Alkaloids Strecker reaction

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]. 

A new cinchona alkaloid-derived catalyst has been developed for the enantioselective Strecker reaction of aryl aldimines via hydrogen-bonding activation. For reference, see Huang, J. Corey, E. J. Org. Lett. 2004, 6, 5027-5029. 

New catalyst design further highlights the utility of the scaffold and functional moieties of the Cinchona alkaloids. his-Cinchona alkaloid derivative 43 was developed by Corey [49] for enantioselective dihydroxylation of olefins with OsO. The catalyst was later employed in the Strecker hydrocyanation of iV-allyl aldimines. The mechanistic logic behind the catalyst for the Strecker reaction presents a chiral ammonium salt of the catalyst 43 (in the presence of a conjugate acid) that would stabilize the aldimine already activated via hydrogen-bonding to the protonated quinuclidine moiety. Nucleophilic attack by cyanide ion to the imine would give an a-amino nitrile product (Scheme 10). 

The catalytic asymmetric Strecker reaction represents one of the most direct and viable methods for the asymmetric synthesis of a-amino adds and their derivatives. Corey and coworkers reported the first successful use of a tinchona alkaloid derived chiral ammonium salt 133 as a catalyst in the asymmetric Strecker reactions of... 

Synthetic use of the a-aminonitrile intermediates from the Strecker reaction have also been investigated.46 In this manner, it was possible to assemble the core scaffold of the indolizidine alkaloids 112. Treating 110, which contained the amine component and a dimethoxyacetal as a latent carbonyl component, with cyanide under acidic conditions initiated an intramolecular cyclization to afford the Strecker reaction intermediate a-aminonitrile 111. While one could hydrolyze the nitrile functionality to unmask a carboxylic acid, in this case, the nitrile was used to introduce the requisite sidechains needed in the construction of the indolizidine alkaloids 112. 

A theoretical investigation of a cinchona-alkaloid-catalysed Strecker reaction using Ti(OPr% indicates that the rate-determining step is the isomerization of HCN to HNC, while the stereodetermination occurs at C-C bond formation. ... 

In 2003, Rawal reported the use of TADDOLs 177 as chiral H-bonding catalysts to facilitate highly enantioselec-tive hetero-Diels-Alder reactions between dienes 181 and different aldehydes 86 (Scheme 6.29A) [82], and also BINOL-based catalysts 178 were found to facilitate this reaction with excellent selectivities [83]. TADDOLs were also successfully used as organocatalysts for other asymmetric transformations like Mukaiyama aldol reactions, nitroso aldol reactions, or Strecker reactions to mention a few examples only [84]. In addition, also BINOL derivatives have been employed as efficient chiral H-bonding activators as exemplified in the Morita-Baylis-Hilhnan reaction of enone 184 with different carbaldehydes 86 [85]. The use of chiral squaramides for asymmetric reactions dates back to 2005 when Xie et al. first used camphor-derived squaric amino alcohols as ligands in borane reductions [86]. The first truly organocatalytic application was described by Rawal et al. in 2008 who found that minute amounts of the bifunctional cinchona alkaloid-based squaramide 180 are... 

The Strecker reaction of dihydroisoquinoline with HCN proceeded with high ee by means of (4d) and a short step synthesis of isoquinohne alkaloid was achieved (Scheme 2.29) [79]. 

Corey et al investigated chiral Cinchona alkaloid-based ammonium salt (28) as a catalyst for the enantioselective Strecker reaction (Scheme 2.69) [131]. They proposed that the acid could be used to hold the aldehyde-derived part of an aldimine, which was activated by hydrogen bonding with the protonated quinuclidine moiety. 

Table 30.10 Asymmetric Strecker reaction using natural occurring alkaloid 85.

Strecker reactions of ethyl cyanoformate with cyclic (Z)-aldimines (indoles and thi-azines) catalysed by chinchona alkaloid derivatives,and with various aromatic and aliphatic A(-benzhydrylimines catalysed by a chiral polyamide (12), " proceed with excellent ee values. 

The Strecker degradation of ornithine proceeds analogously, but the intermediate 4-aminobutanal forms by cychsation the final product, 1-pyrroHne (Figure 2.59). This reaction is important for the development of the characteristic aroma of bread crust (see Section 8.2.12.4.1), the aroma of other cereal products, certain fragrant rice varieties (such as Basmati rice) and in the biosynthesis of pyrrolidine alkaloids in plants (see Section 10.3.2.1.1). It was proposed that pyrrolidine and l-pyrrohne also result upon Strecker-type reaction of proline by a-dicarbonyl compounds. 

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