Strecker reaction intramolecular

Employing a staked plate microreactor (channel dimensions = 100 pm, total volume = 2 ml), Acke and Stevens (2007) reported the continuous flow synthesis of a series of chromenones via a multicomponent route consisting of a sequential Strecker reaction-intramolecular nucleophilic addition and tautomerization, as depicted in Scheme 2. 

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... 

Formylbenzoic acid, potassium cyanide and anilines react in the presence of acetic acid to afford 3-amino-4-arylamino-isocoumarins (Scheme 215). The reaction proceeds via an initial Strecker reaction to form intermediate 786 followed by intramolecular attack of the carboxyl group onto the nitrile (Scheme 215) <2005EJ0817>. 

The stereochemical outcome for the Strecker reaction is rationalized by the reaction pathway described in Fig. (22). A preferred conformation of in situ generated imine 57 may be the one in which the bulky carbamate group directs toward cis to the hydrogen atom on the a-methine carbon of the imino group. TMSCN then attacks intramolecularly the Si face of 57 by means of activation through coordination of the imino group to the hypervalent silicon atom. This may result in the preferential formation of the syn isomer over the anti counterpart. 

Lactacystin 97 inhibits cell proliferation and induces neurite outgrowth as a result of proteosome-mediated peptidase inhibition. In one approach to this target, the a,a-disubstituted a-amino acid contained in this molecule was assembled using an intramolecular asymmetric Strecker reaction.43 Esterification of a-hydroxyketone 93 with Boc-Z,-Phe afforded ester 94. Deprotection of the Boc group and intramolecular imine formation preceeded the addition of cyanide to produce 95. Ozonolysis and treatment with cone. HC1 gave rise to the desired amino acid 96. This advanced intermediate constituted a formal total synthesis of lactacystin 97. 

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 one-pot three-component synthesis of a-iminonitriles 866 via an IBX/tetrabutylammonium bromide-mediated oxidative Strecker reaction has been developed (Scheme 3.346) [1183]. This methodology was employed in a two-step synthesis of indolizidines via a microwave-assisted intramolecular cycloaddition of a-iminonitriles. 

A new diastereoselective route to aromatic cw-erythrinanes represents the combined intramolecular Strecker and Bruylants reactions of the phenethyl-cyclohexanylethylamines 88 (Scheme 11). Deprotection of the carbonyl function and addition of potassium cyanide causes the Strecker reaction to give the angularly substituted hydroindole derivatives 89 in nearly quantitative yields. Then the Bruylants reaction is... 

Aldehydes, ketones, and acetals react with allyltrimethylsilane in the presence of a catalytic amount of BiX3 (X = C1, Br, OTf) to give homoallyl alcohols or homoallyl alkyl ethers (Equation (52)).91-93 The BiX3-catalyzed allylation of aldehydes and sequential intramolecular etherification of the resulting homoallylic silyl ethers are involved in the stereoselective synthesis of polysubstituted tetrahydropyrans (Equation (53)).94,95 Similarly, these Lewis acids catalyze the cyanation of aldehydes and ketones with cyanotrimethylsilane. When a chiral bismuth(m) catalyst is used in the cyanation, cyanohydrines are obtained in up to 72% ee (Equation (54)). a-Aminonitriles are prepared directly from aldehydes, amines, and cyanotrimethysilane by the BiCl3-catalyzed Strecker-type reaction. 

The decomposition of these intermediates leads to the formation of ene-diols, also known as reduc-tones, in redox equilibrium with a-dicarbonylated compounds. These are responsible for the oxidation of plant tissues. The a-dicarbonylated compounds resulting from the rearrangement of the Amadori and Heyns intermediates may in turn add amino acids from must and wine (Figure 8.28). The corresponding addition products develop by intramolecular decarboxylation, according to the well-known Strecker breakdown reaction. Amino acids that become involved in this reaction ultimately become aldehydes. 

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