Alkylidene butyrolactones

A general route to )8-alkylidene-butyrolactones, which are easily converted into the corresponding jS-alkylbutenolides and thence into 3-substituted furans, employs the phosphorane (64), synthesized from maleic anhydride and triphenylphosphine, in Wittig reactions with aldehydes followed by reduction of the ester group with sodium diethylaluminium hydride (Scheme 20). 

The reaction shown in Eq. 9.47 demonstrates a short synthesis ofy-[(trityloxy)methyl]-a-alkylidene-y-butyrolactones having stereodefmed mono- and disubstituted exo-alkylidene... 

The a-alkylidene-y-butyrolactone 3 is isomerized by this method to the buten-olide 4. 

Asymmetric synthesis of cyclopropanes, The reaction of dimethyloxosnifonium methylide with (E)-(2R,3S)-6-alkylidene-3,4-dimethyl-2-phenylperhydro-l,4-oxazepine-5,7-diones (1) yields cyclopropane derivatives (2) and dihydrofuranes (3). The ratio of the products depends on the solvent and temperature. Use of THF at 25° favors formation of 2, whereas formation of 3 is favored by use of DMF at -61°. The products (2 and 3) can be converted into optically pure cyclopropane-1,1-dicarboxylic acids (4) and 3-substituted y-butyrolactones (5), respectively. 

Following these examples, methylene cyclopropene and certain 5,6-dihydrocali-cenes are now obtainable. Adding lithio trimethylsilylcyclopropanes to aldehydes also provides alkylidene cyclopropanes (Peterson olehnation route) . An approach to a-methylene y-butyrolactones starting with dibromocyclopropanes has been opened by a suitable manipulation of intermediate cyclopropyl anions (equation 133). ... 

Chiral cyclopentanones and y-butyrolactones are obtained by asymmetric hydrogenation of the corresponding alkylidene derivatives, catalyzed by binap-Ru complexes in 94-98% e.e. . Olefin geometry does not affect stereochemistry and enantioselectivity. 

Cycloisomerization. 4-AIkynoic acids cyclize to give y-alkylidene-y-butyrolactones under the influence of AU2O3. ... 

Carbonylations. Carbonylation reactions concomitant with cyclization of iodoalkenes leading to cyclopentenones or fZ>a-alkylidene-7-butyrolactones are of apparent interest to chemists in the field of synthesis. Other processes that unite three different components result in allyl ketones and a-methylenephenones. ... 

Divalent palladium-catalyzed clization of allylic alkynoates yields a-alkyliden-y-butyrolactones <94PAC1501,93JCR(S)366>. 

Acid-promoted lactonization of y-hydroxy esters is an important way to construct lactones. For example, Scolastico and co-workers first reported the lactonization of MBH adducts 213 using 0.7 m HCl in ACOH-H2O, obtaining cx-methylene-p-hydroxy-5-butyrolactones 215a,b in moderate yields (Scheme 4.65). Trifluoroacetic acid, CSA and sulfuric acid were also used in such lactonizations. In an alternative method, ot-methylene-p-hydroxy-8-butyrolactone 215c was synthesized by the intramolecular MBH reaction in 62% yield (Scheme 4.66). A series of a-alkylidene-8-butyrolactones and multi-substituted a-methylene-8-butyrolactones have been synthesized from MBH adducts (Figure 4.2). 

P,P-Disubstituted alkylidene derivatives of oxindole, azlactone, and y-butyrolactone are used as precursors of vinylogous enolates, which are highly stabilized owing to the heteroaromatic nature of the enolate components. Although these a,p-unsaturated carbonyl systems can act as electrophilic Michael acceptors, the presence of two p-substituents seems to suppress nucleophilic attack on the P-carbon. 

The reaction of potassium salts of 4-pentynoic acids—prepared from the add and KOBu-t or KH—with 1-bromo-l-alkynes affords 6-( )-alkylidene-y-butyrolactonest (Scheme 21). Lithium and sodium carboxylates have proved unsuccessful. Addition of potassium bromide, use of DMSO, and excess 4-pentynoic acid have been found to increase the yield, whereas 1-iodo-l-alkynes lead to the formation of the expected lactone along with major amounts of S-iodo- y methylene-y-butyrolactone. Tri(o-tolyl)phosphine and tri(2-furyl)phosphine can promote an effident transformation. The latter, however, has been found to give the best results. 

Oxypalladation promoted by hydridopalladium derivatives has been suggested to be involved in the regio- and stereoselective synthesis of y-(Z)-alkylidene- y-butyrolactones from 1-alkynes and (Z)-3-bromopropenoic acid (Scheme 34). 

Allylic alkynoates are a group of special enynes with an electron-deficient triple bond and an ester linkage between the double bond and triple bond. Based on the reaction described in Sect. B.iv.a, an intramolecular version could be developed, for example, au a-alkylidene-y-butyrolactone structure could easily be assembled through halopallada-tion, carbon-carbon double bond insertion, and dehalopalladation " (Scheme 13). The mechanism may be sununatized as shown in Scheme... 

The diastereoselectivity in the Pd(II)-LiX-CuX2-catalyzed cyclization of 2 -alkenyl 2-alkynoates is similar to that in the Pd(II)-LiX-catalyzed cyclization of 4 -het-eroatom-2 -alkenyl 2-alkynoates. The similar diastereoselectivity was observed in the synthesis of a-alkylidene-y-butyrolactams. The diastereoselectivity is further supported by the cascade cyclization reaction. A monocyclic product was obtained in the reaction of l, 5 -hexadien-3 -yl propynoate. The failure of the second cyclization might be due to the trans-configuration of the /S.y-disubstituents in the product. The reaction of r,5 -hexadien-3 -yl 3-substituted 2-aIkynoates under the same conditions yielded the cw-fused bicyclic a-(Z)-chloroalkylidene- y-butyrolactone derivatives implying the cw-diastereochemistry of the /3,y-disubstituents in the first cyclization (Scheme 16). 

As discussed in Sect. V.3.5, halide ions can also add to the palladium 7r-complexes, and the process may be termed halopalladation. Addition of Pd and a halogen, such as Cl and Br, to olefins, acetylenes, allenes, and conjugated dienes has been reported. However, most of the currently useful reactions initiated by halopalladation involve the use of alkynes as the substrates. Halopalladation of aUcynes gives vinylpalladium intermediates, which can undergo intramolecular carbopalladation to form cyclized products. Pd-catalyzed cyclization of ally lie aUcynoates can produce 7r-alkylidene-y-butyrolactones, which represent a basic structural unit in a wide variety of biologically active natural products. 

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