Strecker multicomponent reaction

Scheme 1 The Strecker and Bucherer-Bergs Multicomponent Reactions 1...

Multicomponent reactions, although fashionable these days, have in fact a long history. Indeed, many important reactions such as the Strecker amino acid synthesis (1850)[6], the Hantsch dihydropyridine synthesis (1882) [7], the Biginelli dihydropyrimidine synthesis (1891)[8], the Mannich reaction (1912) [9], and the isocyanide-based Passerini reactions (1921) (Scheme 5.1) [10], among others, are all... 

One may consider the Strecker reaction as the prototypical multicomponent reaction.15 Three reactants, an amine, a carbonyl compound, and a source of cyanide, come together in a single reaction vessel to afford a single product, an a-aminonitrile. Variations on this reaction process include the Bucherer-Bergs, Petasis, Ugi, and amidocarbonylation reactions. 

As many of the classical multicomponent reactions, the Strecker synthesis also takes advantage of the versatile chemistry of the initially formed imine. The formation of the amino nitrile, however, is reversible under the reaction conditions which usually results in lower yields. This problem was elegantly solved in the Bucherer-Bergs variation,3 4-376 where the initially formed aminonitrile is irreversibly trapped by formation of a hydantoin as depicted in Scheme 1.8 (entry b). 

Discovered in the middle of the 19th century, the Strecker reaction is one of the earliest atom-economic multicomponent reactions. Amino nitriles were simply obtained from ammonia, hydrogen cyanide and an aldehyde. These products are important intermediates for the synthesis of natural and unnatural a-aminoacids. Due to the ever-increased demand for enantioenri-chied a-aminoacids, the asymmetric Strecker reaction has emerged as a viable synthetic method. Since the first report published in 1996, the catalytic enantioselective cyanation of preformed imines was intensively studied and several excellent reviews were devoted to this topic. ... 

M. Ayaz, P. De Morales, and C. Hulme, A Carbonyl Compound as ElectrophUic Compound — With an Amine or Analogue as One Nucleophile Component — Third Component Cyanide (Strecker and Strecker-Type Reactions), In T.J.J. MiiUer, editor Multicomponent Reactions 1, Science of Synthesis, Georg Thieme Verlag Stuttgart (2014), p 99. 

The first multicomponent reaction was the Strecker reaction reported in 1850 by Adolf Strecker [241aj. It is a three-component coupling between carbonyl derivatives, amines, and cyanide source, such as hydrogen cyanide, to provide a-aminonitriles which constitute potent starting materials to achieve important a-amino acids by simple hydrolysis. The mechanism of the Strecker reaction involves the initial formation of an imine from condensation of the amine component to the carbonyl component, after which addition of the cyanide component to this imine intermediate follows. Although the first enantioselective, metal-catalyzed Strecker... 

The roots of the U-4CR lie in research reported long before its discovery in the early 1960s. The first multicomponent reaction (MCR) is credited to Laurent and Gerhardt who, in 1838, isolated an unexpected product from a reaction involving benzaldehyde, ammonia, and hydrogen cyanide. The resulting benzoyl azotide (1) presents the Schiff base of the Strecker adduct and benzaldehyde. Ironically, Strecker described such a reaction more than a decade later. In the years that followed, many variations of MCRs were reported, but it wasn t until 1921 that Passerini first utilized the isocyanide functionality and its unique reactivity in a MCR. It was this work that inspired Ugi and led to focused investigations of this reaction process. 

Even though the history of multicomponent reactions dates baek to the second half of the 19th century with the reactions of Strecker, Hantzsch, and Biginelli, it was only in recent decades with the work of Ugi that the concept of the multicomponent reaction has emerged as a powerful tool in synthetic... 

Keywords Strecker reaction, a-aminonitriles, carbonyl compounds, TMSCN, Zr0Cl2.8H20, homogeneous catalyst, one-pot synthesis, multicomponent reaction (MCR), solvent-free, room temperature... 

It is interesting that three multicomponent reactions were broadly used over 150 years, known as name reactions according to their inventors Strecker synthesis of amino acids [3], Hantsch synthesis of 1,4-dihydropyrimidines [4] and particularly the imjxjrtant Mannich reaction [5]. 

Despite the chemical complexity of multicomponent reactions (MCRs), the dawn of MCRs was fairly early in the history of organic chemistry. The first MCR was the so-called Strecker reaction discovered in 1850 [1, 2], which generates amino acids via a three-component reactiOTi between amines, aldehydes (or ketones), and hydrogen cyanide (Scheme 1). Since then, organic chemists have devoted much effort to the discovery of additional MCRs. Thus, we now can find a number of MCRs, including the Biginelli reaction [3], the Gewald reaction [4], the van Leusen three-component reaction [5], the Hantzsch reaction [6], the Mannich reaction [7], the Kabachnik-Fields reaction [8, 9], the Passerini reaction [10], the Ugi reaction [11, 12] and numerous variations thereof [13]. 

Scheme 42 Multicomponent Strecker reaction of diketones 152 and 155 with 1,2-diaminobenzene (153) [100]...

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. 

The first part of this chapter deals with the effects of high pressure on cycloaddition reactions, particularly the Diels-Alder reaction, which is the most important cycloaddition reaction. The second part will illustrate applications of pressure to nucleophilic substitutions, condensations and other reactions (miscellaneous reactions), such as Mannich, Heck, ene, SeAr, Wittig, Horner-Wadsworth Emmons and multicomponent Strecker reactions. 

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