Enantioenriched compounds heterocycles

The utility of the organocatalytic hydroxylamine addition has been demonstrated with the preparation of a wide range of interesting enantioenriched compounds such as, P-antino acids [345,346], P-amino alcohols [345,346], 1,3-diamines [346], and different five- and six-membered nitrogen-containing heterocycles [347], as depicted in Schane 2.122 for the enantioselective synthesis of the alkaloid (+)-Angustureine... 

It was envisioned that the addition of an indole derived from a tryptamine to the activated iminium ion, arising from imidazolidinone catalyst 3 and an a,p-unsaturated aldehyde, would generate a C(3)-quaternary carbon-substituted indo-lium ion. As a central feature this intermediate cannot undergo re-aromatization by means of proton loss, in contrast to the analogous 3-H indole addition pathway. As a result, 5-exo-heterocyclization of the pendant ethylamine would provide the corresponding pyrroloindoline compounds. In terms of molecular complexity, this cascade sequence should allow the rapid and enantioenriched formation of stereochemically defined pyrroloindoline architecture from tryptamines and simple a,/i-unsaturated aldehydes. 

Under the same conditions, diisopropyl ether as the solvent was found to give the best results in terms of chemical yield and enantioselectivity. The absolute configuration of the stereogenic center of the major enantiomer was determined to be (J ) by chemical correlations with previously reported compounds [46]. An example of tin-lithium exchange followed by intramolecular carboHthiation of a carbon-carbon double bond as an efficient entry to the asymmetric synthesis of 3-hydroxy-pyrrolidines was reported by Hoppe et al. [47]. When the easily accessible enantioenriched stannane 173 was treated with n-butyUithium at low temperature, the five-membered heterocycle 174 was obtained in nearly quantitative yield and with excellent diastereo- and enantioselectivity (Scheme 10.57). 

The utilization of copper(I) catalysis in asymmetric transformations is universal due to the special valence electron, Lewis acidity, and coordination characteristic of the metal. Copper salts are easily available, cost-efficient, and nontoxic. Copper(l)-catalyzed asymmetric cycloaddition and cascade addition-cyclization reactions are straightforward methodologies for the stereoselective construction of various biologically and medicinally important heterocyclic compounds. In the past 5 years, main endeavors have been paid into catalytic asymmetric [3+2] cycloadditions other types of cycloaddition protocols are relatively less developed. The examples described in this chapter clearly demonstrate the potential of chiral Cu(I) complexes in the synthesis of enantioenriched heterocycles. Further studies may lie in the diversification of catalytic system, reaction type, and catalysis mode. Research in this field is still challenging and highly desirable, and it would be expected that more discoveries will come in the near future. 

As a result of the many advantages of the allyl p-ketoesters, we were able to quickly prepare a large number of substrates and demonstrate that the reaction gave yields and enantioselectivities equivalent to the other classes of substrates (Table 9). Additionally, we were able to access a number of products that we had not been able to access previously, such as enantioenriched tertiary fluorides, vinylogous esters and thioesters, nitrogen heterocycles, and compounds containing multiple quaternary stereocenters. These advances comprised the bulk of our secmid paper in the field [25]. 

The asymmetric hetero-Diels-Alder reaction involving carbonyl compounds as the heterodienophiles or heterodienes is among the most powerful methodologies for the construction of enantioenriched oxygen-containing heterocycles that have wide synthetic applications in biologically important natural or urmatural molecules. 

Asymmetric hydrogenation of heteroaromatic compounds provides a straightforward synthetic pathway to access enantioenriched heterocycles, which are of great importance in the synthesis of pharmaceuticals and natural products. Rueping et al. reported several examples of enantioselective cascade transfer hydrogenation reaction of heteroaromatic substrates under metal-free conditions [19,20]. The same group also developed a cascade reaction between enamines 42 and oc,P-unsaturated... 

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