The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• cyclic prochiral dicarbonyl substrates. In addition, various approaches could be used for the desymmetrization reactions such as enzyme catalytic-, organocatalyst-, and transition-metal-catalyzed reductions [5][6][7]. Advance about the synthesis of several terpenoid and alkaloid natural products (1–5

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

• substituents. Intuitively, the intrinsic spatial separation among prochiral stereogenic elements, the reactive sites, and the stereochemical-defining substituents makes stereoinduction for non-central chirality using a chiral catalyst or reagent particularly challenging. However, a quantitative

• parameterizing the relay of stereochemical information from the chiral catalysts to the prochiral substrates. In this study, we propose a stereocontrol connectivity index that quantitatively characterizes asymmetric reactions. The index could serve as a basis for classifying asymmetric reactions according to the

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• Technology, Guangzhou 510006, P. R. China 10.3762/bjoc.21.151 Abstract Enantioselective desymmetrization is employed as a powerful tool for the creation of chiral centers. Within this scope, the enantioselective desymmetrization of prochiral 1,3-diols, which generates chiral centers by enantioselective

• functionalization of one hydroxy group, offers beneficial procedures for accessing diverse structural motifs. In this review, we highlight a curated compilation of publications, focusing on the applications of enantioselective desymmetrization of prochiral 1,3-diols in the synthesis of natural products and

• been developed, employing enzymes, metal complexes, or organocatalysts to convert prochiral or meso precursors into chiral motifs. Different from other strategies constructing chiral centers by formation of a new chemical bond at the central carbon, enantioselective desymmetrization is achieved through

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

• enamide 6a and various aldehydes 7 to break the symmetry of substrates 52, which was followed by a one-pot oxidative aromatization mediated by DDQ to yield the quinoline-containing inherently chiral calix[4]arenes 53 (Scheme 15). Notably, the prochiral calix[4]arenes bearing a disubstitution pattern on

• enantioselective desymmetrization strategy [52]. Commencing with phenol-containing prochiral calix[4]arenes 55, the CPA 3-catalyzed asymmetric ortho-C–H amination with electrophilic azo reagents 56 effectively broke the symmetry of the substrate, leading to the formation of inherently chiral calix[4]arenes 57 with

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 novel atropisomeric N-arylindoles 56 bearing an eight-membered lactam in 51–85% yield with 54–92% ee. Of note, these scaffolds exhibited remarkably large Stokes shifts, showing great potential in the development of fluorescent dyes. Desymmetrization of prochiral compounds Beyond DKR

• of bridged biaryls, our group has successfully applied α-acidic isocyanides in the catalytic asymmetric desymmetrization of substrates featuring a prochiral axis, realizing the preparation of structurally complex scaffolds possessing both axial and central chirality. Notably, in these cases, both

• issues of diastereo- and enantioselectivity are required to be addressed appropriately to prevent forming a complex mixture of stereoisomers. In 2022, our group developed a silver-catalyzed desymmetric [3 + 2] cycloaddition between prochiral N-aryl maleimides 57 and α-substituted α-acidic isocyanides

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• reactivity of cyclic diazo imides and mechanism [40]. Palladium-catalyzed annulation of prochiral N-arylphosphonamides with aromatic iodides [41]. Time-dependent enantiodivergent synthesis [42]. Time-controlled palladium-catalyzed divergent synthesis of silacycles via C–H activation [43]. Proposed mechanism

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• into a powerful and versatile tool in asymmetric synthesis, capable of employing a wide array of organometallic reagents that furnish the desired compounds with high efficiency and selectivity. The regioselective asymmetric construction of stereogenic carbon centers from prochiral allylic substrates

• 48 that contain a boron-substituted stereogenic center derived from the prochiral 1,1-diborylalkanes 47 in good yields with high stereoselectivity. DFT calculations of the enantiotopic-group-selective transmetalation between 1,1-diborylalkanes and chiral copper species revealed two possible

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

• prochiral 2-aryloxyisophthalaldehydes 57a,b with a range of aliphatic and aromatic alcohols 58a–g, as well as heteroaromatic amines 60 (Scheme 19). Chiral diaryl ethers of this type received increased attention lately. Biju, Gao, Zhang, and Zeng groups all reported high degrees of yields and

Towards an asymmetric β-selective addition of azlactones to allenoates

• Behzad Nasiri,
• Ghaffar Pasdar,
• Paul Zebrowski,
• Katharina Röser,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1504–1509, doi:10.3762/bjoc.20.134

