Metal and Oxidant Free Construction of Substituted‐ and/or Polycyclic Indoles: A Useful Alternative to Bischler and Related Syntheses

Abstract

A wide range of substituted indoles or polycyclic derivatives containing the indole core are easily accessible by acidic treatment of aromatic amines and 1,2‐diaza‐1,3‐dienes. Unlike the related indole‐Bischler synthesis, the regioselectivity of the method here reported is unique and predictable, the yields are generally good and also electron withdrawing substituted indoles are smoothly recovered.

Indole frameworks via transition-metal-free annulation: a current perspective

“…Meanwhile, Mantellini et al carried out metal and oxidant-free synthesis of functionalized indole derivatives using alternative Bischler-related synthesis. 72 In the first step, aniline 25 and 1,2-diaza-1,3-dienes 45 were allowed to react under mild conditions to obtain α- N -arylaminohydrazone 46 . The next step involved Brønsted acid (Amberlyst 15H)-assisted hydrolysis of hydrazone 46 to α- N -arylaminoketone 47 , which was followed by cyclization employing Amberlyst 15H.…”

Diaza-1,3-butadienes as Useful Intermediate in Heterocycles Synthesis

“…A series of substituted indoles or polycyclic derivatives with indole moiety can be synthesized in three steps from anilines and 1,2-diaza-1,3-dienes [ 32 ]. In the first step, the aza Michael addition of anilines 20 to 1,2-diaza-1,3-dienes 21 , gives α-( N -arylamino)hydrazones 22 with excellent yields at room temperature without the addition of any catalyst ( Scheme 4 ).…”

“…The 1,2-diaza-1,3-dienes used for this reaction, which mainly contains electron-withdrawing substituents, allow the synthesis of indoles bearing ester, amide, and phosphonate groups [ 32 ]. However, 1,2-diaza-1,3-dienes without electron-withdrawing substituents, such as 4-unsubstituted or 3,4-dialkyl substituted diazadienos 25 , tend to degrade and therefore cannot be prepared in advance, instead, they can be generated in situ by basic treatment of α-halo hydrazones 26 , resulting in 3-alkyl- and 3-aryl 2-unsubstituted indoles 27 in good to excellent yields ( Scheme 5 ).…”

Experimental and Theoretical DFT Investigations in the [2,3]-Wittig-Type Rearrangement of Propargyl/Allyl-Oxy-Pyrazolones

“…Quite recently, we have published a preliminary paper, in which, by exploiting the ability of 1,2-diaza-1,3-dienes (DDs) as Michael-acceptors [51][52][53][54][55][56][57][58], we have synthesized α-(prop-2-yn-1-yloxy)hydrazones 3 (Scheme 1) [59]. These compounds containing a propargylic ether function have been demonstrated to be able to give easily and in very mild conditions the [2,3]-Wittig rearrangements.…”