Thermodynamic equilibration

Treatment of A -benzyltnfluoroacetimidoyl chloride with triethylamine in toluene at room temperature leads to in situ generation of trifluoroacetonitrile ben-zylide [4J] (equation 43), which reacts with methyl acrylate to form cycloadducts [43] (equation 44) Although the kinetic ratio of products favors the cis adduct (3 1), thermodynamic equilibration leads to an excess of the trans isomer (7 1). 

John Ward has functionalized an indane using method D in route to tetra-petalone A (46) (Fig. 4.24).25 The o-OBoc benzyl alcohol 44 undergoes addition with two equivalents of Grignard and affords after acidic workup the phenolic indane 45 in 73% yield. Because of steric effects, only one diastereomer is observed after hydrolysis of the enol ether and thermodynamic equilibration of the... 

The crude product consists mainly of the desired product protection of the cis-2,3-diol occurs only to a minor extent. The major side product from the reaction is the 1,3-dioxolane, which can be slowly converted to the required product under thermodynamic equilibrating conditions i.e., further treatment of the dioxolane with... 

Oxidation of the quinine C-9 hydroxy substituent to the ketone is best accomplished using the Woodward3 benzophenone/potassium t-butoxide method, now using toluene. The other oxidation methods investigated (Swern, Jones, ROCI variations) were less effective or limited because of the poor solubility of the substrate. Thermodynamic equilibration of these ketones has also been reported.3... 

As indicated previously, alkane metathesis is a thermodynamically equilibrated reaction. Indeed, for ethane at 150°C, with a AG° = -2kcalmoT, an equilibrium... 

The greater stability of the anti isomer is attributed to the pseudoequatorial position of the methyl group in the chair-like chelate. With larger substituent groups, the thermodynamic preference for the anti isomer is still greater.10 11 Thermodynamic equilibration can be used to control product composition if one of the desired stereoisomers is significantly more stable than the other. 

SR of ethanol has mainly been conducted under similar conditions as methane SR, which means relatively high temperatures, ambient pressure, and primarily with Ni- or Rh-based catalysts." Ideally, one mole of ethanol is converted into 6 moles of hydrogen (13). During SR, ethanol decomposes mainly through two different routes either by dehydrogenation to acetaldehyde (14) or dehydration to ethylene (15). These two intermediates can be further catalytically reformed to a thermodynamically equilibrated reaction mixture of H2, CO, CO2, CH4 and H2O (12, 16-18). ... 

The advantage of using the photocycloaddition of pentacarbonylcarbenechromium complexes over the ketene cycloaddition method is the absence of ketene dimerization and the avoidance of use of excess alkene in the former method. Also, the mild reaction conditions associated with the use of chromium carbene complexes avoids epimerization and thermodynamic equilibration of 2-monosubstituted cyclobutanones. 

When a semiconductor electrode is in contact with an electrolyte solution, thermodynamic equilibration takes place at the interface. This may result in the formation of a space charge layer within a thin surface region of the semiconductor, in which the electronic energy bands are generally bent upwards or downwards, respectively, in the cases of n- and p-type semiconductors. Fig. 2.3... 

The scheme of thermodynamic equilibration, particularly for 3-hydroxyaI-dehydes 75, as described above for FruA catalysis (Scheme 16) can likewise be applied to reactions with RhuA, the enantiomeric enzyme [189,220]. As is to be expected from the complementarity of the stereoselectivities of these enzymes, the corresponding enantiomeric compounds ent-78 are enriched upon equilibration. Owing to the lower diastereoselectivity of the RhuA versus the FruA enzyme, however, the corresponding FucA configurated isomer 85 accumulates more rapidly at the expense of the thermodynamically less favored diastereomer ent-19 (cf. Scheme 18, Sect. 5.2). 

The stereoselectivity of cyclization reactions conducted under conditions of thermodynamic control can often be reliably predicted by estimation or calculation of the energy differences between the diastereomers of the cyclization product (H) or its immediate precursor (G). It has been shown that, even in cases where the (G) to (H) step is not reversible, thermodynamic control of the diastereomer ratio can be influenced through the use of cyclization substrates in which the neutralization step (G to H) is the slow step, thus allowing for equilibration of the diastereomers of (G). Thermodynamic equilibration of dia-stereomeric products will occur only if the reaction reverses to starting materials (A), or interconversion of the diastereomers of the intermediates (B) or (C) occurs in some other way (e.g. the C to D interconversion can equilibrate diastereomers if E = X). 

These stepwise reactions raise yield and selectivity issues in the final acyclic carbonates, due to thermodynamics constraints. The second strategy, the so-called direct route, consists of converting C02 in one-step to create an end-product (Equation 7.8). This reaction is also thermodynamically equilibrated (see below). 

It is important that any attempted equilibrations are performed under identical conditions to those used for the preparation of the adducts under investigation. The only variation made to these attempted equilibration conditions from those used for the syntheses of 41 and 68 was the use of considerably greater excess of the unlabeled bisdiene 37 in order to drive the equilibrium towards the formation of 41. The hexadecadeuterio 2 1 adduct 68 was heated under reflux in toluene with 10 molar equivalents of the bisdiene 37 for ca. 48 hours (Scheme 18). By this time, indications of thermally-promoted degradation of the starting materials had become evident by TLC investigation. If thermodynamic equilibration had been occurring via retro-Diels-Alder reactions of 68, followed by scrambling of the labeled and unlabeled bisdienes, 66 and 37, respectively, prior to recombination... 

Besides its use as a mechanistic probe, deuteriation of anions under kinetically controlled conditions is a potentially promising way to access deuteriated molecules in a regio- and stereo- controlled manner, in opposition to the thermodynamic equilibration in the presence of an excess of deuterium donor. Thus, treatment of the lithium anion of 2-methyltetralone (p E = 7.31, pfsfEa = 10.8, pKkr = 18.1 in water)335, by one equivalent of a solution of deuterium chloride in deuterium oxide, generates the intermediate O-deuteriated enol whose reaction with water or with an excess of deuterium chloride in deuterium oxide conducts to, respectively, the tetralone or the deuteriated tetralone (Scheme 69)336. 

The kinetically controlled nucleophilic addition of preformed lithium enolates onto carbonyl compounds is reversible with a low activation barrier, and the thermal conditions are likely to have a major impact on the stereoisomeric ratio of the final aldols through the retroaldolization and the thermodynamic equilibration of lithium enolates76. The tendency of aldolates to undergo retroaldolization increases with the stability of enolates, and when going from lithium to potassium. On the other hand, boron enolates usually undergo completely irreversible aldol reaction511,512. 

Coordination chemistry is particularly amenable to DCC. The labile nature of most metal-ligand coordination bonds assures facile and reversible connections among the constituents, which enables quick thermodynamic equilibration of the system. Furthermore, metals may assume a wide variety of coordination stoichiometries and geometries, thereby yielding highly diverse DCLs. It is therefore not surprising that some of the first DCC systems were based on coordination complexes,... 

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