3LYP) computed electron affinities (EA) and ionization potentials (IP) of the carbenes. [82] The EA represents the carbene s ability to accept electrons (i.e., its electro-philicity), whereas the carbene s IP reflects its ability to donate electron density (i.e., its nucleophilicity). Where comparisons are possible, there is qualitative agreement between the EA/IP and mcxv analyses of carbenic philicity. Thus, nucleophilic (MeO)2C has a very low EA (-0.62 eV) and a middling IP (9.01 eV) it should be a good electron donor, but a poor electron acceptor. Dichlorocar-bene, with EA = 1.46 eV and IP = 10.16 eV, should be a better electron acceptor and a poorer electron donor than (MeO)2C i.e., it should be much more electrophilic. Thus, according to Sander, [82] nucleophilic carbenes are characterized by low IP s and low EA s electrophilic carbenes, conversely, have high IP s and high EA s. [83]... 

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