Three Strecker

Officially, the history of MCRs dates back to the year 1850, with the introduction of the Strecker reaction (S-3CR) describing the formation of a-aminocyanides from ammonia, carbonyl compounds, and hydrogen cyanide [4]. In 1882, the reaction progressed to the Hantzsch synthesis (H-4CR) of 1,4-dihydropyridines by the reaction of amines, aldehydes, and 1,3-dicarbonyl compounds [5], Some 25 years later, in 1917, Robinson achieved the total synthesis of the alkaloid tropinone by using a three-component strategy based on Mannich-type reactions (M-3CR) [6]. In fact, this was the earliest application of MCRs in natural product synthesis [7]. 

Pyridine A-oxides have been utilized as asymmetric catalysts in the allylation of aldehydes <06JOC1458> and in the Strecker reaction <06T4071>. In the latter, the chiral A-oxides played a key role in the initial activation of the Si-C bond by coordinating an O atom to the Si atom of silyl cyanide and stabilizing the three-membered complex proposed by the... 

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. 

Diastereoselective Slrecker reactions based on (R)-phenylglycine amide as chiral auxiliary are reported. The Strecker reaction is accompanied by an In situ crystallization-induced asymmetric transformation, whereby one diastereomer selecliveiy precipitates and can be isolated in 76-33% yield and dr > gsti. The diastereomeilcaily pure a-amino nitrtie obtained from pivaidehyde (R, = t-Bu, Rj = H) was converted in three steps to (S)-tert-leucine in 73% yieid and >98% ee. 

Scheme 6.15 Representative N-acetyl-Strecker products resulting from the 9-catalyzed three-component acylcyanation reaction.

The Strecker reaction is a three-component reaction of an aldehyde (or ketone), ammonia (86, or another amine) and hydrogen cyanide (87, or equivalents) to give a-amino nitriles and, after hydrolysis, a-amino acids (Scheme 9.16). 

Rohan had suggested that the operative reaction in the development of chocolate aroma might be a Strecker degradation of the amino acid fraction. Bailey et al. (8) demonstrated quantitatively that three aldehydes, which could be related to leucine, valine, and alanine, were prominent in the volatiles from a typical sample of roasted, ground cacao beans. 

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

Amino-3-phenylazetidine is obtained in high yield in three steps from Al-benzhydryl-3-azetidinone by using dibenzylamine as an amine equivalent in a modified Strecker reaction (95SC803). 

Heating of dihydroxyacetone in the presence of phosphate ions in known to produce substantial amounts of pyruvaldehyde (10). Furthermore pyruvaldehyde is assumed to catalyze the formation of 1-pyrro-line by Strecker degradation of proline (11). To study the role of 1-pyrroline and pyruvaldehyde in Acp formation, three additional experiments were conducted. 

A heterocyclic sulfur-containing compound, 2-methyl-thiophene, was identified in boiled crayfish tail meat and pasteurized crabmeat. Thiazole and 3-methylthiopropanal were identified in the crayfish hepatopancreas. Heterocyclic sulfur-containing compounds play important roles in generating meaty aromas in a variety of meat products and are considered important volatile aroma components of marine crustaceans (12— 14). The 2-methylthiophene could be an important flavor cemponent in boiled crayfish tail meat. Both thiazole find 3-methylthiopropanal were important contributors to the desirable meaty aroma associated with crayfish hepatopancreas. The 3-methyl-thiopropanal, identified in boiled crayfish hepatopancreas, is derived from Strecker degradation of methionine (15), and has been considered to be an important cemponent in basic meat flavor (16). Pyridine was detected in the headspace of the hepatopancreas from freshly boiled crayfish. Pyridine and 2-ethylpyridine have been previously reported as components in the atmospheric distillate from a sample of crayfish hepatopancreas frozen for three months (2). 

The duration of the reaction time alone determines whether carbonyl compounds, sodium cyanide and ammonium chloride will generate a cyanohydrin (Figure 9.9, top) or an a-aminonitrile (Figure 9.9, bottom). We are already familiar with the first reaction pattern from the initial reaction of the three-step Kiliani-Fischer synthesis of aldoses (Figure 7.15). The second reaction pattern initiates the Strecker synthesis of a-amino acids, which is completed by a total hydrolysis of the C=N group, as in the Bucherer modification discussed elsewhere (Figure 7.11). 

Rhizopus delemar lipase ribonucleotide reductase ring-opening metathesis Strecker three-component reaction... 

The Strecker reaction of glutaraldehyde with 1,2-diaminoethane gave three products 215, 216, and the perhydro-imidazo[l,2-n]pyridine (217). The yields of 217 were found to be dependent on the concentration of glutaraldehyde and the reaction time. The IH-NMR spectrum of 217 shows the absorption of the 5-H proton at 8 3.94 as a near triplet (7 = 3.6 Hz), indicating the axial CN group in conformation 218 (86H2835). 

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