Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives

• Jan Bartáček,
• Karel Chlumský,
• Jan Mrkvička,
• Lucie Paloušová,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62

• Jan Bartacek Karel Chlumsky Jan Mrkvicka Lucie Palousova Milos Sedlak Pavel Drabina Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic 10.3762/bjoc.20.62 Abstract The new chiral ligands I–III

• also tested in asymmetric aldol reactions. Under the optimised reaction conditions, aldol products with enantioselectivities of up to 91% ee were obtained. Keywords: asymmetric aldol reaction; asymmetric Henry reaction; chiral ligands; enantioselective catalysis; imidazolidine derivatives

• itself constitutes a stereocentre [4]. The specific pairing of a chiral ligand and a metal ion is essential for the catalytic characteristics and its effectiveness of the complex in asymmetric syntheses [1][2][3]. In recent years, our research group has synthesised a series of chiral ligands based on 2

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• without sacrificing stability, while future design of chiral ligands may depend on a better understanding of the chiral space generated when gold is coordinated to carbonyl functionality, rather than the alkene. Key observations include the following: • Mixed solvent effects support the involvement of

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

• reactions include mild reaction conditions and the use of a sole catalyst without the need of other chiral ligands [4][5]. In these reactions, stereoinduction in the products is achieved by the chiral environment present in the catalyst itself. Depending upon the reactivities, organocatalysts can be

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• the catalytic antibody [24]. They are also potential chiral ligands in asymmetric catalysis [25] (Figure 1). Cyclizations and annulations are two major strategies for the synthesis of medium and large phostam, phostone, and phostine derivatives. The cyclizations have been applied in the construction

• because the P–O bond is more stable than the corresponding P–N bond. Much attention should be paid to the synthesis of different ring size phostams in the future. Biologically active agents and chiral ligands containing medium and large phostams, phostones, and phostines. Synthetic strategies for the

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

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• complexes derived from various chiral ligands. The oxidation potential can be determined from the voltammetry curve measured for the quantitatively deprotonated complex. The electrochemical deprotonation using an electro-generated base is the most convenient approach [37][44]. Comparison with the Eox values

• )L1 is given for comparison. Selected examples of the chiral ligands used for synthesis of the Ni(II)–Schiff base complexes. Synthesis of the chiral ligand L7 and its Ni(II) complexes with glycine, serine, dehydroalanine, and cysteine derivatives. The yields and the thermodynamically controlled

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• to be tackled. A highly enantioselective synthesis is still desirable, as the only synthesis offering >90% ee relies on the combination of chiral ligands and chiral auxiliary. Moreover, to date only 6 natural products from the grayanane family were synthesized, out of the more than 160 compounds

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• (BINAP)-assisted hydrogenation with H2 pressure up to 50 bar was also found to be ineffective. By changing the metal complex to Rh(COD)2BF4, we successfully realized the saturation of the double bond. Chiral ligands (R)-BINAP (L1) and (R,R)-phenyl-BPE (L4) gave unsatisfactory selectivity (Table 2

Electrochemical formal homocoupling of sec-alcohols

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masashi Shiota,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2022, 18, 1062–1069, doi:10.3762/bjoc.18.108

• ]. Such scaffolds are widely utilized as versatile building blocks in the synthesis of biologically active compounds [3][4][5][6][7], chiral auxiliaries [8][9], and chiral ligands [10][11][12][13]. Traditional pinacol coupling reactions are performed with a stoichiometric or even excess amount of low

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

• series of 11 efficient enantioselective catalysts was tested to obtain the corresponding nitroaldol 21 in an enantiomeric excess as high as possible. Four of them based on the chiral ligands Ia, IIa, IIIa, and IV were identified as the most effective catalysts. They exhibited mutually comparable

• (1) and rivaroxaban (2). Overview of the chiral ligands that were used for the study of the asymmetric Henry reaction. Syntheses of aldehydes 15–20. Synthesis of linezolid (1) and rivaroxaban (2) from nitroaldols 24 or 26. Asymmetric Henry reactions of aldehyde 15 with nitromethane under various

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• undoubtedly the most efficient way to prepare chiral compounds that our society requires as medicines, materials, or crop protecting agents. Traditionally, enzymes and metal complexes with chiral ligands served as the main type of enantioselective catalysts. Even though small chiral organic compounds have

Efficient synthesis of ethyl 2-(oxazolin-2-yl)alkanoates via ethoxycarbonylketene-induced electrophilic ring expansion of aziridines

• Yelong Lei and
• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 70–76, doi:10.3762/bjoc.18.6

• groups in symmetric and asymmetric ligands widely applied in various organic transformations [7]. Especially, bisoxazolines are a kind of widely applied chiral ligands in diverse transition metal-participating asymmetric catalysis [8][9][10]. Several methods have been developed for the efficient

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

Me₃Al-mediated domino nucleophilic addition/intramolecular cyclisation of 2-(2-oxo-2-phenylethyl)benzonitriles with amines; a convenient approach for the synthesis of substituted 1-aminoisoquinolines

• Krishna M. S. Adusumalli,
• Lakshmi N. S. Konidena,
• Hima B. Gandham,
• Krishnaiah Kumari,
• Krishna R. Valluru,
• Satya K. R. Nidasanametla,
• Venkateswara R. Battula and
• Hari K. Namballa

Beilstein J. Org. Chem. 2021, 17, 2765–2772, doi:10.3762/bjoc.17.186

• ] receptors. They are useful in the synthesis of phosphorescent materials [22][23][24], fluorosensors [25]. and also found as chiral ligands in a variety of transition metal catalysts [26][27][28][29][30]. Given the pharmacological promiscuity of this scaffold, extensive efforts from different groups led to

