Imine anions enantioselective

The interpretation and prediction of the relationship between the configuration of the newly formed chiral center and the configuration of the amine are usually based on steric differentiation of the two faces of the imine anion. Most imine anions that show high stereoselectivity incorporate a substituent which can hold the metal cation in a compact transition state by chelation. In the case of entry 2 in Table 1.3, for example, the observed enantioselectivity is rationalized on the basis of transition state L. 

The condensation of nitro compounds and imines, the so-called aza-Henry or nitro-Mannich reaction, has recently emerged as a powerful tool for the enantioselective synthesis of 1,2-diamines through the intermediate /3-amino nitro compounds. The method is based on the addition of a nitronate ion (a-nitro carbanion), generated from nitroalkanes, to an imine. The addition of a nitronate ion to an imine is thermodynamically disfavored, so that the presence of a protic species or a Lewis acid is required, to activate the imine and/or to quench the adduct. The acidic medium is compatible with the existence of the nitronate anion, as acetic acid and nitromethane have comparable acidities. Moreover, the products are often unstable, either for the reversibility of the addition or for the possible /3-elimination of the nitro group, and the crude products are generally reduced, avoiding purification to give the desired 1,2-diamines. Hence, the nitronate ion is an equivalent of an a-amino carbanion. 

Enantiopure phosphinodihydrooxazoles were used in the Ir-catalyzed enantioselective hydrogenation of imines in CH2C12. Leitner reported that it is possible to replace the organic solvents with scC02 without loss of enantioselectivity, if these Ir catalysts are suitably tailored to the specific properties of the reaction medium by careful choice of the substituents on the chiral ligands and in the anion 365... 

Dicarbonyl donors bearing a thioester has been applied in the Mannich reaction to A -tosyl imines. Ricci presented an enantioselective decarboxylative addition of malonic half thioester 37 to imine 38. In the Mannich-type addition, catalyst 36 deprotonates the malonic acid thioester followed by decarboxylation to generate a stabilized thioacetate enolate. This stabilized anion reacts with facial selectivity to the imine due to steric-tuning from 36 [47] (Scheme 8). 

In 2008, the same group employed chiral dicarboxylic acid (R)-5 (5 mol%, R = 4- Bu-2,6-Me2-CgHj) as the catalyst in the asymmetric addition of aldehyde N,N-dialkylhydrazones 81 to aromatic iV-Boc-imines 11 in the presence of 4 A molecular sieves to provide a-amino hydrazones 176, valuable precursors of a-amino ketones, in good yields with excellent enantioselectivities (35-89%, 84-99% ee) (Scheme 74) [93], Aldehyde hydrazones are known as a class of acyl anion equivalents due to their aza-enamine structure. Their application in the field of asymmetric catalysis has been limited to the use of formaldehyde hydrazones (Scheme 30). Remarkably, the dicarboxylic acid-catalyzed method applied not only to formaldehyde hydrazone 81a (R = H) but also allowed for the use of various aryl-aldehyde hydrazones 81b (R = Ar) under shghtly modified conditions. Prior to this... 

Enantioselective alkylation of ketones. Chiral imines prepared from cyclic ketones and 1 on metalation and alkylation are converted to chiral 2-alkyleyclo-alkanones in 87-100% enantiomeric purity.1 The high cnantioselectivity is dependent on chelation of the lithium ion in the anion by the methoxyl group, which results in a rigid structure. 

An important issue is the right choice of substrate 1 which functions as an anion precursor. Successful organocatalytic conversions have been reported with indanones and benzophenone imines of glycine derivatives. The latter compounds are, in particular, useful for the synthesis of optically active a-amino acids. Excellent enantioselectivity has been reported for these conversions. In the following text the main achievements in this field of asymmetric organocatalytic nucleophilic substitutions are summarized [1, 2], The related addition of the anions 2 to Michael-acceptors is covered by chapter 4. 

In a breakthrough in IL chemistry directed to applications in asymmetric catalysis using chiral reaction media, Leitner and co-workers developed an enantioselective aza-Baylis-Hillman reaction, where enantiocontrol was ensured by the use of IL 36 as solvent. Scheme 1.17 shows the synthesis of the chiral anion. This is the first example in the literature of ees of the order of magnitude of 85% due to the use of a chiral solvent. The imine and the catalyst (10mol.%) are dissolved in the IL, then methyl vinyl ketone is added and the reaction is simply carried out by stirring at rt for 24 h (Scheme 1.18). 

In 2004 Terada and his group revealed that 2 methoxy furan (45) that can be considered as a vinylketene 0,0 acetal was sufficiently nucleophilic to engage Boc imines 44 in Bronsted acid catalyzed Friedel Crafts type reaction to furnish y aminoalkyl substituted furans 46 in excellent yields and up to 97% ee (Table 5.9) [ 16]. As already explained, phosphoric add 47 protonates the imine, thus generating a chiral contact ion pair the anionic counterion of which controls the enantioselectivity of the C C bond forming event. Although typically 2 mol% ofthe Bronsted acid were... 

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