Conformation of ketones

However, the reducing agent may influence the conformation of ketone, and thereby the diastereoselectivity. If the small and medium substituents are close in size, then this model fails to predict the exact selectivity. This model also assumes less interaction between the large group and R group, which is not entirely correct. 

Fig. 14.9. a) Preferred conformation of ketones having a chiral center... 

Schmidt reaction of ketones, 7, 530 from thienylnitrenes, 4, 820 tautomers, 7, 492 thermal reactions, 7, 503 transition metal complexes reactivity, 7, 28 tungsten complexes, 7, 523 UV spectra, 7, 501 X-ray analysis, 7, 494 1 H-Azepines conformation, 7, 492 cycloaddition reactions, 7, 520, 522 dimerization, 7, 508 H NMR, 7, 495 isomerization, 7, 519 metal complexes, 7, 512 photoaddition reactions with oxygen, 7, 523 protonation, 7, 509 ring contractions, 7, 506 sigmatropic rearrangements, 7, 506 stability, 7, 492 N-substituted mass spectra, 7, 501 rearrangements, 7, 504 synthesis, 7, 536-537... 

The case of a, -unsaturated caAonyl compounds is analogous to that of 1,3-dienes, in that stereoelectronic factors favor coplanaiity of the C=C—C=0 system. The rotamers that are important are the s-trans and s-cis conformations. Microwave data indicate that the s-trans form is the only conformation present in detectable amounts in acrolein (2-propenal). The equilibrium distribution of s-trans and s-cis conformations of a,fi-unsatuiated ketones depends on the extent of van der Waals interaction between substituents. Methyl vinyl ketone has minimal unfavorable van der Waals repulsions between substituents and exists predominantly as the s-trans conformer ... 

The fragmentation/cyclization ratio is determined by the relative orientation of the respective molecular orbitals, and thus by the conformation of diradical species 2. The quantum yield with respect to formation of the above products is generally low the photochemically initiated 1,5-hydrogen shift from the y-carbon to the carbonyl oxygen is a reversible process, and may as well proceed back to the starting material. This has been shown to be the case with optically active ketones 7, containing a chiral y-carbon center an optically active ketone 7 racemizes upon irradiation to a mixture of 7 and 9 ... 

Ketones react with alcohols to yield products called acetals. Why does the all-cis isomer of 4- cvf-butyl-l13-cyclohexanediol react readily with acetone and an acid cataty st to form an acetal while other stereoisomers do not react In formulating your answer, draw the more stable chair conformations of all four stereoisomers and the product acetal. Use molecular models for help. 

The study of optical isomers has shown a similar development. First it was shown that the reduction potentials of several meso and racemic isomers were different (Elving et al., 1965 Feokstistov, 1968 Zavada et al., 1963) and later, studies have been made of the ratio of dljmeso compound isolated from electrolyses which form products capable of showing optical activity. Thus the conformation of the products from the pinacolization of ketones, the reduction of double bonds, the reduction of onium ions and the oxidation of carboxylic acids have been reported by several workers (reviewed by Feokstistov, 1968). Unfortunately, in many of these studies the electrolysis conditions were not controlled and it is therefore too early to draw definite conclusions about the stereochemistry of electrode processes and the possibilities for asymmetric syntheses. 

The preparation of ketones and ester from (3-dicarbonyl enolates has largely been supplanted by procedures based on selective enolate formation. These procedures permit direct alkylation of ketone and ester enolates and avoid the hydrolysis and decarboxylation of keto ester intermediates. The development of conditions for stoichiometric formation of both kinetically and thermodynamically controlled enolates has permitted the extensive use of enolate alkylation reactions in multistep synthesis of complex molecules. One aspect of the alkylation reaction that is crucial in many cases is the stereoselectivity. The alkylation has a stereoelectronic preference for approach of the electrophile perpendicular to the plane of the enolate, because the tt electrons are involved in bond formation. A major factor in determining the stereoselectivity of ketone enolate alkylations is the difference in steric hindrance on the two faces of the enolate. The electrophile approaches from the less hindered of the two faces and the degree of stereoselectivity depends on the steric differentiation. Numerous examples of such effects have been observed.51 In ketone and ester enolates that are exocyclic to a conformationally biased cyclohexane ring there is a small preference for... 

