Kinetics of the reactions of halide anions with carbocations: quantitative energy profiles for s(n)1 reactions

Rate constants for the reactions of Laser flash photolytically generated benzhydrylium ions (diarylcarbenium ions) with halide ions have been determined in various solvents, including neat and aqueous acetonitrile as well as some alcohols. Substitution of the rate constants into the correlation equation log k = s(N + E) yields the nucleophilicity parameters N for the halide ions in different solvents. Linear correlations with negative slopes are found between the nucleophilicity parameters N for Cl(-) and Br(-) in different solvents and the solvent ionizing powers Y of the corresponding solvents. Increasing halide solvation reduces the rates of carbocation/chloride combinations by approximately half as much as it increases the rates of ionizations of benzhydryl chlorides. Comparison of the solvent dependent nucleophilicity parameters N of halide anions and the nucleophilicity parameters N(1) for solvents yields a quantitative prediction of common ion rate depression, as demonstrated by the analysis of a variety of literature reported mass-law constants alpha. Combination of the rate constants for the reactions of benzhydrylium ions with halide ions (k(-)()(1)) reported in this work with the ionization constants of benzhydryl halides (k(1)) and the recently reported rate constants for the reactions of benzhydrylium ions with solvents (k(2)) yields complete quantitative free energy profiles for solvolysis reactions. The applicability of Hammond's postulate for interpreting solvolysis reactions can thus be examined quantitatively.     

Free Energy Relationships for Reactions of Substituted Benzhydrylium Ions: From Enthalpy over Entropy to Diffusion Control

Second-order rate constants k(2) for the reactions of various donor- and acceptor-substituted benzhydrylium ions Ar(2)CH(+) with π-nucleophiles in CH(2)Cl(2) were determined by laser flash irradiation of benzhydryl triarylphosphonium salts Ar(2)CH-PAr(3)(+)X(-) in the presence of a large excess of the nucleophiles. This method allowed us to investigate fast reactions up to the diffusional limit including reactions of highly reactive benzhydrylium ions with m-fluoro and p-(trifluoromethyl) substituents. The rate constants determined in this work and relevant literature data were jointly subjected to a correlation analysis to derive the electrophilicity parameters E for acceptor-substituted benzhydrylium ions, as defined by the linear free energy relationship log?k(2)(20 °C) = s(N)(N + E). The new correlation analysis also leads to the N and s(N) parameters of 18 π-nucleophiles, which have only vaguely been characterized previously. The correlations of log?k(2) versus E are linear well beyond the range where the activation enthalpies ΔH(?) of the reactions are extrapolated to reach the value of ΔH(?) = 0, showing that the change from enthalpy control to entropy control does not cause a bend in the linear free energy relationship, a novel manifestation of the compensation effect. A flattening of the correlation lines only occurs for k(2) > 10(8) M(-1) s(-1) when the diffusion limit is approached.     

Photogeneration of Benzhydryl Cations by Near-UV Laser Flash Photolysis of Pyridinium Salts

Laser flash irradiation of substituted N-benzhydryl pyridinium salts yields benzhydryl cations (diarylcarbenium ions) and/or benzhydryl radicals (diarylmethyl radicals). The use of 3,4,5-triamino-substituted pyridines as photoleaving groups allowed us to employ the third harmonic of a Nd/YAG laser (355 nm) for the photogeneration of benzhydryl cations. In this way, benzhydryl cations can also be photogenerated in the presence of aromatic compounds and in solvents which are opaque at the wavelength of the quadrupled Nd/YAG laser (266 nm). To demonstrate the scope and limitations of this method, the rate constants for the bimolecular reactions of benzhydryl cations with several substituted pyridines were determined in acetonitrile and with water in acetone. The obtained data agree with results obtained by stopped-flow UV-vis spectroscopic measurements. The rate constants for the reaction of the 4,4'-bis[methyl(2,2,2-trifluoroethyl)amino]benzhydrylium ion with 4-(dimethylamino)pyridine were also determined in dimethyl sulfoxide, N,N-dimethylformamide, and acetone. From the second-order rate constants, we derived the nucleophilicity parameters N and s(N) for the substituted pyridines, as defined by the linear free energy relationship, log k(2) = s(N)(N + E).     

