Stereoisomers Thermodynamics

Long-chain primary alcohols, eg, triacontanol, can be prepared by the hydroboration, isomerization, and oxidation of the corresponding internal alkenes (437). The less thermodynamically stable stereoisomer can be transformed into the more stable one by heating, eg, i j -into /ra/ j -myrtanjiborane (204). 

The first, and to this writing still only case of a ketone a-cleavage-recombi-nation sequence in the steroid field was reported by Butenandt, who found that 17-ketones epimerize at C-13. Ultraviolet irradiation of either stereoisomer produces an equilibrium mixture in which the thermodynamically more favored 13a-compound cf. (15)] with cw-fusion of rings C and D predominates at room temperature. As ultraviolet absorption energies and intensities of the two isomeric ketones are practically identical, the equilibrium composition depends largely on the rate of the competing recombination process from (14). For further examples of the photoisomerization at C-13 of 17-ketosteroids, see ref. 8, 12, 15 and 43. 

Draw the other stereoisomer that might have been obtained from syn addition of hydrogen to each alkene. Is the observed product for each addition also the thermodynamic product Compare energies for alkene A+ H2 observed and not observed and alkene B+H2 observed and not observed. What structural factors seem to be responsible for the relative stabilities of the two products of each hydrogenation reaction ... 

The product of nucleophilic attack can be anticipated by examining the lowest-unoccupied molecular orbital (LUMO) on protonated cyclopentene oxide. From which direction (top or bottom) would a nucleophile be more likely to approach each epoxide carbon in order to transfer electrons into this orbital Explain. Does one carbon contribute more to the LUMO, or is the orbital evenly spread out over both epoxide carbons Assuming that LUMO shape dictates product stereochemistry, predict which stereoisomers will be obtained, and their approximate relative amounts. Is the anticipated kinetic product also the thermodynamic product (Compare energies of 1,2-cyclopentanediol stereoisomers to tell.)... 

The palladium-catalyzed cyclization of compound 138 amply demonstrates the utility of the Stille reaction as a macrocyclization method (see Scheme 37). This efficient ring closure is just one of many examples disclosed by J.E. Baldwin and his group at Oxford.58 Interestingly, compound 138 can be employed as a stereoisomeric mixture of vinylstannanes because both stereoisomers converge on the same cyclized product. To rationalize this result, it was suggested that the configuration of the vinylstannane moiety is conserved in the cyclization, but that the macrocycle resulting from the (Z)-vinylstannane stereoisomer isomerizes to the thermodynamically favored trans product under the reaction condi-... 

The exocyclic C — C double bond in the chlorin can be reduced by catalytic hydrogenation in tetrahydrofuran/water in the presence of palladium(II) acetate with triethoxysilane as hydrogen source to yield under kinetic control cw-stereoisomers, which can be transformed by treatment with /)-toluenesulfonic acid in methanol to the thermodynamically favored trans-isomers.27d... 

The most common states of a pure substance are solid, liquid, or gas (vapor), state property See state function. state symbol A symbol (abbreviation) denoting the state of a species. Examples s (solid) I (liquid) g (gas) aq (aqueous solution), statistical entropy The entropy calculated from statistical thermodynamics S = k In W. statistical thermodynamics The interpretation of the laws of thermodynamics in terms of the behavior of large numbers of atoms and molecules, steady-state approximation The assumption that the net rate of formation of reaction intermediates is 0. Stefan-Boltzmann law The total intensity of radiation emitted by a heated black body is proportional to the fourth power of the absolute temperature, stereoisomers Isomers in which atoms have the same partners arranged differently in space, stereoregular polymer A polymer in which each unit or pair of repeating units has the same relative orientation, steric factor (P) An empirical factor that takes into account the steric requirement of a reaction, steric requirement A constraint on an elementary reaction in which the successful collision of two molecules depends on their relative orientation. 

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... 

Since compounds with alkyl equatorial substituents are generally more stable, trans-1,2 compounds, which can adopt the ee conformation, are thermodynamically more stable than their cis-1,2 isomers, which must exist in the ae conformation. For the 1,2-dimethylcyclohexanes, the difference in stability is about 2kcal moP (8 kJ mol" ). Similarly, trans-1,4 and cis-1,3 compounds are more stable than their stereoisomers. 

