A-alkylidene-y-lactones

This type of alkynol ether hydrocyanation gives rise to a new stereospecific route to a-alkyli-dene y-lactones. Acidic hydrolysis and cyclization of some of the products obtained, as above, give a-alkylidene-y-lactones in 65-83% yield with the double-bond geometry predetermined via stereoselective hydrocyanation2T... 

Aldol reaction between a ketone and an aldehyde can be controlled by prior conversion of the ketone into the ethyloxalyl derivative before reaction with the aldehyde. The keto-lactone so formed is decomposed to an alkene moiety with base. This method is particularly well suited to the formation of a-alkylidene-cyclo-alkanones (ring size >6) and a-alkylidene-y-lactones (Scheme 73). ... 

A similar synthesis of (Z)-a-alkylidene-y-lactones from alkenyl iodides was reported by Luo et al. In a related procedure,the presence of an acetyl group a to the hydroxyl group of the iodide led to the formation of a,/S-unsaturated butenolides. The presumed intermediate a-methylene lactone probably undergoes isomerization to the more stable butenolide under the reaction conditions, as shown in Scheme 8. 

Martinez V J C, Yoshida M, Gottlieb O R 1981 cu-Ethyl, cu-ethenyl, and cu-ethynyl-a-alkylidene-y-lactones from Clinostemon mahuba. Phytochemistry 20 459-464... 

Occurrence, Biosynthesis, and Biological Activities 149 Table 4.1 Major categories of natural a-alkylidene-y-lactones. 

Nonterpenoid a-alkylidene-y-lactones 3.1. y-Lactones with lignan skeleton... 

Scheme 4.4 Organometallic reagents in the synthesis of a-alkylidene-y-lactones and lactams 26.

Optically active allylboronates bearing chiral auxiliary located at the boron atom found widespread applications in asymmetric synthesis. Enantiomerically enriched a-alkylidene-y-lactones and lactams can also be synthesized following such a synthetic approach. VUlieras et al. (41, 45] demonstrated the potential of chiral allylboronates derived from 2-phenyl-2,3-bomanediol, ephedrine, or norephedrine for this purpose. Chiral allylboronates 46a,b were obtained in a sequence of reactions involving transformation of achiral precursors 32 into the corresponding boronic acids 44 followed by their esterification with enantiomerically pure diol or 1,2-aminoalcohol 45 (Scheme 4.10). In the case of methyl-substituted derivatives 32b (R = Me), initial composition of E- and Z-isomers was transferred to the target allylboronates 46b. Importantly, the isomeric mixture was separated by means of the column chromatography. 

In 2001, Ballini and coworkers [46] demonstrated that convenient method for the preparation of 2-methylene-4-nitroalkanoates 56 relies on a reaction between ethyl 2-(bromomethyl)acrylate 55a with selected nitroalkanes 51 (Scheme 4.14). Originally formed adducts 56 were transformed into target Y-substituted-a-alkylidene-y-lactones 50a in a sequence of reactions involving oxidation of the nitro group to carbonyl group by means ofa Nef reaction, subsequent reduction of4-03K>aIkanoates 57 obtained and acid-mediated cyclization of 4-hydroxyalkanoates. 

Scheme 4.22 Synthesis of a-alkylidene-y-lactones 89 via vinylalumination of epoxides 87.

P-Elimination reaction constitutes one of the most important methods for the formation of carbon-carbon double bond. It can be successfully employed in the synthesis of a-alkylidene-y-lactones and y-lactams when correspondingly functionalized, saturated y-lactones or y-lactams 192 bearing a good leaving group in the I -position are available (Scheme 4.47). 

Oxidation of the C-2 carbon atom in the corresponding 3-alkylidenetetrahydro-furanones 204 constitutes another convenient method for the synthesis of a-alkylidene-Y-lactones 20aa (Scheme 4.50). 

Scheme 4.S0 Oxidative strategies for the preparation of a-alkylidene-y-lactones 20aa.

Another approach to bicyclic a-alkylidene y-lactones requires the preparation of iodinated alkynoate precursors that can undergo a radical cyclization (Equation 2) The resulting alkenyl iodide can be reduced with zinc to provide the trisubstituted alkene or can be further substituted with organocopper reagents to produce the desired y-lactones embedding a tetrasubstituted alkene. 

The convenient synthetic methodology for the a-silyl esters has been ejrtended to the synthesis of a-alkylidenelactones [198, 199]. Peterson reactions of the carban-ion generated from a-silyl-y-butyrolactones 117 with carbonyl compounds afford the corresponding a-alkylidene-y-lactones 118 with high -selectivity (Scheme 2.71). The yields are low when ketones are used as substrates. 

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