Photolytic generation of benzhydryl cations and radicals from quaternary phosphonium salts: how highly reactive carbocations survive their first nanoseconds

UV irradiation (266 or 280 nm) of benzhydryl triarylphosphonium salts Ar(2)CH-PAr(3)(+)X(-) yields benzhydryl cations Ar(2)CH(+) and/or benzhydryl radicals Ar(2)CH(?). The efficiency and mechanism of the photo-cleavage were studied by nanosecond laser flash photolysis and by ultrafast spectroscopy with a state-of-the-art femtosecond transient spectrometer. The influences of the photo-electrofuge (Ar(2)CH(+)), the photo-nucleofuge (PPh(3) or P(p-Cl-C(6)H(4))(3)), the counterion (X(-) = BF(4)(-), SbF(6)(-), Cl(-), or Br(-)), and the solvent (CH(2)Cl(2) or CH(3)CN) were investigated. Photogeneration of carbocations from Ar(2)CH-PAr(3)(+)BF(4)(-) or -SbF(6)(-) is considerably more efficient than from typical neutral precursors (e.g., benzhydryl chlorides or bromides). The photochemistry of phosphonium salts is controlled by the degree of ion pairing, which depends on the solvent and the concentration of the phosphonium salts. High yields of carbocations are obtained by photolyses of phosphonium salts with complex counterions (X(-) = BF(4)(-) or SbF(6)(-)), while photolyses of phosphonium halides Ar(2)CH-PPh(3)(+)X(-) (X(-) = Cl(-) or Br(-)) in CH(2)Cl(2) yield benzhydryl radicals Ar(2)CH(?) due to photo-electron transfer in the excited phosphonium halide ion pair. At low concentrations in CH(3)CN, the precursor salts are mostly unpaired, and the photo-cleavage mechanism is independent of the nature of the counter-anions. Dichloromethane is better suited for generating the more reactive benzhydryl cations than the more polar and more nucleophilic solvents CH(3)CN or CF(3)CH(2)OH. Efficient photo-generation of the most reactive benzhydryl cations (3,5-F(2)-C(6)H(3))(2)CH(+) and (4-(CF(3))-C(6)H(4))(2)CH(+) was only achieved using the photo-leaving group P(p-Cl-C(6)H(4))(3) and the counter-anion SbF(6)(-) in CH(2)Cl(2). The lifetimes of the photogenerated benzhydryl cations depend greatly on the decay mechanisms, which can be reactions with the solvent, with the photo-leaving group PAr(3), or with the counter-anion X(-) of the precursor salt. However, the nature of the photo-leaving group and the counterion of the precursor phosphonium salt do not affect the rates of the reactions of the obtained benzhydryl cations toward added nucleophiles. The method presented in this work allows us to generate a wide range of donor- and acceptor-substituted benzhydryl cations Ar(2)CH(+) for the purpose of studying their electrophilic reactivities.     

How constant are Ritchie's "constant selectivity relationships"? A general reactivity scale for n-, pi-, and sigma-nucleophiles

