Amplification, diastereoselective

Gonzalez-Alverez, A. Alfonso, I. Gotor, V. Highly diastereoselective amplification from a dynamic combinatorial library of macrocyclic oligoimines. Chem. Commun. 2006, 2224-2226. 

The use of chiral Br0nsted acids is illustrated in Eq. 93 as a method for catalyst-controlled double diastereoselective additions of pinacol allylic boronates. Aside from circumventing the need for a chiral boronate, these additions can lead to very good amplification of facial stereoselectivity. For example, compared to both non-catalyzed (room temperature, Eq. 90) and SnCU-catalyzed variants, the use of the matched diol-SnCU enantiomer at a low temperature leads to a significant improvement in the proportion of the desired anti-syn diastereomer in the crotylation of aldehyde 117 with pinacolate reagent (Z)-7 (Eq. 93). Moreover, unlike reagent (Z)-ll (Eq. 91) none of the other diastereomers arising from Z- to E-isomerization is observed. 

Carbonyl-Ene Reaction. BINOL-TiX2 reagent exhibits a remarkable level of asymmetric catalysis in the carbonyl-ene reaction of prochiral glyoxylates, thereby providing practical access to a-hydroxy esters. These reactions exhibit a remarkable positive nonlinear effect (asymmetric amplification) that is of practical and mechanistic importance (eq 19). The desymmetrization of prochiral ene substrates with planar symmetry by the enantiofacial selective carbonyl-ene reaction provides an efficient solution to remote internal asymmetric induction (eq 20). The kinetic resolution of a racemic allylic ether by the glyoxylate-ene reaction also provides efficient access to remote but relative asymmetric induction (eq 21). Both the dibromide and dichloride catalysts provide the (2R,5S)-syn product with 97% diastereoselectivity and >95% ee. 

The regio- and the stereoselectivity of proline-catalyzed a-electrophilic substitution of carbonyl compounds can therefore be successfully explained by the oxazolidinone model, although the diastereoselectivity of the aldol and Mannich reactions was not taken into account in Seebach s discussion. Moreover, the model also could explain the autoinductive effects observed by Blackmond in the proline-catalyzed nitroso aldol and a-amination reactions of aldehydes [29, 31], by simply assuming that the oxazolidinone product acts as a base in the rate-determining enamine formation step. Kinetic resolution of proline, leading to chirality amplification effects, would be accounted for by the greater thermodynamic stability of the matched oxazolidinone product. In fact, the formation of Seebach s oxazolidi-nones, rather than enamines or iminium ion intermediates, from ketones and proline in DMSO solution had been described by List et al. in 2004 [23], but they concluded that this was a parasitic equilibrium leading to an unproductive intermediate. On the other hand, the product oxazolidinone in the proline-catalyzed a-amination of... 

ESI-MS, ultraviolet, and NMR were used to study templating effects on the DCLs, and proved that metal ion binding is the driving force. Recently, the same group reported a highly diastereoselective amplification induced by Cd of the heterochiral form of macrocycle 52 starting from a mixture of (R,R)- and (S,S)-trans-cyclohexane-l,2-diamine [56],... 

SCHEME 22.6 Stereochemical analysis for styrene/CO copolymers, (a) Highly diastereoselective diad formation with 2,2 -bipyiidine. (h) Amplification of stereoselectivity occurs as the polymer chain grows using a diimine ligand 9. 

Zbieg JR, Mclnturff EL, Leung JC, Krische MI (2011) Amplification of anri-diastereoselectivity via Curtin-Hammett effects in ruthenium-catalyzed hydrohydroxyalkylation of 1,1-disubstituted allenes diastereoseleetive formation of all-carbon quaternary centers. J Am Chem Soc 133 1141-1144... 

Hoffmann and coworkers optimized the chiral auxiliary to further improve the diastereomeric excess. Increasing the steric buUdness of R had no effect on the product yield nor the diastereoselectivity (Scheme 18.26), but a change of Ar from phenyl to naphthyl resulted in an amplification of the diastereoselectivity of the cycloaddition, an outcome that was assumed to be due to more effective shielding of one 7i-face of the siloxyallyl cation by the naphthyl than by the phenyl substiment [31]. 

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