[3+2] Cycloaddition of metal-containing azomethine ylides for highly efficient synthesis of mitosene skeleton

• Published in: Tetrahedron Vol. 67; no. 24; pp. 4455 - 4466
• Main Authors: Takaya, Jun, Miyashita, Yuichi, Kusama, Hiroyuki, Iwasawa, Nobuharu
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 17.06.2011; Elsevier
• Subjects: Alkynes; Azomethine ylide; Carbene complex; Chemistry; Chemistry, Organic; Cycloaddition; Derivatives; Electrophilic activation of alkyne; Indole synthesis; Indoles; Insertion; Physical Sciences; PtCl 2; Science & Technology; Synthesis (chemistry); Transition metals; Vinyl ethers; Carbene complex; PtCl 2; Electrophilic activation of alkyne; Indole synthesis; Azomethine ylide; GOLD; CATALYSIS; ACTIVATION; CASCADE REACTIONS; PtCl; ALKYNES; INDOLE; HETEROCYCLES; CONSTRUCTION; DERIVATIVES; CYCLIZATION
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2011.04.017

Efficient synthesis of tricyclic indole derivatives bearing a substituent at the 3-position of the indole nucleus was achieved by the [3+2] cycloaddition reaction of transition metal-containing azomethine ylides derived from N-( o-alkynylphenyl)imines with vinyl ethers. Third-row transition metal complexes, especially PtCl 2, turned out to be highly efficient for the reaction of internal alkynes and imidate substrates with wide generality. Moreover, as strong support for the reaction mechanism, the intermediate Pt–carbene complex was found to undergo intramolecular C–H bond insertion reaction to give tetracyclic indoline derivatives when benzyl vinyl ether was employed as a dipolarophile. This protocol provided a facile synthesis of highly functionalized tricyclic indole derivatives found as the basic skeleton of the mitosene family, such as mitomycin C. [Display omitted]