Novel method for synthesis of aryl hydrazones from α-diazo esters: scope and limitations of nucleophiles

• Published in: Tetrahedron Vol. 65; no. 2; pp. 461 - 468
• Main Authors: Yasui, Eiko, Wada, Masao, Takamura, Norio
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 10.01.2009; Elsevier
• Subjects: Chemistry; Chemistry, Organic; Exact sciences and technology; Fischer indole synthesis; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Hydrazone; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; α-Diazo ester; α-Diazo ester; Fischer indole synthesis; Hydrazone; alpha-Diazo ester; AMINO-ACID ESTERS; Zinc Organic compounds; Nitrogen heterocycle; Alcohol; Pyridine derivatives; Ester; Grignard reagent; Thionyl chlorides; Aromatic compound; Diazo compound; Indole derivatives; Chemical synthesis; Nucleophilic addition; Nucleophile
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2008.11.028

Aryl hydrazones, the precursor of Fischer indole synthesis, were easily obtained by nucleophilic addition of aryllithium reagents to diazo esters. The aryl hydrazones were converted into indoles in good yields by heating with thionyl chloride in alcohol. Grignard reagent was also a good nucleophile, whereas organozinc reagent did not react with diazo esters. Aryllithium reagents were prepared by reacting aryl bromides having various substitutions at 2-, 3-, 4-, or multi positions with n-BuLi. The addition of nucleophiles derived from bromopyridines to diazo esters also gave hydrazones. [Display omitted] Aryl hydrazones were easily obtained by nucleophilic addition of lithium reagents or Grignard reagent and were converted into indoles in good yields.