Bucherer-Bergs 4-component reaction

The Strecker [1] and Bucherer-Bergs [2] reactions are the most important strategies and powerful tools for the synthesis of a-amino acids from a carbonyl compound and cyanide. The classical first approach uses ammonium hydroxide and potassium cyanide to obtain the corresponding aminonitrile compound 1, whereas the second one is a four-component condensation between an aldehyde or ketone derivative reacting with potassium cyanide and ammonium carbonate as source of ammonia and carbon dioxide affording hydan-toin componnds 2 [3], In both cases, final hydrolysis would deliver the corresponding o,a-disubstituted a-amino acid derivatives 3 (Scheme 10.1) [4],... 

The first MCR involving isocyanides (IMCR) was reported in 1921 with the Passerini reaction (P-3CR) [8], and over the years these reactions have become increasingly important and have been highlighted in several publications (for discussions, see below). Another older MCR which leads to (non-natural) a-amino acids is the Bucherer-Bergs reaction (BB-4CR), which was first reported in 1929 [9]. This type of transformation is closely related to the Strecker reaction, with C02 employed as a fourth component. 

Until the 1920s, a-amino acids 5 were synthesized by the hydrolysis of the a-anoino-sub-stituted alkyl cyanides but subsequently the a-amino acids were produced industrially by hydrolyzing the hydantoin derivatives 4 (Scheme 1). The latter can be prepared by the Bucherer-Bergs four-component reaction (BB-4CR),f an MCR of type II that forms 4 from carbon dioxide and the three components of the S-3CR. The a-amino acids thus prepared are obtained in much higher yields than by the S-3CR. 

Linear adducts would be produced from monofunctional inputs whatever the number of components employed [Figure 5.2, reaction (a)]. If one aimed at developing multicomponent syntheses of heterocycles, one simple solution would then be the use of polyfunctional substrates since these imply an intramolecular reaction at a certain stage of the sequence, leading eventually to heterocydes [Figure 5.2, reaction (b)[. Some very simple functional groups such as cyanide and carbonic acid are bifunctional in nature, as in the Bucherer-Bergs reaction. 

---