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

• , planar chirality, and “inherent chirality” are illustrated using the stereocontrol connectivity index produced following a unified 3-step process. Application of such stereochemical classification could facilitate the development of new synthetic methodologies and catalyst systems to construct diverse

• transformations that establish central chirality, axial chirality, planar chirality, and “inherent chirality”. The 3-step procedure for the designation of the stereocontrol connectivity index is derived from the chemical structures of the starting materials and the products, and it does not rely on knowledge in

• chirality derived from C=C bonds. Examples of reactions that establish planar chirality. Examples of reactions that establish “inherent” chirality. Parameterization of asymmetric reactions that establish axial chirality. Supporting Information Supporting Information File 24: The set of code (Python) and

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• ; inherent chirality; N-doped macrocycle; nonplanarity; regioselective cyclization; Introduction Chiral macrocycles have attracted significant research interest owing to their diverse applications in enantioselective recognition [1][2], catalysis [3][4], and circularly polarized luminescence [5][6

• ]. Generally, chirality in macrocycles arises from subunits featuring classical chiral elements [7], such as central, axis, planar and helical configurations. In contrast, inherent chirality represents a non-classical phenomenon where chirality emerges from the rigid and nonplanar architecture of macrocycles

• that inherently lacks symmetry [8][9]. One of the most typical representatives are calix[4]arenes (Figure 1a), first reported by Böhmer in 1994 [10], where asymmetric substitutions on the macrocyclic rim induce inherent chirality. Subsequent advancements have identified other inherent chiral systems

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

• with the more recently introduced inherent chirality. As one of the most prominent chiral organocatalysts, chiral phosphoric acid (CPA) catalysis has proven highly effective in synthesizing centrally and axially chiral molecules. However, its potential in the asymmetric construction of other types of

• within this domain. Keywords: asymmetric catalysis; chiral phosphoric acid; helical chirality; inherent chirality; planar chirality; Introduction Since the seminal works by Akiyama [1] and Terada [2] et al. in 2004 demonstrated the application of BINOL-derived chiral phosphoric acids (CPAs) in

• chirality originating from the rigid conformation of molecules lacking symmetry, which do not fit into the aforementioned four categories, are termed inherent chirality. Notable examples include inherently chiral calix[4]arenes and saddle-shaped medium-sized cyclic compounds. Catalytic asymmetric synthesis

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

• of structurally diverse scaffolds featuring axial, planar, helical, and inherent chirality. Herein, we summarize the exciting achievements in this rapidly evolving field. These elegant examples have been organized and presented based on the reaction type as well as the resulting chirality form

• . Additionally, we provide a perspective on the current limitations and future opportunities, aiming to inspire further advances in this area. Keywords: axial chirality; helical chirality; inherent chirality; isocyanide; planar chirality; Introduction Chirality represents a fundamental property of molecules

• 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

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• ; optoelectronic applications; Introduction Helicenes, a class of non-planar polycyclic aromatic hydrocarbons characterized by ortho-fused aromatic rings forming a helical framework, have attracted significant attention due to their inherent chirality, unique optoelectronic properties, and wide-ranging

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• steps. As before, (S)-malic acid (3) was chosen as the starting material because its inherent chirality reduced the complexity of the synthetic process. Given the fact that the target molecule has C2 symmetry, it was prudent that a synthetic route starting from a common C5 subunit be chosen, with

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• et al. [13], this field of research is continuously booming because of the developments of advanced synthetic organic tools [14][15][16]. Among the PAHs, the buckybowls are of significant importance not only because of the presence of unique inherent chirality (bowl-chirality) originating either from

Attempted synthesis of a meta-metalated calix[4]arene

• Christopher D. Jurisch and
• Gareth E. Arnott

Beilstein J. Org. Chem. 2019, 15, 1996–2002, doi:10.3762/bjoc.15.195

• yielding transformations to azide and 1,2,3-triazole derivatives which may have application in other areas of research. Keywords: calixarene; inherent chirality; mesoionic carbene; mononitration; ruthenacycle; Introduction Calix[4]arenes are a class of diverse macrocyclic compounds which have been the

• whose chiral nature is a result of selective substitution on the calix[4]arene by various functional groups [9]. In particular, we have focused on the less-studied meta-substituted derivatives [10] whose inherent chirality is more commonly introduced by a suitable directing group [11][12][13][14][15