Samarium metal in isopropanol also achieves reduction.195 Like the Meerwein-Pondorff-Verley procedure, these conditions are believed to be under thermodynamic control and the more stable stereoisomer is the main product.196... 

The isomerization barrier of 15.0-20.0 kcal mol-1 (AG ) can be considered to be large enough to allow isolation and characterization of bis(q3-<2 /),A- nms-dodecatrienediyl-Nin stereoisomers of 7b41 as reactive intermediates in the stoichiometric cyclotrimerization process. Furthermore, the trans orientation of the two allylic groups gives rise to an insurmountable barrier for reductive elimination for these cases, which prevents these species from readily leaving the thermodynamic sink via a facile reductive elimination. The isolated intermediates clearly constitute dead-end... 

A thermodynamically stable (silyl)(stannyl)palladium(n) complex is synthesized by an oxidative addition of the Si-Sn linkage to palladium(O) (Scheme 63).267 The complex has the square-planar geometry with a m-arrangement of the silicon and tin atoms. An alkyne reacts with the complex to afford a silastannated product as a mixture of cisjtrans stereoisomers (10 1). 

Free radical addition of HBr to buta-1,2-diene (lb) affords dibromides exo-6b, (E)-6b and (Z)-6b, which consistently originate from Br addition to the central allene carbon atom [37]. The fact that the internal olefins (E)-6b and (Z)-6b dominate among the reaction products points to a thermodynamic control of the termination step (see below). The geometry of the major product (Z)-(6b) has been correlated with that of the preferred structure of intermediate 7b. The latter, in turn, has been deduced from an investigation of the configurational stability of the (Z)-methylallyl radical (Z)-8, which isomerizes with a rate constant of kiso=102s 1 (-130 °C) to the less strained E-stereoisomer (fc)-8 (Scheme 11.4) [38]. 

The transfer of the silyl ligand onto the a-carbon of the substrate is followed by the formation of an intermediate in which the (1-phenylethyl)trichlorosilane product still weakly coordinated in a rj2-fashion. The corresponding endo and exo intermediates (11a and lib, respectively) are 3.5 and 4.2 kcal/mol, respectively, more stable than the endo 7i-complex, 8a Therefore the exo-stereoisomer is again thermodynamically more stable than the endo form. Finally, the oxidative addition of a molecule of trichlorosilane occurs with concomitant liberation of the products. The formation of both R and S products is exothermic by -20 kcal/mol. 

As mentioned above, the calculations performed for styrene as a substrate suggests that the enantioselectivity can be directly correlated with the relative thermodynamic stabilities of the r 3-allylic complexes. Indeed, the exo stereoisomer, precursor of the enantiomeric product found in excess experimentally, becomes favoured with respect to the endo one upon t 3-coordination, and remains thermodynamically more stable until product release. However, the observed energy differences in the relative stabilities of the different allylic forms (1-2 kcal/mol) are certainly at the limit of accuracy of density functional calculations. 

The regio- and diastereo-selectivity of the Michael addition of 2-phenylcyclo-hexanone with a,p-unsaturated ketones are dependent on the reaction conditions. Mixtures of all six diastereoisomers resulting from reaction at either the 2- or 6-position of the cyclohexanone ring can be obtained using solid potassium hydroxide with tetra-n-butylammonium or A-benzylephcdrinium bromide catalysts. At 20°C with tetra-n-butylammonium bromide, the ratio of the 2,2- and 2,6-disubstituted cyclohexanones is ca. 3 2, but at higher temperatures with solid potassium f-butoxide the kinetically formed 2,6-isomer predominates (ca. 5 1) with the (2S,6R, R )-stereoisomer dominant, whereas greater amounts of the thermodynamically preferred 2,2-(2S,lR )-isomer are obtained with the chiral catalyst [61]. 

However, the syn and anti isomers of imines are easily thermally equilibrated. They cannot be prepared as single stereoisomers directly from ketones and amines so this method cannot be used to control regiochemistry of deprotonation. By allowing lithiated ketimines to come to room temperature, the thermodynamic composition is established. The most stable structures are those shown below, which in each case represent the less substituted isomer. 

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. 

The selectivity for the formation of the p-D-pyranoside (equatorial) stereoisomer in the reaction originated from a thermodynamic control. Indeed, starting from D-glucose, after 24 h at room temperature, a mixture of the four possible a,p-furanosides 46 and 47, and a,p-pyranosides stereoisomers 48 and 45a, in which... 

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