Extending NHC-catalysis: coupling aldehydes with unconventional reaction partners
Akkattu T Biju1, Nadine Kuhl, Frank Glorius
1Organisch-Chemisches Institut der Westfälische Wilhelms-Universität Münster, Münster, Germany.
Accounts of Chemical Research
|July 15, 2011
Summary
N-heterocyclic carbene (NHC) organocatalysis offers unique transformations, particularly through Breslow intermediates. This study explores novel reactions of these intermediates with diverse partners, advancing asymmetric catalysis and dual activation mechanisms.
Area of Science:
- Organic Chemistry
- Catalysis
- Organocatalysis
Background:
- Transition metal catalysis has drawbacks like cost and toxicity.
- Organocatalysis, especially N-heterocyclic carbene (NHC) catalysis, provides an attractive alternative with unique transformations.
- NHC-catalyzed umpolung via Breslow intermediates is a key reaction mode.
Purpose of the Study:
- To discuss the reaction of Breslow intermediates with unconventional reaction partners.
- To highlight advancements in NHC-catalyzed umpolung reactions, focusing on selectivity and efficiency.
- To explore the dual activation mechanism in NHC organocatalysis.
Main Methods:
- Utilizing N-heterocyclic carbene (NHC) catalysts for umpolung reactions.
- Developing tailor-made thiazolylidene catalysts for specific transformations.
- Investigating the dual activation mechanism involving Breslow intermediates.
Main Results:
- Achieved high selectivity in intermolecular cross-benzoin reactions, including hydroxymethylation with formaldehyde.
- Developed efficient intermolecular Stetter reactions for α-amino acid derivatives with broad scope and high enantiomeric excess.
- Demonstrated unprecedented coupling of aldehydes with nonactivated olefins, alkynes, arynes, and activated alkyl bromides using thiazolylidene catalysts.
Conclusions:
- NHC organocatalysis, particularly via Breslow intermediates and dual activation, enables unique and efficient organic transformations.
- Tailor-made NHC catalysts significantly expand the scope of umpolung reactions.
- Future developments in NHC catalysis are expected, with asymmetric intermolecular hydroacylation of unactivated olefins remaining a key challenge.
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