One-pot synthesis of indoles and quinolinones from ortho-tosylaminophenyl-substituted para-quinone methides

Abstract

A facile one-pot synthesis has been developed through alkylation/acylation of ortho-tosylaminophenyl-substituted para-quinone methides followed by an intramolecular 1,6-conjugate addition and oxidation sequence.

Construction of Oxygen‐ and Nitrogen‐based Heterocycles from p‐Quinone Methides

“…A one-pot approach has been established by Wang and coworkers for the synthesis of chromene derivatives (75) through a DMAP-catalyzed Rauhut-Currier/oxa-Micheal sequence (Scheme 18). [38] As per the proposed mechanism, DMAP initially attacks the β-carbon of allenoate (74) to generate an intermediate (76), which then undergoes a 1,6-conjugate addition with 73 to form another intermediate 77. After the proton transfer and regeneration of the catalyst, 77 gets converted to an allenoate 78, which successively undergoes deprotection followed by an intramolecular oxa-Micheal reaction to give the chromene derivatives 75.…”

“…tuted indoles through a base-mediated [4 + 1]-annulation of 172 with α-halo ketones followed by DDQ-mediated oxidation of the intermediate 174. [74] Similarly, Anand's group recently reported a combination of inorganic and organic base-mediated approach for the synthesis of 2,3-disubstituted indole derivatives (176) using otosylaminophenyl-substituted p-QMs (172) and substitutedphenacyl bromides (175) [ Scheme 45]. [75] The authors proposed that the inorganic base (Cs 2 CO 3 ) initially abstracts the NHTs proton of 172 and the resulting anion reacts with 175 to give the N-alkylated p-QM 177.…”

DataSheet1.PDF

“…Although great progress has been witnessed in this field, the employment of p-QMs substrates in the construction of heterocyclic frameworks, especially nitrogen-containing heterocyclic frameworks, still remains underdeveloped (Scheme 1A). Very recently, the group of Hu and Zhao pioneered the design of in situ generated ortho-tosylaminophenyl-substituted p-QMs and transformations of this class of substrates in [4 + 1] ( Wang et al, 2019;Wang et al, 2020a) and [4 + 2] ( Wang et al, 2018;Si et al, 2020) annulation reactions, providing a straightforward access to construct valuable tetrahydroquinoline and 2,3-dihydroindole derivatives, respectively (Scheme 1B). Those transformations avoid the utilization of presynthesized p-QMs, which greatly enhance the step and atom economy of this strategy.…”