Synthesis of C2‐Phosphorylated Indoles via Metal‐Free 1,2‐Phosphorylation of 3‐Indolylmethanols with P(O)‐H Species

• Published in: Advanced synthesis & catalysis Vol. 361; no. 23; pp. 5311 - 5316
• Main Authors: Zou, Yun‐Xiang, Liu, Xiao‐Yan, Zhang, Jing, Yang, Hong‐Li, Yang, Xin‐Yue, Liu, Xiao‐Ling, Chu, Yi‐Wen, Chen, Long
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 03.12.2019; Wiley Subscription Services, Inc
• Subjects: 1,2-addition; 3-Indolylmethanols; Chemistry; Chemistry, Applied; Chemistry, Organic; Diketones; Hydroxyl groups; Indoles; Ketones; Metal-free; Phosphines; Phosphonates; Phosphorylated indoles; Phosphorylation; Physical Sciences; Science & Technology; Substrates; Synthesis; Phosphorylation; Metal-free; REGIOSPECIFIC SYNTHESIS; S(N)1-TYPE REACTION; ALKYLATION; SIGMATROPIC REARRANGEMENTS; Phosphorylated indoles; PALLADIUM-CATALYZED AMINATION; ALCOHOLS; 1; CROSS-COUPLING REACTIONS; 2-addition; ORTHO-ESTER REARRANGEMENT; H-PHOSPHINE OXIDES; ENE REACTION; 3-Indolylmethanols
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.201900987

An efficient and practical method for synthesis of C2‐phosphorylated indoles has been disclosed via a metal‐free 1,2‐phosphorylation of 3‐indolylmethanols with H‐phosphine oxides or H‐phosphonates. This alternative protocol features a broad substrate scope with respect to both 3‐indolylmethanols derived from isatins, acyclic α‐keto amide, α‐keto ester, 1,2‐diketone and simple ketones and H‐phosphine oxides or H‐phosphonates, moderate to high yields and mild reaction conditions. Mechanistic studies indicate that this reaction proceeds via an unusual direct 1,2‐addition pathway, in which the existence of an electron‐withdrawing group adjacent to the hydroxyl group of 3‐indolylmethanols plays a decisive role.