Intermolecular competition reactions

The electronic nature of silylsilver intermediate was interrogated through inter-molecular competition experiments between substituted styrenes and the silylsilver intermediate (77).83 The product ratios from these experiments correlated well with the Hammett equation to provide a p value of —0.62 using op constants (Scheme 7.19). Woerpel and coworkers interpreted this p value to suggest that this silylsilver species is electrophilic. Smaller p values were obtained when the temperature of the intermolecular competition reactions was reduced [p = — 0.71 (8°C) and —0.79 (—8°C)]. From these experiments, the isokinetic temperature was estimated to be 129°C, which meant that the product-determining step of silver-catalyzed silylene transfer was under enthalpic control. In contrast, related intermolecular competition reactions under metal-free thermal conditions indicated the product-determining step of free silylene transfer to be under entropic control. The combination of the observed catalytically active silylsilver intermediate and the Hammett correlation data led Woerpel and colleagues to conclude that the silver functions to both decompose the sacrificial cyclohexene silacyclopropane as well as transfer the di-terf-butylsilylene to the olefin substrate. 

Scheme 7.45. Intermolecular competition reactions that examine the relative rates of cycloaddition and cyclization.

Fig. 9. The structures of L-methionine, GSMe, GSH, 5 -GMP and dGpG used as model compounds in intermolecular competition reactions...

This simple model is valid in fact for P isotope effects and does not take into account the existence of intermolecular competitive reactions which occur frequently in transformations involving C-H bond breaking (refs. 7, 8). Indeed the abstraction of a hydrogen atom from a group in the substrate having n equivalent germinal and m equivalent vicinal positions AHn BHm, involves a set of different isotope effects... 

In order to characterize the nature of the oxygenating species formed in the reactions of H2O2, PhIO, MCPBA, and dioxygen plus aldehyde, we studied stereoselectivity in c/5-stilbene epoxidation, regioselectivity in (+)-limonene and norbornene epoxidations, and intermolecular competitive reactions between cyclohexene... 

Scheme 9.1 Intermolecular competitive reaction of nitrobenzene and styrene in an acetonitrile suspension of Ti02 in the presence of oxalic acid as a hole scavenger...

In order to safely identify k0 with intramolecular carbenic reactions (e.g., k and the formation of alkene 4 in Scheme 1), product analysis should demonstrate that the yield of intramolecular products exceeds 90%, while dimer, azine, and solvent-derived (intermolecular) carbene products should be absent or minimal. If these conditions are not met, mechanistic interpretation is often ambiguous, a result that is well illustrated by the saga of benzylchlorocarbene (see below, Section IV.C). Less desirably, k0 can be corrected for competitive intermolecular carbenic reactions. Bimolecular reactions like dimerization and azine formation can be minimized by working at low carbene precursor concentrations, and careful experimental practice should include quantitative product studies at several precursor concentrations to highlight potential product contamination by intermolecular processes. 

DFT studies of the intramolecular ene-like (or the so-called 1,3-dipolar ene) reaction between nitrile oxides and alkenes show that this reaction is a three-step process involving a stepwise carbenoid addition of nitrile oxide to form a bicyclic nitroso compound, followed by a retro-ene reaction of the nitrosocyclopropane intermediate. The competitive reactions, either the intramolecular [3 + 2] cycloaddition between nitrile oxides and alkenes or the intermolecular dimerization of nitrile oxides to form furoxans, can overwhelm the intramolecular 1,3-dipolar ene reaction if the tether joining the nitrile oxide and alkene is elongated, or if substituents such as trimethylsilyl are absent (425). 

In the hydroxycyclopropanation of alkenes, esters may be more reactive than N,N-dialkylcarboxamides, as is illustrated by the exclusive formation of the disubstituted cyclopropanol 75 from the succinic acid monoester monoamide 73 (Scheme 11.21) [91]. However, the reactivities of both ester- as well as amide-carbonyl groups can be significantly influenced by the steric bulk around them [81,91]. Thus, in intermolecular competitions for reaction with the titanacydopropane intermediate derived from an alkylmagnesium halide and titanium tetraisopropoxide or methyltitanium triisoprop-oxide, between N,N-dibenzylformamide (48) and tert-butyl acetate (76) as well as between N,N-dibenzylacetamide (78) and tert-butyl acetate (76), the amide won in both cases and only the corresponding cyclopropylamines 77 and 79, respectively, were obtained (Scheme 11.21) [62,119]. 

The intramolecular kinetic isotope effect determined in reaction of BTNO with p-MeO-C6H4CH(D)0H gave a h/ d ratio of 5.6 in MeCN , consistent with a rate-determining H-abstraction step. Additional determinations gave a h/ d of 7 with PhCH(D)OH, and 12 for the intermolecular competition of fluorene vs. 9,9-dideuteriofluorene. The latter value supports the contribution of tunnelling already commented on for reaction of PINO with various C—H donors ( h/ d values in the 11-27 range) . ... 

