Conformations substituent

The principles involved in the conformational analysis of six-membered rings containing one or two trigonal atoms, for example, cyclohexanone and cyclohexene are similar. The barrier to interconversion in cyclohexane has been calculated to be 8.4-12.1 kcal mol . Cyclohexanone derivatives also assume a chair conformation. Substituents at C2 can assume an axial or equatorial position depending on steric and electronic influences. The proportion of the conformation with an axial X group is shown in Table 4.4 for a variety of substituents (X) in 2-substituted cyclohexanones. 

From a strictly chemical point of view, the synthesis of glycosides still presents a formidable challenge to synthetic chemists in spite of major advances in the area [1], Unlike peptidic bonds, the formation of the glycosidic linkage is subject to various factors that include, among others, electronic, stereoelectronic, conformational, substituent, and reactivity effects generally associated with incipient oxocarbenium ions derived from carbohydrates. 

One reason for the rather low quantum yields for product formation from Z-1,3,5-hexatriene is thought to be that the ground state conformer distribution is heavily weighted in favor of the relatively unreactive fZf-conformer . Substituents and structural constraints have quite substantial effects on the conformer distribution, and hence on the quantum yields and distribution of products obsCTved. These effects are well understood, having been worked out independently by Havinga and coworkers, who examined the photochemistry of various 2-alkyl- and 2,5-dialkyl-l,3,5-hexatrienes (120 and 121, respectively) , and by Dauben and coworkCTs with their studies of the photochemistry of substituted 6,6,9,9-tetramethyl-A -hexalins (122). Both bodies of work were predicated on the effects of substituents at the 2- and/or 5-positions of the... 

In addition to the familiar axial and equatorial description of substituents in chair conformations, substituents in non-chair conformers of six-membered rings also have their descriptors there are four isoclinal, four pseudoaxial and four pseudoequatorial bonds in skew cyclohexane and four pseudoaxial, four... 

There is an extensive literature on interproton coupling over four bonds V(H, H ) in saturated and unsaturated molecules. With modern NMR instrumentation, these data are easily obtainable now but are often difficult to interpret because of their sensitivity to conformational, substituent, and ring-size effects. 

Effects of conformation, substituents, ligands, and metal were assessed using models a-d shown in Fig. 1. Results for the Qy transitions are presented in Table 1 for the 7 BCHLs ... 

Cyclobutane adopts a puckered conformation. Substituents then occupy axial-like or equatorial-like positions. 1,3-Disubstituted cyclobutanes show small energy... 

The oxidation of inositols to inososes (cycloses) by Acetobacter suboxydans is of importance in the determination of configuration (e.g., Posternak s work on mi/o-inositol, p. 275) and in the interconversion of inositols by reduction of the inosose. Bertrand s rule (p. 133) accurately predicts the point of attack in the acyclic series, but the situation is more complex in the inositol series. The specificity of A, suboxydans appears to be related to the conformation of the cyclohexane ring of the inositols. Inositols, like other substituted cyclohexanes, may exist in boat or chair forms (86), (See Chapter I.) The chair form in which the distances between the hydroxyl groups is at a maximum appears to be the preferred conformation. Substituents that are oriented nearly parallel to the average plane of the puckered ring are called equatorial. They lie alternately above and below the plane. Substituents that are perpendicular are called axial (formerly, polar) (87), Conversion to the second chair form causes interchange of... 

The physical, chemical cind biological properties of a molecule often depend critically upo the three-dimensional structures, or conformations, that it can adopt. Conformational analysi is the study of the conformations of a molecule and their influence on its properties. Th development of modem conformational analysis is often attributed to D H R Bcirton, wh showed in 1950 that the reactivity of substituted cyclohexanes wcis influenced by th equatoricil or axial nature of the substituents [Beirton 1950]. An equcilly important reaso for the development of conformatiorml analysis at that time Wcis the introduction c analytic il techniques such as infreired spectroscopy, NMR and X-ray crystaillograph] which actucilly enabled the conformation to be determined. 

The addition of large enolate synthons to cyclohexenone derivatives via Michael addition leads to equatorial substitution. If the cyclohexenone conformation is fixed, e.g. as in decalones or steroids, the addition is highly stereoselective. This is also the case with the S-addition to conjugated dienones (Y. Abe, 1956). Large substituents at C-4 of cyclic a -synthons direct incoming carbanions to the /rans-position at C-3 (A.R. Battersby, 1960). The thermodynamically most stable products are formed in these cases, because the addition of 1,3-dioxo compounds to activated double bonds is essentially reversible. 

