Alkenes philicity

Hydroboration-oxidation (Sections 6 11-6 13) This two step sequence achieves hydration of alkenes in a ste reospecific syn manner with a regiose lectivity opposite to Markovnikov s rule An organoborane is formed by electro philic addition of diborane to an alkene Oxidation of the organoborane inter mediate with hydrogen peroxide com pletes the process Rearrangements do not occur... 

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. 

The overall reaction catalyzed by epoxide hydrolases is the addition of a H20 molecule to an epoxide. Alkene oxides, thus, yield diols (Fig. 10.5), whereas arene oxides yield dihydrodiols (cf. Fig. 10.8). In earlier studies, it had been postulated that epoxide hydrolases act by enhancing the nucleo-philicity of a H20 molecule and directing it to attack an epoxide, as pictured in Fig. 10.5, a [59] [60], Further evidence such as the lack of incorporation of 180 from H2180 into the substrate, the isolation of an ester intermediate, and the effects of group-selective reagents and carefully designed inhibitors led to a more-elaborate model [59][61 - 67]. As pictured in Fig. 10.5,b, nucleophilic attack of the substrate is mediated by a carboxylate group in the catalytic site to form an ester intermediate. In a second step, an activated H20... 

The radical versus electrophilic character of triplet and singlet carbenes also shows up in relative reactivity patterns shown in Table 10.1. The relative reactivity of singlet dibromocarbene toward alkenes is more similar to that of electrophiles (bromination, epoxidation) than to that of radicals ( CC13). Carbene reactivity is strongly affected by substituents.61 Various singlet carbenes have been characterized as nucleophilic, ambi-philic, and electrophilic as shown in Table 10.2. This classification is based on relative reactivity toward a series of different alkenes containing both nucleophilic alkenes, such as tetramethylethylene, and electrophilic ones, such as acrylonitrile. The principal structural feature that determines the reactivity of the carbene is the ability of the substituents to act as electron donors. For example, dimethoxycarbene is devoid of electrophilicity toward... 

Philicity. A principal feature of the carbene-alkene addition reaction (Scheme 7.1) is the carbene s phihcity, that is the electronic character of its selectivity or response to the alkene s substituents. Early work of SkeU and Garner and Doering and Henderson showed that CBr2 and CCI2 preferentially... 

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). " ... 

Extreme cases were reactions of the least stabilized, most reactive carbene (Y = CF3, X = Br) with the more reactive alkene (CH3)2C=C(CH3)2, and the most stabilized, least reactive carbene (Y = CH3O, X = F) with the less reactive alkene (1-hexene). The rate constants, as measured by LFP, were 1.7 x 10 and 5.0 X lO M s, respectively, spanning an interval of 34,000. In agreement with Houk s ideas,the reactions were entropy dominated (A5 —22 to —29e.u.). The AG barriers were 5.0 kcal/mol for the faster reaction and 11 kcal/ mol for the slower reaction, mainly because of entropic contributions the AH components were only —1.6 and +2.5 kcal/mol, respectively. Despite the dominance of entropy in these reactive carbene addition reactions, a kind of de facto enthalpic control operates. The entropies of activation are all very similar, so that in any comparison of the reactivities of alkene pairs (i.e., ferei)> the rate constant ratios reflect differences in AA//t, which ultimately appear in AAG. Thus, car-benic philicity, which is the pattern created by carbenic reactivity, behaves in accord with our qualitative ideas about structure-reactivity relations, as modulated by substiment effects in both the carbene and alkene partners of the addition reactions. " Finally, volumes of activation were measured for the additions of CgHsCCl to (CH3)2C=C(CH3)2 and frani-pentene in both methylcyclohexane and acetonitrile. The measured absolute rate constants increased with increasing pressure Ayf ranged from —10 to —18 cm /mol and were independent of solvent. These results were consistent with an early, and not very polar transition state for the addition reaction. 

Azides have been found to add to acetylenic compounds to give 1,2,3-triazoles.1 255-301 Huisgen reported that the dipolaro-philic activity of alkynes is similar in magnitude to that of alkenes concluding that the transition state of the cycloaddition does not profit from the aromatic resonance of the products.133... 

Our earlier studies of the bimolecular alkene addition reactivity of a,a-difluoro alkyl radicals indicated that they exhibited little philicity , reacting with styrene and pentafluorostyrene (IPs 8.43 and 9.20, respectively) at virtually the same rate [70]. Their significantly greater reactivity in bimolecular additions, hydrogen-abstraction reactions and unimolecular cyclizations can therefore be largely attributed to their pyramidal nature, with some possible thermodynamic con-... 

It should be noted that it is in many cases conceivable that isoxazoles and isoxazolines are formed from chloroximes without the intermediacy of a nitrile oxide. This route could occur if the substrate acted as a nucleophile to give an intermediate, such as the alkynyloxime (25) from an acetylide, which can cyclize to the isoxazole (26). In this case, by trapping with nonnucleo-philic alkenes, the reaction has been shown to involve a nitrile oxide.60,71 However, experiments on reactions of chloroximes with other nucleophiles suggest that a nitrile oxide is not invariably involved.72,73... 

The elementary reactions of carbocationic polymerizations can be separated into three types. Deactivation of carbenium ions with anions and transfer to counteranion are ion-ion reactions, propagation and transfer to monomer are ion-dipole reactions, and ionization is a dipole-dipole reaction [274]. Ion-ion and dipole-dipole reactions with polar transition states experience the strongest solvent effects. Carbocationic propagation is an ion-dipole reaction in which a growing carbenium ion adds electro-philically to an alkene it should be weakly accelerated in less polar solvents because the charge is more dispersed in the transition state than in the ground state [276]. However, a model addition reaction of bis(p-methoxyphenyl)carbenium ions to 2-methyl- 1-pentene is two times faster in nitroethane (e = 28) than in methylene chloride (e = 9) at - 30° C [193]. However, this is a minor effect which corresponds to only ddG = 2 kJ morit may also be influenced by specific solvation, polarizability, etc. [276,277]. 

