Enols, protection

The final example demonstrates that microwave irradiation allows a perfect fine-tuning of reaction conditions to obtain different products from the same starting materials. In the procedure developed by Garcfa-Tellado and coworkers [41], two domino processes were coupled. The first process consists of a high-yielding synthesis of enol-protected propargylic alcohols 10-111 starting from alkyne 10-109 and aldehyde 10-110 (Scheme 10.28). In the second process, transformation into... 

Tejedor and coworkers have utilized a combination of two domino processes for a microwave-promoted synthesis of tetrasubstituted pyrroles [344]. The protocol combines two coupled domino processes the triethylamine-catalyzed synthesis of enol-protected propargylic alcohols and their sequential transformation into pyrroles through a spontaneous rearrangement from 1,3-oxazolidines (Scheme 6.183). Overall, these two linked and coupled domino processes build up two carbon-carbon bonds, two carbon-nitrogen bonds, and an aromatic ring in a regioselective and efficient manner. The tetrasubstituted pyrroles could be directly synthesized from the enol-protected propargylic alcohols and the primary amines by microwave irradia-... 

Treatment of 26 with benzylamine under microwave irradiation led to the formation of 1,3-oxazolidine 27 which subsequently rearranged to give the pyrrole 28. The serendipitous discovery of the latter reaction provides a novel domino process for the formation of pyrroles from acyclic enol-protected propargyl alcohols which are also be derived from a domino process, the double condensation of alkynoates with aldehydes <04JA8390>. 

The selective intermolecular addition of two different ketones or aldehydes can sometimes be achieved without protection of the enol, because different carbonyl compounds behave differently. For example, attempts to condense acetaldehyde with benzophenone fail. Only self-condensation of acetaldehyde is observed, because the carbonyl group of benzophenone is not sufficiently electrophilic. With acetone instead of benzophenone only fi-hydroxyketones are formed in good yield, if the aldehyde is slowly added to the basic ketone solution. Aldols are not produced. This result can be generalized in the following way aldehydes have more reactive carbonyl groups than ketones, but enolates from ketones have a more nucleophilic carbon atom than enolates from aldehydes (G. Wittig, 1968). 

Selective reduction of a benzene ring (W. Grimme, 1970) or a C C double bond (J.E. Cole, 1962) in the presence of protected carbonyl groups (acetals or enol ethers) has been achieved by Birch reduction. Selective reduction of the C—C double bond of an a,ft-unsaturated ketone in the presence of a benzene ring is also possible in aprotic solution, because the benzene ring is redueed only very slowly in the absence of a proton donor (D. Caine, 1976). 

In all cases examined the ( )-isomers of the allylic alcohols reacted satisfactorily in the asymmetric epoxidation step, whereas the epoxidations of the (Z)-isomers were intolerably slow or nonstereoselective. The eryfhro-isomers obtained from the ( )-allylic alcohols may, however, be epimerized in 95% yield to the more stable tlireo-isomers by treatment of the acetonides with potassium carbonate (6a). The competitive -elimination is suppressed by the acetonide protecting group because it maintains orthogonality between the enolate 7i-system and the 8-alkoxy group (cf the Baldwin rules, p. 316). 

A conceptually surprising and new route to prostaglandins was found and evaluated by C.R. Johnson in 1988. It involves the simple idea to add alkenylcopper reagents stereo-selectively to a protected chiral 4,5-dihydroxy-2-cyclopenten-l-one and to complete the synthesis of the trisubstituted cyclopentanone by stereoselective allylation of the resulting enolate. 

Chemoselective C-alkylation of the highly acidic and enolic triacetic acid lactone 104 (pAl, = 4.94) and tetronic acid (pA, = 3.76) is possible by use of DBU[68]. No 0-alkylation takes place. The same compound 105 is obtained by the regioslective allylation of copper-protected methyl 3,5-dioxohexano-ate[69]. It is known that base-catalyzed alkylation of nitro compounds affords 0-alkylation products, and the smooth Pd-catalyzed C-allylation of nitroalkanes[38.39], nitroacetate[70], and phenylstilfonylnitromethane[71] is possible. Chemoselective C-allylation of nitroethane (106) or the nitroacetate 107 has been applied to the synthesis of the skeleton of the ergoline alkaloid 108[70]. 

Other methods of protecting the aldehyde group include formation of an enol acetate, an enamine, or an imine (174,175). In the enamine route, regeneration of the aldehyde is accompHshed simply by the addition of water. 

The carbonyl group forms a number of other very stable derivatives. They are less used as protective groups because of the greater difficulty involved in their removal. Such derivatives include cyanohydrins, hydrazones, imines, oximes, and semicarbazones. Enol ethers are used to protect one carbonyl group in a 1,2- or 1,3-dicarbonyl compound. 

Trimethylsilyl enol ethers can be used to protect ketones, but in general are not used for this purpose because they are reactive under both acidic and basic conditions. More highly hindered silyl enol ethers are much less susceptible to acid and base. A less hindered silyl enol can be hydrolyzed in the presence of a more hindered one. ... 

Silylated cyanohydrins have also been prepared via silylation of cyanohydrins themselves and by the addition of hydrogen cyanide to silyl enol ethers. Silylated cyanohydrins have proved to be quite useful in a variety of synthetic transformations, including the regiospecific protection of p-quinones, as intermediates in an efficient synthesis of a-aminomethyl alcohols, and for the preparation of ketone cyanohydrins themselves.The silylated cyanohydrins of heteroaromatic aldehydes have found extensive use as... 

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