Organocatalytic Intramolecular [4+2] Cycloaddition between In Situ Generated Vinylidene ortho‐Quinone Methides and Benzofurans

Abstract

Described herein is the enantioselective construction of oxygen-containing [5-6-5] tricyclic heterocycles by an organocatalyzed asymmetric [4+2] cycloaddition of vinylidene ortho-quinone methides and benzofurans. According to this methodology, a series of oxygen-containing [5-6-5] tricyclic heterocycles with various functional groups were synthesized in excellent enantio- and diastereoselectivities (>99 % ee, >20:1 d.r.). Furthermore, the deuterium-labeling experiments and high-resolution mass spectroscopy demonstrated that a vinylidene ortho-quinone methide intermediate was involved and possibly resulted from a prototropic rearrangement of 2-ethynylphenol. Remarkably, a catalyst loading as low as 0.1 mol %, and a gram-scale synthesis were achieved for this transformation.

Organocatalytic Atroposelective Intramolecular [4+2] Cycloaddition: Synthesis of Axially Chiral Heterobiaryls

“…Recently, we reported the first enantioselective intramolecular [4+2] cycloaddition of vinylidene ortho ‐quinone methides (VQMs), derived from 2‐ethynylphenol derivatives, with benzofuran . To explore the application of VQMs in enantioselective synthesis, we presumed that the highly active VQM intermediate might be subjected to a hetero‐Diels–Alder cycloaddition in the presence of alkyne to form chiral aryl‐naphthopyran skeleton (a new member of heterobiaryl skeletons).…”

Catalytic Asymmetric Construction of Axially Chiral Indole‐Based Frameworks: An Emerging Area

“…Recently,t he Yang roup devised an innovative strategy for constructing axially chiral C2-naphthylindoles 48 via asymmetric catalysis based on their understanding of vinylidene orthoquinone methide (VQM) chemistry. [33] As illustrated in Scheme 13 a, they proposed that ortho-alkynylanilines 47 could transform into chiral VQM intermediates in the presence of the chiral Brønsted base C12,a nd these intermediates subsequently underwent an intramolecular cyclization to generate an indole ring and C2-arylindole axis. [34] Notably,t his strategy could be utilized for the decagram-scale synthesis of C2-naphthylindole 48 a in an excellent yield with perfect enantioselectivity (Scheme 13 b).…”

Enantioselective Control of Both Helical and Axial Stereogenic Elements though an Organocatalytic Approach

“…[11] Inspired by Iriesp ioneering work in the transformation of vinylidene ortho-quinone methides (VQMs), [12] recently, our research group has developed various organocatalyzed atroposelective methods for the synthesis of axial chiral styrenes and heterobiaryls based on VQMs. [13] To further expand the application scope of VQMs in asymmetric syntheses,w ea re interested in developing an asymmetric synthesis of chiral helicenes and their derivatives using VQMs as ak ey intermediate.W ea nticipated that the substrate 1a would undergo ap rototropic rearrangement (tautomerization) to furnish the corresponding chiral VQM intermediate I, subsequently,c yclization produces an intermediate II containing astereogenic axis.T he following tautomerization and cyclization will generate ahelix and another stereogenic axis (Scheme 1b). Consequently,w er eport herein an organocatalytic strategy for the efficient one-pot synthesis of molecules containing valuable chiral helicenes and stereogenic axes.…”