Interestingly, the newly developed Ar3BiCl2/DBU oxidants [Ar = p-nitrophenyl, p-(trifluoromethyl)phenyl] rapidly oxidize 2,2,2-trifluoro-l-phenylethanol [81], which is generally known to resist oxidation [85-87], to the corresponding trifluor-omethyl ketone within 5-50 min at room temperature (Scheme 21). The difference in the reaction rates among the bismuth(V) oxidants is in good agreement with the results obtained for the intermolecular competition experiments. 

In sharp contrast to simple alkenes that undergo silylcarbonylation, genuine silylformylation of an olefinic moiety is attained only by an intramolecular technique (Equation (33)). Since the most serious competitive reaetion is an intermolecular hydrosilylation reaction to form 192, the key for the successful transformation depends on an appropriate combination of substituents R and R. ... 

Ameline, G. Vaultier, M. Mortier, J. Directed metalation reactions. Intermolecular competition of the carboxylic acid group and various substituents. Tetrahedron Lett. 1996, 37, 8175— 8176. 

A key feature of the competitive isotope fractionation measurements is the use of natural abundance O2. Isotope effects are, therefore, determined for the reactions of the most abundant isotopologues 160-160 and 180-160. It is the intermolecular competition of these species that is reflected in the isotope effect. Aside from the obvious advantage of not requiring costly enriched materials, the competitive measurements also avoid the error that could arise from small leaks in the vacuum manifold and dilution due to ambient air. 

Reactions ofN-acetyl-L-Methionine Complexes ofPtu(en) with 5 -GMP and dGpG. Recently, intermolecular competition was studied in more de-... 

To evaluate the effect of the substituent more accurately, a competition study with equimolar mixtures of C6H6-C6H5X(X = OH, F, Cl) was carried out by Norseyev and colleagues50. Quantitative evaluation of intermolecular competition for hydrogen replacement was performed on the basis of the Hammett relationship applying the yields of replacement products instead of reaction rate constants, according to equation 10 ... 

These results indicate that when the intermediate 3-halo- 1-adamantyl radical couples with Ph2P" ions, it forms the radical anion (38)" which reacts via two competitive reactions. One is the intramolecular ET to the C—X <7 bond, which fragments to give the radical 39 that enters the propagation cycle to give ultimately 36 or is being reduced to 37. The other possibility is the intermolecular ET to the substrate to give the monosubstitution product 38 (equation 46). 

Certain diazoketones, for example diazopyruvate, alkyl 2-diazo-3-oxobutyrate or 3-diazo-2,4-pentanedione, react with vinyl ethers under metal catalysis to give dihydrofurans rather than cyclopropanes l Most work on this type of transformation has been that of Wenkert and Alonsoand their respective groups. A representative example is shown in equation 107. Finally, carbenoid dimerization is also a competitive reaction in metal catalysed intermolecular cyclopropanation. However, control of the chemoselectiv-ity to favour the cyclopropanation is possible. In general, the dimeric product can be avoided by using excess of alkene or by very slow addition of the diazo compound to a mixture of alkene and catalyst... 

Treatment of trichlorogermylphosphine 183 with a twofold excess of DBU in tetrahydrofuran gave bis[bis(trimethylsilyl)methyl]diphosphene (186), bis(trimethylsilyl)methylphosphine (187), and diphosphine 188 in the proportions 55 25 20. The proposed reaction mechanism is depicted in Scheme 4. Compound 184 was probably first formed through the elimination of germanium dichloride, and then reacted further with an excess of DBU in two competitive reaction routes to give compounds 186-188. Intermolecular dehydrochlorination of 184 afforded diphosphene 186, while intramolecular dehydrochlorination of 184 resulted in 187 and 188 via the triplet phos-phinidene intermediate 185 (84CC1621). 

In intermolecular competition, a mixture of labeled and unlabeled reactants compete for a limited amount of reagent reactions (1) and (2) thus go on in the same mixture, and we measure the relative amounts of H—Z and D—Z t. oduced. (Sometimes, larger amounts of the reagent Z are used, and the relative amounts of the two reactants—ordinary and labeled—left unconsumed are measured the less reactive will have been used up more slowly and will predominate. The relative rates of reaction can be calculated without much difficulty.)... 

By intermolecular competition of an allylsilane and a homoallylstannane for reaction with an electrophile, the P-effect of silicon has been shown to be more effective than the y-effect of tin in activating the double bond towards addition.40 41... 

Rare-earth metal complexes have proven to be very efficient catalysts for intramolecular hydroamination reactions involving aminoalkenes, aminoalkynes, aminoallenes, and conjugated aminodienes [88, 97]. They are significantly less efficient in intermolecular hydroamination reactions and only a limited number of examples are known [98-102]. The difficulties in intermolecular hydroamination reactions originate primarily from inefficient competition between strongly binding amines and weakly binding alkenes for vacant coordination sites at the catalytically active metal center. 

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