Enol acid-labile

Titanium enolates. The labile la, prepared from isobutylene, decomposes to 2, which reacts with acid chlorides to give titanium enolates (3) of methyl ketones (equation I). 

The direct selenenylation technique is well suited to ketones that are not acid labile but cannot be applied to acid-sensitive derivatives however, in such cases an alternative procedure which employs basic conditions is commonly used. The ketone is first converted to the lithium enolate, usually with lithium diisopropylaniide, and then selenenylated with phenylselenenyl chloride or bromide or diphenyl diselenide8. 

The phosphorus ylide may be obtained from a wide range of different halides, and thus ketones may be converted into a range of unsaturated compounds. A useful reaction with the methoxymethylene Wittig reagent leads, via the acid-labile enol ether, to an aldehyde (Scheme 3.48). 

For some functionalized alkenylboranes, cleavage with methanol may be preferable to cleavage with a carboxylic acid. Relatively unhindered alkenyldialkylboranes, such as 9-alkenyl-9-BBNs, are readily cleaved by 1 equiv. of methanol under gentle heating. More hindered derivatives may require catalysis by 2,2-dimethylpropanoic acid, but these mild, almost neutral conditions may be beneficial for acid-labile functionalities. For example, methanolysis has been used for production of enol ethers e.g. equation 61). ... 

We have seen that, due to their carbonyl radical, these sugars may be balanced and converted by enolization. The labile, acid character of hydrogen atoms in the a of the carbonyl makes aldoliza-tion and ketohzation reactions predictable. These involve the condensation of two sugar molecules or, on the contrary, the breakdown of one molecule (Figure 3.8). These reactions play a vital role in the synthesis mechanisms of hexoses in photosynthesis and their breakdown during fermentation. These aldolization and hydroxyketonization reactions have been observed in vivo, but they also take place in vitro. 

The related imidophosphorane wherein Z = PhCH2N, and its acyclic analogue PhCH2N=P(NMe2)3, are very efficient catalysts for the protective acylation of alcohols in the presence of enol esters [96]. Acid-labile groups (such as acetal and epoxide) survive and groups such as TBS and disulfide [which undergo... 

The cross-aldol reaction is actively studied with the aim of improved control of the stereoselectivity.58 The use of silyl enol ethers for a condensation with aldehydes constitutes important progress, but catalysis by Lewis acids can be unsatisfactory for acid labile substrates, and the predominant anti stereoselectivity is not always optimal. An attempt was made to solve this problem by running the reaction sonochemically in the presence of alumina, without any solvent.59 products are absent, and the anti-isomer forms predominantly (Eq. 16). 

Phosphoric acid also forms esters with enols, the most interesting of these is phosphopyruvic acid, in which the enolized pyruvic acid is combined with H3PO4. Very acid-labile and very alkaline-labile, it is readily split by oxidizing scents liberating phosphoric acid. 

Ketones with labile hydrogen atoms undergo enol acetylation on reaction with ketene. Strong acid catalysis is required. If acetone is used, isoptopenyl acetate [108-22-5] (10) is formed (82—85). Isopropenyl acetate is the starting material for the production of 2,4-pentanedione (acetylacetone) [123-54-6] (11). 

A -dien-3-ol ethers gives rise to 6-substituted A" -3-ketones. 6-Hydroxy-A" -3-ketones can be obtained also by autooxidation.Structural changes in the steroid molecule may strongly affect the stability of 3-alkyl-A -ethers. Thus 11 j5-hydroxyl and 9a-fluorine substituents greatly increase the lability of the enol ether/ while halogens at C-6 stabilize this system to autooxidation and acid hydrolysis. 

Symmetrical labile ethers such as cycloalkenyl ethers (15) or mixed acetals (16) can also be prepared from the 3-hydroxyl group by acid-catalyzed exchange etherification or by acid-catalyzed addition to cyclohexanone methyl enol ether. 

Only in 1961 did Woodward and Olofson succeed in elucidating the true mechanism of this interesting reaction by making an extensive use of spectroscopic methods. The difficulty was that the reaction proceeds in many stages. The isomeric compounds formed thereby are extremely labile, readily interconvertible, and can be identified only spectroscopically. The authors found that the attack by the anion eliminates the proton at C-3 (147) subsequent cleavage of the N—0 bond yields a -oxoketene imine (148) whose formation was established for the first time. The oxoketene imine spontaneously adds acetic acid and is converted via two intermediates (149, 150) to an enol acetate (151) whose structure was determined by UV spectra. Finally the enol acetate readily yields the W-acyl derivative (152). 

A system of parallel reactions as shown in Fig. 5.3-9 was studied by Paul et at. (1992). The reactions are an acid-base neutralization and a base-catalysed hydrolysis of product (C). The labile compound (Q is in solution in an organic solvent, and aqueous NaOH is added to raise the pH from 2 to 7. Enolization occurs under basic conditions and is accompanied by irreversible decomposition (ring opening), which is not shown in the figure. The system was studied in the laboratory using the 6-Iitre reactor shown in Fig. 5.3-10. 

Excess reagents are conveniently renoved by either evaporation with a strean of nitrogen or partitioning with an aqueous solution of a weak base Byproduct fonation is generally not a najor problen except for analytes which are labile to acidic or basic conditions at elevated teaperatures [476,478,479,485,486]. Under conditions where the anhydride can lead to undesirable side reactions (dehydration, enolization, etc.), the haloalkylacyl-iaidazole reagent can sometimes be employed. 

With these results in hand, we have next introduced new types of Lewis acids, e.g scandium tris(-dodecyl sulfate) (4a) and scandium trisdodecanesul-fonate (5a) (Chart 1).[1S1 These Lewis acid-surfactant-combined catalysts (LASCs) were found to form stable colloidal dispersions with organic substrates in water and to catalyze efficiently aldol reactions of aldehydes with very water-labile silyl enol ethers. 

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