Substituted 2-(Cyanomethyl-amino)-acetamides by a Novel Three-Component Reaction

Abstract

S u b s t i t u t e d 2 -( C y a n o m e t h y l -a m i n o ) -a c e t a m i d e sAbstract: A novel three-component, one-pot reaction between primary (S)-amino acid amides, aldehydes and isocyanides in the presence of acetic acid yielding substituted 2-(cyanomethylamino)-acetamides 4 in good yields, is described. First efforts to investigate the mechanism of this reaction were undertaken.

Asymmetric Multicomponent Reactions (AMCRs): The New Frontier

“…At this juncture, the pathway changes: Instead of an external attack by the carboxylic acid derivative, the attack takes place by the amide moiety to form a cyclic sixmembered anhydride-type intermediate, which isomerizes to yield the nitrile 90 with moderate diastereoselectivity. [155] …”

Chemistry and Biology Of Multicomponent Reactions

“…First, the reaction of amino acid derived α-amino amides with oxocomponents and isocyanides, surprisingly yield α-aminoacyl nitriles (compound 83 ). 72 Second, the reaction of amino acid derived α-amidoisocyanides also yields α-aminonitriles (compound 84 ). 73 Both reactions are clearly complementary since they represent different scaffolds and populate different areas of the chemical space of α-amino nitriles.…”

Synthesis of 2‐Amino‐3‐cyano‐4H‐chromene‐4‐carboxamide Derivatives by an Isocyanide‐Based Domino Conjugate Addition/O‐Trapping Rearrangement Sequence

“…Then, the solution was poured into saturated aqueous solution of NaHCO 3 (20 mL) and extracted with ethyl acetate (2 ϫ 20 mL). The combined organic phases were dried with anhydrous MgSO 4 , filtered, and concentrated in vacuo. Crude products 5a-i were purified by flash chromatography (n-hexane/ethyl acetate).…”

“…[3][4][5][6][7][8][9][10] However, intramolecular O-trapping rearrangements in which the O atom of the carboxamide moiety is involved in stabilization have received relatively little attention. [3][4][5][6][7] Moreover, isocyanide addition to activated alkenes has been examined. [11][12][13][14] To the best of our knowledge, isocyanide conjugate addition followed by intramolecular stabilization has been rarely investigated.…”