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. 2023 Sep 1;88(17):12821-12825.
doi: 10.1021/acs.joc.3c01089. Epub 2023 Aug 17.

An NHC-Catalyzed Desulfonylative Smiles Rearrangement of Pyrrole and Indole Carboxaldehydes

Caitlin Swaby  1 , Alfie Taylor  1 , Michael F Greaney  1
Affiliations

An NHC-Catalyzed Desulfonylative Smiles Rearrangement of Pyrrole and Indole Carboxaldehydes

Caitlin Swaby et al. J Org Chem. .

Abstract

The use of catalysis methods to enable Smiles rearrangement opens up new substrate classes for arylation under mild conditions. Here, we describe an N-heterocyclic carbene (NHC) catalysis system that accesses indole and pyrrole aldehyde substrates in a desulfonylative Smiles process. The reaction proceeds under mild, transition-metal-free conditions and captures acyl anion reactivity for the synthesis of a diverse array of 2-aroyl indoles and pyrroles from readily available sulfonamide starting materials.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Smiles Rearrangements
Scheme 2
Scheme 2. Substrate Scope
0.1 mmol scale.
Scheme 3
Scheme 3. Pyrrole Smiles–Truce Optimization
0.1 mmol scale.
Scheme 4
Scheme 4. Product Derivatization
Reaction conditions: (a) 0.1 mmol scale, NBS (1.2 equiv), DMF (0.1 M), rt 3 h; (b) 0.1 mmol scale, NaBH4 (3 equiv), MeOH (0.1 M), 0 °C, 16 h; (c) 0.1 mmol scale, MeI (2 equiv), K2CO3 (2.5 equiv), DMF (0.1 M), rt, 16 h; (d) 0.1 mmol scale, Zn (4.2 equiv), AcOH, EtOH:H2O (3 mL, 1:2 EtOH:H2O), 80 °C, 3 h; (e) 0.1 mmol scale, Cs2CO3 (2 equiv), DMF (0.1 M), substrate 4e, 70 °C, 16 h.
Scheme 5
Scheme 5. Crossover Experiment
0.1 mmol scale, standard conditions, NMR yields.
Scheme 6
Scheme 6. Mechanistic Pathway
See this image and copyright information in PMC

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