Kinetically controlled reactions alkylation

Nitroolefins also offer the possibilities of 1,2 cycloaddition (37,57) or simple alkylation (57-59) products when they are allowed to react with enamines. The reaction of nitroethylene with the morpholine enamine of cyclohexanone led primarily to a cyclobutane adduct in nonpolar solvents and to a simple alkylated product in polar solvents (57). These products are evidently formed from kinetically controlled reactions since they cannot be converted to the other product under the conditions in which the other... 

In both cations 221 and 225 the alkyl groups are easily split off by halide ions. Whereas addition to the carbenium ion leads in a kinetically controlled reaction to the addition products 226 and 227, this type of reaction leads to the thermodynamic stable unsaturated phosphinic acid esters 228 and 229. 

Despite the unfavorable experimental conditions in a batch system for kinetically controlled reactions, a selectivity of 80% in n-butane was achieved through ethylation of ethane. The results show, however, that to succeed in the direct alkylation the following conditions have to be met. (i) The olefin should be completely converted to... 

Thioamides (86) can react with electrophiles either at the sulfur or the nitrogen atom the former reaction occurs with acids to yield the Sprotonated species and with alkyl halides to give imidothiolic esters (94) (Scheme 51). On the other hand, with primary or secondary thioamides, N-alkylation may occur, possibly via kinetically controlled S-alkylation, to give an intermediate product which subsequently rearranges under appropriate conditions (Scheme 52). 

Dihydroquinazolines are in equilibrium with 3,4-dihydroquinazolines, which are generally thermodynamically more stable. In order to obtain 1,4-dihydroquinazoIines it is necessary to have a substituent at N-1 so as to freeze the tautomerism. The proportion of l//-l,4-hydroquinazoline produced in a kinetically controlled reaction can, however, be appreciable. This is demonstrated in the following reactions. 4-Phenylquinazoline was reduced with sodium in tetrahydrofuran to the monomeric dianion. When the dianion was treated with water or one equivalent of methyl iodide, only 4-phenyl- and 4-methyl-4-phenyl- 3,4-dihydroquinazolines were isolated. If, however, two molecular equivalents of methyl iodide were added, a mixture of 1,4-dimethy 1-4-phenyl- (16%) and 3,4-dimethyl-4-phenyl- (42%) 3,4-dihydroquinazolines was formed. The monomeric dianion of 2,4-diphen-ylquinazoline gave l,4-dimethyl-2,4-diphenyl- and 3,4-dimethyl-2,4-diphen-yl-3,4-dihydroquinazoline in 60% and 27% yields, respectively, with methyl iodide. If ethyl chloroformate was used as alkylating agent, on the other hand, an 85% yield of l,4-bisethoxycarbonyl-2,4-diphenyl-3,4-dihydroquin-azoline was formed. A similar behavior was observed when methyl lithium reacted with 2,4-diphenylquinazoline followed by methylation of the intermediate lithium salts [Eq. (8)]. ... 

Further reaction of diaziridines is responsible for the formation of bicyclic compounds 122a-c from aldehydes, chloramine and ammonia. The isomers 122a and 122b (R = various alkyl, aryl, and aralkyl groups) are obtained in a kinetically controlled reaction work-up in the presence of ammonium chloride yields an additional isomer 122c as a result of thermodynamic control. 

Despite the unfavorable experimental conditions in a batch system for kinetic controlled reactions, a selectivity of 80% in n-butane was achieved through ethylation of ethane. The results show, however, that to succeed in the direct alkylation the following conditions have to be met (1) The olefin should be totally converted to the reactive cation (incomplete protonation favors the polymerization and cracking processes) this means the use of a large excess of acid and good mixing. (2) The alkylation product must be removed from the reaction mixture before it transfers a hydride to the reactive cation, in which case the reduction of the alkene is achieved. (3) The substrate to cation hydride transfer should not be easy for this reason the reaction shows the best yield and selectivity when methane and ethane are used. 

The calculated reaction coordinate reveals higher stability and lower energy of the transition state alkyl borane on the prim-C-atom than on the scc-C-atom, although the energy content of the product prim-alcohol is higher than that of the sec-alcohol. The whole process is a typical example of a kinetically controlled reaction. 

Anotheranalogy between the enolate anions derived from a,)3-unsatura ted ketones and the corresponding enamines is encountered in their alkylation reactions (57), which proceed by the kinetically controlled attack at the a-carbon atom. For instance, Stork and Birnbaum (51) found that the alkylation of the morpholine enamine of /J -octalone-2 (117) with methyl iodide gave the C-1 methylated derivative (118). 

