Acyl-Strecker reaction

Scheme 10.37 Three-component acyl-Strecker reaction catalyzed by thiourea.

S. C. Pan, B. List, Synlett 2007, 318-320. Catalytic one-pot, three-component acyl-Strecker reaction, (d) A. Heydari, A. Arefi, S. Khaksar, R. K. Shiroodi, J. Mol. Catal. A Chem. 

Jacobsen s thiourea derivatives are relevant catalysts for cyanosilylation of ketones [34] or acyl-Strecker reaction [35,36]. 

Table 30.5 Asymmetric acyl-Strecker reaction supported by thiourea 30.

Table 30.5 Asymmetric acyl-Strecker reaction supported by thiourea 30. 1-5 mol% 30,1.5 equiv. AcCN...

This catalyst was also applicable in the Strecker reaction of ketiinines including quinoline and isoquinoline (Scheme 6.112) [139]. Acid chlorides were combined for use in making iminium cations to enhance the reactivity of this class of poorly electrophihc substrate. Thus the reaction involves dual activation of the acyl quinolium or isoquinolinium ion and MejSiCN by the Lewis acid (Al) and the Lewis base (oxygen atom of phosphor oxide) of 93, respectively. The reaction proceeded with moderate to high enantioselectivity. 

The first organocatalytic asymmetric three-component Strecker reaction was reported by List and Pan using Jacobsen s thiourea catalyst 75. Diverse a-aminonitriles 76 and 77 were formed in excellent yields and enantioselectivities from aliphatic and aromatic aldehydes, different amines, and acyl cyanides by using 5mol% of catalyst 75 (Scheme 10.33) [97]. 

The MC Strecker reaction is the key step in this synthesis for the preparation of intermediate aminonitrile 81 further acylation of that compound with benzothiadiazine acid 82 under the standard conditions followed by in situ addition of triethylamine provided the desired aminotetramic acid 83. 

List and coworkers implemented the imine-forming step in a three-component Strecker reaction using Jacobsen s catalyst 30 (Scheme 30.12) [31]. In this way, different amines, acyl cyanides, and aldehydes were allowed to react with catalyst... 

Acyl anion equivalents include cyanide ion (makes a-hydroxy acids via cyanohydrins and a-amino acids via the Strecker reaction), alkynyl anions, and dithianes. 

As has been outlined for the Strecker synthesis, the Ugi reaction also proceeds via initial formation of a Schiff base from an aldehyde and an amine. The imine intermediate is attacked by the isocyanidc, a process which is supported by protonation of the imine by the carboxylic acid component. The resulting a-amino nitrilium intermediate is immediately trapped by the carboxylate to give an 6>-acyl imidiate. All steps up to this stage are reversible. Only the final oxygen to nitrogen acyl shift is irreversible and delivers the A-acyl-a-amino amide as the thermodynamically favored product which contains two amide groups. 

A-Acyliminium ions are more reactive partners for condensation reactions than the standard Strecker intermediate 24 they are not generally isolable, but must be generated in situ and trapped to give the stable product. However, with proper choice of acyl group, they provide a-amidophosphorus analogues that are appropriately protected for peptide synthesis. 

DSM developed a slightly different approach towards enantiopure amino acids. Instead of performing the Strecker synthesis with a complete hydrolysis of the nitrile to the acid it is stopped at the amide stage. Then a stereoselective amino acid amidase from Pseudomonas putida is employed for the enantioselective second hydrolysis step [83], yielding enantiopure amino acids [34, 77, 78]. Although the reaction is a kinetic resolution and thus the yields are never higher than 50% this approach is overall more efficient. No acylation step is necessary and the atom efficiency is thus much higher. A drawback is that the racemisation has to be performed via the Schiff s base of the D-amide (Scheme 6.23). 

Alder, cyanation, allylation, Michael reaction, and Friedel-Crafts acylation). The same catalyst was also effective in three-component reactions such as Mannich-type reactions, Strecker, and quinoline-forming reactions. The polymer catalyst was recovered and reused many times without loss of activity (Eq. 31). 

The Lewis acidity of lanthanide complexes has been known for a long time. It was exploited extensively in their use as NMR shift reagents, mainly Eu(fod)3. They show strong affinity toward carbonyl oxygens and, therefore, have been widely used as catalysts for cycloaddition of dienes with aldehydes [25]. Moreover, the ability of catalytic amounts of lanthanide compoimds to activate coordinating nitriles as well as imines has also been recognized [26]. In recent years lanthanide (III) complexes have demonstrated clear effectiveness in catalyzing not only hetero-Diels-Alder reactions, but also Michael, aldol, Strecker and Friedel-Crafts acylation reactions [27]. 

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