Strecker Thiourea catalyzed

Scheme 6.7 Thiourea-catalyzed Strecker reactions of ketoimines.

Significant levels of syn diastereoselectivities (5 1 to 16 1) were observed for all substrates, with the exception of an ortho-chloro-substituted aryl imine, which provided only 2 1 syn selectivity. The catalyst was viable for a variety of nitroalkanes, and afforded adducts in uniformly high enantioselectivities (92-95% ee). The sense of enantiofacial selectivity in this reaction is identical to that reported for the thiourea-catalyzed Strecker (see Scheme 6.8) and Mannich (see Tables 6.18 and 6.22) reactions, suggesting a commonality in the mode of substrate activation. The asymmetric catalysis is likely to involve hydrogen bonding between the catalyst and the imine or the nitronate, or even dual activation of both substrates. The specific role of the 4 A MS powder in providing more reproducible results remains unclear, as the use of either 3 A or 5 A MS powder was reported to have a detrimental effect on both enantioselectivities and rates of reaction. 

Scheme 4.3 The thiourea-catalyzed Strecker reaction reported by Jacobsen.

Scheme 10.37 Three-component acyl-Strecker reaction catalyzed by thiourea.

Scheme 105 Thiourea-catalyzed Strecker reaction in the s oitheses of (—)-calycotomine (476), (—)-salsolidine (477), and (—)-camegine (478)...

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. °... 

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],... 

In screening a library of these molecules with a variety of metal ions, it was found that the ligand in the absence of added metal was more active than the metal complexes tested. Three libraries were synthesized where sequential changes were made in the structures contained in each library. Ultimately, ligand 64, with a thiourea linker, was found to catalyze the Strecker reaction between benzaldehyde and HCN in 91% ee (Scheme 8). This system also catalyzed the addition of HCN to aliphatic aldehydes with selectivities of > 80% ee. 

Furthermore, a highly efficient route to A-tert-butoxycarbonyl (Boc)-protected p-amino acids via the enantioselective addition of silyl ketene acetals to Al-Boc-aldimines catalyzed by thiourea catalyst 4 has been reported (Scheme 12.2)." From a steric and electronic standpoint, the A-Boc imine substrates used in this reaction are fundamentally different from the A-alkyl derivatives used in the Strecker reaction. 

Scheme 6.43 Recycling study Polymer-bound Schiff-base thiourea 41 catalyzed the Strecker reaction of pivalaldimine without loss of activity or enantioselectivity even after 10 catalytic cycles.

This tertiary amide-functionalized Schiff base thiourea was found to efficiently catalyze the asymmetric Strecker reaction [157] of N-benzyl-protected aldimines and also one ketimine in high enantioselectivities (86-99% ee) and proved superior to 42 examined under the same conditions (1 mol% loading, toluene, -78 °C, HCN) (Scheme 6.46) [198]. 

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