Meso-succinic anhydride

Enantioselective desymmetrization of meso-succinic anhydrides with diphenylzinc is catalyzed by Pd(OAc)2/chiral diphosphine 209 (Equation (113)).470... 

Chen and coworkers have developed a bifunctional quinine-derived squaramide-promoted enantioselective alcoholysis of meso-succinic anhydride 36 [116]. Whereas modest enantioselectivity can be obtained in the presence of a catalytic amount of squaramide 22, high enantioselectivity was realized when more than 1 equivalent of squaramide was utQized (Scheme 10.36). The utility of the squaramide-catalyzed desymmetrization was nicely illustrated by carrying out an efficient synthesis of (-f)-biotin from the enantioenriched hemiester 37, which, in turn, was obtained by desymmetrization of 36. 

Scheme 10.36 Enantioselective alcoholysis of meso-succinic anhydride 36.

Alcoholysis of meso-cycYic anhydrides offers a versatile route to succinate and glu-tarate half-esters. Although a number of stoichiometric approaches to this problem have been investigated, a successful catalytic version of this reaction appeared as recently as 2003. ° Bolm and coworkers have developed a protocol for the metha-nolysis of a variety of succinic anhydrides using cinchona alkaloids [Eq. (10.50)]. The reaction may be made catalytic in alkaloid when pentamethylpiperidine is used as a stoichiometric additive. A moderate decrease in enantioselectivity is observed in a number of cases, although excellent selectivities are still attainable. More problematic is the reaction time (6 days under catalytic conditions) ... 

Syntheses of (2) and flOf were conveniently effected tScheme 4) starting from diethyl succinate (12) (28). The resultant dienolate (13). obtained by the action of two equivalent of lithium di-isopropylamide (29) gave on alkylation with methylenedioxybenzyl bromide in excellent yield a mixture of the ( )-ester (14) and meso-cster (15) which by alkaline hydrolysis yielded the dicarboxylic acid mixture (16) and (17). Without separation, this mixture on heating wih acetic anhydride gave the known /ron.r-dipiperonylsuccinic anhydride (18) (30). Reduction of (18) with lithium aluminium hydride gave ( )-dihydrocubebin Q), acetylation of which yielded ( )-ariensin (10). 

Catalysts which lead to cis polymer show a significantly higher stereoselectivity in the bond forming reaction. When (ir-allyl nickel iodide)2 modified with TiCl is employed, the 1, 2 deuterium stereochemistry is 70% dl, and 30% meso as revealed by analysis of succinic anhydride. In addition, monomer isomerization is extensive, and could account for a large fraction of the meso structures which are formed, j ke use of (ir-allyl nickel trifluoroacetate)2 as catalyst led to a similar result (32% meso), accompanied by little if any monomer isomerization. Thus, it appears that in reactions to form cis polymer, some, but not always all, of the stereochemical information present in the starting diene is preserved in the polymer. In contrast, none of the initial diene stereochemistry can be detected in the trans polymer. 

A sample of the deuteriated polymer (0.531 g) was ozonized as a suspension in CH2CI2, and the product treated with formic acid-hydrogen peroxide as described previously in this section. Cyclization to d2-succinic anhydrides and derivatization to form the d2 N-(o-biphenyl) succinimides were also performed by previously described methods. %-NMR (acetone-d6, 200 MHz, ) resonances at 6 2.62 (s), 2.62 (d, J 4.4 Hz), 2.84 (s), 2.84 (d, J 4.4Hz), 7.48 (m). Measurement of peak areas by triangulation indicated that the d2-N-(o-biphenyl) succinimide produced in the above experiment was 55% meso-isomer and 45% d>l-isomer. 

Figures. The C NMR spectrum of the oligomers of succinic anhydride and meso-erythritol (3 1 mole ratio) formed after 7 hours in r vxing diaxane. Structures in Scheme IV are similar to these.

When an anhydride such as succinic anhydride is reacted with a racemic alcohol in organic solvent with a lipase, an enantioselective resolution can be achieved [89]. The enantioselective opening of racemic or meso cyclic anhydrides can constitute a good method for the preparation of nearly optically pure esters [90-93]. Examples of these reactions are depicted in Scheme 13. 

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