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

• active compounds in medicinal chemistry and as chiral ligands in asymmetric catalysis. Chiral phosphoric acids are recognized as efficient organocatalysts for a variety of enantioselective transformations. In this review, we summarize the recent development of chiral phosphoric acid-catalyzed synthesis

• construction of axial chirality [7][8][9][10][11][12][13][14]. Axially chiral biaryl and heterobiaryl units are widely used as basic building blocks for chiral ligands [14], chiral catalysts [14][15][16][17] (Figure 1), various natural products, drugs and bioactive molecules [18][19], pharmaceutical agents [20

• obtained in moderate to good yields (58–95%) with excellent enantioselectivity (90–95% ee, Scheme 8b) [53]. The synthesized axially chiral phenylindoles have the potential to be used as chiral ligands in asymmetric catalysis [54] and are ubiquitous in natural products with considerable bioactivity [55][56

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• between N-heteroarenes 69 and redox-active esters 68. In 2018, Gong and co-workers [43] used benzyltrifluoroborates 71 as a benzylic radical source for the visible-light-induced alkylation of imines 70. In the catalytic system, chiral ligands initiated benzylic radical formation and governed the

• with diverse chiral ligands to provide a chiral environment for asymmetric control. Despite the remarkable achievements in this field, copper-based catalytic asymmetric reactions still remain a challenging task because of the difficulty of stereocontrol of the highly reactive radical intermediates

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• vinylindoline derivatives 125 was achieved by utilizing chiral ligands like chiral binaphane (Scheme 37) [91]. They had observed that the formation of six- and seven-membered rings required elevated temperatures. Subsequently, the same group studied the cyclization of arylene 126 to furnish naphthalene

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• compounds to produce the corresponding biaryl products with high enantiopurity using vanadium chelated with chiral ligands, such as tridentate asymmetric imine ligands, have been reported. For instance, (S)-binol derivatives could be successfully prepared from 2-naphthols using a dimeric vanadium complex

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

Metal-free synthesis of biarenes via photoextrusion in di(tri)aryl phosphates

• Hisham Qrareya,
• Lorenzo Meazza,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 3008–3014, doi:10.3762/bjoc.16.250

• active compound is a common practice in medicinal chemistry [1][2][3]. In particular, the biaryl moiety is a privileged scaffold largely present in the skeleton of natural substances [4][5][6][7] and in useful chiral ligands [8][9][10]. The synthesis of biaryl derivatives remains, however, a considerable

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• likely operates via a radical chain mechanism. Initiation begins with the reductive quenching of the photocatalyst using iPr2NEt as a sacrificial reductant to give [Ru]•−, which then reduces the Lewis acid-coordinated enone 271 to give alkyl radical 271•. In the presence of a second enone 270 and chiral

• ligands L1, an initial RCA occurs to generate α-carbonyl radical 272•, followed by cyclisation with the enolate to give ketyl radical 273•. Radical 273• can then reduce another molecule of 271 to propagate the chain reaction and generate the desired formal photocycloaddition products 274 in good yields

Hierarchically assembled helicates as reaction platform – from stoichiometric Diels–Alder reactions to enamine catalysis

• David Van Craen,
• Jenny Begall,
• Johannes Großkurth,
• Leonard Himmel,
• Oliver Linnenberg,
• Elisabeth Isaak and
• Markus Albrecht

Beilstein J. Org. Chem. 2020, 16, 2338–2345, doi:10.3762/bjoc.16.195

• periphery of hierarchically assembled titanium(IV) helicates formed from mixtures of achiral, reactive and chiral, unreactive ligands was investigated in detail. Following the pathway of the chiral induction, the chiral ligands, solvents as well as substituents at the dienophile were carefully varied. Based

• or rigid chiral ligands. In addition, a solvent screening was performed in which solvents were used which favor the dimer. This is imminent for good enantioselectivities because the presence of a high amount of stereolabile monomer switches off the selectivity [13]. Solvent dependence Initially the

• lithium cations. Chloroform showed the best induction with 32% ee followed by dichloromethane with 25% ee, both with 50% yield (Table 1). Ligand screening In a second optimization step, the chiral ligands have been varied. An increase of stereoselectivity was achieved by using the helicates with a

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

• ][22][23]. On the other hands, further extension of these molecules leads to homochiral carbon nanotubes which can produce innovative perception in chiral sensing, chiral catalysis, separation techniques and chiral ligands for organocatalysis [24]. Additionally, control on the bowl-to-bowl inversion

Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination

• Yuqing Wang,
• Gaigai Wang,
• Anatoly A. Peshkov,
• Ruwei Yao,
• Muhammad Hasan,
• Manzoor Zaman,
• Chao Liu,
• Stepan Kashtanov,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163

• stereocontrol was achieved with the aid of different Lewis acid promoters bearing chiral ligands, while the most recent and at the same time the most general procedure developed by Liu, Tan and co-workers relied on the stereoinduction by a chiral phosphoric acid (Table 1) [40]. In the standard Ugi four

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• variety of methods employing the chiral ligands L9–L13 that, in combination with copper, efficiently catalysed the ACA of diethylzinc to 5,6-dihydro-2-pyranone (Scheme 8), providing access to chiral β-substituted lactones with high enantioselectivity and conversion [33][34][35][36][37]. Although the

• copper catalysts to activate both the organometallics and heterocyclic acceptors for the reaction. The development of a wide variety of chiral ligands allowed an impressive scope of heterocycles to undergo reactions with organometallics. However, the current state of the field is certainly incomplete