Butyrolactones lithium enolate

The method has been extended to other polyfunctionnal systems, such as O-ethyl S-(tetrahydro-2-oxo-3-furanyl)dithiocarbonate. Treatment of y-butyrolactone with bis [methoxy(thiocarbonyl)]disulfide in the presence of 2.2 equivalents of lithium diisopropy-lamide at —78 °C in THF provides the lithium enolate which reacts with MgCla to furnish the magnesium enolate (equation 17). 

Danheiser and coworkers described a convenient preparation of oxetanones via the condensation of thioester lithium enolates with carbonyl compounds and subsequent lac-tonization under proper conditions592. The asymmetric version was reported later593, the configuration of the new chiral center being established by a stereospecific dyotropic rearrangement to the y-butyrolactone (Scheme 125)594. 

Lactone enolates typically show poor simple diastereoselection. For example, in connection with a synthesis of ( )-podorhizol, Ziegler and Schwartz added the lithium enolate of butyrolactone (82) to 3,4,5-trimethoxybenzaldehyde (equation 74). Although the diastereofacial selectivity of the chiral enolate is complete, aldols (83) and (84) are formed in a ratio of 50 50 in THF and 25 75 in an equimolar mixture of dimethoxyethane and ether. ... 

Widdowson and coworkers investigated aldol reactions of butyrolactone itself with benzaldehyde (equation 75). The lithium enolate gives diastereomers (85) and (86) in a ratio of 40 60 to 30 70, depending upon reaction temperature. If 0.5 mol equiv. ZnCb is added to the reaction mixture prior to enolate formation, the (85) (86) ratio is 56 44 to 70 30, depending upon reaction temperature. 

The synthetic utility of a-silyl esters has been amply demonstrated by several examples. The basis for this chemistry is the observation that ester lithium enolates can be directly C-silylated with methyldiphenylchlorosilane, a reagent which avoids the more common O-silylation153. The a-silyl-y-valerolactone 80 was converted in two steps and high yield to racemic ancepsenolide by condensation of its lithium enolate with decane 1,10-dicarboxaldehyde followed by isomerization to the endocyclic double bonds of the natural product154 (equation 160). Treatment of the a-silyl-y-butyrolactone 81 or 80 with a Grignard reagent followed by pyridinium chlorochromate (PCC) oxidation provides 4-oxo aldehydes and 1,4-diketones, respectively155 (equation 161). 

Bis-sulfenylation of y-butyrolactone, as well as of cyclic ketones, has been achieved with this reagent via the corresponding lithium enolates. This reaction has been utilized in an efficient synthesis of 3-substituted 2-buten-4-olides (eq 4). 

The Pd-catalyzed a-allylation of esters was first achieved by the reactions of aUylic carbonates with ketene silyl acetals that can be generated by treating esters with McsSiCl in the presence of a base. The yields of the desired products based on ketene silyl acetals were generally good except in the allylation of lactones (Scheme Selection of solvents is critical since the use of nitriles, such as MeCN and PhCN, leads only to the formation of a,/3-unsaturated esters rather than the a-ally-lated products. Both Reformatsky reagents and lithium enolates of esters have also been successfully a-allylated in the presence of Pd catalysts (Scheme 10). A highly regio- and stereospecific allylation of y-butyrolactone with ( )-2-hexenyl acetate is noteworthy. Since the lithium enolate of esters would react with allylic chlorides even in the absence of a Pd catalyst, however, it is not clear to what extent the reaction is catalyzed by a Pd complex. 

Moderate erythro- ecx y Xy is observed in the reaction of the lithium enolate of butyrolactone with ben2aldehyde in the presence of ZnClg. The 3-alkoxy-enolates (157) are methylated to give /roni-butyrolactones (158) in good yield and with approximately 9 1 selectivity (Scheme 92). ... 

Recent studies have suggested that coordination with a lithium cation may be responsible for the stereochemical outcome in Meyers-type enolate alkylations . In fact, the hypothesis that the diastereofacial selectivity observed in these reactions might result from specific interactions with a solvated lithium cation was already proposed in 1990 . Nevertheless, the potential influence exerted by solvation and lithium cation coordination was not supported by a series of experimental results reported by Romo and Meyers , who stated that it would appear that neither the aggregation state of the enolate nor the coordination sphere about lithium plays a major role in the observed selectivity. This contention is further supported by recent theoretical studies of Ando , who carried out a detailed analysis of the potential influence of solvated lithium cation on the stereoselective alkylation of enolates of y-butyrolactones. The results showed conclusively that complexation with lithium cation had a negligible effect on the relative stability of the transition states leading to exo and endo addition. The stereochemical outcome in the alkylation of y -butyrolactones is determined by the different torsional strain in the endo and exo TSs. 

A procedure which could be useful in the construction of annulated butyrolactones is outlined in Scheme 38.3< ° Vinyl lithium intermediates do not undergo cyclisation it is a pity that the introduction of the lactone carbonyl group into the initial product requires so many steps A rather neat application of the enolate... 

The a-methylene-) -butyrolactone grouping is incorporated in a large number of sesquiterpenoids, many of which have significant biological activity. A number of routes have been devised for the synthesis of this moiety but recently an important contribution from Ourisson s laboratory has demonstrated that the more accessible a-methyl-y-lactones can be converted in two steps into the a-methylene analogues.This is achieved by reaction of the lactone (263 R = H) with triphenylmethyl-lithium and quenching the resultant enolate with 1,2-dibromoethane. Dehydrobromination of the derived bromide (263 R = Br) with diazabicyclononene gives exclusively the exocyclic methylene lactone (264). This method is only suitable for c/s-y-lactones since the trans-lactone yields exclusively the endocyclic isomer. To illustrate this method Ourisson et at. have converted dihydro-6-epi-santonin (265) into (- )-frullanolide (266). More recently the same authors have developed a method which is applicable to... 

Addition of tributylstannyl-lithium to crotonaldehyde and protection of the resulting alcohol with chloromethyl methyl ether gives the stannane (192), which reacts with both alkyl and aryl aldehydes RCHO to form specifically the t/rr o-hydroxy-enol ethers (193). These latter compounds have been used to prepare tra/i5-4,5-disubstituted butyrolactones by hydrolysis and subsequent oxidation. Palladium-catalysed carbonylation of RX in the presence of organotin species constitutes a useful synthesis of unsymmetrical ketones, and in the example reported this year RX is an arenediazonium salt. The reaction, which is basically an aromatic acylation, proceeds in good to excellent yield. Another Pd-catalysed reaction of aromatics, this time aryl bromides, is their reaction with acetonyltributyltin (194), prepared from methoxytributyltin and isopropenyl acetate, to give the arylacetones (195). ... 

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