Synthesis of amino acids and related compounds. 18. Synthesis of .alpha.-[(aminomethylene)amino]acrylic acid esters

Exploiting the Divergent Reactivity of α‐Isocyanoacetate: Multicomponent Synthesis of 5‐Alkoxyoxazoles and Related Heterocycles

“…The reaction performed in DMSO produced compound 10 a but with a much-reduced yield. [24] Neither imidazoline [14] nor amidine, [13] as a result of the competitive aldol-and Mannich-type condensations, were observed. A plausible reaction scenario that accounts for the formation of 10 a is shown in Scheme 6.…”

“…The chemistry of a-isocyanoacetate (1) was thoroughly investigated in the 1970s, mainly by the groups of Schçllkopf [11,12] and Matsumoto. [13] One particularly powerful transformation is the reaction of metallated 1 with polar multiple bonds to afford heterocycles. By taking advantage of the higher acidity of a-phenyl-a-isocyanoacetate (2), Orru and co-workers described an elegant three-component synthesis of imidazolines (3) without the need for pre-metallation (Scheme 1a).…”

Modulating the Reactivity of α‐Isocyanoacetates: Multicomponent Synthesis of 5‐Methoxyoxazoles and Furopyrrolones

“…The chemistry of methyl α‐isocyanoacetate ( 1 ) was investigated thoroughly in the 1970s, mainly by the research groups of Schöllkopf and Matsumoto 1. 4 One particularly powerful transformation is the reaction of metalated 1 with polar multiple bonds to afford heterocycles 2. By taking advantage of the higher acidity of the α‐phenyl‐α‐isocyanoacetate 2 , Orru and co‐workers recently developed an elegant three‐component synthesis of imidazolines 5 without the need for premetalation (Scheme 1) 3.…”

“…The reaction was initiated by the nucleophilic addition of the α carbanion derived from 2 to an iminium ion generated in situ from 3 and 4 , which was followed by cyclization and protonation. The presence of the phenyl group is essential for this one‐pot process: The reaction with α‐isocyanoacetate 1 under otherwise identical conditions provided the corresponding imidazoline in low yield 4. The phenyl group was thought to render the α CH position acidic enough to be deprotonated by a weak base.…”

“…The phenyl group was thought to render the α CH position acidic enough to be deprotonated by a weak base. In general, the exploitation of the nucleophilicity of the α carbon atom and the electrophilicity of the divalent carbon atom of the isocyanide for the effective construction of CC and CN bonds characterized the known chemistry of α‐isocyanoacetates 1–4. In all these transformations, the ester functionality served only as an activator without participating in the bond‐forming process, and the nucleophilicity of the divalent carbon atom of the isocyanide was exploited only for trapping a proton.…”