Kinetic control Subject

Under the usual conditions their ratio is kinetically controlled. Alder and Stein already discerned that there usually exists a preference for formation of the endo isomer (formulated as a tendency of maximum accumulation of unsaturation, the Alder-Stein rule). Indeed, there are only very few examples of Diels-Alder reactions where the exo isomer is the major product. The interactions underlying this behaviour have been subject of intensive research. Since the reactions leadirig to endo and exo product share the same initial state, the differences between the respective transition-state energies fully account for the observed selectivity. These differences are typically in the range of 10-15 kJ per mole. ... 

The optical rotatory dispersion curves of steroidal ketones permit a distinction to be made between the conformations, and assignment of configuration is possible without resorting to chemical methods (see, e.g. ref. 36) which are often tedious. The axial halo ketone rule and, in the more general form, the octant rule summarize this principle and have revealed examples inconsistent with the theory of invariable axial attack in ketone bromination. 2-Methyl-3-ketones have been subjected to a particularly detailed analysis. There are a considerable number of examples where the products isolated from kinetically controlled brominations have the equatorial orientation. These results have been interpreted in terms of direct equatorial attack rather than initial formation of the axial boat form. 

These results have led to the conclusion (11) that the formation of enammonium salts is kinetically controlled, while the protonation on the 3-carbon atom is subject to thermodynamic control, t Only tertiary enamines will be considered,... 

The reactivity of the methyl group in 4-methylcinnoline ethiodide indicates that the structure of this compound is 5, and this evidence has also been interpreted to mean that N-1 is the basic group in cinnolines. However, evidence of this type is only indicative since the formation of quaternary salts is subject to kinetic control, whereas protonation yields predominantly the thermodynamically more stable cation. The quinazoline cation has been shown to exist in the hydrated, resonance-stabilized form 6 7 by ultraviolet spectro-... 

Representatives of the bridged sulfone system 70 have been subjected to ruthenium catalysed ring-closing metathesis reactions (Grubbs catalyst) and shown to afford, in low yields, a few selected cyclic dimers and trimers, of all the possibilities available. The diastereoselectivities observed were rationalised in terms of kinetic control involved with internal ruthenium/sulfonyl oxygen coordination . 

In 1994, Diederich and co-workers reported a very important approach for the regioselective formation of multiple adducts of Cjq by tether-directed remote functionalization [75]. This technique allows for the synthesis offullerene derivatives with addition patterns that are difficult to obtain by thermodynamically or kinetically controlled reactions with free untethered addends. This important subject has been extensively reviewed [26, 76, 77]. 

The preparation of 620, a tricyclic intermediate suited for elaboration into quadrone, has been reported by Monti and Dean Following introduction of the proper C5, stereochemistry by alkylation of 618 under kinetically controlled conditions, diketone 619 was subjected to acid-catalyzed rearrangement. After functional group manipulation, a tandem intramolecular aldol-pinacol rearrangement gave 620. 

Dimerization of lff-azepines is an extensively studied phenomenon and involves a temperature dependent cycloaddition process. At low (0°C for 1 R = Me) or moderate (130 °C for 1 R = C02R or CN) temperatures a kinetically controlled, thermally allowed [6 + 4] dimerization to the exo -adduct (73) takes place, accompanied by a small amount (<10%) of symmetrical dimer (74). The latter are thermodynamically favored and become the major products (83%) when the Iff-azepines are heated briefly at 200 °C. The symmetrical dimers probably arise by a non-concerted diradical pathway since their formation from the parent azepines by a concerted [6+6]tt cycloaddition, or from dimer (73) by a 1,3-sigmatropic C-2, C-10 shift are forbidden on orbital symmetry grounds. Dimerization is subject to steric restraint and is inhibited by 2-, 4- and 7-substituents. In such cases thermolysis of the lif-azepine brings about aromatization to the correspondingly substituted JV-arylurethane (69JA3616). 

The products obtained in a reaction subject to kinetic control are not necessarily the same as those obtained under equilibrium control. Indeed, the equilibrium constant for interconversion of fert-butyl bromide and isobutyl... 

There are exceptions to favored endo stereochemistry of Diels-Alder additions. Some of these exceptions arise because the addition reaction is reversible, dissociation being particularly important at high temperature. The exo configuration is generally more stable than the endo and, given time to reach equilibrium (cf. Section 10-4A), the exo isomer may be the major adduct. Thus endo stereospecificity can be expected only when the additions are subject to kinetic control. 

Why is only one of these products formed To understand this, you must recognize that aldol reactions are reversible and therefore are subject to equilibrium rather than kinetic control (Section 10-4A). Although the formation of 10 is mechanistically reasonable, it is not reasonable on thermodynamic grounds. Indeed, while the overall A/7° (for the vapor) calculated from bond energies is —4 kcal mole 1 for the formation of the aldol, it is +20.4 kcal mole-1 for the formation of 1Q.2 Therefore, the reaction is overwhelmingly in favor of the aldol as the more stable of the two possible products. 

When the cyclization substrate (A Scheme 3) contains stereogenic centers, and the formation of the C—Z bond generates a new stereogenic center, two diastereomers of the cyclization product (H) can be formed (stereospecific anti addition assumed). The factors which lead to high stereoselectivity in this process are of considerable importance and have been the subject of numerous studies in recent years. This reaction mechanism shows that all pathways leading to cyclic products are potentially reversible thus, the ratios of products in these reactions may be the result of thermodynamic rather than kinetic control. Unfortunately, many studies have not determined which type of control was operating under the reaction conditions used. 

Stereoelectronic effects should also play an important role in the nucleophilic 1,4-additions of anions to conjugated systems. These effects should therefore influence the Michael reaction as well as the hydrocyanation of a,6-unsaturated ketones. Studies on these reactions provided evidence that the kinetically controlled addition of a nucleophile to a cyclohexenone derivative is indeed subject to stereoelectronic effects. 

The formation of mixed crystals by means of a solid-state reaction occurs under kinetic control and may be subject to different constraints than the formation of mixed crystals grown closer to equilibrium conditions from the melt or from solvents. However, whether or not mixed crystallization is possible, and to what extent, is still determined by the structural similarity of the reactant and the product. Kitaigorodskii suggested guidelines based on a volume analysis which indicate that chemically compatible compounds which have optimized overlapping volumes larger than ca. 75% are likely to form solid solutions [66],... 

The most interesting aspect of these cycloadditions is their high regioselectivity. However, the direction of cycloaddition may well be subject to kinetic and thermodynamic control. For example, when 2,2-dimethylpyrrolidine N- oxide and ethyl acrylate were mixed at room temperature (thermodynamic control), the pyrrolidinoisoxazolidine (187) was formed quantitatively. When the mixture of the two reagents was heated at 100 °C, the kinetically controlled 1 1 cycloadduct (186) was obtained in 98% yield (63JCS4693). 

Unlike groundwater flow and transport models, thermodynamic models, in principal, do not need any calibration. However, considering surface-controlled or kinetically controlled reaction models might be subject to calibration. 

Since the formation of silyl enol ethers from the corresponding ketones is subject to dther thermodynamic or kinetic control, Ais reagent can be used (as demonstrated in equation 36) to achieve useful regiospecific cleavages. 

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