Chiral nitrogen-containing heterocycles

The asymmetric hydrogenation of 2,4-diaryl-l,5-benzodiazepines by Hj in CH2CI2 to chiral nitrogen-containing heterocycles with 85/15 dr and 96% ee is catalysed by Ir complexes of dendritic ligands with BArF as the counteranion. A positive dendritic effect on catalytic activity is observed, and the dendritic catalyst is usable three times but at the expense of relatively low catalytic activities. ... 

Aqueous aza-Diels-Alder reactions of chiral aldehydes, prepared from carbohydrates and with benzylamine hydrochloride and cyclopentadiene, were promoted by lanthanide triflates (Eq. 12.65).137 The nitrogen-containing heterocyclic products were further transformed into aza sugars, which are potential inhibitors against glycoprocessing enzymes. 

Dipolar addition of azomethine ylides to electron-deficient olefins is a versatile route to nitrogen-containing heterocycles. Applying this approach to ( )-ethyl 3-fluoroacrylates utilizing L-menthol as a chiral auxiliary provides a stereoselective and regioselective synthesis of enantiopure-fluorinated prolines 28 and 29. Careful... 

Recently, there has been considerable progress in the synthesis of nitrogen-containing heterocycles based on (ox)indole skeleton. Oxindole derivatives serve as useful reaction partners in various domino transformations. Michael addition of aliphatic aldehydes to electron-deficient olefinic oxindole motifs gave chiral intermediates, which were further combined with diverse activated olefins or imines to afford spirocyclic oxindoles with high molecular complexity (Scheme 8.27). Spiro-oxindole derivatives were also assembled by a Michael/Michael/aldol cascade of oxindole and two equivalents of enal. " ... 

On the other hand, the alkaloid (-)-crinine (47) can be prq>ared in enantiomerically pure form by a similar approach (Scheme 23), possibly due to dm different reaction conditions applied or because of the additional chiral -phenylethyl residue. This method also applied very well for odier nitrogen-containing heterocycles, including other ring sizes. 

In 2013, Carreira and coworkers presented an attractive strategy for the synthesis of chiral pyrrolidones via ruthenium-catalyzed intramolecular hydrocar-bamoylation of allylic formamides under CO atmosphere (Eq. (7.2)) [7]. A formal ruthenium-catalyzed intramolecular insertion into the formamide C-H bond and concomitant C-C bond formation by olefin hydrocarbamoylation were involved in the reaction, which made the reaction complete atom economy. The cycliza-tion performed with a broad substrate scope. More interestingly, even homoallylic and bis-homoallylic formamide substrates were used, the reactions afforded five-membered nitrogen-containing heterocycles only. 

The enantioselective hetero-Diels-Alder reaction of siloxydienes, such as Danishefsky s and Brassard s dienes, with imines provides an efficient route for the preparation of functionalized nitrogen-containing heterocycles in optically active forms. Akiyama and coworkers reported the first catalytic enantioselective hetero-Diels-Alder reaction of Danishefsky s diene (21) with aromatic imines 20 using chiral phosphoric acid catalyst la (Scheme 11.7a) [14]. The desired dihydropyridi-nones 22 were obtained in good yields with high enantioselectivities. Notably, the addition of an equimolar amount of acetic acid was effective in improving the enantioselectivity. Akiyama and coworkers also reported an enantioselective... 

FIGURE 30.4. Selected bioactive natural compounds having saturated nitrogen-containing heterocycles and chiral amines as drugs. 

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