The kinetics of 82 reactions of benzhydrylium ions (Ar(2)CH(+)) with n-nucleophiles has been determined at 20 degrees C. Evaluation by the equation log k = s(N + E) delivered the reactivity parameters N and s for 15 n-nucleophiles (water, hydroxide, amines, etc.). All nucleophiles except water (s = 0.89) and (-)SCH(2)CO(2)(-) (s = 0.43) have closely similar slope parameters (0.52 < s < 0.71), indicating that the reactions of most n-nucleophiles approximately follow Ritchie's constant selectivity relationship (s = constant). The different slope parameter for water is recognized as the main reason for the deviations from the Ritchie relationship reported in 1986. Correlation analysis of the rate constants for the reactions of benzhydrylium ions with the n-nucleophiles (except H(2)O) on the basis of Ritchie's equation log k = N(+) + log k(0) yields a statistically validated set of N(+) parameters for Ritchie-type nucleophiles and log k(0) parameters for benzhydrylium ions. The N and s parameters of the n-nucleophiles derived from their reactions with benzhydrylium ions were combined with literature data for the reactions of these nucleophiles with other carbocations to yield electrophilicity parameters E for tritylium, tropylium, and xanthylium ions. While the E parameters for tropylium and xanthylium ions appear to be generally applicable, it is demonstrated that the E parameters of tritylium ions can be used to predict reactivities toward n-nucleophiles as well as hydride transfer rate constants but not rates for the reactions of tritylium ions with pi-nucleophiles. It is now possible to merge the large data sets determined by Ritchie and others with our kinetic data and present a nucleophilicity scale comprising n- (e.g., amines), pi- (e.g., alkenes and arenes), and sigma-nucleophiles (e.g., hydrides).     

Characterization of the nucleophilic reactivities of thiocarboxylate, dithiocarbonate and dithiocarbamate anions

The kinetics of the reactions of thiocarboxylate and thiocarbonate anions with benzhydrylium ions have been determined in acetonitrile solution using laser-flash photolytic techniques. The second-order rate constants (k) correlate linearly with the electrophilicity parameters E of the benzhydrylium ions, as required by the correlation log k (20 °C) = s(N)(N + E) (J. Am. Chem. Soc., 2001, 123, 9500-9512), allowing us to calculate the nucleophile-specific parameters N and s(N) for these anions. With these parameters, a direct comparison of the reactivities of thiocarboxylate, dithiocarbonate and dithiocarbamate anions with other nucleophiles becomes possible.     

Nucleophilic reactivities of carbanions in water: the unique behavior of the malodinitrile anion

The kinetics of the reactions of nine carbanions 1a-i, each stabilized by two acyl, ester, or cyano groups, with benzhydrylium ions in water were investigated photometrically at 20 degrees C. Because the competing reactions of the benzhydrylium ions with water and hydroxide ions are generally slower, the second-order rate constants of the reactions of the benzhydrylium ions with the carbanions can be determined with high precision. The rate constants thus obtained can be described by the Ritchie equation, log(k/k(0)) = N(+) (eq 1), which allows us to calculate Ritchie N(+) parameters for a series of stabilized carbanions, for example, malonate, acetoacetate, malodinitrile, etc., and compare them with those of other n-nucleophiles in water (hydroxide, amines, azide, thiolates, etc.). Because the Ritchie relationship (eq 1) is a special case of the more general relationship log k = s(N + E) (eq 4), the reactivity parameters N and s for the carbanions 1a-i can also be calculated and compared with the nucleophilic reactivities of a large variety of n-, pi-, and sigma-nucleophiles, including reactivities of carbanions in dimethyl sulfoxide. While the acyl and ester substituted carbanions are approximately 3 orders of magnitude less reactive in water than in dimethyl sulfoxide, the malodinitrile anion (1i) shows almost the same reactivity in both solvents. Correlations between the nucleophilic reactivities of carbanions with the pK(a) values of the corresponding CH acids reveal that the malodinitrile anion (1i) is considerably more nucleophilic than was expected on the basis of its pK(a) value. This deviation is assigned to the exceptionally low Marcus intrinsic barriers of the reactions of the malodinitrile anion (1i).     