• synthesis approaches. Our group has a longstanding focus on the development of asymmetric organocatalytic methods to access non-natural chiral α- and β-AA [14][15][16][17][18][19]. Hereby we are especially interested in utilizing simple (prochiral) starting materials and carry out stereoselective α

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• yield (92%) and formed the diol 77, after the removal of the Boc-protecting group, where the prochiral hydroxymethyl groups ultimately paved the way towards the natural products (Scheme 22). Bernhardson and coworkers developed a simple scalable route towards ertugliflozin (80), a C-glycoside containing

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• preclude chirality as in the transformation of a prochiral molecular entity into a chiral one [1]. It is a powerful and elegant strategy in asymmetric synthesis [2], which combined with the use of chiral ligands and transition-metal catalysts enabled many valuable transformations to increase molecular

Spatial arrangements of cyclodextrin host–guest complexes in solution studied by ¹³C NMR and molecular modelling

• Konstantin Lebedinskiy,
• Ivan Barvík,
• Zdeněk Tošner,
• Ivana Císařová,
• Jindřich Jindřich and
• Radim Hrdina

Beilstein J. Org. Chem. 2024, 20, 331–335, doi:10.3762/bjoc.20.33

• modelling and solid-state X-ray analysis, provides a detailed description of the spatial arrangement of cyclodextrin host–guest complexes in solution. The chiral cavity of the cyclodextrin molecule creates an anisotropic environment for the guest molecule resulting in a splitting of its prochiral carbon

• signals in 13C NMR spectra. This signal split can be correlated to the distance of the guest atoms from the wall of the host cavity and to the spatial separation of binding sites preferred by pairs of prochiral carbon atoms. These measurements complement traditional solid-state analyses, which rely on the

• anisotropy of the chiral cavity is expressed by differences in the magnetic shielding of prochiral atoms, resulting in signal splitting of the prochiral carbons of the guest molecule in 13C NMR spectra. Adamantan-2-amine hydrochloride was used as a model guest molecule containing three sets of prochiral

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• compounds, including diaryl- and dialkyl ketones and prochiral ketones, respectively (Scheme 36) [50]. Riant, Leyssens and co-workers investigated the mechanism of the hydrosilylation reaction of ketones using DFT, in situ FTIR, NMR, and kinetic methods [51][52]. The catalytic characteristics of sterically

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• desymmetrization step during which the chiral enolate attacks (Si-face) the prochiral cyclohexadienone ring via a chair-like transition state. The reaction requires an excess amount of base, resulting in the formation of a more favorable lithium enolate. Subsequent oxidation of the boronates gave the corresponding

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• yield was actually noted with (PhSe)2 as electrophile, 5 being obtained in 62% yield, enabling thus an evaluation of the next desymmetrization step. An overview of the scientific literature revealed that, while the asymmetric desymmetrization of prochiral 2,5-cyclohexadienones is a rich topic of

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• prochiral cyclopropene 2j from the less sterically hindered side. This is consistent with previous experiments in which 3-substituted-1,2-diphenylcyclopropenes were utilized as dipolarophiles. Regretfully, neither methyl 1-methylcycloprop-2-enecarboxylate (2k) [37] nor 3-methyl-1,2,3-triphenylcycloprop-1

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban

• Martin Vrbický,
• Karel Macek,
• Jaroslav Pochobradský,
• Jan Svoboda,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46

• highly efficient catalysts based on copper complexes of different types of chiral ligands, 2-(pyridin-2-yl)imidazolidine-4-ones (I–III), bis-oxazolines (IV–VII), or diamine (VIII) were chosen for the study (Figure 2). Furthermore, the modification of the structure of the prochiral aldehyde intermediates

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

• bulky group into the ortho-position of prochiral 3,3’-bisindoles allowed the synthesis of new members of axially chiral biaryls (3,3’-bisindole derivatives) bearing both axial and central chirality in high yields and excellent stereoselectivities. Moreover, this methodology represents a new strategy for

• the catalytic enantioselective synthesis of axially chiral 3,3’-bisindole backbones from prochiral substrates [66]. The atroposelective synthesis of a new class of 3,3'-bisindoles 51 with axial and central chirality by dynamic kinetic resolution of 2-substituted 3,3'-bisindoles via asymmetric

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• catalyst in the presence of a substrate possessing a prochiral migrating group or (2) stereospecifically by means of a chiral α-ketol. As an example of an enantioselective rearrangement, complexes of nickel(II) with a series of chiral 1,2-diaminopropane or pyridineoxazoline ligands were evaluated for their

