Reactions alkaloid-induced asymmetric

There is an example of alkaloid-induced asymmetric reactions in an IL medium. Dimethyl malonate reacted with chalcone under the action of potassium carbonate in the presence of quininium-derived phase transfer catalyst (PTC) 27 in a [bmim] [PFg] melt to give adduct 28 in high yield but with a slightly lower enantioselectivity than in conventional organic solvents (DMSO or toluene) (Scheme 22.10) [49]. Most surprisingly, the absolute configuration of product 28 reversed in the IL medium. Additional experiments with quinine or N-(4-nitrobenzyl)quininium bromide as PTC indicated that the reversal of enantioselectivity was not due to the PTC but can be attributed to the cation associated with the anion of the ionic liquid. The process was successfully repeated in the presence of the recovered IL/PTC system without a reduction in reaction rate or product yield. 

In view of the multifold important biological activities of isoquinoline and P-carboline alkaloids, increasing efforts have been made to perform Pictet-Spengler reactions stereoselectively. The most obvious chiral auxiliary to induce asymmetric control is the stereogenic center of the corresponding aromatic amino acids, such as DOPA or tryptophan. 

Hetero Diels-Alder reactions with imino dienophiles have been employed as key step in several syntheses of naturally occuring alkaloids. With regard to stereoselective transformations, the approach to (S)-anabasin worked out by Kunz et al. impressively illustrates the high utility of natural carbohydrates as source of chirality in asymmetric synthesis [505]. The N-galactosyl imine 7-28 underwent a Lewis acid catalysed aza Diels-Alder reaction with Danishefsky s diene which proceeded with excellent induced diastereoselectivity to yield the adduct 7-29. A short sequence then afforded the desired alkaloid 7-30. This work also deals with the suitability of several other dienes and imino dienophiles for such transformations (Fig. 7-7). 

As mentioned in the previous section, nowadays, readily available and inexpensive cinchona alkaloids with pseudoenantiomeric forms, such as quinine and quinidine or cinchonine and cinchonidine, are among the most privileged chirality inducers in the area of asymmetric catalysis. The key feature responsible for their successful utility in catalysis is that they possess diverse chiral skeletons and are easily tunable for diverse types of reactions (Figure 1.2). The presence of the 1,2-aminoalcohol subunit containing the highly basic and bulky quinuclidine, which complements the proximal Lewis acidic hydroxyl function, is primarily responsible for their catalytic activity. 

This chapter has presented the current stage in the development of metal-promoted asymmetric C—C and C—X bond forming reactions, in which cinchona alkaloids are utilized as chirality inducers. As shown in many of the examples discussed above, cinchona alkaloids and their derivatives have great potential to serve as chiral ligands or cobase catalysts in diverse metal-promoted asymmetric C—C and C—X bond forming reactions. However, despite the scientific achievements that have been made... 

In the previons section, secondary chiral amines were employed that give rise to enamine formation npon reaction with ketones or aldehydes. Chiral tertiary amines, unable to form enamines, are nevertheless capable of inducing enantioselectivity in case substrates are used that contain sufficiently acidic protons such as aldehydes, ketones or active methylene compounds [33]. The cinchona alkaloids, by far the most versatile source of Brpnsted base catalysts, have played a prominent role in various types of asymmetric organocatalytic reactions [34], which is also true for the Mannich reaction. 

In these cases, the polymer was used as an asymmetric support to induce the formation of optically pure product (cf. Worster et al., 1979). Few reports of the use of polymer-bound asymmetric reagents seem to exist in the literature. In this application, the reagent is used either to promote the asymmetric coupling of two groups or to add a group to a compound in an asymmetric manner. By far the largest number of applications have been those in which the polymer-bound asymmetric centers act as catalysts. Asymmetric catalysts, based on either amino acids or cinchona alkaloids, have been used to catalyze the Michael reaction in an... 

Early in 2003, Choudary et al. studied the catalytic activity of a unique tri-functional heterogeneous catalyst system consisting of palladium, osmium, and tungsten species for tandem Heck olefination followed by asymmetric dihydro>ylation reaction induced by cinchona alkaloid (DHQD)2PHAL in the presence of a tertiary amine such as N-methylmorpholine (NMM) in one pot. The trimetal catalyst system of Pd-Os-W was embedded into hexagonal layered double-hydroxides (LDHs). As shown in Scheme 7.57, the corresponding almost enantiopure diol was achieved in high yield. This remarkable result was not clearly understood by the authors. 

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