Catalytic Asymmetric Synthesis of Atropisomers Bearing Multiple Chiral Elements: An Emerging Field

Abstract

With the rapid development of asymmetric catalysis, the demand for the enantioselective synthesis of complex and diverse molecules with different chiral elements is increasing. Owing to the unique features of atropisomerism, the catalytic asymmetric synthesis of atropisomers has attracted a considerable interest from the chemical science community. In particular, introducing additional chiral elements, such as carbon center chirality, heteroatomic chirality, planar chirality, and helical chirality, into atropisomers provides an opportunity to incorporate new properties into axially chiral compounds, thus expanding the potential applications of atropisomers. Thus, it is important to perform catalytic asymmetric transformations to synthesize atropisomers bearing multiple chiral elements. In spite of challenges in such transformations, in recent years, chemists have devised powerful strategies under asymmetric organocatalysis or metal catalysis, synthesizing a wide range of enantioenriched atropisomers bearing multiple chiral elements. Therefore, the catalytic asymmetric synthesis of atropisomers bearing multiple chiral elements has become an emerging field. This minireview summarizes the rapid progress in this field and indicates challenges, thereby promoting this field to a new horizon.

Atroposelective Synthesis of Axially Chiral Diaryl Ethers by N-Heterocyclic-Carbene-Catalyzed Sequentially Desymmetric/Kinetic Resolution Process

“…5 Due to the extensive occurrence of axially chiral compounds in natural products, chiral ligands, as well as chiral catalysts, asymmetric synthesis of these frameworks has drawn widespread interest over the past few decades. 6 of an atropisomeric diaryl ether through dynamic resolution. 10 Thereafter, the Clayden, Zeng and Zhong, and Yang groups realized the atroposelective construction of the axially diaryl ethers via biocatalytic or organocatalytic desymmetrization of prochiral diaryl ethers respectively (Scheme 1a).…”

Catalytic Asymmetric Diastereodivergent Synthesis of 2-Alkenylindoles Bearing both Axial and Central Chirality

“…17−28 However, in stark contrast, catalytic asymmetric diastereodivergent reactions for the synthesis of chiral compounds bearing both axial and central chirality remain largely unexplored (Scheme 1b) 29,30 in spite of the importance of atropisomers bearing multiple chiral elements. 31 The challenges in realizing such diastereodivergent reactions mainly include: 1) simultaneously controlling the axial chirality and central chirality to achieve excellent diastereoselectivity and enantioselectivity; 2) finding suitable reaction conditions for diastereodivergent generation of two chiral elements. Therefore, it is highly desired to develop efficient strategies toward settling these challenges and realize catalytic asymmetric diastereodivergent reactions for the synthesis of chiral compounds bearing both axial and central chirality.…”

“…Catalytic asymmetric diastereodivergent reactions have recently been recognized as a class of powerful methods for synthesizing each stereoisomer of chiral compounds using the same set of starting materials by slightly modulating the reaction conditions. − Thus, developing catalytic asymmetric diastereodivergent reactions has attracted intensive attention from the scientific community. − Among them, catalytic asymmetric diastereodivergent reactions for the synthesis of chiral compounds bearing multiple central chirality have been well-developed (Scheme a). − However, in stark contrast, catalytic asymmetric diastereodivergent reactions for the synthesis of chiral compounds bearing both axial and central chirality remain largely unexplored (Scheme b) , in spite of the importance of atropisomers bearing multiple chiral elements . The challenges in realizing such diastereodivergent reactions mainly include: 1) simultaneously controlling the axial chirality and central chirality to achieve excellent diastereoselectivity and enantioselectivity; 2) finding suitable reaction conditions for diastereodivergent generation of two chiral elements.…”

“…Axially chiral indole-based scaffolds, a class of unique axially chiral skeletons, − are widely found in natural products, − pharmaceutically relevant molecules, − and chiral catalysts. − Therefore, catalytic asymmetric construction of axially chiral indole-based scaffolds has become an emerging field. , As shown in Scheme a, various elegant strategies have been developed for the enantioselective construction of axially chiral (hetero)­arylindoles, such as five-six-membered axially chiral arylindoles ,− and five-five-membered axially chiral (hetero)­arylindoles. ,,− However, in sharp contrast, axially chiral alkenylindoles, more challenging axially chiral...…”

Organocatalytic diastereo- and atropo-selective construction of eight-membered bridged (hetero)biaryls via asymmetric intramolecular [3 + 2] cycloaddition

“…As is known, significant challenges exist in the preparation of this kind of skeleton, such as the development of new strategies, the design of reasonable substrates and good enantio- and diastereocontrol of multiple chiral elements, which hindered the development of this topic. 11 …”