A,p-unsaturated methylation

Besides chalcones, other types of a,p-unsaturated carbonyls affording five-membered S-heterocycles were cinnamaldehyde, 12, and the a,p-unsaturated methyl ketone 13 and phenyl ketones 14 and 15. However, another phenyl ketone, 16, substituted at the a position or tertiary butyl ketone 17 failed to yield S-heterocycles. 

Annulation Using (P-(Trimethylsilyl)acryloyl)silane and Lithium Enolate of a,p-Unsaturated Methyl Ketone ... 

Structurally, cystothiazole B (2) consists of two linked thiazoles of which one is substituted by a simple alcohol residue, while the other bears a longer aliphatic chain comprising two adjacent stereogenic centers and an -configured a,P-unsaturated methyl ester moiety. This side chain is probably a product of the polyketide pathway. 

The selective hydrolysis of acetyl groups, led in methanol in presence of concentrated sulphuric acid, gives the a,P unsaturated methyl ester 13e. Therefore the two hydroxyls at C-3 and at C-4, in sin position each other, are protected by means of formation of isopropylidene function, doing react the methyl ester 13e with 2,2-dimetiioxypropane in acetone in presence of catalj tic quantity of strongly acidic resin, so obtain the 3,4-O-isopropylidene derivative 13f. 

The elimination is completely chemoselective with l-(l-hydroxyalkyl)-8-lactones and with methyl P-hydroxy-a-selenoalkylcarboxylates (precursors of ( )-a,p unsaturated methyl carboxylates Scheme 39, b and Scheme 170), but not with the other stereoisomer which produces a mixture of (Z)-a,p un-saturated methyl carboxylates (by formal selenenic elimination) and a-seleno-a,p-unsaturated methyl carboxylates (by formal elimination of water). 

ANNULATION USING A [p-(TRIMETHYLSILYL)ACRYLOYL]SILANE AND THE LITHIUM ENOLATE OF AN a,p-UNSATURATED METHYL KETONE (1R, 6S, 7S )-4-(tert-BUTYLDIMETHYLSILOXY)-6-... 

The Robinson annnlation was introduced in 1935 by Sir Robert Robinson and William Sage Rapson targeting the synthesis of building blocks of sterols. The condensation is an unprecedented reaction of alkali metal derivative of cyclohexanones and a,P-unsaturated methyl ketones that produces cycloketones and polycycloketones as precursors for sterols synthesis. 

The Robinson annulation is the reaction of alkali metal derivatives of cyclohexanones with a-,p>unsaturated methyl ketones to produce cycloketones and polycycloketones. The standard method for Robinson annulation is exemplified in the mechanism shown above. For the synthesis of the 1,5-diketone side chain, the enolate nucleophile reacts with a Michael acceptor this Michael acceptor is usually a substituted vinyl ketone or the parent methyl vinyl ketone (MVK), although the latter gives low yield due to its propensity to polymerize under the standard reaction conditions. To overcome the drawbacks for using MVK, Robinson, McQuillin and Du Feu introduced the Robinson-Mannich variation of the annulation reaction. This modification uses a quatemized Mannich base formed from the vinyl entity the Maimich base is made in situ and acts as a methyl vinyl ketone precursor after it is converted to its methiodides. The formed methiodides of the Mannich adduct 4-(trimethylamino-2-butanone) is condensed with sodioderivatives of ketones or with the parent ketone in the presence of sodium ethoxide. 

In addition to the more active a, p-enal, hydroalkylation of less active enones 162 also proceeded smoothly (Scheme 60) [95]. Under the catalysis of 30 mol% of BF3 Et20 and with comparatively active tertiary C-H as hydride donor, the substrate 162a or 162b carrying a, p-unsaturated methyl and phenyl ketone units were efficiently transformed into spirocycles 163a and 163b, respectively, in excellent yields and moderate diastereoselectivities. 

Copper-catalysed enantioselective conjugate addition of Grignard reagents to a,p-unsaturated methyl esters is sueeessfully carried out to provide p-substituted chiral esters in good yields and with excellent enantioselec-tivities (Scheme 15.24). A combination of copper iodide and commercially available chiral (R)-2,2 -bis(di-p-tolyl-phosphino)-l,l -binaphthyl (Tol-BINAP) is also effective. ... 

Scheme 15.24 Copper-catalysed asymmetric conjugated addition of Grignard reagents to a,p-unsaturated methyl esters.

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