Stereoselective Syntheses of Chiral Heterocycles

Heterocycles are very important in pharmaceutical research [49,50] and the stereo-controlled synthesis of chiral heterocyclic compounds is therefore a major task in modem organic chemistry. Besides catalytic methods, auxiliaries are valuable for asymmetric syntheses of chiral heterocycles. Carbohydrates have been used as auxiliaries in the stereoselective formation of heterocycles, as well as in the stereoselective introduction of functionalities into the heterocyclic framework. 

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Kunz, H, Weymann, M, Follmann, M, Allef, P, Oertel, K, Schultz-Kukula, M, Hofmeister, A, Stereoselective syntheses of chiral heterocycles and alkaloids using carbohydrate auxiliaries, Polish J. Chem., 73, 15-27, 1999. 

The examples described above also illustrate the potential of carbohydrate auxiliaries in stereoselective syntheses of chiral carbocylic compounds via cycloadditions. Furthermore, their use can be extended to the stereoselective synthesis of heterocyclic compounds. 

Carbohydrate-derived auxiliaries exhibit an efficient stereoselective potential in a number of nucleophilic addition reactions on prochiral imines. a-Amino acids, P amino acids and their derivatives can be synthesized in few synthetic steps, and with high enantiomeric purity. A variety of chiral heterocycles can readily be obtained from glycosyl imines by stereoselective transformations, providing evidence that carbohydrates have now been established as useful auxiliaries in stereoselective syntheses of various interesting classes of chiral compounds. 

This method can he used for a variety of alkenes. The siliranes can he efficiently applied for thermal di-terf-butylsilylene transfer reactions to form other di-terf-hutylsiliranes (8), other thermal and photochemical ring expansion reactions, eg, to diastereoselectively form seven- (6,11), eight- (7), or nine-memhered heterocycles (12). Furthermore the siliranes may he applied to synthesize y-lactones (13), selective synthesis of tiiols, and homoallylic alcohols (14) or stereoselective formation of chiral allylic silanes (15) have also been reported. The following experimental procedure of isonitrile insertions exemplifies the silirane s high reactivity and facile formation of 1,1-di-terf-butyl-iminosilacyclobutanes (1,1-di-tert-butyl-iminosiletans or silacyclobutanimines) (4,5). 

The 3-nitro analog was also synthesized by Isobe laboratory with the intention of using it as another convenient chiral dienophile in highly stereoselective cycloaddition approaches to heterocyclic systems of natural products. 

Butyllithium is also used for the stereoselective a-lithiation of chiral sulfonyl compounds/ chiral 2-alkenyl carbamates, various heterocyclic amine derivatives with chiral auxiliaries appended on the nitrogen (e.g. oxazoline or formamidine groups) (eq 10)7 and chiral oxazolidinones derived from ben-zylamines (eq 11). These elegant reactions have been applied to the asymmetric syntheses of a number of natural products. ... 

More complex heterocyclic structures have been synthesized efficiently and with high stereoselectivities using tandem AROM-RCM sequences [85] similarly, application of tandem AROM/CM to functionalized norbomenes affords enantio-pure highly functionalized cydopentanes [86]. A polymer-supported chiral molybdenum catalyst for enantioselective metathesis effidendy promotes ARCM (kinetic resolution as well as desymmetrization) and AROM reactions and can be recycled [87]. 

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