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. 2022 Apr 4;134(15):e202117524.
doi: 10.1002/ange.202117524. Epub 2022 Feb 18.

NHC Catalysis for Umpolung Pyridinium Alkylation via Deoxy-Breslow Intermediates

Terence Wu  1 , Matthew R Tatton  2 , Michael F Greaney  1
Affiliations

NHC Catalysis for Umpolung Pyridinium Alkylation via Deoxy-Breslow Intermediates

Terence Wu et al. Angew Chem Weinheim Bergstr Ger. .

Abstract
in English, German

Umpolung N-heterocyclic carbene (NHC) catalysis of non-aldehyde substrates offers new pathways for C-C bond formation, but has proven challenging to develop in terms of viable substrate classes. Here, we demonstrate that pyridinium ions can undergo NHC addition and subsequent intramolecular C-C bond formation through a deoxy-Breslow intermediate. The alkylation demonstrates, for the first time, that deoxy-Breslow intermediates are viable for catalytic umpolung of areniums.

NHC deoxy‐Breslow catalysis offers new umpolung possibilities for electron‐poor arene rings. NHC organocatalysis is largely restricted to aldehydes, with other electrophiles proving difficult to harness. It is shown that a pyridinium system can react successfully with an NHC, enabling intramolecular C−C bond formation with a Michael acceptor through a deoxy‐Breslow intermediate.

Keywords: Deoxy-Breslow Intermediate; N-Heterocyclic Carbenes; Organocatalysis; Pyridinium Substrates; Umpolung.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Breslow and deoxy‐Breslow intermediates for umpolung catalysis.
Scheme 2
Scheme 2
Proposed catalysis cycle for NHC addition to pyridinium 5.
Scheme 3
Scheme 3
Standard conditions: Pyridinium 5 (0.10 mmol), pre‐NHC A (0.02 mmol), DBU (0.20 mmol), MeOH (4.0 mL), 85 °C, 30 min. [a] Reaction conducted with DMF instead of MeOH. [b] Isolated as a mixture of Me and Et esters (2 : 1). p‐FBn = p‐fluorobenzyl
Scheme 4
Scheme 4
Transformation of indenopyridine products. p‐FBn = p‐fluorobenzyl.
Scheme 5
Scheme 5
Mechanistic insights. p‐FBn = p‐fluorobenzyl
See this image and copyright information in PMC

References

    1. None
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    2. Angew. Chem. 1979, 91, 259–278.
    1. Reviews:
    1. Enders D., Niemeier O., Henseler A., Chem. Rev. 2007, 107, 5606–5655; - PubMed

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