Kinetics of enzyme-catalysed desymmetrisation of prochiral substrates: product enantiomeric excess is not always constant

• Peter J. Halling

Beilstein J. Org. Chem. 2021, 17, 873–884, doi:10.3762/bjoc.17.73

• Peter J. Halling WestCHEM, Dept Pure & Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, Scotland, UK 10.3762/bjoc.17.73 Abstract The kinetics of enzymatic desymmetrisation were analysed for the most common kinetic mechanisms: ternary complex ordered (prochiral ketone reduction); ping

• -pong second (ketone amination, diol esterification, desymmetrisation in the second half reaction); ping-pong first (diol ester hydrolysis) and ping-pong both (prochiral diacids). For plausible values of enzyme kinetic parameters, the product enantiomeric excess (ee) can decline substantially as the

• study if and how the product ee declines at high conversion. Keywords: enantiomeric excess; enzyme; kinetic mechanisms; kinetic parameters; prochiral; Introduction There is great interest in using enzymatic catalysis in the synthesis of homochiral molecules. An early approach was to use

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• cyclized diastereomeric radicals trans-22m,n and two radicals cis-22m,n result, which differ in their orientation with respect to the racemic silyloxy group (cf. Scheme 9). The situation in the azaspiro[4,4] and azaspiro[4][5] radicals 22m,n is, however, more complex since they are prochiral, and thus

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• enantioselective functional group interconversions on prochiral or racemic difluorocyclopropane and difluorocyclopropene derivatives have provided important ways of obtaining enantiomerically pure cyclopropanes. The key reactions in this context are the enzyme-catalyzed formation and hydrolysis of esters and the

• hydrogenation of difluorocyclopropenes [73][79]. Enzymatic hydrolysis or esterification: The first example of the enzymatic resolution of gem-difluorocyclopropanes was reported by Itoh et al. [80]. The prochiral diacetate of cis-1,2-bis-(hydroxymethyl)-3,3-difluorocyclopropane was converted into the

• [81]. The authors obtained the chiral monoacetate intermediates (R)-78 and (S)-80 by lipase-catalyzed methods. The lipase-catalyzed asymmetric transesterification of prochiral diol 77 and the deacetylation of the prochiral diacetate 79 resulted in the formation of the (R)-monoacetate (R)-78 and (S

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• photochemical reactions, including photoisomerization, photocyclodimerization, and H2 evolution [7][23]. Chirality induction in a prochiral guest via photochemical reactions is a delightful approach. This can not only transfer the chirality of the host cavity to the molecular photoproduct via excited-state

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• ., Flemingovo nám. 2, 166 10 Prague 6, Czech Republic 10.3762/bjoc.16.226 Abstract The prochiral 4-(allyloxy)hepta-1,6-diynes, optionally modified in the positions 1 and 7 with an alkyl or ester group, undergo a chemoselective ring-closing enyne metathesis yielding racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H

• for other catalytic reactions, e.g., for the Pauson–Khand reaction [14]. In the enantioselective RCM, prochiral trienes have been most often employed, leading to chiral cycloalkenes. The Schrock molybdenum precatalysts [15][16][17] proved to be more effective than the Grubbs or Collins ruthenium

• significantly more demanding strategy uses prochiral substrates and chiral metathesis precatalysts. Despite many examples of enantioselective RCM, only two examples of an enantioselective RCEYM have been reported (both featuring a dienyne substrate and a Schrock complex) [21][30], no enantioselective enediyne

Water-soluble host–guest complexes between fullerenes and a sugar-functionalized tribenzotriquinacene assembling to microspheres

• Si-Yuan Liu,
• Xin-Rui Wang,
• Man-Ping Li,
• Wen-Rong Xu and
• Dietmar Kuck

Beilstein J. Org. Chem. 2020, 16, 2551–2561, doi:10.3762/bjoc.16.207

• is clearly a consequence of the prochiral nature of the TBTQ core. We also note that such splitting phenomenon was reported for neither six-fold sugar-functionalized cyclotriveratrylenes [41], which are directly comparable to TBTQ-(OAcG)6, nor for six-fold sugar-functionalized triptycene [42], and

• of three magnetically equivalent tentacles at the rigid, prochiral TBTQ skeleton. The mass spectrometric characterization of TBTQ-(OAcG)6 turned out to be quite difficult. The MALDI-(+) mass spectrum (see Figure S10 and Table S1 in Supporting Information File 1), recorded with α-cyano-4