Thio urea Catalysts for the Strecker Reaction

91% ee) showed that no difference in asymmetric introduction existed, whether ( )-isomers or the (cyclic) (Z)-isomer of the imine was used. Although application of the soluble catalyst 25 led to 2-4% higher ee s the use of the resin-bound analog 24 is more practical since the catalyst can be removed by simple filtration and be reused several times with no remarkable loss of catalyst reactivity or product enantioselectivity. 

Facing the requirements of large-scale application of the Strecker reaction, Jacobsen addressed these problems with the revised second-generation catalyst 33 (Table 30.4) [21]. Reactions using the old catalyst generation suffered from the need for cryogenic temperatures (below 0 °C) and used hazardous and expensive cyanide sources (TMSCN/MeOH or HCN). Synthesis of either soluble catalyst 25 

Intensive studies using NMR methods, kinetic experiments, and computational calculations were conducted to elucidate the catalytic mechanism and observed stereoinduction [22]. The data revealed that the hydrocyanation catalyzed by 33 presumably proceed over an initial amido-thiourea catalyzed proton transfer from hydrogen isocyanide to imine 32 to generate a catalyst-bound diastereomeric iminium/cyanide ion pair. Thereby, hydrogen isocyanide, as the tautomeric form of HCN, is stabilized by the thiourea moiety of 33. The stabilization degree of the formed iminium ion by the catalyst is seen as the basis for enantioselectivity. Subsequent collapse of the ion pair and bond formation between the electrophile and the cyanide ion forms the a-amino nitrile. It should be emphasized that the productive catalytic cycle with 33 does not involve a direct imine-urea binding, although this interaction was observed both kinetically and spectroscopically in the Strecker reaction catalyzed by 25 (see above) [19], 

Bifunctional catalysts bearing both an acidic and a basic/nucleophilic functionality are interesting for asymmetric organocatalysis. The catalysts 39 and 40 consist 

Building upon an early observation that a-oxonitriles readily react with imines to form the corresponding N-acylamino nitriles [26-28], List devised an asymmetric organocatalyzed acetylcyanation variant (Table 30.5) [29, 30]. Acetyl cyanide is commercially available and, as a Uquid, is convenient to use. In addition, the use of acetyl cyanide makes further derivatization of the hydrocyanation compounds with, for example, TFAA obsolete. Using catalyst 30, the reaction gave high enan-tioselectivities and high yields with aromatic, aliphatic, heteroaromatic, aUphatic-branched and -unbranched, and unsaturated imines. 

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Thio)urea Catalysts for the Strecker Reaction 885 sieves to bind the reaction water resulting from... 

A pioneer in the field of the asymmetrie (thio)urea organocatalysis was Eric Jacohsen, who first reported a chiral (polymer-hound) Schiff base thiourea derivative for asymmetric Strecker reactions optimised from parallel synthetic libraries/ These catalysts can be used either in solution or immobilised to a polystyrene resin, with the latter retaining efficiency, after repeated recycling/ The key factors responsible for high enantioselectivities were the presence of bullqr substituents at both the amino acid position and at the 3-position of the aromatic ring (Scheme 19.3). 

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