Ni/NHC-catalyzed C5-H alkylation and alkenylation of challenging furan(thiophene)-2-carboxaldehydes enabled by recyclable imine protecting group

Ni/NHC-catalyzed C5-H alkylation and alkenylation of challenging furan(thiophene)-2-carboxaldehydes enabled by recyclable imine protecting group Full article

Journal

Communications Chemistry
ISSN: 2399-3669

Output data

Year: 2025, Volume: 8, Number: 1, Article number : 253, Pages count : DOI: 10.1038/s42004-025-01653-5

Authors

Khazipova Olga V. ¹ , Khazipov Oleg V. ¹ , Shepelenko Konstantin E. ^1,4 , Kashin Alexey S. ² , Zhang Yu ³ , Chernyshev Victor M. ^1,4 , Ananikov Valentine P. ^1,2

Affiliations

1	Platov South-Russian State Polytechnic University (NPI), Novocherkassk, Russia
2	Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
3	Guangzhou Institute of Energy Conversion, Chinese Academy of Sciences, Guangzhou, China
4	Skolkovo Institute of Science and Technology, Moscow, Russia

Transition-metal-catalyzed C-H alkylation of heteroaromatics with alkenes represents an atom-economical and cost-effective strategy for accessing industrially and pharmaceutically relevant compounds. However, the selective C5-H alkylation of biomass-derived furfural and its isosteric analog, thiophene-2-carboxaldehyde, highly challenging yet industrially vital substrates, has remained elusive. Herein, we disclose a Ni/NHC-catalyzed strategy for the C5-H alkylation of furan- and thiophene-2-carboxaldehydes with styrenes and norbornene, enabled by a readily installable and recyclable N-PMP (p-methoxyphenyl) imine protecting group. This method also achieves selective C5-H alkenylation with internal alkynes. Mechanistic studies suggest that C-H alkylation proceeds via a ligand-to-ligand hydrogen transfer (LLHT) pathway. The N-PMP imine group effectively suppresses undesirable benzoin condensation of these reactive aldehydes and prevents NHC trapping in Breslow intermediates, a major catalyst deactivation pathway. The protecting group is efficiently cleaved under acid hydrolysis, yielding C5-functionalized aldehydes, while the liberated anisidine can be recycled for imine substrate preparation. This work also highlights the largely unexplored potential of the N-aryl imine group as the protecting group for distal C(sp²)-H functionalization of heteroaromatic aldehydes under Ni catalysis.

Khazipova O.V. , Khazipov O.V. , Shepelenko K.E. , Kashin A.S. , Zhang Y. , Chernyshev V.M. , Ananikov V.P.
Ni/NHC-catalyzed C5-H alkylation and alkenylation of challenging furan(thiophene)-2-carboxaldehydes enabled by recyclable imine protecting group
Communications Chemistry. 2025. V.8. N1. 253 . DOI: 10.1038/s42004-025-01653-5 WOS OpenAlex

Web of science:	WOS:001556210700001
OpenAlex:	W4413450653

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