Stereochemistry ketones, base effect

Acyclic Ketones. The stereochemistry of the reduction of acyclic aldehydes and ketones is a function of the substitution on the adjacent carbon atom and can be predicted on the basis of the Felkin conformational model of the TS,63 which is based on a combination of steric and stereoelectronic effects. 

The ammonium catalyst can also influence the reaction path and higher yields of the desired product may result, as the side reactions are eliminated. In some cases, the structure of the quaternary ammonium cation may control the product ratio with potentially tautomeric systems as, for example, with the alkylation of 2-naph-thol under basic conditions. The use of tetramethylammonium bromide leads to predominant C-alkylation at the 1-position, as a result of the strong ion-pair binding of the hard quaternary ammonium cation with the hard oxy anion, whereas with the more bulky tetra-n-butylammonium bromide O-alkylation occurs, as the binding between the cation and the oxygen centre is weaker [11], Similar effects have been observed in the alkylation of methylene ketones [e.g. 12, 13]. The stereochemistry of the Darzen s reaction and of the base-initiated formation of cyclopropanes under two-phase conditions is influenced by the presence or absence of quaternary ammonium salts [e.g. 14], whereas chiral quaternary ammonium salts are capable of influencing the enantioselectivity of several nucleophilic reactions (Chapter 12). 

Nagai, T. Nishioka, G. Koyama, M. Ando, A. Miki, T. Kumadaki, I. Reactions of trifluoromethyl ketones. IX. Investigation of the steric effect of a trifluoromethyl group based on the stereochemistry on the dehydration of trifluoromethyl homoallyl alcohols./. Fluorine Chem. 1992, 57, 229-237. 

Now that you know about the anomeric effect, you should add it to your mental array of ways of explaining unexpected results. Here is an example. Many fruit flies have pheromones based around a spiroketal structure, which we could represent without stereochemistry as shown below. You can imagine the spiroketal (that is, an acetal of a ketone made of two rings joined at a single atom) being made from a dihydroxyketone—and, indeed, this is very often how they are made synthetically. But this is a bad representation because these compounds do have stereochemistry, and the stereochemistry is very interesting. 

Rules 1 and 2 may be accepted as a generalization based primarily on the results obtained over platinum catalysts. However, there have been known many examples of the exception to this rule,153 since the stereochemistry of hydrogenation may be influenced by many factors, such as the solvent, the temperature, the hydrogen pressure, and the basic or acidic impurity associated with catalyst preparation, as well as the activity of the catalyst, and since the effects of these factors may differ sensitively with the catalyst employed and by the structure of the ketone hydrogenated. 

Scheme 7.4 presents some representative examples of Claisen-Schmidt reactions. Entries 1 and 2 are typical base-catalyzed condensations at methyl groups. Entry 3 illustrates the use of a cyclic ketone, and reaction occurs at the methylene group, where dehydration is possible. The stereochemistry presumably places the furan ring trans to the carbonyl group for maximum conjugation. Entry 4 shows the use of phthalaldehyde to effect a cyclization. Entry 5 illustrates the preference for condensation at the more-substituted position under acidic conditions. 

Perhaps the most interesting developments in the area of selective lithiations to appear this year have been concerned with the control of absolute stereochemistry. The application of chiral amide bases to the enantioselective deprotonation of epoxides was first described some years ago by Whitesell and co-workers, but this year several groups have reported on other aspects of these useful reaqents. Symmetrically substituted ketones (5 R=Me, CH2Ph) have been shown by Simpkins to undergo an enantioselective deprotonation under kinetically controlled conditions to give, after reaction with an electrophile (iodomethane, allyl bromide or acetic anhydride), optically active ketones (6) or enol acetates (7) (Scheme 2). The ability of a number of bases to discriminate between the two prochiral protons present in (5) were evaluated and the most effective of those studied was the camphor derivative (8) deprotonation of (5 R=Me) proceeded in 74% enantiomeric excess... 

Control of Regioselectivity and Stereoselectivity. The recognition by Ireland and co-workers that Hexamethylphosphoric Triamide has a profound effect on the stereochemistry of lithium enolates has led to the examination of the effects of other additives, as the ability to control enolate stereochemistry is of utmost importance for the stereochemical outcome of aldol reactions. Kinetic deprotonation of 3-pentanone with Lithium 2,2,6,6-Tetramethylpiperidide at 0 C in THF containing varying amounts of HMPA or TMEDA was found to give predominantly the (Z)-enolate at a base ketone additive ratio of ca. 1 1 1, whereas with a base.ketone.additive ratio 1 0.25 1, formation of the ( )-enolate was favored (Table I). This remarkable result contrasts with those cases where HMPA base ratios were varied towards larger amounts of HMPA, which favored formation of the (Z)-enolate. ... 

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