Organocatalytic Approach for Assembling Flavanones via a Cascade 1,4-Conjugate Addition/oxa-Michael Addition between Propargylamines with Water

Abstract

A DBU-catalyzed one-pot cascade reaction of propargylamines and water for the synthesis of flavanones has been developed. This process proceeds via a sequence of 1,4-conjugate addition of water to alkynyl o-quinone methide (o-AQM), followed by the alkyne–allene isomerization and subsequent intramolecular oxa-Michael addition. This strategy provides a convenient method for accessing a broad range of flavanones in good to excellent yields with good functional-group tolerance, in particular, the reactive halo functional groups.

DMAP-Catalyzed Annulation Approach for Modular Assembly of Furan-Fused Chromenes

“…o -Alkynyl quinone methide ( o -AQM) − is a reactive intermediate generated in situ from modular propargylamines, which can be straightforwardly obtained via a three-component reaction between aromatic aldehyde, terminal alkyne, and amine. − Inspired by the rich reactivity of o -AQM for annulation and the chemistry of acylpyridinium methylides involving O -cyclization processes, we are intrigued whether these two substrates could be combined to enable facile construction of structurally diversified furan-fused chromenes. In continuing our research interest in polycycle assembly , and o -AQM chemistry, − we here show our development of a tandem reaction between propargylamine and pyridinium ylide catalyzed by DMAP (Scheme d). This transition-metal-free procedure features simple operation (can be performed without inert atmosphere protection) and good functional group tolerance (e.g., −Br, −Cl, −NO 2 , −CN, −OH, −SO 2 Me, and alkene).…”

Copper-Catalyzed Cascade 1,4-Addition/Annulation/Hydrolysis of Propargylamines with 2-Hydroxynaphthalene-1,4-diones: Direct Formation of 12-Phenacyl-11H-benzo[b]xanthenes

“…Literature procedures were used for the preparation of propargylamines ( 1a – 1a′ ) and 2-hydroxy­naphthalene-1,4-diones ( 2b – 2f ), and all the substrates were known compounds. 2-Hydroxy­naphthalene-1,4-dione ( 2a ) was used as received from commercial suppliers.…”

“…In particular, alkynyl o -quinone methides ( o -AQMs), which are prepared from o -hydroxyl propargylic alcohols and o -hydroxyl propargylamines, readily undergo cycloaddition and 6π electrocyclization reactions with various polarized dienophiles for the formation of pyran skeletons . We previously employed o -AQMs for the synthesis of diverse oxa -heterocyclic compounds . As part of our continuing interest in o -AQMs chemistry and continuing interest in the design of new cascade reactions in organic synthesis, herein, we disclose the realization of an unprecedented Cu­(OAc) 2 -catalyzed cascade reaction of in situ generated o -AQMs and commercially available 2-hydroxy­naphthalene-1,4-diones, involving a sequential oxa -Diels–Alder cycloaddition/dehydration/hydrolysis of alkyne/enol-ketone tautomerization process (Scheme c).…”

Rapid Access of Alkynyl and Alkenyl Coumarins via a Dipyridinium Methylide and Propargylamine Cascade Reaction

“…A proposed mechanism is shown in Scheme 5b. On the basis of precedent reports, 27,34 we postulate that this one-pot cascade reaction involves the initial deamination of the propargylamine In summary, the manipulation of the physical properties of coumarin by installing alkynyl or alkenyl moieties has been found to be highly useful toward the advancement of material science. Precedent methods for accessing these structural motifs depend on the transition-metal-catalyzed cross-coupling of prefunctionalized coumarin triflate/tosylate/bromide with an alkyne or alkene under an inert atmosphere, or the oxidative coupling between two nucleophilic fragments in the presence of an oxidant.…”

“…A proposed mechanism is shown in Scheme b. On the basis of precedent reports, , we postulate that this one-pot cascade reaction involves the initial deamination of the propargylamine 1a and subsequently generates the o -AQM intermediate in the presence of the DMAP catalyst. The 1,4-conjugate addition of dipyridinium methylide to o -AQM proceeds to give intermediate A .…”