Lithiated areneacetonitriles react with a,/i-unsaturated ketones at low temperatures using short reaction times to give both 1,2- and 1,4-adducts. The 1,2-addition is reversible and under thermodynamic control (higher temperatures and longer reaction times) only the 1,4-adducts, i.e., <5-oxonitriles, arc obtained. When lithiated arylacetonitrile is added to 2-substituted 2-cy-cloalkenones in THF or in THF/HMPA mixtures at — 70-0°C, followed by protonation or alkylation under kinetically controlled conditions, predominantly cis- or fnms-2,3-disubstitut-ed cycloalkanones respectively, are obtained. 

In contrast to the results of the reaction of tertiary and secondary alkyl cations with carbon monoxide (Figs. 1-5), which were obtained under thermodynamically controlled conditions, the results of the carbonylation with the vinyl cations were obtained under kinetically controlled conditions. This presents a difficulty in explaining the occurrence of the 1,2-CH3 shift in the reaction 16->-17, because it involves a strong increase in energy. The exclusive formation of the Z-stereoisomer 18 on carbonylation of the 1,2-dimethylvinyl cation 16 is remarkable, but does not allow an unambiguous conclusion about the detailed structure— linear 19 or bent 20—of the vinyl cation. A non-classical structure 21 can be disregarded, however, because the attack... 

Kinetic data on the carbonylation of vinyl cations have not been obtained so far, but it is likely to be a diffusion-controlled reaction as in the case of primary alkyl cations (Section IV, A). 

Later work examined substituent effects on kinetically controlled alkylations [68, 69] (Scheme 32). Substitution at the 5-position is well tolerated in these reactions. Reductive lithiation of a series of 4-phenylthio-l,3-dioxanes and quenching of the axial alkyllithium intermediate with dimethyl sulfate provided the flzzfz -l,3-diols in good yield, with essentially complete selectivity. 

The tuning of solubility with a relatively small jump or fall in pressure can possibly bestow many benefits with respect to rates, yields, and selectivity. Reaction parameters can be changed over a wide range. Replacement of solvents with high boiling points by supercritical (SC) fluids offers distinct advantages with respect to removal of the solvent. SC fluids like CO2 are cheap and environmentally friendly the critical temperature of CO2 is 31 C and the critical pressure 73.8 atm (Poliakoff and Howdle, 1995). Eckert and Chandler (1998) have given many examples of the use of SC fluids. Alkylation of phenol with tcrt-butanol in near critical water at 275 °C allows 2- erf-butyl phenol to be formed (a major product when the reaction is kinetically controlled 4-rert-butyl phenol is the major product, when the reaction is... 

A catalyst used for the u-regioselective hydroformylation of internal olefins has to combine a set of properties, which include high olefin isomerization activity, see reaction b in Scheme 1 outlined for 4-octene. Thus the olefin migratory insertion step into the rhodium hydride bond must be highly reversible, a feature which is undesired in the hydroformylation of 1-alkenes. Additionally, p-hydride elimination should be favoured over migratory insertion of carbon monoxide of the secondary alkyl rhodium, otherwise Ao-aldehydes are formed (reactions a, c). Then, the fast regioselective terminal hydroformylation of the 1-olefin present in a low equilibrium concentration only, will lead to enhanced formation of n-aldehyde (reaction d) as result of a dynamic kinetic control. 

The first silicon-organophosphorus betaine with a thiolate center (15a) was synthesized by the reaction of stable silanethione (14) with trimethyl-methylenephosphorane (Scheme 8) and characterized by multinuclear NMR spectroscopy.14 Compound 15a is formed under kinetic control and is transformed, under the thermodynamically controlled conditions, into the silaacenaphthene salt (16). The processes presented in this scheme reflect the competition of the basicity and nucleophilicity of phosphorus ylides. Betaine 15b prepared from less nucleophilic and less basic ylide with phenyl substituents at the phosphorus atom is much less resistant toward retro-decomposition compared to the alkyl analog. Its equilibrium concentration does not exceed 6%. 

The relative extent of alkylation of 10, R = H, at N2 and N3 has been observed to vary substantially with the reaction conditions employed, and it now appears likely that the Nj-alkylated compound is the product of kinetic control. The betaines (79) are reasonably stable compounds and can readily be isolated they do, however, undergo both dealkylation (with regeneration of 10, R = H) and rearrangement to the 3-isomers on... 

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