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

Pd-catalyzed asymmetric Suzuki–Miyaura coupling reactions for the synthesis of chiral biaryl compounds with a large steric substituent at the 2-position

• Yongsu Li,
• Bendu Pan,
• Xuefeng He,
• Wang Xia,
• Yaqi Zhang,
• Hao Liang,
• Chitreddy V. Subba Reddy,
• Rihui Cao and
• Liqin Qiu

Beilstein J. Org. Chem. 2020, 16, 966–973, doi:10.3762/bjoc.16.85

• from chemists because of their widespread appearance in biologically active compounds [1][2][3][4] such as vancomycin [5] and korupensamine A [6] and as useful chiral ligands in asymmetric catalysis. Different strategies with various metals and phosphine ligands had been successfully employed for the

Copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters with chiral phenol–carbene ligands

• Shohei Mimura,
• Sho Mizushima,
• Yohei Shimizu and
• Masaya Sawamura

Beilstein J. Org. Chem. 2020, 16, 537–543, doi:10.3762/bjoc.16.50

• chiral p-tol-BINAP/copper catalyst established the excellent utility of chiral bisphosphine ligands for this type of reaction [4]. Surprisingly, however, chiral ligands based on N-heterocyclic carbenes (NHCs) [12] have not been applied to the conjugate reduction of α,β-unsaturated carbonyl compounds

• product 2i with comparable results (Table 2, entry 10, 81% yield, 79% ee). Proposed catalytic cycle Based on the experimental observations and previous knowledge of the catalysis of phenol–NHC chiral ligands [14][15][16][17][18], we propose a catalytic cycle as shown in Scheme 1. LiOt-Bu abstracts the two

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• family of privileged chiral ligands in asymmetric catalysis [12]. In these compounds, the C2 axis of symmetry helps in increasing the selectivity of the formation of certain enantiomers by inhibiting other possible reaction pathways [93]. In particular, biarylphosphines and bidentate 2,2'-bis

• coordination making it ideal for syntheses of chiral ligands [118]. In the recent decades, Ugi’s amine has been one of the major interesting chiral ferrocenyl derivatives because the configuration at the α-ferrocenylmethyl position can be retained after nucleophilic substitution [115]. Drahonovsky et al. [120

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• listed above can be converted into various other synthetically useful groups, such as ketones, esters, carboxylic acids, and (Weinreb) amide groups. More recently, some works were reported, which showed that through a judicious selection of chiral ligands and a fine-tuning of the reactivities of both

• , and thus opening a new field for the total synthesis of natural products. We hope that the results collected in this review will encourage chemists on one hand to continue the search for improved procedures combining simple, easily accessible chiral ligands, lower catalytic loadings, high ee values

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• corresponding bromo-cyclopropane 17 [24]. According to the authors, the passage of larger amounts of charge to facilitate product isolation might be responsible for the observed lower asymmetric yields. In 1998, Moutet’s group reported for the first time that transition metal complexes with chiral ligands can

Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene

• Anna Kmieciak and
• Marek P. Krzemiński

Beilstein J. Org. Chem. 2019, 15, 2493–2499, doi:10.3762/bjoc.15.242

• research groups [1]. Compounds with a phosphorus atom attached to a stereogenic carbon center in acyclic and cyclic structures play an important role as chiral ligands in transition metal complexes [2]. They were applied to various catalytic asymmetric reactions [3][4], such as hydrogenations [3][4][5][6

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• -diamine complexes are air and moisture-stable (Scheme 49). In 2011, two nickel-catalyzed protocols for the enantioselective α-fluorination of β-ketoesters were reported separately. In van Leeuwen’s reaction, SPANamine derivatives were synthesized and applied as chiral ligands in the asymmetric α

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• chiral compounds were converted into the corresponding pyridin-4-ol derivatives and tested as chiral ligands in asymmetric catalysis [37]. Using the N-trityl-substituted proline as carboxylic acid provided the expected β-ketoenamide KE42 in low yield and as major product we isolated compound 7 in 49

Synthesis of C₃-symmetric star-shaped molecules containing α-amino acids and dipeptides via Negishi coupling as a key step

• Sambasivarao Kotha and
• Saidulu Todeti

Beilstein J. Org. Chem. 2019, 15, 371–377, doi:10.3762/bjoc.15.33

• peptide dendrimers. Keywords: amino acids; cyclotrimerization; Negishi coupling; peptide; Introduction Optically active C3-symmetric molecules are valuable synthons to design dendrimers, chiral ligands, polymers, and supramolecules [1][2][3][4]. In this regard, 1,3,5-triarylbenzene derivatives are

Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine

• Piotr Pomarański,
• Piotr Roszkowski,
• Jan K. Maurin,
• Armand Budzianowski and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2018, 14, 2384–2393, doi:10.3762/bjoc.14.214

• essential stereochemical element of many popular, commercially available chiral catalysts [3]. Several ortho-substituted arylpyridine derivatives belong to a very important class of axially chiral compounds which have gained interest due to their role as chiral ligands in cross-coupling reactions, or being

Chiral bisoxazoline ligands designed to stabilize bimetallic complexes

• Deepankar Das,
• Rudrajit Mal,
• Nisha Mittal,
• Zhengbo Zhu,
• Thomas J. Emge and
• Daniel Seidel

Beilstein J. Org. Chem. 2018, 14, 2002–2011, doi:10.3762/bjoc.14.175

• pyridazine-bridged, and bis-nickel as well as bis-palladium pyrazole-bridged complexes were obtained. Keywords: bimetallic complexes; bisoxazolines; chiral ligands; heterocycles; Introduction Metal-centered asymmetric catalysis most commonly relies on monometallic complexes of various chiral ligands, among

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

•  20. In 2016, Zhang and Yang reported an asymmetric palladium-catalyzed addition of arylboronic acids 60 to sterically hindered N-tert-butylsulfonylisatin imines 61 [80]. Among a variety of chiral ligands investigated, including different pyridine-oxazolines, oxazolines and (R)-BINAP, the chiral

Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines

• Felix Scheidt,
• Christian Thiehoff,
• Gülay Yilmaz,
• Stephanie Meyer,
• Constantin G. Daniliuc,
• Gerald Kehr and
• Ryan Gilmour

Beilstein J. Org. Chem. 2018, 14, 1021–1027, doi:10.3762/bjoc.14.88

• ranging from drug delivery through to tissue engineering [3][4]. Collectively, the importance of the 2-oxazoline scaffold for translational research, together with its strategic value in the design of chiral ligands and auxiliaries [5][6][7], has culminated in a rich and innovative arsenal of synthetic