Diversity-Oriented Enantioselective Construction of Atropisomeric Heterobiaryls and N -Aryl Indoles via Vinylidene Ortho -Quinone Methides

Abstract

Diversity-oriented enantioselective construction of atropisomeric heterobiaryls and N-arylindoles via vinylidene ortho-quinone methides (VQMs)

Cinchonidine-Catalyzed Synthesis of Oxazabicyclo[4.2.1]nonanones from N-Aryl-α,β-unsaturated Nitrones and 1-Ethynylnaphthalen-2-ols

“…In 2020, Jiang and co-workers reported a [4 + 3] cycloaddition of nitrones with 1-ethynylnaphthalen-2-ols and subsequent [3,3]-rearrangement of N–O bonds and dehydration to afford polycyclic indoles by quinine catalysis (Scheme -A) . Based on the easily dearomative 1-ethynylnaphthalen-2-ols and our studies of the reactivity of α,β -unsaturated nitrones, , we proposed that a hydrogen-bonding bifunctional catalyst could catalyze the cycloaddition of α,β-unsaturated nitrones to vinylidene o -quinone methides generated from 1-ethynylnaphthalen-2-ols to produce seven-membered N–O vinyl intermediates. Then it will undergo a selective [1,3]-rearrangement on the N -atom rather than a [3,3]-rearrangement on the phenyl ring owing to the lower steric hindrance of the styrenyl group connecting to the N , O -acetal .…”

Organocatalytic atroposelective construction of axially chiral N, N- and N, S-1,2-azoles through novel ring formation approach

“…In recent years, vinylidene ortho -quinone methide (VQM) intermediates have evolved into an important tool for catalytic asymmetric synthesis because their intrinsic axial chirality can be generated from readily available ortho -alkynylnaphthols with a chiral catalyst and further subjected to downstream transformations with excellent stereocontrol 32 – 38 . Based on our previous work on VQM chemistry for heterobiaryl atropisomer synthesis 39 – 43 , we believed that VQMs could be an ideal template synthon for the collective synthesis of axially chiral 1,2-azoles. Nevertheless, reported VQMs are mostly limited to those bearing an arene ring at 5-position, so axial chiral architectures were confined to benzo- or naphtho-fused analogues 39 – 44 .…”

Organocatalytic enantioselective construction of axially chiral (1H)-isochromen-1-imines

“…Recently, the enantioselective construction of atropisomers has been intensively investigated by synthetic chemists. [11][12][13][14][15][16][17][18][19] While biaryl atropisomers [20][21][22][23][24][25][26] have been extensively studied as important scaffolds of chiral ligands or catalysts, axially chiral styrenes [27][28][29][30][31][32][33][34][35][36] have gained increasing interest in recent years due to their relatively lower rotational barriers. In contrast, heterocycloalkenyl atropisomers, derived from biaryl atropisomers and axially chiral styrenes, are beneficial for improving the pharmacological activity and structural diversity due to the participation of heteroatoms.…”

“…40 Despite these breakthroughs, synthesis strategies to construct atropisomeric lactones are limited. Inspired by the development of vinylidene quinone methides (VQMs) [27][28][29][30][31][32][33][34][35][36]41 for the organocatalytic enantioselective construction of axially chiral styrenes, we surmised that alkyne precursors could be activated by an electrophilic halogen source to form VQM intermediates. These VQM intermediates then underwent intramolecular annulation to obtain (1H)-isochromen-1-imines, which could be easily converted to atropisomeric lactones (Scheme 1d).…”