Modular Construction of Heterobiaryl Atropisomers and Axially Chiral Styrenes via All‐Carbon Tetrasubstituted VQMs

Abstract

Here we report a new type of chiral all-carbon tetrasubstituted VQMs generated via chiral phosphoric acids catalyzed nucleophilic addition of 2-alkynylnaphthols to o-quinone methides or imines, which can be captured intramolecularly as a result of cycloaddition reaction. A new class of naphthyl-2H-chromenes bearing axially and centrally chiral elements and axially chiral quinone-naphthols were prepared efficiently with good to excellent yields, diastereoselectivities and enantioselectivities. Noteworthy, the enantioselective cycloaddition of alkynylnaphthols with o-quinone methides proceeded via a [2+2] cycloaddition, followed by a retro-4π-electrocyclization and a 6π re-cyclization. While the cycloaddition of alkynylnaphthols with imines proceeded via a sequential [2+4] cycloaddition and an auto oxidation reaction. Moreover, the obtained axially chiral naphthols can be converted into valuable phosphine ligands and other functional molecules.

Enantioselective Access to Triaryl-2-pyrones with Monoaxial or Contiguous C–C Diaxes via Oxidative NHC Catalysis

“…Axially chiral compounds have played an essential role as chiral ligands and catalysts in asymmetric synthesis. , This class of molecules is widely found in numerous pharmaceutical agents and natural products . Out of different axially chiral structures, substituted biaryls ( A and B , Scheme a) have been extensively developed and applied. − More recently, other atropisomers including alkenes and aryl amides ( C and D , Scheme a) have also been under active investigation. − However, these studies mainly focused on the preparation of atropisomers with a single stereogenic axis. Methods to assemble axially chiral molecules with more than one stereogenic axis ( E and F , Scheme a) have rarely been reported, owing to the formidable challenges involved in the assembly of multiple stereogenic axes with high enantiocontrol.…”

Advances in Catalytic Asymmetric Reactions Involving o-Hydroxybenzyl Alcohols

“…由于邻羟基苄醇在苯并含氧杂环骨架催化不对称构建 中的独特优势, 科研工作者开始尝试将此类底物用于非 芳环轴手性骨架的催化不对称构建. 2022 年, 周岭课题 组 [44] 在手性磷酸(R)-C25 催化下, 实现了邻羟基苄醇 [45] , 而邻羟基苄醇与芳烃亲核试剂的催化不 对称加成反应可以发展为构建该类骨架的一种高效策 略.…”

Brønsted acid–catalyzed asymmetric dearomatization for synthesis of chiral fused polycyclic enone and indoline scaffolds

“…Compared with the well-established transition metalcatalyzed transformations, asymmetric organocatalysis based on the activation of inert alkynes has been relatively less exploited (16,17). Recently, vinylidene-quinone methides (VQMs) derived from 2-alkynylnaphthols under organocatalysis, a well-known variant of ortho-QMs (18), have been widely used in such organocatalytic enantioselective alkyne transformations (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). The VQMs were first used to asymmetric synthesis by Irie and colleagues in 2013 (19) and later were extensively exploited by the same group (20) and Yan and colleagues (21)(22)(23)(24)(25)(26)(27)(28).…”

“…2A) (28,29). In this regard, stateof-the-art advances from Tan, Houk, and colleagues take advantage of ortho-alkynyl-naphthols or ortho-alkynyl-naphthylamines as precursors of VQMs to accomplish a chiral Brønsted acid (BA)-catalyzed asymmetric hydroarylation of alkynes (30), thus providing an alternative avenue for organocatalytic asymmetric alkyne functionalization via the activation of inert alkynes (31)(32)(33). Despite these remarkable achievements, these BA-catalyzed reactions of alkynes were invariably used to construct axially chiral compounds (Fig.…”