Reference scales for the characterization of cationic electrophiles and neutral nucleophiles

Twenty-three diarylcarbenium ions and 38 pi-systems (arenes, alkenes, allyl silanes and stannanes, silyl enol ethers, silyl ketene acetals, and enamines) have been defined as basis sets for establishing general reactivity scales for electrophiles and nucleophiles. The rate constants of 209 combinations of these benzhydrylium ions and pi-nucleophiles, 85 of which are first presented in this article, have been subjected to a correlation analysis to determine the electrophilicity parameters E and the nucleophilicity parameters N and s as defined by the equation log k(20 degrees C) = s(N + E) (Mayr, H.; Patz, M. Angew. Chem., Int. Ed. Engl. 1994, 33, 938-957). Though the reactivity scales thus obtained cover more than 16 orders of magnitude, the individual rate constants are reproduced with a standard deviation of a factor of 1.19 (Table 1). It is shown that the reactivity parameters thus derived from the reactions of diarylcarbenium ions with pi-nucleophiles (Figure 3) are also suitable for characterizing the nucleophilic reactivities of alkynes, metal-pi-complexes, and hydride donors (Table 2) and for characterizing the electrophilic reactivities of heterosubstituted and metal-coordinated carbenium ions (Table 3). The reactivity parameters in Figure 3 are, therefore, recommended for the characterization of any new electrophiles and nucleophiles in the reactivity range covered. The linear correlation between the electrophilicity parameters E of benzhydryl cations and the corresponding substituent constants sigma(+) provides Hammett sigma(+) constants for 10 substituents from -1.19 to -2.11, i.e., in a range with only very few previous entries.     

Ambident reactivities of pyridone anions

The kinetics of the reactions of the ambident 2- and 4-pyridone anions with benzhydrylium ions (diarylcarbenium ions) and structurally related Michael acceptors have been studied in DMSO, CH(3)CN, and water. No significant changes of the rate constants were found when the counterion was varied (Li(+), K(+), NBu(4)(+)) or the solvent was changed from DMSO to CH(3)CN, whereas a large decrease of nucleophilicity was observed in aqueous solution. The second-order rate constants (log k(2)) correlated linearly with the electrophilicity parameters E of the electrophiles according to the correlation log k(2) = s(N + E) (Angew. Chem., Int. Ed. Engl. 1994, 33, 938-957), allowing us to determine the nucleophilicity parameters N and s for the pyridone anions. The reactions of the 2- and 4-pyridone anions with stabilized amino-substituted benzhydrylium ions and Michael acceptors are reversible and yield the thermodynamically more stable N-substituted pyridones exclusively. In contrast, highly reactive benzhydrylium ions (4,4'-dimethylbenzhydrylium ion), which react with diffusion control, give mixtures arising from N- and O-attack with the 2-pyridone anion and only O-substituted products with the 4-pyridone anion. For some reactions, rate and equilibrium constants were determined in DMSO, which showed that the 2-pyridone anion is a 2-4 times stronger nucleophile, but a 100 times stronger Lewis base than the 4-pyridone anion. Quantum chemical calculations at MP2/6-311+G(2d,p) level of theory showed that N-attack is thermodynamically favored over O-attack, but the attack at oxygen is intrinsically favored. Marcus theory was employed to develop a consistent scheme which rationalizes the manifold of regioselectivities previously reported for the reactions of these anions with electrophiles. In particular, Kornblum's rationalization of the silver ion effect, one of the main pillars of the hard and soft acid/base concept of ambident reactivity, has been revised. Ag(+) does not reverse the regioselectivity of the attack at the 2-pyridone anion by increasing the positive charge of the electrophile but by blocking the nitrogen atom of the 2-pyridone anion.     

Nucleofugality and nucleophilicity of fluoride in protic solvents

A series of p-substituted benzhydryl fluorides (diarylfluoromethanes) were prepared and subjected to solvolysis reactions, which were followed conductometrically. The observed first-order rate constants k(1)(25 °C) were found to follow the correlation equation log k(1)(25 °C) = s(f)(N(f) + E(f)), which allowed us to determine the nucleofuge-specific parameters N(f) and s(f) for fluoride in different aqueous and alcoholic solvents. The rates of the reverse reactions were measured by generating benzhydrylium ions (diarylcarbenium ions) laser flash photolytically in various alcoholic and aqueous solvents in the presence of fluoride ions and monitoring the rate of consumption of the benzhydrylium ions by UV-vis spectroscopy. The resulting second-order rate constants k(-1)(20 °C) were substituted into the correlation equation log k(-1) = s(N)(N + E) to derive the nucleophilicity parameters N and s(N) for fluoride in various protic solvents. Complete Gibbs energy profiles for the solvolysis reactions of benzhydryl fluorides are constructed.     

