Enantioselective Synthesis of Carbazole-Thioisatin Spirocycles via NHC-Catalyzed Remote N–H Activation
- 1Department of Organic Chemistry, Faculty of Science, Charles University, Hlavova 2030/8, Prague, Czech Republic, 128 00
- 2Department of Inorganic Chemistry, Faculty of Science, Charles University, Hlavova 2030/8, Prague, Czech Republic, 128 00
Abstract
An enantioselective NHC-catalyzed strategy for the synthesis of spirocyclic carbazole derivatives was developed through oxidative remote N–H activation of readily available 1-formylcarbazoles. Catalytic generation of aza-ortho-quinone methides enables efficient annulation with thioisatins, underexplored electrophiles in asymmetric NHC catalysis. The protocol is also compatible with conventional isatins, affording structurally diverse spirocyclic heteroaromatic products in acceptable to good yields (up to 76%) and enantiomeric ratios up to 98:2 er. The utility of the method was demonstrated on gram-scale, while successful coupling with an acyclic ketone further illustrates the broader synthetic potential of this remote N–H activation process.
Related
- Enantioselective synthesis of β-aryl-β-acyl esters as unsymmetrical 1,4-dicarbonyl compounds via oxidative aryl rearrangement using λ3-perchrolate iodane
- Convergent Approach for the Asymmetric Synthesis of Vinyl Sulfoximines via Ruthenium-Catalyzed Enantioselective Alkylation of Sulfenamides with (Diazomethyl)phosphonates
- Optical-handedness-driven enantioselective synthesis and programmable chirality encoding of covalent organic frameworks
- Beyond metal purity with upcycled rare earth mixtures from electronic waste for enantioselective synthesis
- Novel Carbazole–Acylthiourea Derivatives: Synthesis, Antimicrobial, Antioxidant, Hemocompatibility, Cytotoxicity, and ADME‐Tox Profiling
BibTeX
@misc{loska2026enantioselective,
title = {{Enantioselective Synthesis of Carbazole-Thioisatin Spirocycles via NHC-Catalyzed Remote N–H Activation}},
author = {Ladislav Lóška and Ivana Císařová and Jan Veselý},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15009225/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009225/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Enantioselective Synthesis of Carbazole-Thioisatin Spirocycles via NHC-Catalyzed Remote N–H Activation
AU - Ladislav Lóška
AU - Ivana Císařová
AU - Jan Veselý
PY - 2026
DA - 2026/09/22
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009225/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009225/v1
AB - An enantioselective NHC-catalyzed strategy for the synthesis of spirocyclic carbazole derivatives was developed through oxidative remote N–H activation of readily available 1-formylcarbazoles. Catalytic generation of aza-ortho-quinone methides enables efficient annulation with thioisatins, underexplored electrophiles in asymmetric NHC catalysis. The protocol is also compatible with conventional isatins, affording structurally diverse spirocyclic heteroaromatic products in acceptable to good yields (up to 76%) and enantiomeric ratios up to 98:2 er. The utility of the method was demonstrated on gram-scale, while successful coupling with an acyclic ketone further illustrates the broader synthetic potential of this remote N–H activation process.
ER -