Strecker’s synthesis

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

The carboxyl terminated ACPA, 4,4 -azobis-(4-cya-nopentanoic acid), turned out to be a suitable reagent in condensation reactions. This compound can be prepared by Strecker s synthesis from levulinic acid following the method of Haines and Waters [12]. Regarding the formation of polymeric azo initiators, Matsakuwa et al. [13] reported on the condensation of ACPA with various diols and diamines in the presence of a condensation agent, I-methyl-2-chlorpyridinium iodide, and a cata-... 

Stilbenes synthesis by Heck coupling, 43 Stille coupling aryl triflate + organylstannane, 42 Stobbe condensation, 58-59 Stork reagent, 328-329 Strain, steric. See Steric strain Strecker s synthesis of a-amino acids, 50, 301 L-Streptose synthesis, 267 Styrene. See Benzene, ethenyl-Succinic acid. See Butanedioic acid Succinimide. See 2,5-Pyrrolidinedione Sugars. See Monosaccharides Oligosaccharides inexpensive derivs. pr. (table), 263-264 Sulfafurazole, 307 Sulfamethoxazole, 308 Sulfenic acids, esters ... 

Sodium i-nitro-2-naphtholate, 13, 78 Sodium perbenzoate, 13, 86 Sodium succinate, 12, 72 Sodium sulfide, 12, 68, 76 Stannous chloride, 13, 28 Strecker s synthesis, 11, 4 Styrene, 14, 89 Succinic acid, 12, 66 Succinic anhydride, 12, 66 13, 12 Sugar, 14, 62... 

DOPA decarboxylase, should permit more efficient utilization of DOPA. A compound very closely related structurally to the substrate for the enzyme fulfills this function. Carbidopa 168 was designed for this purpose. Carbidopa s synthesis begins with a modified Strecker reaction using hydrazine and potassium cyanide on arylacetone 165 to give 166. This is then hydrolyzed with cold HC1 to give carboxamide 167. 

Previous preparations by Scolastico were based on the Strecker synthesis of aminonitrile and lacked steroselectivity [74,75]. More recently, two formal syntheses were reported from the same ketone 71. In Rama Rao s synthesis (Scheme 11.19) [76], 71 was condensed with vinyl magnesium bromide to give the tertiary alcohol 72 as a single isomer. This compound was then transformed into the vinyl epoxide 73 that, under palladium catalysis, reacted with 4-methoxyphenyl isocyanate to produce the oxazohdinone 74 with retention of its configuration. The remainder of the synthesis consisted of heterocycle opening and adjustment of the oxidation level to provide the lactone 75. Excision of two carbons was necessary to form the known aldehyde 76, previously transformed into myriocin [74]. 

Harusawa, S., Hamada, Y, and Shioiri, T., Diethyl phosphorocyanidate (DEPC). A novel reagent for the classical Strecker s a-amino nitrile synthesis. Tetrahedron Ij- tt.. 20, 4663, 1979. 

A modification of the cyanohydrin synthesis is provided by Strecker s amino acid synthesis, in which an <%-amino nitrile is obtained by the action of hydrogen cyanide and ammonia on an aldehyde or ketone ... 

Soc 75 4090 1953, Beilstein 1 II 111, 1 III 2745, 1 IV 3214.] Trifluoioacetone has been used to prepare trifluoromethylimines of chiral amines in order to prepare R or S enantiopure a-trifluoromethyl alanines, diamines and amino alcohols via a Strecker-type synthesis in a few steps [Huguenot Brigand J Org Chem 71 7075 2006. It has also been used to synthesise 2-trifluon)metltyl-7-azaindoles from 2,6-dihalopyridines [Schirok et al. Synthesis 251 2007],... 

The relative positions of the substituents on the two adjacent asymmetric carbon atoms are not known and these formulas are therefore quite arbitrary in that respect. Ehrlich synthesized a mixture of L-iso-leucine and n-alloisoleucine from (-l-)a-methylbutyric aldehyde by Strecker s method. From this and also another mixture which was produced by inversion of the configuration of the a-carbon atom, n-alloiso-leucine was obtained by removal of the L-isoleucine with yeast, which only attacks the latter isomeride. A synthesis and resolution of iso-leucine was carried out by Locquin (1907), while Abderhalden and Zeisset (1931a) prepared and resolved alloisoleucine these authors also described... 

Prof. Hao s synthesis commenced with the copper(I) chloride-catalyzed oxidation of the tryptamine derivative to afford ketone 42 [74], A three-component Strecker-type reaction was designed to react the ketone 42 with tryptamine and TMSCN to finish the first ring closure. After examining a series of both Lewis acid and Bronsted acids, the authors found a catalytic amount of TMSOTf promoted the transformation and afforded nitrile intermediate 43, which is ready for the Houben-Hoesch-type cyclization [75]. Treatment by TfOH (trifluoromethanesulfonic acid) [76] in DCM and the... 

The method is very useful for the synthesis of physiologically interesting a-mcthylamino acids, e.g., methyl dopa from the 3,4-dimethoxybenzyl derivative. The excellent stereoselection achieved in the process, however, is caused by the preferential crystallization of one pure diastereomerfrom the equilibrium mixture formed in the reversible Strecker reaction. Thus, the pure diastcrcomers with benzyl substituents, dissolved in chloroform or acetonitrile, give equilibrium mixtures of both diastereomers in a ratio of about 7 347. This effect has also been found for other s-methylamino nitriles of quite different structure49. If the amino nitrile (R1 = Bn) is synthesized in acetonitrile solution, the diastereomers do not crystallize while immediate hydrolysis indicates a ratio of the diastereomeric amino nitriles (S)I(R) of 86 1447. 

In Ugi four-component reactions (for mechanism, see Section 1.4.4.1.) all four components may potentially serve as the stereodifferentiating tool65. However, neither the isocyanide component nor the carboxylic acid have pronounced effects on the overall stereodiscrimination60 66. As a consequence, the factors influencing the stereochemical course of Ugi reactions arc similar to those in Strecker syntheses. The use of chiral aldehydes is commonly found in substrate-controlled syntheses whereas the asymmetric synthesis of new enantiomerically pure compounds via Ugi s method is restricted to the application of optically active amines as the chiral auxiliary group. 

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]. 

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