Strecker thio urea

Figure 6.12 Polystyrene-bound Schiff base (thio)urea catalysts HTS-optimized in the asymmetric Strecker reaction between N-allyl-protected benzaldimine and TBSCN key results obtained from the different libraries.

On the basis of the observed stereoinduction trend, the addition of HCN took place over the diaminocyclohexane portion of the catalyst away from the amino acid and amide unit. The last hypothesis led to the prediction that a more sterically demanding amino acid or amide unit (Figure 6.14) could additionally favor the cyanide attack compared to the less bulky diaminocyclohexane unit and thus making the Schiff base catalyst more enantioselective in Strecker reactions of aldimines and ketimines. To evaluate this perspechve, the authors performed a model-(mechanism-) driven systematic structure optimizations by stepwise modification of the amide, the amino acid, and the (thio)urea unit of catalyst 42 and examined these derivatives of 42 (lmol% loading ) in the model Strecker reaction (toluene ... 

Strecker reaction Rhodia ChiRex Jacobsen (thio-)urea... 

Scheme 9.6 Supposed mechanism of the (thio)urea catalysed Strecker reaction...

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). 

Scheme 19.3 First asymmetric thio(urea) catalyst. Enantioselective Strecker reaction.

Initial mechanistic analysis of the Strecker reaction catalyzed by a urea-based organocatalyst (Scheme 3.18) revealed that the catalytic activity is provided by the urea functionality of structurally complex catalyst 1. However, further studies revealed a bifunchonal character of urea and thiourea-based catalysts " as well as the possibility of multiple mechanistic pathways in catalysis of nucleophile-electrophile addition reactions. " Simplified but sufficiently effective (thio)urea catalysts 4a and 4b were used in the hydrocyanation reaction (Scheme 3.19) that was subjected to a combined experimental and computational study. °... 

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

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