Synthetically useful stereoselective reductions have been possible with cyclic carbonyl compounds of rigid conformation. Reduction of substituted cyclohexanone and cyclopentan-one rings by hydrides of moderate activity, e.g. NaBH (J.-L. Luche, 1978), leads to alcohols via hydride addition to the less hindered side of the carbonyl group. Hydrides with bulky substituents 3IQ especially useful for such regio- and stereoselective reductions, e.g. lithium hydrotri-t-butoxyaluminate (C.H. Kuo, 1968) and lithium or potassium tri-sec-butylhydro-borates or hydrotri-sec-isoamylborates (=L-, K-, LS- and KS-Selectrides ) (H.C. Brown, 1972 B C.A. Brown, 1973 S. Krishnamurthy, 1976). 

As illustrated in Scheme 8.1, both 2-vinylpyrroles and 3-vinylpyiroles are potential precursors of 4,5,6,7-tetrahydroindolcs via Diels-Alder cyclizations. Vinylpyrroles are relatively reactive dienes. However, they are also rather sensitive compounds and this has tended to restrict their synthetic application. While l-methyl-2-vinylpyrrole gives a good yield of an indole with dimethyl acetylenedicarboxylate, ot-substitiients on the vinyl group result in direct electrophilic attack at C5 of the pyrrole ring. This has been attributed to the stenc restriction on access to the necessary cisoid conformation of the 2-vinyl substituent[l]. 

Curiously enough, bulky substituents on nitrogen increase this reactivity towards methyl iodide (119). This has been related to a steric decompression of the thiocarbonyl group in the transition state. Furthermore, knowledge of the ratio of conformers in the starting 4-alkyl-3-i-Pr-A-4-thiazoline-2-thiones and in the resulting 4-alkyl-3-i-Pr-2-methylthiothi-azolium iodides combined with a Winstein-Holness treatment of the kinetic data indicates that in the transition state, the thiocarbonyl bond is approximately 65% along the reaction coordinate from the initial state... 

For 4-nitro-5-alkylthiazoles, the prefered conformations of the alkyl substituents relative to the ir-system could be evaluated, and the interactions between alkyl and nitro groups were demonstrated to be negligible. 

The log(k/ko) value for 4-isopropyl-2,5-dimethylthiazole is twice that expected if the curve were linear, which implies a rate constant 6.5 times smaller than expected. This result can be explained by the existence of a privileged conformation, induced by the presence of the methyl group in the 5-position and that has a lower reactivity (258). This result also leads to a limitation in the use of Tafts Eg parameter to cases where the environment of a substituent does not induce particular conformation for this latter (258). 

It IS no accident that sections of our chair cyclohexane drawings resemble saw horse projections of staggered conformations of alkanes The same spatial relationships seen m alkanes carry over to substituents on a six membered ring In the structure... 

The most important result of ring inversion is that any substituent that is axial in the original chair conformation becomes equatorial in the ring flipped form and vice versa... 

Their heats of combustion (Table 3 2) reveal that trans 1 4 dimethylcyclohexane is 7 kJ/mol (17 kcal/mol) more stable than the cis stereoisomer It is unrealistic to believe that van der Waals strain between cis substituents is responsible because the methyl groups are too far away from each other To understand why trans 1 4 dimethylcyclo hexane is more stable than cis 1 4 dimethylcyclohexane we need to examine each stereoisomer m its most stable conformation... 

The methyl groups are described as cis because both are up relative to the hydrogen present at each carbon If both methyl groups were down they would still be cis to each other Notice that ring flipping does not alter the cis relationship between the methyl groups Nor does it alter their up versus down quality substituents that are up m one conformation remain up m the ring flipped form... 

If a disubstituted cyclohexane has two different substituents then the most stable conformation is the chair that has the larger substituent m an equatorial orientation This IS most apparent when one of the substituents is a bulky group such as tert butyl Thus the most stable conformation of cis 1 tert butyl 2 methylcyclohexane has an equatorial tert butyl group and an axial methyl group... 

Conformational inversion (ring flipping) is rapid in cyclohexane and causes all axial bonds to become equatorial and vice versa As a result a monosubstituted derivative of cyclohexane adopts the chair conforma tion in which the substituent is equatorial (see next section) No bonds are made or broken in this process... 

The following are representations of two forms of glucose The six membered ring is known to exist in a chair conformation in each form Draw clear representations of the most stable con formation of each Are they two different conformations of the same molecule or are they stereoisomers Which substituents (if any) occupy axial sites ... 

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