• potential implications for asymmetric catalysis, due to the inherent chirality of the calix[4]arene, coupled with the point chirality from, for example, a tetrahedral ruthenium center. We therefore decided to apply the methods reported by Albrecht to a calix[4]arene system in order to prove this theory

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• ][14][15][16][17][18][19][20][21]. In general, chirality can be introduced into the calixarene platform either by incorporation of a chiral group or by asymmetric placement of achiral substituents, creating chirality associated with form. This is termed inherent chirality [22]. Although chiral

• selectivity was the chiral oxazoline unit and not the inherent chirality of calixarene skeleton. Asymmetric hydrogenation Starting with distally O-dialkylated calixarene precursors, a series of BINOL-derived calix[4]arene-diphosphite ligands 40a–g were synthesized by Liu and Sandoval through phosphorylation

• the inherent chirality of calix[4]arene for α-chloroacetophenone and ortho-chloroacetophenone. The results clearly showed the effect of both denticity of ketone reactant and cooperativity between normal and inherent chirality on the selectivity. More recently, Al(III)–calix[4]arene complexes 116a–c

Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial

• Tamara Šmidlehner,
• Ivo Piantanida and
• Gennaro Pescitelli

Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5

• (see chapter 2.3., characterization), the difference in the ECD spectrum caused by ligand binding is obtained by subtracting the intrinsic spectrum. However, it should be taken into account that the observed change in the ECD spectrum can have several origins: a) a change of the ligand’s inherent

• chirality due to the structural changes caused by binding; b) an induced (I)CD as a result of ligand insertion into chiral binding sites; c) exciton coupling between multiple aggregated ligand molecules. The appearance of one or more isodichroic points (the CD equivalent of isosbestic points) during ECD

Inclusion complexes of β-cyclodextrin with tricyclic drugs: an X-ray diffraction, NMR and molecular dynamics study

• Franca Castiglione,
• Fabio Ganazzoli,
• Luciana Malpezzi,
• Andrea Mele,
• Walter Panzeri and
• Giuseppina Raffaini

Beilstein J. Org. Chem. 2017, 13, 714–719, doi:10.3762/bjoc.13.70

• compound 1. Compounds 1 and 2 are not planar and the exocyclic double bond prevents the free rotation of the side chain with respect to the ring system. Consequently, 1 and 2 show inherent chirality [9] as lacking of symmetry elements. The main purpose of the work is the comparison of the structural

Inherently chiral calix[4]arenes via oxazoline directed ortholithiation: synthesis and probe of chiral space

• Simon A. Herbert,
• Laura J. van Laeren,
• Dominic C. Castell and
• Gareth E. Arnott

Beilstein J. Org. Chem. 2014, 10, 2751–2755, doi:10.3762/bjoc.10.291

• ) as our means of probing the inherent chirality of our ligands. For comparison we also synthesised planar ligands 10–12 using conventional methods (see Supporting Information File 1). The catalytic runs were conducted under the identical conditions reported by Dai (for comparison purposes) and are

• due to the point chirality of the oxazoline and not the inherent chirality of the calixarene. Since these results are entirely consistent with those of the planar chiral ferrocene system reported by Dai et al., we believe future ligand design may better exploit the inherently chiral calix[4]arene

• inherent chirality on the calix[4]arenes can be also be used to drive asymmetric transformations/reactions. Experimental See Supporting Information File 1. N,S Ligands. Synthesis of inherently chiral calix[4]arenes. Synthesis of tert-butyloxazoline calix[4]arenes. Tsuji–Trost reaction. Results of

Benzyne arylation of oxathiane glycosyl donors

• Martin A. Fascione and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2010, 6, No. 19, doi:10.3762/bjoc.6.19

• utilising the inherent chirality of the sugar to determine the stereochemistry of the key benzylic centre in the chiral auxiliary, and also facilitates regioselective attachment of the auxiliary group to O-2. The benzylated oxathiane ether 18 also afforded a glycosyl acetate 25 in 57% yield but on this

Novel banana-discotic hybrid architectures

• Hari Krishna Bisoyi,
• H. T. Srinivasa and
• Sandeep Kumar

Beilstein J. Org. Chem. 2009, 5, No. 52, doi:10.3762/bjoc.5.52

• properties such as ferroelectric or anti-ferroelectric switching [1][2][3][4][5][6][7]. The occurrence of superstructural chirality in the mesophase of bent-core compounds with no inherent chirality is not only of fundamental scientific interest but also of industrial application as this chirality can be