Catalytic strecker reaction

Computational analysis of the catalytic cycle was made for the simplified catalyst 6. The possibilities of either HCN or HNC addition have been analyzed separately however, the key transition states were found to be similar in structures and in relative energies for both mechanisms. 

For the analysis of the origin of enantioselectivity computations were made for a more realistic model catalyst 7. 

It was concluded that enantioselectivity is controlled by different degrees of iminium ion stabilization via H-bonding interactions between the iminium ion NH proton and both the amide carbonyl group and the thiourea-bound cyanide ion. However, distinct structural features responsible for that more effective stabilization are not easy to specify. The 3D structures of TSIU, TS2U, TSlS, and TS2S can be found in the CD. 

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The asymmetric catalytic Strecker reaction is an elegant means of synthesis of optically active a-amino acids. The Jacobsen group developed optimized organocata-lysts [21, 44-48], optically active urea or thiourea derivatives, which were found to be the most efficient type of catalyst yet for asymmetric hydrocyanation of imines (see also Section 5.1 on the hydrocyanation of imines). Because of its high efficiency, Jacobsen hydrocyanation technology has already been used commercially at Rodia ChiRex [49]. The concept of the reaction is shown in Scheme 14.7. In the presence of a catalytic amount (2 mol%) of the readily available organocatalyst... 

The first enantioselective catalytic Strecker reaction of ketoimines to give chiral quaternary cyanohydrins was demonstrated by the Jacobsen group using 45b (Scheme 6.7) [41]. A series of substituted aryl and aliphatic N-benzyl methylketo-imines (48) reacted with HCN in the presence of 45b to provide essentially quantitative yields of the Strecker adducts in high optical purities (70-95% ee). The adducts were crystalline, and their recrystallization from hexanes increased their enantiopurities to >99.9% ee. The a-quaternary Strecker adducts (49) could be converted to a-quaternary a-amino acids through formamide protection of the secondary amine, followed by sequential hydrolysis of the nitrile and the formamide, followed by hydrogenolytic debenzylation. 

The only known metal catalyst for the asymmetric catalytic Strecker reaction is the aluminum salen catalyst 465 (Sch. 65) recently reported by Sigman and Jacobsen [97]. They prepared 11 different chiral salen complexes from different transition and main group metals and screened these complexes for the addition of trimethylsilyl cyanide to imine 460 at room temperature. The aluminum catalyst 465 was optimum in terms both of asymmetric induction and rate. This constitutes the first aluminum salen complex successfully developed for an asymmetric catalytic reaction. 

Table 11.10 Asymmetric catalytic Strecker reaction with cyanohydrin under PTC conditions.

A review elsewhere discusses catalytic Strecker reactions including guanidine catalysts [64]. 

A catalytic Strecker reaction (Scheme 15.24) has been developed, with 105 as a pre-catalyst, which is in situ converted into the corresponding N,N -dioxide on... 

Scheme 12.25 Asymmetric phase-transfer catalytic Strecker reaction...

A very efficient and universal method has been developed for the production of optically pue L- and D-amino adds. The prindple is based on the enantioselective hydrolysis of D,L-amino add amides. The stable D,L-amino add amides are effidently prepared under mild reaction conditions starting from simple raw materials (Figure A8.2). Thus reaction of an aldehyde with hydrogen cyanide in ammonia (Strecker reaction) gives rise to the formation of the amino nitrile. The aminonitrile is converted in a high yield to the D,L-amino add amide under alkaline conditions in the presence of a catalytic amount of acetone. The resolution step is accomplished with permeabilised whole cells of Pseudomonas putida ATCC 12633. A nearly 100% stereoselectivity in hydrolysing only the L-amino add amide is combined with a very broad substrate spedfidty. 

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. 

Optically active a-amino acids are prepared by a cyanide addition to imines, known as the Strecker reaction. Several organobase catalysts and metal complex catalysts have been successfully applied to the asymmetric catalytic Strecker amino... 

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 "... 

For catalytic enantioselective Strecker reaction of ketoimines from other groups, see ... 

One of the most important approaches to a-amino acids is based on the Strecker reaction. Although there are already a number of catalytic asymmetric variants, the cyanation of imines still challenges modem organic chemists. 

Groger H (2003) Catalytic enantioselective Strecker reactions and analogous syntheses. Chem Rev 103(8) 2795-2827... 

Several years later, Corey disclosed the C2 symmetric bicyclic guanidine 19 as an effective bifunctional catalyst for the Strecker reaction (Scheme 5.40) [74]. According to the catalytic cycle, HCN should hydrogen bond to the catalyst to form guanidinium-cyanide complex A. A subsequent increase in acidity of the catalyst N—H proton allows donation of a hydrogen bond to the aldimine to form TS assembly B. Enantiofacial attack of CN to the bound aldimine gives the Strecker product. 

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.

Tsogoeva and co-workers explored the catalytic potential of pyridyl- and imida-zoyl-containing thiourea derivatives (e.g., thiourea 92 and 93) in the asymmetric model Strecker reactions [157] of N-benzyl- and benzhydryl-protected benzaldi-mine with HCN [258], The observed enantioselectivities were consistently very low (4—14% ee) for all catalyst candidates and were far below synthetically useful levels, while imidazoyl-thiourea 93 was reported to be highly active and displayed 100% conversion (at 7% ee) of the N-benzhydryl-protected benzaldimine (Scheme 6.99). X-ray structure analysis of a pyridyl-thiourea revealed an intramolecular hydrogen-bond between the basic ring nitrogen and one amide proton. This could make this... 

Scheme 6.164 Strecker reaction for examination of the catalytic efficiency of guanidine-functionalized diketopiperazine 177.

Scheme 6.165 Enantioselective Strecker reactions catalyzed by biflinctional hydrogen-bonding guanidine organocatalyst 178. Catalytic action of 178 HCN hydrogen bonds to 178 and generates a guanidinium cyanide complex after protonation, which activates the aldimine through single hydrogen bonding and facilitates stereoselective cyanide attack and product formation.

The cyanation of imines, generally known as the Strecker reaction, has been one of the most aggressively studied transformations of asymmetric catalysis over the past several years. Very recent efforts in this area have resulted in the discovery of several highly efficient catalytic systems capable of providing a-ami-... 

The wide assortment of catalytic asymmetric Strecker reaction methodologies devised to date can be divided into two major categories based on the nature of catalyst utilized 1) Lewis acid-promoted and 2) metal-free (or organo-catalytic) systems. Both classes of catalysis will be discussed and key results will be highlighted. 

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