DMAP‐Catalyzed [3+3] Annulation of Cyclopropenones with α‐Bromoketones for Synthesis of 2‐Pyrones

Abstract

DMAP‐catalyzed [3+3] annulation of cyclopropenones with α‐bromoketones is described, which provides a simple and convenient synthesis of 2‐pyrones in good yields with a broad scope. The reaction features advantages of transition metal‐free conditions, readily available starting materials, and excellent regioselectivity. Experimental investigation and DFT calculations suggest a mechanism encompassing pyridium ylide‐initiated ring opening of cyclopropenones, elimination of DMAP catalyst, and final 6π‐electrocyclization.

Access to functionalized 2-pyrones through cascade reactions of α-halothioesters involving DBU-derived ammonium ylides

“…2 Due to the biological and synthetic utility of 2-pyrones, much effort has been directed toward the preparation of diversely functionalized 2-pyrones and many sophisticated works have been reported. 3 For example, Smith 3 e developed a one-pot isothiourea-mediated Michael addition/lactonization/thiol elimination cascade sequence from (phenylthio)acetic acids and α,β-unsaturated trifluoromethyl ketones to produce trifluoromethyl-substituted 2-pyrones (Scheme 2a). Chi 3 j reported a carbene-catalyzed oxidative [3 + 3] cycloaddition reaction between enals and pyridinium ylides for quick access to 2-pyrones (Scheme 2b).…”

Base- and sulfur-promoted oxidative lactonization of chalcone-acetate Michael adducts: access to pyran-2-ones

“…6 Consequently, considerable efforts have been devoted to developing effective synthesis. Notable examples include the reaction of diarylcyclopropenones with sulfonium ylides, 7 sulfoxonium ylides, 8 sulfur ylides, 9 β-ketoethers, 10 α-bromoketones, 11 and α-ammoniumketones. 12 Along with the involvement of a strong base 9–11 or an expensive Rh catalyst, 8 the significant drawbacks of these methods are the use of diarylcyclopropenone substrates, which require multistep syntheses.…”

“…Notable examples include the reaction of diarylcyclopropenones with sulfonium ylides, 7 sulfoxonium ylides, 8 sulfur ylides, 9 β-ketoethers, 10 α-bromoketones, 11 and α-ammoniumketones. 12 Along with the involvement of a strong base 9–11 or an expensive Rh catalyst, 8 the significant drawbacks of these methods are the use of diarylcyclopropenone substrates, which require multistep syntheses. Moreover, control of regiochemistry for nonsymmetrical diarylcyclopropenone substrates remains an unsolved challenge.…”

Recyclable Polymer Supported DMAP Catalyzed Cascade Synthesis of α-Pyrones

“…43 Annulation reactions of cyclopropenones with either α-haloketones or activated sulfur ylides have been reported by several groups (Scheme 1d). 45,46 On the other hand, 5H-oxazol-4-one is one of the strategic C-center pronucleophiles and serves as a potential surrogate of α-hydroxy carboxylic acid. 51 Oxazolones have been extensively used in many asymmetric transformations yielding structurally diverse scaffolds.…”

“…Moreover, natural 2-pyrones exhibit a huge array of biological activities with enormous therapeutic significance, such as telomerase inhibitory, HIV protease inhibitory, anti-inflammatory, antifungal, antibacterial, antimicrobial, anti-influenza, neurotoxic, cytotoxic, and cardiotonic effects . In addition, they serve as important synthons for constructing complex molecules. , Considering the significant biological importance and synthetic potential of α-pyrones, development of efficient methods for such an ambitious framework has attracted much attention. , Synthetic strategies leading to 2-pyrones with metal catalyzed reactions include ring expansion, annulations, − cycloadditions, , C–H activations, , and coupling reactions. − Traditional approaches − on the organocatalytic pathways majorly rely on reactions of α-halocarbonyls through ammonium/sulfur ylides − and NHC. − Among representative recent findings, Tiwari and Chen groups independently disclosed carbene-catalyzed reaction of α-haloaldehydes (Scheme a–b). − Very recently, Jin and Zhang developed a base promoted cascade reactions of dithiomalonate/α-halothioester with β,γ-unsaturated α-keto esters (Scheme c) . Annulation reactions of cyclopropenones with either α-haloketones or activated sulfur ylides have been reported by several groups (Scheme d). , …”