Titanium Strecker reaction

Representative metal complexes employed for the catalytic asymmetric Strecker reaction are summarized in Figure 4.2. Aluminum-, titanium-, lanthanoid-, and zirconium-based catalysts are highly efficient. Direct one-pot synthesis starting from aldehydes, and amines is reported using the Zr complex described in Figure 4.2. ... 

Snapper and Hoveyda reported a catalytic enantioselective Strecker reaction of aldimines using peptide-based chiral titanium complex [Eq. (13.11)]. Rapid and combinatorial tuning of the catalyst structure is possible in their approach. Based on kinetic studies, bifunctional transition state model 24 was proposed, in which titanium acts as a Lewis acid to activate an imine and an amide carbonyl oxygen acts as a Bronsted base to deprotonate HCN. Related catalyst is also effective in an enantioselective epoxide opening by cyanide "... 

Byrne, J. J., Chavarot, M., Chavant, P.-Y., Vallee, Y. Asymmetric Strecker reactions of ketimines catalysed by titanium-based complexes. Tetrahedron Lett. 2000, 41, 873-876. 

Strecker reaction A robust heterogeneous self-supported chiral titanium cluster (SCTC) catalyst applied both in batch and continuous mode [44] enabled imine cyanation as well as a three-component Strecker reaction using the corresponding aldehydes and amines under continuous flow conditions in a PBR giving aminonitriles enantiomeric excess values of up to 98%. 

Following Snapper and Hoveyda s reports, Vilaivan and coworkers employed titanium complex of simple N-salicyl-P-amino alcohol (10 mol%) for catalytic asymmetric Strecker reaction of N-benzyl substituted imines with TMSCN, affording the Strecker adducts in excellent yields and up to >98% ee [229]. The presence of a protic additive is found to be essential to ensure good conversion and reaction rate (Scheme 14.97). 

Banphavichit V, Mansawat W, Bhanthumnavin W et al (2004) A highly enantioselective Strecker reaction catalyzed by titanium-Af-salicyl-yS-aminoalcohol complexes. Tetrahedron 60 10559-10568... 

Snapper and Hoveyda have investigated ligands that incorporate a Schiff base onto a peptide motif for enantioselective Strecker reactions of non-en-olizable substrates (Scheme 10.23) [111]. The synthetic utility of this transformation was elegantly highlighted in the catalytic enantioselective synthesis of the aromatic amino nitrile 155 (98%, 93 % ee) in the presence of titanium complexes of peptide ligand 154. This core subunit 155 was subsequently used in a total synthesis of the anti-HIV agent chloropeptin I (156) [112],... 

Two other types of catalysts have been investigated for the enantioselective Strecker-type reactions. Chiral N-oxide catalyst 24 has been utilized in the trimethylsilyl cyanide promoted addition to aldimines to afford the corresponding aminonitriles with enantioselectivities up to 73% ee [14]. Electron-deficient aldimines were the best substrates, but unfortunately an equimolar amount of catalyst 24 was used in these reactions. The asymmetric Strecker addition of trimethylsilyl cyanide to a ketimine with titanium-based BINOL catalyst 25 gave fast conversions to quarternary aminonitriles with enantiomeric excesses to 59%... 

The successful results and the green credentials of the process (water as cosolvent and only the nontoxic titanium dioxide as final residue) make this reaction an excellent, cheaper, and favorable alternative to the classical Strecker synthesis, which also requires the hydrolysis of cyanide to the amido group (Scheme 14.8c). 

The addition of cyanide to imine (Strecker-type reaction) can also be catalyzed by chiral Ti complexes. In a pioneering work reported by Snapper and Hoveyda, a series of titanium complexes of tripeptide-based Schiffbase ligands have been discovered by combinatorial chemistry approach for the addition of TMSCN to imine derivatives with >93% conversion of substrates and excellent enantioselectivities (85-97% ee) [227]. This methodology has provided a practical procedure for the... 

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