Friedrich et al. [45] discovered that a catalytic amount of titanium(IV) chloride as a Lewis acid greatly facilitates cyclopropanation reactions of alkenes by the system CFl2Br2-Zn-CuCl. The Lewis acid catalyst might bind to the oxygen atom of the allylic alcohol present as the (iodomethyl)zinc alkoxide, and thus increase the electro-philicity of the methylene group [46]. 

The first breakthroughs in this chemistry appeared with the independent works of Breslow [5] and Mansuy [6] who reported the use of Fe(III) and Mn(ni) porphyrins complexes with tosylimidoiodobenzene (Phi = NTs) [7] as an N centered electro philic oxidant (Scheme 12.3). Treatment of an alkene with a high valent Mn nitrene favored the C H insertion product over the competing aziridination reaction. However, yields in these intermolecular reactions remained low. A mixture of N tosylated allylic products was obtained with the product distribution best ratio nalized by a radical C H abstraction/rebound process [6]. 

Arylation of alkenes catalyzed by palladium compounds is known as the Heck reaction [65]. While these reactions are very sensitive to steric effects, subtle electronic contributions to the regiochemical outcome may be assessed by comparing reactions of alkenes with similar substitution patterns. The arylating agents, being the nudeo-philic arylpalladium species, tend to dictate the fadlity of their reaction with unsym-metrical, electron-deficient alkenes. 

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. 

Eq. 4 enabled an empirical analysis of carbenic selectivity (or philicity). (1) It correlated the selectivities of many of the carbenes that had been studied up to 1976. [8,17] (2) It quantitated the qualitative concepts of carbene-aUcene addition reactions that were prevalent. (3) Most importantly, it could be used to estimate the selectivity of new carbenes. (4) It led to the identification of ambi-philic carbenes. (5) It would later be found to parallel conclusions drawn from ah intio electronic structure calculations of carbene-alkene addition reactions. Eet s examine features (1) - (4) ah initio calculational results will be considered below, in Section 2.1. 

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. ... 

Mendez and Garcia-Garibay analyzed carbene/alkene charge transfer by density functional theory and ab initio methods. [81] Electrophilicity and nucleo-philicity were assessed by calculating AN, which represented charge transfer between the carbene and alkene cf., Eq. 8. Here, p is the chemical potential taken as -(I+A)/2, where I represents ionization potential, and A represents electron affinity, rj is the hardness of the alkene or carbene, defined as (I-A)/2. 

Figure 7 depicts the computed AN values for 15 carbenes adding to 4 alkenes. The alkenes include Me2C=CMe2, tra 5 -MeCH=CHMe, CH2=CH2, and CH2=CHCN, thus spanning electron-rich to electron-poor substrates. The carbenes span electrophiles (CCI2, CFCl, CF2), ambiphiles (MeOCCl, MeOCF), and nucleophiles (C(OH)2, C(OMe)2). The philicities measured by AN [81] are found to be in reasonable accord with conclusions that we reached on the basis... 

Despite the dominance of entropy in these reactive carbene addition reactions a kind of defacto enthalpic control operates the entropies of activation are all very similar, so that in any comparison of the reactivities of alkene pairs (i.e., rgi), the rate constant ratios reflect differences in AAHi, which ultimately appear in AAGf Thus carbenic philicity, which is the pattern created by carbenic reactivity, behaves in accord with our qualitative ideas about structure/reactivity relations, as modulated by substituent effects in both the carbene and alkene partners of the addition reactions. [66,99]... 

What about the classic ambiphile, MeOCCl In Table 8, we summarize values for MeOCCl, determined by a combination of absolute and relative rate measurements. [101] Also included are analogous data for PhCOMe, [102] MeCOMe, [73] and MeCOCH2CF3. [103] For MeOCCl, we note that the ambi-philic reactivity pattern emerges from the absolute rate constants of Table 8 as clearly as it does from the relative rate constants of Table 4 high reactivity toward electron-rich or electron-poor alkenes, but low reactivity toward aUcenes of intermediate electron density. However, whereas the relative rate data can only inform us about the carbene s selectivity pattern, the absolute rate data reveals the carbene s true reactivity. In fact, for the addition of MeOCCl to trans-butene (3.3 x 10 M s ) is the lowest bimolecular rate constant yet measured for a carbene/aUcene addition in solution. [101] And with 1-hexene, only 5% of MeOCCl addition was observed this reaction is so slow that other competitive processes prevail. [101]... 

Although we have restricted our discussions of carbenic philicity to carbene/ alkene addition reactions, the use of other substrates can also be informative. For example, both MeCOMe and (MeO)2C react with (oligomeric) methanol in pentane to give the formal 0-FI insertion products, 36 and 37, respectively. [72,73] As we would expect, the reaction of MeCOMe (7x10 M" s" ) is more rapid than that of (MeO)2C (2.5 x 10 M" s" ). Further study of the reactions of (MeO)2C with a wide range of hydroxylic substrates shows that log inversely proportional to the of ROFI, affording a Bronsted relation with a = -0.66. [107] Furthermore, from the absolute rate constants for (MeO)2C reactions with MeOH and MeOD, the primary kinetic isotope effect for the... 

It is also possible to maintain catalysts in the upper SCCO2 phase using a CO2-philic phosphine as a ligand. Hydroformylation of water-soluble alkenes is catalyzed... 

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