The first element of stereocontrol in aldol addition reactions of ketone enolates is the enolate structure. Most enolates can exist as two stereoisomers. In Section 1.1.2, we discussed the factors that influence enolate composition. The enolate formed from 2,2-dimethyl-3-pentanone under kinetically controlled conditions is the Z-isomer.5 When it reacts with benzaldehyde only the syn aldol is formed.4 The product stereochemistry is correctly predicted if the TS has a conformation with the phenyl substituent in an equatorial position. 

Summary of the Relationship between Diastereoselectivity and the Transition Structure. In this section we considered simple diastereoselection in aldol reactions of ketone enolates. Numerous observations on the reactions of enolates of ketones and related compounds are consistent with the general concept of a chairlike TS.35 These reactions show a consistent E - anti Z - syn relationship. Noncyclic TSs have more variable diastereoselectivity. The prediction or interpretation of the specific ratio of syn and anti product from any given reaction requires assessment of several variables (1) What is the stereochemical composition of the enolate (2) Does the Lewis acid promote tight coordination with both the carbonyl and enolate oxygen atoms and thereby favor a cyclic TS (3) Does the TS have a chairlike conformation (4) Are there additional Lewis base coordination sites in either reactant that can lead to reaction through a chelated TS Another factor comes into play if either the aldehyde or the enolate, or both, are chiral. In that case, facial selectivity becomes an issue and this is considered in Section 2.1.5. 

Entry 6 involves a titanium enolate of an ethyl ketone. The aldehyde has no nearby stereocenters. Systems with this substitution pattern have been shown to lead to a 2,2 syn relationship between the methyl groups flanking the ketone, and in this case, the (3-siloxy substituent has little effect on the stereoselectivity. The configuration (Z) and conformation of the enolate determines the 2,3-vyn stereochemistry.113... 

The stereoselectivity then depends on the conformation of the enone and the location of substituents that establish a steric bias for one of the two potential directions of approach. In the ketone 11, the preferred approach is from the (3-face, since this permits maintaining a chair conformation as the reaction proceeds.132... 

Coleman, Kobylecki, and Utley studied the electrochemical reduction of the conformationally fixed ketones 4-tert-butylcyclohexanone and 3,3,5-tri-methylcyclohexanone 82>. Stereochemically, the cleanest reductions took place at a platinum cathode in a mixture of hexamethylphosphoramide and ethanol containing lithium chloride. Under these conditions the equatorial alcohol predominated heavily (95% from 4-fer/-butylcyclohexane and 91% from 3,3,5-trimethylcyclohexanone).In acidic media roughly equal quantities of axial and equatorial alcohol were produced. It was suggested that organo-lead intermediates are involved in the reductions in aqueous media. This is reasonable, based upon the probable mechanism of reduction in acid 83F Reductions in acid at mercury cathodes in fact do result in the formation of... 

When diketone 55 was reduced to hydroxyl ketone 56, an interesting change occurred in the H NMR that gave us significant insight into for our proposed conformations of these systems. A selected region of the H NMR for compounds 2 and 56 is shown in Fig. 8.9. 

Based on the three-dimensional structure of CHS, we proposed that the initiation/elongation/cyclization cavity serves as a structural template that selectively stabilizes a particular folded conformation of the linear tetraketide, allowing the Claisen condensation to proceed from C6 to Cl of the reaction intermediate.14 In contrast, CTAL formation can occur either in solution or alternatively while sequestered in the enzyme active site. In either case, enolization of the C5 ketone followed by nucleophilic attack on the Cl ketone with either a hydroxyl group (in solution) or the cysteine thiolate (enzyme bound) as the leaving group results in CTAL. Similar lactones are commonly formed as by-products of in vitro reactions in other PKS systems.36 38... 

Since carbocations are structurally similar to ketones, they are discussed here. Schleyer s force field incorporates carbocation parameters, and Harris is exploring their application in conformational analysis (188). The calculated angles in a series of rigid polycyclic carbocations correlated well with ketone infrared frequencies (188a). The calculated relative stabilities among various conformers of tertiary cations of methylcyclohexane, methylcycloheptane, and methyl-cyclooctane do not contradict the limited MNR observations of these species at low temperature (188b). 

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