Organocatalyzed Asymmetric Synthesis of Axially, Planar, and Helical Chiral Compounds

Abstract

Axially, planar, and helical chiral compounds are indispensable building blocks in modern organic synthesis. A wide variety of chiral ligands and catalysts were designed based on these chiral scaffolds, and these chiral ligands and catalysts were used for various catalytic asymmetric transformations to produce important chiral compounds in an optically enriched form. Furthermore, these chiral skeletons are found in the structure of biologically active natural products. Thus, the development of efficient enantioselective methods for the synthesis of these chiral compounds is an important task in the field of organic chemistry. In the last few years, organocatalyzed approaches, which are one of the most reliable catalytic asymmetric methods, became a hot topic. This Focus Review summarizes asymmetric organocatalytic methods for the synthesis of axially, planar, and helical chiral compounds as useful chiral building blocks.

Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

“…In these reactions, multipoint recognition by the catalysts favors the specific conformations of the substrates in the transition state. Several successful results and a recent trend in organocatalytic atroposelective reactions, including enantioselective formation of chiral axes [ 17 – 24 ], dynamic kinetic resolution [ 25 – 41 ], kinetic resolution [ 42 – 47 ], desymmetrization [ 48 – 54 ], de novo annulation [ 55 – 61 ], and point-to-axial chirality transfer [ 58 – 59 ] (for reviews, see references [ 31 , 62 – 63 ]), motivated us to expand on the utility of this class of small-molecule catalysts. We have recently demonstrated that bifunctional organocatalysts can also be applied to the asymmetric synthesis of axially chiral compounds (biaryls bearing isoquinoline N -oxides or quinolines and phenolic moieties) by translating a specific conformation, recognized by bifunctional organocatalysts, into axial chirality [ 36 – 37 ].…”

Atroposelective Synthesis of Axially Chiral All‐Benzenoid Biaryls by the Gold‐Catalyzed Intramolecular Hydroarylation of Alkynones

“…The atroposelective construction of biaryl skeletons has attracted much attention because of their high utility in the synthesis of chiral catalysts and natural products For this purpose, transition‐metal‐catalyzed atroposelective aromatic ring construction reactions have been studied extensively . For example, a number of transition‐metal‐catalyzed atroposelective [2+2+2] cycloaddition reactions have been reported by using rhodium(I), iridium(I), and cobalt(I) complexes as catalysts.…”

Catalytic asymmetric synthesis of chiral trisubstituted heteroaromatic allenes from 1,3-enynes

“…Classic approaches typically involve (kinetic) resolution of racemic allenes 4,5 or chirality transfer from optically pure propargylic precursors [6][7][8][9][10] . Recent years have witnessed a tremendous development on metal-catalyzed enantioselective synthesis of chiral allenes [11][12][13][14][15][16] , such as nucleophilic addition to 1,3-enynes [17][18][19] , enantioselective functionalization of racemic allenes [20][21][22] , β-hydride elimination from enol triflates 23 , rearrangement of propargylic compounds [24][25][26][27] , coupling of terminal alkynes with diazo compounds [28][29][30][31] , and enantioselective addition of terminal alkynes to aldehydes 32 . In addition, several asymmetric organocatalytic protocols have also been reported, such as nucleophilic addition to activated enynes 33,34 , isomerization of alkynes 35,36 , phase-transfer-catalyzed alleno-Mannich reaction 37,38 , alkynylogous Mukaiyama aldol reactions 39 , and chiral ion-pair catalysis involving a formal propargylic carbocation from racemic propargylic alcohols 40 .…”