Enantioselective Alcoholysis of meso‐Glutaric Anhydrides Catalyzed by Cinchona‐Based Sulfonamide Catalysts

Abstract

The bifunctional Cinchona-based sulfon-A C H T U N G T R E N N U N G amide catalysts showed the highest levels of enantioselectivity reported to date in the alcoholytic desymmetrization of meso-glutaric anhydrides. Density functional theory (DFT) computational studies provide detailed insight into the observed sense of enantioselectivity. Moreover, detailed experimental studies and single crystal X-ray analysis confirmed that these bifunctional organocatalysts 3 do not form Hbonded self-aggregates in both solution and solid state. The synthetic utility of this methodology was also demonstrated in the synthesis of pharmaceutically important g-amino acids, such as (S)-pregabalin. Of the many asymmetric syntheses of enantiomerically pure (S)-pregabalin reported to date, our synthesis requires the least number of and the simplest steps.

Synthesis of GABOB and GABOB‐Based Chiral Units Possessing Distinct Protecting Groups

“…On the other hand, the use of modified alkaloids, including ethers,37 ureas or thioureas,38 and sulfonamides,39 in catalytic amounts, has also been studied. Of these modified compounds, sulfonamides (Figure 5) have a slightly better overall performance.…”

“…General Methods: All reactions were carried out under an argon atmosphere. Anhydride 11 16 and catalyst Q‐TS 39 were prepared according to literature procedures. Buffer pH 5.4 was prepared by dissolving NaH 2 PO 4 dihydrate (17.78 g) and citric acid monohydrate (7.78 g) in 1 L of water.…”

Chemical Studies on Bioactive Natural Products Directed toward Development of Novel Antiinfective and Anticancer Medicines

“…24) Toward this end, the binuclear nickel-chiral Schiff base complex 27, studied extensively by Shibasaki's group, was the catalyst of choice. [25][26][27][28] For this type of transformation, chiral organocatalysts including cinchona alkaloids have been widely used, 29) although the availability of conditions for glutaric anhydride with sterically small substituents at the 3-position was limited. Moreover, naturally occurring alkaloids or their synthetic derivatives do not always guarantee the same level of selectivity upon obtaining enantiomeric products [30][31][32] since pseudo-enantiomeric organocatalysts were used for this purpose.…”

Understanding the mechanism of procedure-controlled enantioselectivity switch in cinchona alkaloid thiourea catalyzed [3+2] cycloaddition: H-bonds controlled enantioselectivity

“…A variety of new chiral compounds have been synthesized as organocatalysts and showed high efficiency, excellent selectivity and great universality . Among these catalysts, the bifunctional systems [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41], which mimic the natural enzymes, can bind with the substrates on two sites, so are usually more effective. Lately cinchona alkaloid based aminothiourea catalysts, one kind of bifunctional catalysts, are applied in a series of asymmetric reactions and exhibit excellent stereoselectivity [42][43][44][45][46][47][48][49].…”