Strecker products

Furthermore, Rueping and coworkers applied their reaction conditions to the cyanation of ketimines [54]. The use of A-benzylated imines derived from aryl-methyl ketones generally gave comparable yields, but lower enantioselectivities. However, this method furnished Strecker products bearing a quaternary stereogenic center, which are valuable intermediates for the preparation of optically active a,a-disubstituted a-amino acids. 

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

Scheme 6.47 Strecker products obtained from the 47-catalyzed asymmetric acetylcyanation using acetyl cyanide as cyanide source.

Hydrolysis of the diastereoisomerically pure Strecker product under racemization-free acidic conditions, followed by hydrogenolysis of the benzylic C-N bond, results in a 73% overall yield of (S)-tert-leucine (11). The amino acid 11 is an interesting, sterically constrained amino acid that is applied in various new antiviral and anti-HIV (human immunodeficiency virus) agents. 

The combination of Me2AlCN and BINOL (1.2 equiv.) also induced the cyanation of imines derived from benzaldehyde, affording the Strecker products in up to 70% ee [76]. Finally, N-allylbenzaldimines have been reported to react with HCN in the presence of chiral ammonium salt catalysts [77, 78]. 

Coffee flavors form during roasting from dicarbonyl compounds which derive from carbohydrates. The thermal degradation of hexoses is thought to be the preciu ors of fin ones like HDMF. The presence of alkylpyrazines affords the characteristic roast notes. These pyrazines are formed through Strecker degradation and the condensation of the resulting Strecker products (60). 

Aziridine 2-carboaldimines, 201, have been used to provide ready access to a variety of diamines <05T9281>. A number of nucleophiles were added to imine 201 to provide products 202 and 203. Grignard reagents and a ketene sUyl acetal added to the imine in very good yields when catalyzed with BF3 OEt2- The Strecker product, R = CN, was obtained in very good yield but with only moderate diastereoselectivity by reaction with TMSCN and BFj OEtj. 

Hydrocyanation to imines with HCN, the Strecker reaction, is one of the most direct and efficient methods for natural and unnatural a-amino acids. Asymmetric Strecker-type reaction with chiral aluminum Lewis acids has been developed. As shown in Scheme 6.48, the research group of Jacobsen reported chiral Al(salen)Cl complex (67a) as an effective asymmetric catalyst for catalytic enantioselective Strecker reaction of aromatic N-allylimines with HCN [62]. Compared to the reactions of aromatic imines, that of a-branched aliphatic imines (R = Cy and t-Bu) gave Strecker products in only moderate optical yield. Additionally, the use of TMSCN instead of HCN dramatically reduced in the enantioselectivity. 

The first highly enantioselective reaction catalyzed by a chiral guanidine was reported by Corey and coworkers in 1999 [128], C2-symmetric guanidine 46 was shown to be a highly effective catalyst in the Strecker reaction of aromatic aldi-mines, affording the Strecker products in high yields and enantioselectivities (Scheme 10.43). 

Through the synthesis of parallel combinatorial libraries, Jacobsen and coworker discovered a new dass of catalysts for the Strecker reaction [15]. Because of its modular assembly, the new catalyst type was amenable to solid-phase synthesis and fast preparation, screening, and lead optimization were feasible. The best catalyst candidate afforded the Strecker product from N-allylbenzaldimine in 78% yield and 91% ee. Catalyst 21 was prepared as the soluble variant of the optimized candidate and proved to be an effective catalyst for a range of imine derivates 20, affording aromatic amino nitriles 22 in moderate to good yields (65-92%) and high enantioselectivities (70-91% ee) (Scheme 30.4). In addition, aliphatic aldimines 20... 

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