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. 2021 Mar 19;23(6):2063-2068.
doi: 10.1021/acs.orglett.1c00205. Epub 2021 Mar 1.

A Thiol-Mediated Three-Step Ring Expansion Cascade for the Conversion of Indoles into Functionalized Quinolines

Nantachai Inprung  1 , Michael J James  1 , Richard J K Taylor  1 , William P Unsworth  1
Affiliations

A Thiol-Mediated Three-Step Ring Expansion Cascade for the Conversion of Indoles into Functionalized Quinolines

Nantachai Inprung et al. Org Lett. .

Abstract

An operationally simple, high yielding three-step cascade process is described for the direct conversion of indole-tethered ynones into functionalized quinolines. A single "multitasking" thiol reagent is used to promote a three-step dearomatizing spirocyclization, nucleophilic substitution, and one-atom ring expansion reaction cascade under remarkably mild conditions. In addition, a novel route to thio-oxindoles is described, which was discovered by serendipity.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Transformations of Indole-Tethered Ynones
Scheme 2
Scheme 2. Scope of the Three-Step Thiol-Mediated Cascade for the Conversion of Ynones 1 into Quinolines 4
1 (1 equiv) and RSH (1.6 equiv) were stirred in DCE (0.1 M) for 20 h at RT unless specified. Reaction performed at 60 °C. HS-Tol = 4-methylbenzenethiol.
Scheme 3
Scheme 3. Conversion of Ynones 1 into Thio-Oxindoles 9 via a Desilylative Cascade Process
1 (1 equiv) and thiol 11 (1.6 equiv) were stirred in DCE (0.1 M) for 20 h at 60 °C.
Scheme 4
Scheme 4. Proposed Mechanism and Control Reactions
See this image and copyright information in PMC

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