Geminal dicarboxylates

Trost BM, Lee CB (2001) Geminal dicarboxylates as carbonyl surrogates for asymmetric synthesis part II scope and applications. J Am Chem Soc 123 3687-3696... 

In addition to cyclic allylic substrates, malonate nucleophiles have been used in reactions with both symmetrical" and unsymmetrical" acyclic systems, and with geminal dicarboxylates. Malonates and Meldrum s acid have also been used as nucleophiles in the desymmetrization of meso diesters. 

The a-sulfenyl group can be replaced by a benzothiazolthio group, as demonstrated in the synthesis of the 1,4-diketone (CXXXIV), a precursor of cw-jasmone [Eq. (65)] [10]. The geminal dicarboxylic acid (CXXXVI) can also be transformed into the 1,4-diketone (CXXXIV) by electrochemical decarboxylation as in Eq. (66) [6], suggesting that the substituted malonic acid group is synthetically equivalent to a carbonyl group. 

The only examples of this class of substrates, that have been studied, are geminal dicarboxylates 44 which are readily prepared from aldehydes [44,45]. Enantioselective displacement of one of the enantiotopic carboxylate groups by the chiral catalyst leads to the chiral allyl complex 45 (Scheme 18). This intermediate which is of the same type as 18 (Scheme 12) has been shown to undergo regioselective nucleophihc addition at the acetoxy-bearing terminus with inversion of configuration (see Sect. 9.5). 

Allylic geminal dicarboxylates 285 are prepared by Pd-catalyzed reaction of propargyl acetate 284 with AcOH [104], Two products 287 and 288 are obtained from gem-allylic compounds 286, and 288 is an allylic ester and undergoes the second allylation. Several applications to asymmetric syntheses have been reported [48]. Reaction of 289 with dimethyl methylmalonate afforded 290 with 95% ee. 

Sol 1. (c) Geminal dicarboxylic acid (i.e., compounds in which the two carboxyl groups are on the same carbon atom) and p-ketocarboxylic acid obtained by the oxidation of diols II and IV, respectively, readily undergo decarboxylation on heating. 

Leaving groups other than halides are also suitable for this type of geminal dialkylation reaction. Thus, diethyl spiro[3.4]oct-6-ene-2,2-dicarboxylate (5) is isolated in 75% yield from the reaction between diethyl malonate and 3-cyclopentene-1,1-dihydroxymethyl di-4-bro-mobenzenesulfonate (4).19... 

Pd - and PT-catalyzed carbonylation of geminal vinylic dibromides gives diynes or dicarboxylic acids using benzene or t-amyl alcohol as a solvent, respectively (eq. (10)) [135]. 

Scheme 1. TADDOLs, Analogs, and Derivatives Thereof Constructed from +)- or (-)-Tar-trate. Aldehydes or Ketones, and a Grignard Reagent (shown here is the structure derived from (+)-(i ,i )-tartrate). Instead of tartrate acetals (R = H) or ketals (R, R H) [12], other chiral nonracemic dicarboxylates may be employed in the Grignard reaction [13] [14], Aryl = Ph can be hydrogenated to CgHn [15] [16], and the diastereoisomeric derivatives with geminal Ph/Me instead of Aryl/Aryl groups are available through the 4,5-dibenzoyl-dioxolane [14], For examples, for OH derivatizations, and for OH/Y and OH/Z substitutions, see Schemes 2 and 3.

Substitution of a cyclopropane by two geminal electron-withdrawing groups makes the three-membered ring very susceptible to nucleophilic attack. The readily-prepared phosphonium salt (480) condenses with the p-keto-ester anion (479) to furnish the cyclopentene (481). Similar nucleophilic attack on cyclopropane-l,l-dicarboxylic ester derivatives has been adapted to the synthesis of several prostaglandins. ... 

Spicer has reported that dimethylacetylene dicarboxylate reacted with norbomene at room temperature in the presence of TMANO to give the cyclopentenone in 73% yield. However, the cobalt complex is thermally unstable and mild PKR conditions were required for success. The intramolecular and inter-molecular PKR of alkynones has been reported by Hoye in 30-90% yields. In the intramolecular examples, improved yields were observed when a geminal dimethyl was incorporated into the tether. In the intermolecular examples, the ketone was found in the 3-position of the cyclopentenone. The vinylogous 48 ynone cyclised in 62% yield to provide the tricyclic product 49 as a 2.7 1 mixture of cis/trans isomers. An interesting intramolecular example was disclosed by de Meijere in which ketone 50 produced the spirocyclopropane 51 in 63% yield. ... 

In Scheme 22 one can observe that stereoisomeric dicarboxylic acids are also formed (1 2 molar ratio to the monocarboxylic one) through oxidative carbonylation leading to stoichiometric liberation of palladium(O). Their formation is enhanced by the lack of geminal substituents. If oxidative conditions are used (CO -l- O2), dicarboxylated products become predominant. 

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