Organocatalytic cycloaddition–elimination cascade for atroposelective construction of heterobiaryls

Abstract

An organocatalytic asymmetric cycloaddition–elimination cascade reaction of aryl enecarbamates with azonaphthalenes has been developed to access axially chiral heterobiaryls in excellent yields and enantioselectivities.

Recent advances in the catalytic asymmetric construction of atropisomers by central-to-axial chirality transfer

“…Inspired by these reports, the cycloaddition-elimination cascade could be expanded to the reaction of 2-naphthols or phenol-derived enecarbamates 55 with azonaphthalenes 56 (Scheme 13b). 65 In this case, a similar stepwise CPA-catalyzed [3 + 2] cycloaddition and central-to-axial chirality transfer occurred, giving C2unsubstituted axially chiral aryl-C3-benzoindoles 57 efficiently.…”

Organocatalytic cycloaddition of alkynylindoles with azonaphthalenes for atroposelective construction of indole-based biaryls

“…Consequently, developing protocols for the catalytic enantioselective construction of axially chiral scaffolds has attracted a great deal of interest among researchers in synthetic chemistry 4 , 5 . Many strategies have been developed, including desymmetrization or kinetic resolution of prochiral biaryls 6 – 12 , aryl–aryl coupling 13 – 15 , direct arylation 16 – 22 , chirality conversion 23 – 33 , cycloaddition 34 – 39 , and so on 40 – 48 . Recently, the catalytic enantioselective construction of chiral atropisomeric heterobiaryl backbones has received increasing attention from the chemistry community.…”

“…Indole-based biaryls have been found in nature and have been used as ligands for asymmetric synthesis 49 – 51 . Recently, a few outstanding cases of the enantioselective synthesis of indole–aryl skeletons have been reported 22 , 29 , 33 , 52 – 66 . Generally, there are two strategies to construct indole-based biaryls enantioselectively.…”

“…In fact, transition metal catalyzed cyclization reaction of azobenzene derivatives with alkynes to construct indole derivatives without chiral axis has been reported 67 – 69 . Although organo-catalyzed cycloaddition of alkenes with azonaphthalenes has been well documented 22 , 29 , 33 , 70 , the organo-catalyzed asymmetric cycloaddition reaction of azo benzene derivatives with alkynes is still lacking. The reason may be ascribed to a relative lower reactivity of alkyne than that of alkene in the cycloaddition reaction with azonaphthalenes.…”

Hydrogen Bond Assisted Central-to-Spiro Chirality Transfer and Central-to-Axial Chirality Conversion: Asymmetric Synthesis of Spirocycles

“…Recently, we have developed a conversion of two stereocenters to two chiral axes via a chiral phosphoric acid-catalyzed cycloaddition and a mild oxidative dehydrogenation, wherein sulfonate derivatives were utilized in order to avoid the dearomatization reaction (Scheme ). Given our interest in developing central chirality conversions and dearomatizations, we envisaged that the naphthol substrate would be oxidized to generate a spiro stereocenter and a stereogenic axis by a one-pot chirality transfer and conversion strategy. To the best of our knowledge, simultaneous transfer and conversion of stereocenters to one spiro stereocenter and a chiral axis in one operation is unprecedented.…”