Recent advances in the stereoselective synthesis of distal biaxially chiral molecules

• Fanxing Zhou,
• Chen Zhang,
• Lingyu Sun,
• Yiyun Fang,
• Siming Zheng,
• Lina Hu,
• Mengyang Shen,
• Zhen Zhao,
• Wei Xu,
• Yunqiang Sun and
• Zi-Qiang Rong

Beilstein J. Org. Chem. 2026, 22, 461–479, doi:10.3762/bjoc.22.34

• one chiral axis followed by the second, and transformation from central chirality to axial chirality. We anticipate that this review will facilitate the development of novel synthetic strategies for remote biaxial chiral molecules, improve asymmetric synthesis efficiency, and expand their applications

• to axial chirality for constructing distal biaxial systems Building on the advances in the direct one-step construction of distal biaxial chiral molecules and sequential formation of each chiral axis, another powerful strategy emerged that exploits central chirality as a stereochemical template to

• aromatics 96 and chloronitroalkenes 97 as starting materials, they synthesized the key enantioenriched central chiral dihydrobenzofuran precursor through an organocatalyzed domino reaction. This unique bidirectional catalyst-controlled strategy successfully achieved the transformation from central chirality

Synthesis and stereochemical analysis of dynamic planar chiral oxa[7]orthocyclophene

• Yukiho Hashimoto,
• Yuuya Kawasaki,
• Kazunobu Igawa and
• Katsuhiko Tomooka

Beilstein J. Org. Chem. 2026, 22, 436–442, doi:10.3762/bjoc.22.30

• successfully transformed into central chirality by epoxidation without loss of enantiomeric purity. Keywords: dynamic chirality; medium-sized heterocycle; orthocyclophene; planar chirality; stereochemical analysis; Introduction In the course of our study on planar chiral medium-sized cyclic molecules [1][2

• shape for the CD spectra of the first eluates, thus we determined that the absolute stereochemistry of the first and second eluates corresponds to the (R)- and (S)-isomers, respectively. Transformation of planar chirality of 1ab to central chirality The planar chirality of the methyl-substituted

• oxacyclophene can be transformed into central chirality without loss of enantiomeric purity. For example, (S)-1ab obtained by chiral HPLC separation using an OJ-H column was treated with m-CPBA, in which (S)-1ab was smoothly consumed at 0 °C within 30 minutus to afford epoxide 8 in 61% yield (Scheme 4). HPLC

Non-central chirality in organic chemistry

• Ken Tanaka and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2026, 22, 370–371, doi:10.3762/bjoc.22.24

• , planes, helices, and more global structural features can equally serve as stereogenic elements, giving rise to what is broadly termed non-central chirality. Rather than constituting a single structural motif, non-central chirality encompasses a diverse family of stereogenic architectures whose

• commonality lies in how chirality emerges from extended molecular frameworks, dynamic conformational landscapes, or topological constraints. As such, non-central chirality challenges both our synthetic capabilities and our conceptual understanding of stereochemical control. Numerous reviews have addressed

• axial, planar, or helical chirality individually, often organized along specific molecular classes or application-driven themes such as asymmetric catalysis or chiral materials. In contrast, this Thematic Issue deliberately brings together diverse manifestations of non-central chirality under a single

Measuring the stereogenic remoteness in non-central chirality: a stereocontrol connectivity index for asymmetric reactions

• Ivan Keng Wee On,
• Yu Kun Choo,
• Sambhav Baid and
• Ye Zhu

Beilstein J. Org. Chem. 2025, 21, 1995–2006, doi:10.3762/bjoc.21.155

• remained an intuitive and empirical practice, particularly for reactions that create non-central chirality. We put forward a stereocontrol connectivity index to parameterize asymmetric reactions according to the bond connectivity relationships between the prochiral stereogenic elements, the reactive sites

• molecule is characterized by the absence of mirror planes and centers of inversion. Central chirality arises when four distinct substituents (a, b, c, and d) are arranged tetrahedrally around a central atom (Scheme 1A). Non-central chirality – such as axial and planar chirality – are becoming increasingly

• important in pharmaceuticals, catalysts, and advanced materials due to their unique stereogenic scaffolds and associated properties. Consequently, synthetic chemists have been pursuing molecules featuring these forms of non-central chirality, where the stereogenic elements are not localized on a single

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• .21.145 Abstract Chiral molecules, distinguished by nonsuperimposability with their mirror image, play crucial roles across diverse research fields. Molecular chirality is conventionally categorized into the following types: central chirality, axial chirality, planar chirality and helical chirality, along

• catalytic kinetic resolution of racemic helical polycyclic phenols through an organocatalyzed enantioselective dearomative amination reaction [30]. The racemic polycyclic phenol derivatives 25, which exist as single diastereomers featuring both central chirality and helical chirality, were readily prepared

