Strecker synthesis catalysts

Scheme 3. Asymmetric Strecker synthesis with chiral Alm-Salen catalyst 5 (Sigman and Jacobsen). TFAA = trifluoroacetic anhydride.

Scheme 4. Asymmetric Strecker synthesis with salicylimine catalyst 9 (Vachal and Jacobsen). Bn = benzyl.

Scheme 6. Asymmetric Strecker synthesis with bifunctional Lewis acid-Lewis base catalyst 14 (Shibasaki and co-workers). DDQ = 2,3-dichloro-5,6-dicyano-l, 4-benzoquinone.

Scheme 9. Three-component Strecker synthesis with chiral zirconium binuclear catalyst 22 (Kobayashi and co-workers).

Ishitani, H., Komiyama, S., Hasegawa, Y., Kobayashi, S. Catalytic Asymmetric Strecker Synthesis. Preparation of Enantiomerically Pure a-Amino Acid Derivatives from Aidimines and Tributyitin Cyanide or Achirai Aidehydes, Amines, and Hydrogen Cyanide Using a Chiral Zirconium Catalyst. J. Am. Chem. Soc. 2000,122, 762-766. 

Lipton and co-workers employed the cyclic dipeptide 13 (Figure 10.13) bearing a guanidinium moiety as a catalyst in the Strecker synthesis in 1996. Corresponding a-aminonitriles were obtained with high enantioselectivities (Equation 10.27). 

The a-amino acids prepared by the synthetic methods just described are racemic unless a resolution step is included, enantiomerically enriched reactants are used, or the reaction is modified so as to become enantioselective. Considerable progress has been made in the last of these methods, allowing chemists to prepare not only L-amino acids, but also their much rarer D-enantiomers. We have already seen one example of this approach in the synthesis of the anti-parkinsonism drug L-dopa by enantioselective hydrogenation (see Section 14.14). A variation of the Strecker synthesis using a chiral catalyst has recently been developed that gives a-amino acids with greater than 99% enantioselectivity. 

Recently, a general aminocatalytic synthesis of aldimines catalysed by pyrrolidine has been described. DABCO was the catalyst of choice for isomerisation of 5-hydro yl-2,3-dienoate. ° The Strecker synthesis of a-amino acids is one of the simplest and most atom economical reactions. Tri-methylsilyl cyanide has been widely used for this purpose. Recently, Feng and coworkers have used a catal) c amount of tetramethylguanidine (TMG) to carry out the Strecker reaction of aldehydes and ketones under solvent-free conditions. ... 

There has been striking success in adapting the Strecker synthesis to the preparation of a-amino acids with greater than 99% enantioselectivity. The numerous methods that have been developed employ specialized chiral reagents or catalysts and feature enantiose-lective generation of a chirality center by nucleophilic addition to an imine. 

A new enantioselective Strecker synthesis of a-aminonitriles and a-amino-acids reacts A-benzhydrylimines with hydrogen cyanide in the presence of achiral guanidine catalyst the mechanistic basis of the enantioselectivity is analysed." ... 

Asymmetric cyanation of imines, a modified Strecker synthesis, affords enantiomerically enriched a-aminonitriles, which can be converted into a-amino acids. Seayad and Ramahngam reported a homogeneous catalyst system that was derived... 

Tsogoeva et al developed a novel bifunctional thiourea catalyst (12), derived from 1,2-diaminocyclohexane, and applied it to the Strecker synthesis and nitro Michael reactions (Scheme 2.47) [100]. 

Lipton et al employed a cyclic dipeptide bearing guanidine moiety (20) as a catalyst for the Strecker synthesis [120, 121]. Corresponding a-amino nitrile was obtained highly enantioselectively (Scheme 2.61). 

We have previously met the Strecker synthesis of amino acids (Figure 22.20, Section 14,3.4) like the two previous methods, this normally produces racemic amino acids. However, if the reaction is catalyzed by various additives such as the Jacobsen catalyst, 22.24, aliphatic a-aminonitriles have been isolated in 80 %-90 % enantiomer excess. 

Miscellaneous Reactions. Sodium bisulfite adds to acetaldehyde to form a white crystalline addition compound, insoluble in ethyl alcohol and ether. This bisulfite addition compound is frequendy used to isolate and purify acetaldehyde, which may be regenerated with dilute acid. Hydrocyanic acid adds to acetaldehyde in the presence of an alkaU catalyst to form cyanohydrin the cyanohydrin may also be prepared from sodium cyanide and the bisulfite addition compound. Acrylonittile [107-13-1] (qv) can be made from acetaldehyde and hydrocyanic acid by heating the cyanohydrin that is formed to 600—700°C (77). Alanine [302-72-7] can be prepared by the reaction of an ammonium salt and an alkaU metal cyanide with acetaldehyde this is a general method for the preparation of a-amino acids called the Strecker amino acids synthesis. Grignard reagents add readily to acetaldehyde, the final product being a secondary alcohol. Thioacetaldehyde [2765-04-0] is formed by reaction of acetaldehyde with hydrogen sulfide thioacetaldehyde polymerizes readily to the trimer. 

The addition of cyanide to imines, the Strecker reaction, constitutes an interesting strategy for the asymmetric synthesis of a-amino acid derivatives. Sigman and Jacobsen150 reported the first example of a metal-catalyzed enan-tioselective Strecker reaction using chiral salen Al(III) complexes 143 as the catalyst (see Scheme 2-59). 

To date, the most frequently used ligand for combinatorial approaches to catalyst development have been imine-type ligands. From a synthetic point of view this is logical, since imines are readily accessible from the reaction of aldehydes with primary or secondary amines. Since there are large numbers of aldehydes and amines that are commercially available the synthesis of a variety of imine ligands with different electronic and steric properties is easily achieved. Additionally, catalysts based on imine ligands are useful in a number of different catalytic processes. Libraries of imine ligands have been used in catalysts of the Strecker reaction, the aza-Diels-Alder reaction, diethylzinc addition, epoxidation, carbene insertions, and alkene polymerizations. 

Shibasaki et al. developed a polymer-supported bifunctional catalyst (33) in which aluminum was complexed to a chiral binaphtyl derivative containing also two Lewis basic phosphine oxide-functionahties. The binaphtyl unit was attached via a non-coordinating alkenyl Hnker to the Janda Jel-polymer, a polystyrene resin containing flexible tetrahydrofuran-derived cross-Hnkers and showing better swelling properties than Merifield resins (Scheme 4.19) [105]. Catalyst (33) was employed in the enantioselective Strecker-type synthesis of imines with TMSCN. 

A clean, Strecker-type synthesis of a-aminonitriles has been developed amine, aldehyde, tributyltin cyanide, and scandium(III) triflate (as catalyst) are mixed together at room temperature. Yields for a range of aliphatic and aromatic aldehydes are typically ca 90%, the solvent can be organic or aqueous, the 10% catalyst loading is recoverable and reusable, and the tin reagent is similarly recyclable. 

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. ... 

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