A novel method for the direct derivatization of straight-chain aliphatic carboxylates after trapping on anion-exchange resin

A novel procedure for the characterization of traces of lipophilic straight-chain aliphatic carboxylate ions in aqueous samples is described. The carboxylates are adsorbed on an Amberlyst A26 [Cl^-] resin column. The resin is then dried and suspended in methyl iodide at room temperature. A gas Chromatographic analysis of the methyl iodide solution allows the determination of the carboxylates as their methyl esters. Full characterization of each carboxylate with an overall recovery over 84% from 1 ppm aqueous sample solutions is attained.     

Di-, tri-, and tetranuclear zinc hydroxamate complexes as structural models for the inhibition of zinc hydrolases by hydroxamic acids

Attempts to produce Zn analogues of the structural model complexes [M2(mu-O2CR)2(O2CR)2(mu-H2O)(tmen)2] (M = Ni, Co, Mn; R = CH(3), C(CH3)3, CF3) by the reaction of a series of zinc carboxylates with N,N,N',N'-tetramethylethylenediamine (tmen), resulted in the mononuclear complexes [Zn(OAc)(2)(tmen)] (1) and [Zn(crot)2(tmen)].(0.5)H2O (2) for R = CH3 and (CH)2CH3, respectively, and the dinuclear complexes [Zn(2)(mu-piv)(2)(piv)(2)(mu-H2O)(tmen)2] (3) and [Zn2(mu-OAc(F))2(OAc(F))2(mu-H2O)(tmen)2] (4) for R = C(CH3)3 and CF3, respectively. In contrast to the analogous imidazole series, i.e., [M2(mu-O2CR)2(O2CR)2(mu-H2O)(Im)4] (M = Ni, Co, Mn; R = CH3, C(CH3)3, CF3), zinc carboxylates react with imidazole to give only the mononuclear complexes [Zn(OAc)2(Im)2] (5), [Zn(crot)2(Im)2].H2O (6), [Zn(piv)2(Im)2].(0.5)H2O (7), and [Zn(OAc(F))2(Im)2] (8). Reaction of 1, 2, and 3 with either acetohydroxamic acid (AHA) or benzohydroxamic acid (BHA) gives the dinuclear complexes [Zn2(O2CR)3(R'A)(tmen)], where R'A = acetohydroxamate (AA) (9, 10, 11) or benzohydroxamate (BA) (13, 14, 15). In these complexes, the zinc atoms are bridged by a single hydroxamate and two carboxylates, with a capping tmen ligand on one zinc and a monodentate carboxylate bonded to the second zinc atom. This composition models closely the observed structure of the active site of the p-iodo-d-phenylalanine hydroxamic acid inhibited Aeromonas proteolyticaaminopeptidase enzyme. In contrast, 4 reacts with AHA to give [Zn2(OAc(F))3(tmen)2(AA)] (12) with an additional tmen ligand so that both Zn atoms are 6-coordinate, whereas reaction with BHA gives the trinuclear complex [Zn3(OAc(F))4(tmen)2(BA)2] (16). Reactions of 3 and 4 with glutarodihydroxamic acid (GluH2A2) produce the tetranuclear complexes [Zn4(piv)6(tmen)4(GluA2)] (18) and [Zn4(OAc(F))6(tmen)4(GluA2)] (19).     