• with allylboronic acid pinacol ester (41) led to efficient kinetic resolution, yielding the recovery of (Sp)-40 with high enantiopurity (Scheme 12). Notably, the allylation products 42, possessing both planar chirality and central chirality, were produced with high enantioselectivity and

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• and manifests in diverse forms (Figure 1a). While central chirality based on stereogenic centers (e.g., C, P, S, etc.) is the most conventional type, non-central chirality, such as axial [1][2][3][4], planar [5][6][7], helical [8][9][10], and inherent chirality [11][12], has gained increasing

• could be applied to synthesize more complex structures. As shown in Scheme 1b, when N-(2-iodophenyl)methacrylamide 3 and 1a were employed as starting materials, compound 4 bearing nonadjacent planar and central chirality was obtained in good yield and enantioselectivity (4a, 54%, 90% ee; 4b, 32%, 97% ee

• with both axial and central chirality, followed by 2) ring-strain and aromatization-driven elimination, which elucidating the observed unusual torsional strain-independent reactivity. In addition, products bearing a tert-butyl ester group were smoothly converted into structurally novel axially chiral

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• transformation is an asymmetric conjugate addition leading to a central chiral intermediate that tautomerizes to the axially chiral product. Chiral phosphoric acid C33 was utilized in the construction of products 136 bearing both axial and central chirality (Scheme 40) [68] through the reaction of bisindoles 134

• , bearing both axial and central chirality, were prepared by organocatalytic asymmetric addition of bisindoles 145 and isatin-derived imines 146 catalyzed by CPA C26 (Scheme 43) [71]. The scope of the reaction showed efficient stereocontrol by consistently high diastereo- and enantioselectivity with

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• stereoselective aromatization serves as a pivotal step in the transfer of central chirality to axial chirality (Scheme 52). To harness the full potential of CO2 as a renewable and abundant carbon source, He et al. [82] proposed an innovative strategy that married asymmetric yne-allylic substitution with CO2

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• generating a complex molecular topology of 2,3-disubstituted indoles bearing both axial and central chirality. The aza-Friedel–Crafts reaction would allow the nucleophile to selectively attack the C=N plane of the electrophile as directed by a triple hydrogen-bonded complex between the catalyst and the

• electrophilic substitution also gave a quaternary aza-stereocenter in the pyrazolone moiety. Axial chirality associated with central chirality in the product structures was influenced by chiral phosphoric acid catalyst P23. To freeze the C–C bond rotation, the pyrazole moiety in 99 required sterically demanding

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• central chirality information to the axial chirality to give the chiral biaryldiols (Scheme 3) [14]. In 2013, Akiyama and co-workers described the enantioselective preparation of multisubstituted biaryls by the desymmetrization strategy, which was further enhanced by the subsequent asymmetric reaction

• enantioselectivity (91:9 to 98:2 er, Scheme 15) [65]. In addition, the authors also succeeded in preparing naphthylindoles 46, which exhibit both axial and central chirality, through the addition reaction of racemic naphthylindoles 42 and o-hydroxybenzyl alcohols 45 using chiral phosphoric acid CPA 13. This reaction

• also achieved the first catalytic asymmetric construction of axially chiral 3,3’-bisindole scaffolds 49 bearing both axial and central chirality by employing the CPA-14-catalyzed asymmetric addition reaction of 2-substituted 3,3’-bisindoles 47 to isatin-derived 3-indolylmethanols 48. The isatin-derived

Design and synthesis of quasi-diastereomeric molecules with unchanging central, regenerating axial and switchable helical chirality via cleavage and formation of Ni(II)–O and Ni(II)–N coordination bonds

• Vadim A. Soloshonok,
• José Luis Aceña,
• Hisanori Ueki and
• Jianlin Han

Beilstein J. Org. Chem. 2012, 8, 1920–1928, doi:10.3762/bjoc.8.223

• *) and (Ra*,Ph*,Rc*) occurs by intramolecular trans-coordination of Ni–NH and Ni–O bonds providing a basis for a chiral switch model. Keywords: axial chirality; central chirality; chiral switches; coordination bonds; functional materials; helical chirality; modular structural design; molecular devices

• expect, these desired structural and stereochemical considerations can be seriously compromised by the presence of central chirality in the starting ligand 4. For instance, application of racemic ligands 4 will give rise to at least four diastereomeric products rendering the designed diastereomeric

• instance, the torsion angle C(19)–N(3)–C(20)–C(21) of 32.0(3)° sets the element of helical chirality, while the axial chirality is located through the N(1)–C(8) bond with the torsion angle C(9)–N(1)–C(8)–C(7) of −139.5(2)°. The central chirality is located on N(2) as, coordinated to Ni(II), nitrogen is