Abstract
Ynones are a unique class of structural motifs that show remarkable chemical versatility. Chiral ynones, particularly those possessing an α-stereogenic center, are highly attractive templates for structural diversification. So far, only very limited examples have been reported for asymmetric α-functionalization of ynones. Asymmetric double α-functionalization of ynones remains elusive. Here we describe a streamlined strategy for asymmetric α-difunctionalization of ynones. We developed a gold-catalyzed multicomponent condensation reaction from a simple ynone, an amine, and an electrophilic alkynylating reagent to generate a 1,2-dialkynyl enamine, a key stable and isolable intermediate. This intermediate can undergo asymmetric fluorination catalyzed by a chiral phosphoric acid derivative. Chiral ynones with an α-quaternary carbon and containing a fluorine and an alkyne can be synthesized in high yield and high ee. The synthetic utility of this method is demonstrated by the synthesis of enantioenriched tri(hetero)arylmethyl fluorides.
Highlights
Ynones are a unique class of structural motifs that show remarkable chemical versatility
Ynones are abundant structural motifs and versatile synthetic intermediates that are useful in the synthesis of natural products and other complex molecular structures[1,2,3]
We reported ester-substituted enamines that can be used in an enantioselective Povarov reaction and α-iodoenamine useful in direct α-cyclopropanation of aldehydes[36,37]
Summary
Ynones are a unique class of structural motifs that show remarkable chemical versatility Chiral ynones, those possessing an α-stereogenic center, are highly attractive templates for structural diversification. We developed a gold-catalyzed multicomponent condensation reaction from a simple ynone, an amine, and an electrophilic alkynylating reagent to generate a 1,2-dialkynyl enamine, a key stable and isolable intermediate. This intermediate can undergo asymmetric fluorination catalyzed by a chiral phosphoric acid derivative. The unique property and reactivity of alkynes, coupled with the chemical versatility of carbonyl compounds, makes ynones an indispensable template for rapid structural proliferation and diversification[4,5,6,7].
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