Coupling of Quinone Monoacetals Promoted by Sandwiched Brønsted Acids: Synthesis of Oxygenated Biaryls

Abstract

Ungewöhnliche Protonen: Brønsted‐Säuren zwischen zwei Schichten aus festen Säuren, z. B. Montmorilloniten, aktivieren Chinonmonoacetale 1 für die selektive Reaktion mit aromatischen Nucleophilen 2 in einer zuvor unbekannten Substitutionsreaktion. Die Nützlichkeit dieser Strategie zur Synthese hoch oxygenierter Biaryle 3 wurde anhand der Herstellung von Gilvocarcin‐Aglyconen demonstriert.

Practical Organocatalytic Synthesis of Functionalized Non‐C2‐Symmetrical Atropisomeric Biaryls

“…The coupling of quinone monoacteals with alkoxyarenes has only been demonstrated in the presence of solid acids such as montmorillonite (MT) clay. [12] Surprisingly, traditional Brønsted or Lewis acids were found to be completely ineffective in these studies. We argued that if quinone monoacetals ( 1 ) were reacted with unprotected naphthols ( 2 ) in the presence of a strong Brønsted acid catalyst, an acetal exchange would afford the corresponding mixed-acetals ( 3 , Scheme 1).…”

Efficient Synthesis of Oxygenated Terphenyls and Other Oligomers: Sequential Arylation Reactions Through Phenol Oxidation–Rearomatization

“…Our developed approach involves two important steps: 1) the oxidation of phenols to the quinone monoacetal [4] and 2) a bond-forming rearomatization reaction of the quinone monoacetal. [5,6] The quinone monoacetal 1 a' was first synthesized by treatment of a solution of phenol 1 a in methanol with an oxidant, specifically, the hypervalent iodine reagent, PhI-A C H T U N G T R E N N U N G (OAc) 2 (Scheme 1). [7,8] The obtained quinone 1 a' was then subjected to a controlled coupling reaction with an oxygenated aromatic nucleophile (Ar 1 H) in the presence of a solid acid promoter in the form of montmorillonite (MT) clay; [5a] the aryl-aryl bond was formed successfully when the reaction was carried out in a solvent mixture containing a fluoroalcohol, [9] thus giving biaryl 2 aa, that is, the monoarylated intermediate.…”

Tin Tetrachloride‐Catalyzed Regiospecific Allylic Substitution of Quinone Monoketals: An Easy Entry to Benzofurans and Coumestans

“…Sartori realized an S N 2′ reaction of quinone monoacetals and phenols in the presence of a stoichiometric amount of EtAlCl 2 leading to the coupling products only in 25–60% yields 6. Significantly, an attractive strategy has been established recently for controlling the regioselectivity of the S N 2′ reactions of quinone monoketals with electron‐rich arenes7a,c or alkenes7b (Scheme , A ). In these reactions, the ketal moiety was required to be activated, depending on the nature of nucleophiles, by an unusaul sandwiched solid acid,7a a Brønsted acid activated by a hydrogen bond donor (perfluorinated alcohol)7b or by a Pt(IV)‐aqua complex 7c.…”

“…Significantly, an attractive strategy has been established recently for controlling the regioselectivity of the S N 2′ reactions of quinone monoketals with electron‐rich arenes7a,c or alkenes7b (Scheme , A ). In these reactions, the ketal moiety was required to be activated, depending on the nature of nucleophiles, by an unusaul sandwiched solid acid,7a a Brønsted acid activated by a hydrogen bond donor (perfluorinated alcohol)7b or by a Pt(IV)‐aqua complex 7c. The high selectivity of these reactions is believed to lie in the steric block of the β‐position arising from the activation, which leads to an attack of nucleophiles at the less hindered α‐carbon of quinone monoketals 7.…”

“…The high selectivity of these reactions is believed to lie in the steric block of the β‐position arising from the activation, which leads to an attack of nucleophiles at the less hindered α‐carbon of quinone monoketals 7. This strategic protocol proved to be efficient and has been successfully applied in the synthesis of natural products 7a,c. Undoubtedly, a new method for selective S N 2′ reactions of quinone monoketals that can be applied to a range of different classes of nucleophiles, especially allowing access to valuable chemicals, is desired but remains a challenge.…”