Asymmetric Conjugate Addition of Grignard Reagents to Pyranones

Abstract

An efficient enantioselective synthesis of lactones was developed based on the catalytic asymmetric conjugate addition (ACA) of alkyl Grignard reagents to pyranones. The use of 2H-pyran-2-one for the first time in the ACA with Grignard reagents allows for a variety of further transformations to access highly versatile building blocks such as β-alkyl substituted aldehydes or β-bromo-γ-alkyl substituted alcohols with excellent regio- and stereoselectivity.

Iron‐Catalyzed Reactions of 2‐Pyridone Derivatives: 1,6‐Addition and Formal Ring Opening/Cross Coupling

“…Extensive screening in this laboratory showedt hat iron is almost uniquelyc apable in catalyzing this transformation. [32] Since iron salts react instantly with polar organometallic reagents to give ate-complexes [33][34][35][36] and/or low valent iron species, [34,37,38] the reasonsf or the unusually facile addition to pyrones and pyridones are likely rooted in am ore specific affinity to substrates of this kind. It is, however, exceedingly difficult to establish the nature of the active species generated in situ, not least because low valent organometallic iron complexes are highly sensitive, often paramagnetic, and tend to "age" rapidly;moreover,the exact speciation is strongly dependento nt he chosen conditions and the presence/absence of polar additives in the mixture.…”

Copper‐Catalysed Conjugate Addition of Grignard Reagents to 2‐Methylcyclopentenone and Sequential Enolate Alkylation

“…In our recent work, [11][12][13] we focus on the use of Grignard reagents, because of their straightforward preparation from readily available alkyl bromides. [15,17,18,24,25] In these studies, however, a-substitution (2-substitution) is lacking, a situation no different from reports with other organometallic reagents. [15,17,18,24,25] In these studies, however, a-substitution (2-substitution) is lacking, a situation no different from reports with other organometallic reagents.…”

Transition Metal Mediated C–H Activation of 2‐Pyrones, 2‐Pyridones, 2‐Coumarins and 2‐Quinolones

“…2‐Pyrones are very good model systems with which to test new methodologies, as they can possess aromatic, diene and enone properties and they have been shown to ring‐open under some cross‐coupling conditions (Figure ).…”