Brønsted‐Säure‐katalysierte konjugierte Addition von β‐Dicarbonylverbindungen an in situ erzeugte ortho‐Chinomethide – enantioselektive Synthese von 4‐Aryl‐4H‐chromenen

Abstract

4H-Chromene sind wichtige Strukturelemente vieler Naturstoffe und biologisch aktiver Verbindungen. Mithilfe einer enantioselektiven konjugierten Addition von b-Diketonen an in situ erzeugte ortho-Chinomethide gelingt nach dehydratisierender Cyclisierung eine breit anwendbare und hochselektive Synthese wertvoller 4-Aryl-4H-chromene. Eine Binol-basierte chirale Phosphorsäure wird zur In-situ-Erzeugung der ortho-Chinomethide aus ortho-Hydroxybenzhydrylalkoholen eingesetzt und katalysiert den C-C-bindungsbildenden Schritt. Ortho-ChinomethidesindhochreaktiveIntermediateinderorganischen Chemie, die in jüngerer Vergangenheit zunehmend genutzt werden, vor allem in der Synthese von Chromansystemen. Sie lassen sich auf vielfältige Weise aus einfachen Vorläufern in situ erzeugen und reagieren als polarisierte elektronenarme 1-Oxabutadiene bevorzugt mit elektronenreichen [2 p]-Komponenten in Hetero-Diels-AlderReaktionen mit inversem Elektronenbedarf oder mit Nucleophilen in konjugierten 1,4-Additionen jeweils unter Rückbildung des aromatischen p-Systems.

Advancements in the Preparation of 4H‐Chromenes: An Overview

“…In 2014, Schneider and co‐workers pioneered the catalytic asymmetric [4+2]‐cycloaddition/dehydration reaction based on o ‐hydroxy benzylic alcohols for the synthesis of enantioenriched 4‐aryl‐4 H ‐chromenes [51a] . By using BINOL‐based chiral phosphoric acid 63 b as a Brønsted catalyst, the formal [4+2]‐cycloaddition comprising a conjugate addition of β‐diketones 200 to in situ generated ortho ‐quinone methides from o ‐hydroxy benzylic alcohols 199 , followed by adding p ‐TsOH to catalyze the cyclodehydration furnished the final optically active 4 H ‐chromenes 201 in generally excellent yields and high ee values (Scheme 55).…”

Chiral Phosphoric Acid Catalyzed Asymmetric Synthesis of Hetero‐triarylmethanes from Racemic Indolyl Alcohols

“…[1] Therefore,t he development of efficient strategies for enantioenriched heterotriarylmethane derivatives is of great interest to the synthetic community.D iarylmethanols have emerged as versatile precursors for the construction of hetero-triarylmethane derivatives. [2] Ther acemic alcohols used can be easily converted into active intermediates,such as quinone methides (QMs) or carbocationic species,b ya na cid-catalyzed dehydration pathway.R ecently,g reat achievements have been made in the catalytic asymmetric 1,4-additions and formal S N 1 substitutions of diarylmethanols to deliver hetero-triarylmethanes.A sar esult, various activation patterns have been successfully documented, such as bifunctional modes, [3] coordination catalysis, [4] and dual ion-pairing modes. [5] However, the enantioselective transformations based on the more challenging monoactivation mode still remain unexplored.…”

Phosphoric Acid Catalyzed Asymmetric 1,6‐Conjugate Addition of Thioacetic Acid topara‐Quinone Methides

“…[5] Recently, ortho-quinone methides (o-QMs) have been extensively studied in catalytic enantioselective processes. [6,7] To our surprise, para-quinone methides (p-QMs), which are structural isomers of o-QMs and have been employed in the synthesis of natural products and bioactive molecules, [8] have been scarcely investigated in catalytic asymmetric transformations.I tm ay be due to the fact that the distance and space position between the carbonyl and carbon-carbon double bond of p-QMs are not favorable for stereocontrol (Scheme 1). To date,o nly very limited examples of enantioselective additions of p-QMs have been documented.…”