Masked Unsaturated Esters/Amides in Asymmetric Organocatalysis

This Concept article summarizes strategies and developments regarding the use of masked unsaturated esters/amides in asymmetric organocatalysis. Useful substrates are categorized by the design of their inherent carboxylate template. This template group not only enables their functionality as ester surrogates, but also define their accessibilities, modes of interactions with catalysts and the simplicity with which they transform back to the parent carboxylates. Both covalent and noncovalent catalytic systems are discussed and examples showing the entire process (from substrates‐to‐functionalized ester/amides) are given.     

G3(MP2) study of the C3H6O+* isomers fragmented from 1,4-dioxane+*

The fragmentation process of ionized 1,4-dioxane and the reactions between the C3H6O+* ions, one of the major fragments, and various reactants (including acetonitrile, formaldehyde, ethylene, and propene) have been studied experimentally with mass spectrometry. In the present work, G3(MP2) calculations were carried out to investigate these processes theoretically. In agreement with experiment, isomers CH3OCHCH2+* (1) and *CH2CH2OCH2+ (2) were found to be the C3H6O+* ions fragmented from ionized 1,4-dioxane, with 2 being the major product. The mechanisms of the formation of 1 and 2 were successfully established. In addition, the characteristic reactivities, as well as the corresponding reaction mechanisms, of both isomers were rationalized with the aid of calculations. Finally, a minor reaction between isomer 2 and propene was identified, and the presence of the product of this reaction was found to be useful in explaining the aforementioned mass spectrometric data.     

Characterization of anthraquinone-2-carbonyl chloride as an alcohol derivatization reagent for negative ion chemical ionization mass spectrometry

Anthraquinone-2-carbonyl chloride has been utilized as a derivatization reagent for alcohols to impart electron affinity and aid in transport via a particle beam liquid chromatography-mass spectrometry (LC/MS) interface. In addition, the gas chromatographic-mass spectrometry, UV, fluorescence, and electrochemical characteristics of the derivatives were determined. A series of model compounds, 2-phenylethanol (phenethyl alcohol), 1-phenyl-2-propanol, 2-methyl-l-phenyl-2-propanol, hexanol, and methyl 2-methylglycerate, were used as analytes. The particle beam LC/MS properties of the resultant anthraquinone carboxylate esters were determined in electron impact (EI) and negative ion chemical ionization (NCI) modes. The NCI responses of these anthraquinone carboxylate esters were compared with the corresponding 3,5-dinitrobenzoate esters. The anthraquinone carboxylate esters exhibited an NCI to EI sensitivity enhancement of 113 and were detected in NCI at a tenfold lower concentration than the corresponding 3,5-dinitrobenzoate esters. A detection limit of 26 pg injected on column was achieved for phenethyl anthraquinone carboxylate in NCI by using selected ion monitoring.     

Imidazolium carboxylates as versatile and selective N-heterocyclic carbene transfer agents: synthesis, mechanism, and applications

N,N'-Disubstituted imidazolium carboxylates, readily synthetically available, isolable, air- and water-stable reagents, efficiently transfer N-heterocyclic carbene (NHC) groups to Rh, Ir, Ru, Pt, and Pd, to give novel NHC complexes, e.g., [Pd(NHC)3OAc]OAc and [Pt(NHC)3Cl]Cl (NHC = 1,3-dimethyl imidazol-2-ylidene). The NHC esters are also effective. Tuning the reaction conditions for NHC transfer can give either mono- or bis-NHCs, or bis- and tris-NHCs. A net N to C rearrangement of the N-alkyl imidazole complex to the corresponding NHC complex was seen with (MeO)2CO (DMC). DFT calculations identify the steps needed to form the carboxylate from imidazole and DMC: SN2 methyl transfer from DMC to imidazole, followed by proton transfer from the imidazolium CH to the carboxylate counterion, produces the free NHC H-bonded to MeOH with a weakly associated CO2. The nucleophilic NHC attacks CO2 to form NHC-CO2. NHC transfer to the metal with loss of CO2 has been calculated for Rh(cod)Cl. A proposed two-cis-site reactivity model rationalizes the experimental data: two such vacant sites at the metal are needed to allow coordination of the NHC-CO2 carboxylate and subsequent CC cleavage with NHC transfer. Partial cod decoordination or chloride loss is thus required for Rh(cod)Cl. Chloride dissociation, calculated to be easier in polar solvent, is confirmed experimentally from the retarding effect of excess chloride.     

