Enol acylation

P-Keto acids 34 can be converted into 5,6-dialkyl-4-hydroxypyran-2-ones by thermolysis of the Meldrumls acid derivatives 35. A Fries rearrangement of the derived enol acylates and reduction of the resulting 3-acylpyranone with EtjSiH provides a route to the 3,6-dialky Ipyranones 36 (Scheme 17) <99T4783>. 

Di-2-pyridyl thionocarbonate, 127 Formaldehyde, 136 Iodomethyltrimethylsilane, 315 Palladium(II) acetate, 232 Tributyl(iodomethyl)tin, 314 Ene reaction Ethylaluminum dichloride, 5 Oxygen, singlet, 228 8-Phenylmenthol, 243 Zinc bromide, 349 Enol acylation... 

FIGURE 13.8 Alcohols produced through asymmetric hydrogenation of enol acylates 33. 

Fig. 13.74. Tandem reaction, consisting of a Michael addition and an enolate acylation (the major tautomer of the reaction product is not shown).

Enolate acylation and alkylation.1 The yield from acylation and alkylation of lithium ketone enolates is markedly improved by addition of dimethylzinc, which... 

Z75. (a) Dieckmann of dimethyl adipate, alkylation by allyl bromide, hydrolysis and decarboxylation (c) Robinson with CH3CH = CHCOCH3 then reduction (d) form enamine or enolate, acylate with CICOOEt, methylate with CH3I, do aldol with benzaldehyde. 

The formation of the acyl chloride with SOCl2 and the conversion of the a-bromoacyl chloride into the bromoester with MeOH are simple nucleophilic substitutions at the carbonyl group, just like the synthesis of esters from acyl chlorides in Chapter 12. The intermediate stage, the bromination of the very easily enolized acyl chloride, is a typical enol bromination. 

Members of this class usually have an amine and a fluorine atom on the benzene ring as well as other embellishments as in ofloxacin, a recent example. The preparation of ofloxacin starts with two enolate acylations. 

The phosphoric acid ester of an enol ether is even more readily hydrogenolyzed than an enol acylate. When the (Z)-enol phosphate 51 was subjected to hydrogenation in ethyl acetate at 0.3 MPa H2, the hydrogenolysis products were isolated in 95% yield not only over platinum oxide but also over 5% Pd-C and 5% Rh-Al203 (eq. 13.50).94 The hydrogenolysis of an enol phosphate has been utilized in conversion of one of two oxo groups to the methylene as shown in eq. 13.51 95... 

Enolate Acylation. Acylation of these enolates provides a direct route to p-dicarbonyl systems. Acylations generally proceed with >95% diastereoselection in 83-95% yields, with the valine-derived auxiliary providing slightly higher selectivity (eq 18). The sense of induction is consistent with reaction through the chelated lithium (Z)-enolate, and the newly generated stereocenter is retained through routine manipulations. 

A second entry to dicarbonyl substrates utilizes the aldol reaction to establish the a-methyl center prior to oxidation of the p-hydroxyl moiety. Commonly, this oxidation is performed using the Sulfur Trioxide-Pyridine complex, which results in <1% epimerization of the methyl-bearing center (eq 34). Interestingly, this procedure procures the opposite methyl stereochemistry from that obtained through enolate acylation of the same enantiomer of oxazolidinone. 

Tabuchi, H., Hamamoto, T., Ichihara, A. Modification of the Fries type rearrangement of the O-enol acyl group using W,W-dicyclohexylcarbodiimide and 4-dimethylaminopyridine. Synlett 1993, 651-652. 

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