Alkylidenesuccinic acids

Carboxylation. Under phase-transfer conditions, propargyl and allenyl halides in the presence of CO and Ni(CN)2 are converted into allenic acids. Further reaction gives rise to 2-alkylidenesuccinic acids. 

Carbonylation and hydroformylation. With PEG as a PTC, COjCCO), mediates the carbonylation of benzylic halides. A more complex system is used in the transformation of propargylic alcohols into 2-alkylidenesuccinic acids (9 examples, 84-97%). Very similar results are obtained from the carbonylation of alkynyl ketones. "... 

Succinic esters condense with aldehydes and ketones in the presence of bases, eg, sodium alkoxide or piperidine, to form monoesters of alkylidenesuccinic acids, eg, condensation of diethyl succinate with acetone yields ethyl 2-isopropylidenesuccinate (eq. 3). This reaction, known as Stobbe condensation, is specific for succinic esters and substituted succinic esters (98,99). 

The dicarboxyic acid 66 (alkylidenesuccinic acid), obtained by hydrolysis and decarboxylation of the triester 65, resembles the product (half-ester) 73 of the Stobbe condensation (Scheme 11-21) [21]. In order to prepare the half-ester, carbonylation in benzyl alcohol to prepare the monomethyl ester and dibenzyl ester 75, followed by hydrogenolysis of the dibenzyl ester, was attempted, expecting the formation of the halfester. However, /S-keto ester 76 was obtained, an entirely different product (Scheme 11-22) [22]. The mechanism of this unexpected reaction is unknown. 

Allylic carbonates are most reactive. Their carbonylation proceeds under mild conditions, namely at 50 C under 1-20 atm of CO. Facile exchange of CO2 with CO takes place[239]. The carbonylation of 2,7-octadienyl methyl carbonate (379) in MeOH affords the 3,8-nonadienoate 380 as expected, but carbonylation in AcOH produces the cyclized acid 381 and the bicyclic ketones 382 and 383 by the insertion of the internal alkene into Tr-allylpalladium before CO insertion[240] (see Section 2.11). The alkylidenesuccinate 385 is prepared in good yields by the carbonylation of the allylic carbonate 384 obtained by DABCO-mediated addition of aldehydes to acrylate. The E Z ratios are different depending on the substrates[241]. 

When the alkylidenesuccinic ester is derived from an aldehyde [e.g. (26)], functional group modification provides a route to y-keto acids and the overall process relates to the disconnection strategy outlined above. The required modifications are hydrolysis of the diester to the diacid and photocatalysed... 

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