Gem-Dicarboxylates

Scheme 25 Diastereo- and enantioselective tinti-(hydroxy)allylation employing allylic gem-dicarboxylates as allyl donors via iridium-catalyzed transfer hydrogenation...

SE.3.1.2. Desymmetrization of gem-Dwarboxylates An equivalent of asymmetric carbonyl addition can be achieved by the alkylation of gem-dicarboxylates (Scheme 8E.17). The alkylation of gem-dicarboxylates, which are easily prepared by the Lewis acid-catalyzed addition of acid anhydrides to an aldehyde, converts the problem of differentiating the two enantiotopic 7t-faces of a carbonyl group into that of asymmetric substitution of either enantiotopic C-O bond of the gem-dicarboxylate. Although asymmetric induction may be derived from enantio-discrimination in the ionization step or in the alkene coordination step, the fast and reversible nature of alkene coordination suggests that the ionization step is more likely to be the source of enantio-discrimination. 

Excellent enantioselectivities are observed in the alkylation of various gem-dicarboxylates with both carbon and heteroatom nucleophiles as summarized in Table 8E.2 [71]. Screening various chiral ligands from the DPPBA module revealed that 1,2-diaminocyclohexane derived ligand 5 gives the best results, and the mnemonic of Figure 8E.8 correctly predicts the enantiomer obtained in this reaction. Notably, the corresponding desymmetrization by enzymatic hydrolysis or acylation is not feasible with these 1,1-diol derivatives. 

Allylic gem.-diacetatesIn the presence of this Pd(0) catalyst, propargyl acetates react with acetic acid to form (H)-allylic g< m-diacetates in 55-79% yield (equation 1). Mixed gem-dicarboxylates can also be prepared. 

An enantioselective synthesis of allylic esters was achieved by a novel asymmetric alkylation of allylic gem-dicarboxylates. The catalyst derived from r-allylpalladium chloride (1) and (1/J, 2/ )-bis[(diphenylphosphino)benzamido]cyclohexane induced the alkylation process with a variety of nucleophiles to provide the substituted esters in good yields, with enantiomeric excesses reaching 93% (eq 56). ... 

The benzoic acid derivative 457 is formed by the carbonylation of iodoben-zene in aqueous DMF (1 1) without using a phosphine ligand at room temperature and 1 atm[311]. As optimum conditions for the technical synthesis of the anthranilic acid derivative 458, it has been found that A-acetyl protection, which has a chelating effect, is important[312]. Phase-transfer catalysis is combined with the Pd-catalyzed carbonylation of halides[3l3]. Carbonylation of 1,1-dibromoalkenes in the presence of a phase-transfer catalyst gives the gem-inal dicarboxylic acid 459. Use of a polar solvent is important[314]. Interestingly, addition of trimethylsilyl chloride (2 equiv.) increased yield of the lactone 460 remarkabiy[3l5]. Formate esters as a CO source and NaOR are used for the carbonylation of aryl iodides under a nitrogen atmosphere without using CO[316]. Chlorobenzene coordinated by Cr(CO)j is carbonylated with ethyl formate[3l7]. 

Silylation of carboxylic acids.1 The reagent converts carboxylic acids into silyl carboxylates within 15-20 minutes in CC14 at 65-77° in the absence of a catalyst. The by-product is 2-oxazolidinone (insoluble in CC14). It is particularly useful for silylation of gem- or 1,2-dicarboxylic acids, which are easily decarboxylated when heated or in the presence of bases. 

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. 

---