Construction of Axially Chiral Compounds via Central‐to‐Axial Chirality Conversion

Abstract

Central-to-axial chirality conversion represents a fascinating class of chemical processes consisting of the destruction of stereogenic centers and the simultaneous installation of axial chiral elements, which provides efficient methods for the preparation of axially chiral compounds. Using the strategy, a wide range of axially chiral compounds, including biaryls, heterobiaryls, aromatic amides, allenes and vinyl arenes, have been synthesized with high efficiency and excellent enantioselectivity. In addition, central-to-axial chirality conversion strategy has been applied to the synthesis of natural products. The strategy has undoubtedly become and will continue to be a hot research topic in the field of asymmetric catalysis and synthesis. In this minireview, we selected some examples to introduce the developments and trends in the central-to-axial chirality conversion strategy up to April 2020.

Atroposelective transformation of axially chiral (hetero)biaryls. From desymmetrization to modern resolution strategies

“…4 A third alternative consist of central-toaxial chirality transfer processes, in which one or more stereogenic centers are destroyed with simultaneous installation of axial chirality. 5 Alternatively, methodologies based on the construction of aromatic rings by cycloadditions or cyclizations, using either metal catalysis or organocatalysis are also versatile alternatives for the asymmetric synthesis of (hetero)biaryls. 6 Finally, these compounds can be accessed from pre-existing,…”

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.…”

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

“…Owing to the importance of atropisomers, substantial efforts have been made for accessing these molecular skeletons, including (a) atroposelective coupling of two units, 14–17 (b) functionalization of racemic or prochiral precursors, 18–23 (c) central-to-axial chirality transfer 24,25 and (d) de novo arene formation (Fig. 2).…”

“…[4][5][6][7] In addition, an ever-growing number of biologically active atropisomeric structures have also been realized and the stereochemistry of the axial chirality was proved to be a critical factor in the pharmaceutical activities. [8][9][10][11][12][13] Owing to the importance of atropisomers, substantial efforts have been made for accessing these molecular skeletons, including (a) atroposelective coupling of two units, [14][15][16][17] (b) functionalization of racemic or prochiral precursors, [18][19][20][21][22][23] Xiao-Long Min Xiao-Long Min was born in Anhui province (China) (c) central-to-axial chirality transfer 24,25 and (d) de novo arene formation (Fig. 2).…”