Nucleophilicities of primary and secondary amines in water

The kinetics of the reactions of 26 primary and secondary amines with benzhydrylium ions in water were investigated photometrically. Because the parallel reactions of the benzhydrylium ions with hydroxide and water are much slower, the second-order rate constants for the reactions of amines with benzhydrylium ions could be determined reliably. Reactivities of anilines were also studied in acetonitrile solution. Plots of log k2,N for these reactions vs the electrophilicity parameters E of the benzhydrylium ions were linear, which allowed us to derive the nucleophilicity parameters N and s for amines as defined by the equation log k(20 degrees C)=s(E+N). Because the slope parameters for the different amines are closely similar; the relative nucleophilicities are almost independent of the electrophiles and can be expressed by the nucleophilicity parameters N. The correlation between nucleophilicity N and pKaH values is poor, and it is found that secondary alkyl amines and anilines are considerably more nucleophilic, while ammonia is much less nucleophilic than expected on the basis of their pKaH values.     

Does electrospray ionization produce gas-phase or liquid-phase structures?

Electrospray ionization of tyrosine from a 3:1 (v:v) CH3OH/H2O solution is found to afford an M - H ion which is a 70:30 mixture of phenoxide and carboxylate ions. This corresponds to the gas-phase equilibrium composition and not the liquid-phase proportions. In contrast, the carboxylate is produced as the dominant ion (approximately 95%) from anhydrous CH3CN and CH3CN/H2O mixtures. The addition of small amounts of CH3OH to the solvent, however, convert the M - H ion back into the gas-phase isomeric ratio. The isomeric structure therefore depends on the solvent system from which an ion is sprayed.     

Carboxylate-substituted radicals from phenylselenide derivatives. Designs on models for coenzyme B12-dependent enzyme-catalyzed rearrangements

Laser flash photolysis (266 nm) of alpha- and beta-phenylselenyl esters, carboxylic acids, and carboxylates in aqueous acetonitrile media gave the corresponding radicals by homolytic cleavage of the phenylselenyl groups. In the beta-substituted systems, acid and carboxylate radicals reacted in intramolecular reporter reactions with approximately equal rate constants. For the alpha-substituted systems, an ester- and carboxylic acid-substituted radical reacted in an intramolecular reporter reaction with the same rate constants, but the analogous alpha-carboxylate radical, a radical anion, reacted an order of magnitude less rapidly and with an activation energy that is 3 kcal/mol greater than that found for analogues. A kinetic titration of the equilibrating alpha-acid and alpha-carboxylate radicals gave pKa = 4.6. The results indicate that alpha-ester and alpha-carboxylic acid radicals are unlikely to be appropriate models for alpha-carboxylate radicals, the intermediates formed in a large subset of coenzyme B12-dependent enzyme-catalyzed reactions.     

Nucleophilicities of Cyclic α-Diazo Carbonyl Compounds

The one-bond nucleophilic reactivities of seven cyclic α-diazo carbonyl compounds in dichloromethane were determined by analyzing the kinetics of their reactions with benzhydrylium ions (one-bond reference electrophiles) at 20 °C according to the Mayr-Patz equation. Though not calibrated for pericyclic reactions, the identified nucleophilicities also reflect relative reactivities of the α-diazo carbonyl compounds in 1,3-dipolar cycloadditions with dimethyl acetylenedicarboxylate. These (3+2)-cycloadditions primarily gave spirocyclic 3H-pyrazoles, which underwent thermal [1,5]-sigmatropic (van Alphen-Hüttel) rearrangements to furnish 1H-pyrazole-fused tricyclic products.