We report an efficient method for the preparation of various 2,2′-dihalobiaryls from cyclic diaryliodonium salts. With cheap halogen sources as starting materials, a broad range of 2,2′-diiodobiaryls, 2-bromo-2′-iodobiaryls, and 2-chloro-2′-iodobiaryls were obtained under mild reaction conditions. More importantly, a chiral copper–bisoxazoline catalyst system was further developed for the preparation of axially chiral 2,2′-dihalobiaryls in excellent yields and enantioselectivities, which can serve as versatile precursors for the synthesis of various chiral ligands.
Here, we report a chiral copper(II)-bisoxazolinecatalyzed enantioselective ring opening of cyclic diaryliodonium salts with heteroaryl thiols. The readily available 2-mercaptobenzoxazole and 2-mercaptobenzothiazole derivatives reacted efficiently with cyclic diaryliodonium salts and afforded various axially chiral biaryls bearing iodine and sulfur functional groups in excellent yields and enantioselectivities. The products were further transformed into diverse enantiopure alkyl biaryl sulfides, which can be employed as chiral ligands.B iaryl atropisomerism is a type of axial chirality arising from aryl−aryl single-bond rotation restriction, which is ubiquitous in complex natural products, 1,2 biologically active compounds, 3 chiral ligands, 4 organocatalysts, 5 etc. It also plays an important role in medicinal chemistry because each axially chiral enantiomer of a racemic bioactive molecule may interact with different target proteins and exhibit markedly divergent pharmacological activities in vivo. 6 Hence, quite a few elegant methods have been reported for the axially chiral biaryl synthesis due to their widespread applications in synthetic chemistry and medicinal chemistry. 7−9 The asymmetric ring-opening strategy represents one of the most powerful synthetic approaches to an axially chiral skeleton. A series of ring cleavage reactions for the construction of chiral biaryls have been reported via this strategy (Scheme 1a). For example, the Bringmann group and the Zhang and Yin group reported axially chiral biaryl synthesis via C(O)−O bond cleavage of a lactone skeleton through dynamic kinetic resolution 7 and iridium-catalyzed asymmetric hydrogenation, respectively. 10 The Hayashi group reported the axially chiral biaryl synthesis via nickel-catalyzed asymmetric C−S bond cleavage of dinaphthothiophenes with Grignard reagents, 11 and the same group also reported the first example of palladium-catalyzed C−I bond cleavage of cyclic diaryliodoniums, 12,13 although with only one example with 28% ee (Scheme 1a). 14 Recently, by employing a catalytic system similar to that of Gaunt, MacMillan, and Zhu, 15 Gu and coworkers developed a series of Cu/chiral box-catalyzed asymmetric ring-opening reactions of cyclic iodonium salts with amines, diarylphosphine oxides, and potassium thioates, providing excellent examples of Cu-catalyzed atropisomer synthesis from cyclic diaryliodoniums (Scheme 1b). 16 Our group also independently reported Cu-catalyzed enantioselective acyloxylation of cyclic diaryliodonium salts with diverse carboxylic acids. 17 More recently, the Gu group reported the enantioselective C−C bond cleavage of 9-aryl-9H-fluoren-9-ols
A simple and novel method for the synthesis of novel 1,3-dioxepine-fused (tricyclic) bispyrazoles is described. It involves a Cs2CO3-mediated O-alkylation of readily available pyrazolone derivatives with dichloromethane as the methylene source followed by PhI(OAc)2-mediated intramolecular oxidative biheteroaryl coupling under mild conditions. This scalable protocol was applied for the preparation of valuable and novel 1,3-dioxepine-fused (tricyclic) bispyrazoles that could find applications in medicinal or material chemistry.
The transition metal catalyzed ortho-functionalization of cyclic diaryliodonium salts have been well developed. Herein we present a transition-metal free meta-halogenation of readily available cyclic diaryliodonium salts for the preparation of...
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