Esters regioselective formation

In his cephalosporin synthesis methyl levulinate was condensed with cysteine in acidic medium to give a bicyclic thiazolidine. One may rationalize the regioselective formation of this bicycle with the assumption that in the acidic reaction mixture the tMoI group is the only nucleophile present, which can add to the ketone. Intramolecular amide formation from the methyl ester and acid-catalyzed dehydration would then lead to the thiazolidine and y-lactam rings. The stereochemistry at the carboxylic acid a-... 

Scheme 10.6 Regioselective formation of 3-hydroxylated enol esters resulting from anti-Markovnikov addition.

The seven-membered ring analog, 327, showed different properties than those observed for 324 (eq. 64).85 Complete regioselective formation of 328 was observed for the acryloyl or crotyl derivatives. In these aza-annulation reactions, the use of acid chloride reagents resulted in higher yields than the corresponding ethyl esters. 

The C-17 to C-22 subunit of ionomycin (937) is synthesized by regioselective fragmentation of an appropriately substituted tetrahydrofuran (935), which is readily accessible from (R)-malic acid (Scheme 137) [205]. Alkylation of the dianion of diethyl (7 )-malate (897) with methyl iodide provides anti-929 in 69% yield with 10 1 stereoselectivity. Reduction of the esters, acetal formation, oxidation of the primary alcohol of 930 to an aldehyde, and Wittig olefination furnishes a,j -unsaturated ester 931. 

The first naphthyl isoquinoline alkaloid to be synthesized in optically active form was ancistrocladine (1) itself, the most important and widespread of all the Ancistrocladus alkaloids (see Scheme 31). The effectivity of the ester bridge assisted aryl coupling method (as presented in Section V.D.) was demonstrated by the regioselective formation of the highly strained lactone 124, which— different from the corresponding triphyophylline precursor 108 (see Scheme... 

The introduction of a phosphate moiety into a polyhydroxy compound by classic chemical methods is tedious since it usually requires a number of protection and deprotection steps. Furthermore, oligophosphate esters as undesired byproducts arising from overphosphorylation are a common problem. Employing enzymes for the regioselective formation of phosphate esters can eliminate many of these disadvantages thus making these syntheses more efficient. Additionally, enantioselective transformations are also possible involving the desymmetrization of prochiral or weso-diols or the resolution of racemates. 

Regioselectivity becomes important, if unsymmetric difunctional nitrogen components are used. In such cases two different reactions of the nitrogen nucleophile with the open-chain educt may be possible, one of which must be faster than the other. Hydrazone formation, for example, occurs more readily than hydrazinoLysis of an ester. In the second example, on the other hand, the amide is formed very rapidly from the acyl chloride, and only one cyclization product is observed. 

The photochemical addition of azirines to the carbonyl group of aldehydes, ketones, and esters is also completely regiospecific (77H(6)143). Besides the formation of the isomeric oxazolines (50) from (39) and ethyl cyanoformate, there is also formed the imidazole (51) from addition to C=N in the expected regioselective manner. Thioesters lead to thiazolines (52), while isocyanates and ketenes produce heterocycles (53). 

A further improvement utilizes the compatibility of hindered lithium dialkylamides with TMSC1 at —78 °C. Deprotonation of ketones and esters with lithium dialkylamides in the presence of TMSC1 leads to enhanced selectivity (3) for the kinetically generated enolate. Lithium t-octyl-t-butyl-amide (4) appears to be superior to LDA for the regioselective generation of enolates and in the stereoselective formation of (E) enolates. 

Regioselectivity and Stereoselectivity in Enolate Formation from Ketones and Esters... 

A type Ilac synthesis of functionalized pyrroles was developed that adapted the Larock indole synthesis <06OL5837>. For example, treatment of iodoacrylate 19 and trimethylsilylphenylacetylene 20 with palladium acetate led to the formation of pyrrole-2-carboxylate 21 with excellent regioselectivity. 19 was prepared by iodinating (N-iodosuccinimide) the corresponding commercially available dehydroamino ester. 

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