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

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.

Indole Editing Enabled by HFIP‐Mediated Ring‐Switch Reactions of 3‐Amino‐2‐Hydroxyindolines

“…As a consequence, substantial efforts have been devoted to the synthesis and functionalization of indoles, [2] including molecule editing such as a skeletal rearrangement [3] . In conventional indole editing, the C2‐C3 bond‐breaking transformation achieved by oxidative cleavage, [4a–c] and ring‐expansion with alkyne moieties, [4d–e] which require harsh conditions or transition metals. In 2021, Levin and co‐workers reported the use of new azine reagents as carbynyl cation equivalents to edit indole ring involving the C2‐C3 bond‐breaking transformation, affording quinolines (Scheme 1A) [5] .…”

Synthesis of medium-ring lactams and macrocyclic peptide mimetics via conjugate addition/ring expansion cascade reactions

“…Cascade reaction sequences are widely used in synthetic chemistry to streamline the preparation of complex molecules. 1,2 Performing multiple reaction steps in a single operation brings obvious benefits in terms of the overall brevity of synthetic routes and can obviate the need to directly handle reactive and/or toxic intermediates. This strategy can also lead to the development of synthetic cascades greater than the sum of their parts, whereby the overall cascade reaction proceeds more efficiently than the analogous stepwise process.…”

Efficient Synthesis of 7H‐Chromeno[3,2‐c]quinolin‐5‐ium Salts and Quinolin‐4‐ones through Acid‐Promoted Cascade Reaction of 3‐Formylchromones and Anilines

“…In particular, the application of quinolinium salts in biological studies needs new synthetic methods for the synthesis of diverse substituted quinolinium salts. In contrast to many synthetic methods for quinolines, [18–21] few methods have been developed to synthesize quinolinium salts. A well‐known method to these compounds involves the reaction of nucleophilic quinolines with electrophilic alkyl halides [22–23] .…”