Enols regiochemistry

Aldehyde, Ketone, and Ester Enolates 867 Enolate Regiochemistry 872 The Aldol Condensation 873 Mixed Aldol Condensations 878 Chalcones From the Mulberry Tree to Cancer Chemotherapy 880 The Claisen Condensation 882 Intramolecular Claisen Condensation The Dieckmann Cyclization 884 Mixed Claisen Condensations 885 Acylation of Ketones with Esters 886 Alkylation of Enolates 887 The Acetoacetic Ester Synthesis 889 The Malonic Ester Synthesis 891 Alkylation of Chiral Enolates 893 Enolization and Enol Content 895 a Halogenation of Aldehydes and Ketones 900... 

Choice of Base/Reaction Conditions Determines Enolate Regiochemistry... 

Normally, phenylhydrazine reacts with the enol form of 1,1,1-trifluorometh-ylpentane-2,4-dione to give 5-methyl-l-phenyl-3-tnfluoromethylpyrazole as the major product. However, the use of pyrrolidine as a transient carbonyl-blocking group can completely reverse the regiochemistry of the addition and leads to 3-methyl-l-phenyl-5-trifluoromethylpyrazole [102] (equation 88)... 

The chemistry of alkynes is dominated by electrophilic addition reactions, similar to those of alkenes. Alkynes react with HBr and HC1 to yield vinylic halides and with Br2 and Cl2 to yield 1,2-dihalides (vicinal dihalides). Alkynes can be hydrated by reaction with aqueous sulfuric acid in the presence of mercury(ll) catalyst. The reaction leads to an intermediate enol that immediately isomerizes to yield a ketone tautomer. Since the addition reaction occurs with Markovnikov regiochemistry, a methyl ketone is produced from a terminal alkyne. Alternatively, hydroboration/oxidation of a terminal alkyne yields an aldehyde. 

Scheme 2.11 shows some examples of Robinson annulation reactions. Entries 1 and 2 show annulation reactions of relatively acidic dicarbonyl compounds. Entry 3 is an example of use of 4-(trimethylammonio)-2-butanone as a precursor of methyl vinyl ketone. This compound generates methyl vinyl ketone in situ by (3-eliminalion. The original conditions developed for the Robinson annulation reaction are such that the ketone enolate composition is under thermodynamic control. This usually results in the formation of product from the more stable enolate, as in Entry 3. The C(l) enolate is preferred because of the conjugation with the aromatic ring. For monosubstituted cyclohexanones, the cyclization usually occurs at the more-substituted position in hydroxylic solvents. The alternative regiochemistry can be achieved by using an enamine. Entry 4 is an example. As discussed in Section 1.9, the less-substituted enamine is favored, so addition occurs at the less-substituted position. 

Conditions for kinetic control of enolate formation can be applied to the Robinson annulation to control the regiochemistry of the reaction. Entries 5 and 6 of Scheme 2.11 are cases in which the reaction is carried out on a preformed enolate. Kinetic... 

This regiochemistry is consistent with the electrophilic character of Pd(II) in the addition step. Solvent and catalyst composition can affect the regiochemistry of the Wacker reaction. Use of /-butanol as the solvent was found to increase the amount of aldehyde formed from terminal alkenes, and is attributed to the greater steric requirement of /-butanol. Hydrolysis of the enol ether then leads to the aldehyde. 

Mattay et al. examined the regioselective and stereoselective cyclization of unsaturated silyl enol ethers by photoinduced electron transfer using DCA and DCN as sensitizers. Thereby the regiochemistry (6-endo versus 5-exo) of the cyclization could be controlled because in the absence of a nucleophile, like an alcohol, the cyclization of the siloxy radical cation is dominant, whereas the presence of a nucleophile favors the reaction pathway via the corresponding a-keto radical. The resulting stereoselective cis ring juncture is due to a favored reactive chair like conformer with the substituents pseudoaxial arranged (Scheme 27) [36,37]. 

Among these are the factors controlling the regiochemistry of the reaction, the employed diene compounds, and the possible intramolecular cyclization of various alk-4-enol and ene-diene radical cations (Scheme 49) [70-72], Also, by changing the nucleophile from the generally used methanol to, for instance, acetonitrile can yield photo-NOCAS products in good yields [73,74],... 

The regiochemistry of arylation of ketones has not been studied systematically, but there are sufficient data in the literature to allow reasonable predictions to be made. With enolates having one r-alkyl group attached to the carbonyl (e.g. "Cl COBu ) or with those derived from aryl alkyl ketones, clearly no prob-... 

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