Stereoselective Intramolecular Dearomatizative [4+2] Cycloaddition of Linked Ethynylnaphthol–Benzofuran Systems

Abstract

A base‐catalyzed stereoselective intramolecular dearomatizative [4+2] cycloaddition of o‐phenylene‐linked ethynylnaphthol–benzofuran systems was explored. In this reaction, we presume the involvement of electrophilic vinylidene o‐quinone methides (4π), which add across the electron‐rich furan double bonds (2π) to produce elaborate, fused oxa‐polyheterocyclic frameworks with consecutive quaternary and tertiary asymmetric carbon atoms as single diastereomers. The catalytic and enantioselective synthesis of these chiral fused polyheterocyclic structures is also feasible with the use of a prevalent cinchonidine or cinchonine chiral base.

Recent Dearomatization Strategies of Benzofurans and Benzothiophenes

“…Irie and co-workers in 2017, demonstrated a triethylamine (Et 3 N) catalyzed intramolecular [ synthesis of polycyclic systems 19. [9] Electron-donating groups on the benzofuran are more favourable compared to electronwithdrawing ones for this reaction. Moreover, naphthofurans were found to be more feasible than benzofurans with a shorter reaction time.…”

“…Irie and co‐workers in 2017, demonstrated a triethylamine (Et 3 N) catalyzed intramolecular [4+2] cycloaddition of o ‐phenylene‐linked ethynylnaphthol‐benzofuran systems 17 via the formation of VQM (vinylidene ortho ‐quinone methide) intermediates 18 by a 1,5‐proton shift (Scheme 4A) for the synthesis of polycyclic systems 19 [9] . Electron‐donating groups on the benzofuran are more favourable compared to electron‐withdrawing ones for this reaction.…”

Organocatalyzed Oxa-Diels–Alder Reactions: Recent Progress

“…In 2017, Irie and co-workers developed a base-catalyzed diastereoselective­ intramolecular dearomatizative [4+2] cycloaddition­ reaction of an o -phenylene-linked ethynylnaphthol-benzofuran scaffold for the construction of fused oxa-polyheterocyclic frameworks 140 with contiguous chiral­ centers (not shown in the scheme). 32c…”

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

“…[9] Thee fficient construction of chiral complex molecules,especially those containing helicenes and different types of stereogenic elements,h ave attracted more and more attention, since these molecules may provide geometrically chiral environments owing to the broad range of topologies. [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).…”