Mayr electrophilicity/nucleophilicity scales

Recent works of Mayr and co-workers4-14 have illustrated this trend. In fact, these authors have established, in contrast to the accepted opinion about the relative character of the experimental electrophilicity/nucleophilicity scales for many reactions in organic and organometallic chemistry, that it would be possible to define nucleophilicity and electrophilicity parameters that are independent of the reaction partners. Mayr et al. proposed that the rates of reactions of carbocations with uncharged nucleophiles obey the linear free energy relationship given by 4-14... 

Dinitrobenzofuroxan (DNBF) is known as a superelectrophile due to its high reactivity both as an electrophile and in its pericyclic addition reactions. NMR studies show that reaction with 2-aminothiazole and its 4-methyl derivative yield anionic carbon-bonded adducts such as (11) by reaction at the 5-position, whereas the 4,5-dimethyl derivative reacts via the exocyclic amino group. Kinetic studies of the first two compounds, both in acetonitrile and in 70 30 (v/v) water-DMSO, have been used to assess their carbon nucleophilicities and place them on the Mayr nucleophilicity scale.55 In a related study, the nucleophilic reactivity, in acetonitrile, of a series of indoles with both DNBF and with benzhydryl cations have been compared and used to determine nucleophilicity parameters for the indoles.56... 

H. Mayr, M. Patz, Scales of Nucleophilicity and Electrophilicity A System for Ordering Polar Organic and Organometallic Reactions, Angew. Chem. Int. Ed. Engl. 1994, 33, 938-958. 

Mayr and Patz have recently evaluated 56 reaction series, mostly for reactions as described in this article, and derived Eq. (23), in which carbo-cations are characterized by the electrophilicity parameter E, whereas nucleophiles are characterized by the nucleophilicity parameter N and the slope parameter s [182]. The latter quantity, s, which basically describes the slopes of plots as shown in Figs. 10 and 11, ranges from 0.8 to 1.2 for 91 % of the 7r-nucIeophiles investigated. The mathematical form of Eq. (23) implies that the exact value of s will usually only be of importance when rate constants, which strongly deviate from 1 (e.g., (log > 5), are considered. Some of the characterized nucleophiles and electrophiles are listed in Scheme 53, where the two scales are arranged in such a way that electrophiles and nucleophiles which are located at the same level are predicted to combine with rate constants of lg k = -5 s. With s 1 one expects slow combinations for electrophile-nucleophile pairs at the same level, whereas reactions of nucleophiles with electrophiles located below them are expected to be very slow or not to occur at all at 20° C. 

It is generally believed that it was Ingold [1] in the early 1930s who proposed the first global electrophilicity scale to describe electron-deficient (electrophile) and electron-rich (nucleophile) species based on the valence electron theory of Lewis. Much has been accomplished since then. One of the widely used electrophilicity scales derived from experimental data was proposed by Mayr et al. [5-12] ... 

A considerable improvement in the construction of reference scales for the quantitative characterization of nucleophiles and electrophiles in solution has been made by Mayr et al. [598] by means of Eq. (5-109a),... 

Mayr H, Patz M (1994) Scales of nucleophilicity and electrophilicity a system for ordering polar organic and organometallic reactions. Angew Chem Int Ed 33 938-957... 

Mayr H, Bug T, Gotta MF, Hering N, Irrgang B, Janker B, Kempf B, Loos R, Ofial AR, Remennikov G, Schimmel H (2001) Reference scales for the characterization of cationic electrophiles and neutral nucleophiles. J Am Chem Soc 123 9500-9512... 

Mayr has extended his electrophilicity scale to benzaldehyde-derived iminium ions through measurement of rate constants for their reactions with C-nucleophiles such as enamines, silylated ketene acetals and enol ethers." With an E value of -9.27 for Ph-CH=NMe2" (in a range from -8.34 to -10.69 forpara-C j, andpura-OMe, respectively), these iminium ions are 10 orders more reactive than the parent aldehydes. However, the values are restricted to C-nucleophiles the iminium ions react 10 -10 times faster with water and amines than these E values would predict. Such reactions benefit from the anomeric stabilization of 0,Af-acetals and Af,Af-aminals. 

Mayr has recently started to introduce quantitative measures for electrophilic-ity and nucleophilicity in the organocatalytic field by including the iminium [17], and other organocatalytic intermediates [18], in the context of the Mayr scale. Note that the possibility of using an Sul-type reaction in organocatalysis is strictly connected to the presence of water in the reaction medium, or due to the catalytic cycle (Figure 26.3). 

Water is a nucleophile and is at a precise position on the Mayr scale [12] the presence of water can compete in an S l-type reaction, hampering the nucleophilic addition of substrates. In addition, the formation of highly electrophilic cationic intermediates can induce its reaction with the precursor, in particular this problem is often observed when alcohols are used as precursor in Sul-type reactions [19]. 

The nucleophilicity of 32 amine, amide, carbamate, amidine, and pyridine nucleophiles was calculated at the B3LYP/6-31G(d,p) level of theory using the gas-phase ionization potential based on the nucleophilicity index The correlation coefficient for the calculated pyridine nucleophilicity against Mayr s values was 0.947, and it was 0.987 against the inverse of the electrophilicity scale Mm. The site selectivity predicted for the nucleophiles with more than one nucleophilic centre correlates well with that predicted by the local nucleophilicity index and the philicity index m. ... 

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