Chiral bifunctional sulfide-catalyzed enantioselective bromolactonizations of α- and β-substituted 5-hexenoic acids

• Sao Sumida,
• Ken Okuno,
• Taiki Mori,
• Yasuaki Furuya and
• Seiji Shirakawa

Beilstein J. Org. Chem. 2024, 20, 1794–1799, doi:10.3762/bjoc.20.158

• Sao Sumida Ken Okuno Taiki Mori Yasuaki Furuya Seiji Shirakawa Institute of Integrated Science and Technology, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan 10.3762/bjoc.20.158 Abstract Enantioselective halolactonizations of sterically less hindered alkenoic acid substrates

• required to achieve highly enantioselective halolactonizations (Scheme 1a) [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Enantioselective halolactonizations of sterically less hindered alkenoic acid substrates without substituents on the carbon–carbon double bond have

• -substituted 4-pentenoic acids without additional substituents on the carbon–carbon double bond (Scheme 1c) [26][27]. Chiral α-substituted γ-butyrolactone products as important building blocks for pharmaceutical development were obtained in a highly enantioselective manner in our catalytic system using

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• dearomatization of 33 via enantioselective hydroxylation using molecular oxygen and generates cyclohexadienone 34. As demonstrated by Corey [36] and Nicolaou [37], highly reactive intermediate 34 likely dimerizes non-enzymatically through stepwise reactions involving (1) an initial intermolecular Michael addition

• diversity, the research group achieved the synthesis of various dearomatized compounds, and the total synthesis of a member of the sorbicillinoid family. Enantioselective intermolecular Diels–Alder reaction to assemble core scaffolds: chalcomoracin and kuwanons Chalcomoracin (3) and kuwanons bearing a

• the Diels–Alder reactions (Scheme 6B). Notably, MaDA-3 exhibited high exo-selectivity (original MaDA: endo-selective) and enabled the enantioselective rapid total synthesis of guangsangon J (60) and mongolicin F (61), which are epimers of 58 and 3, respectively. Comparative analysis of the X-ray

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• different functional groups at the 5-position. The Shi group reported the use of Pd(II) and Selectfluor to enable the enantioselective β-fluorination of α-amino acids (Figure 6) [40]. The presence of 2-(pyridin-2-yl)isopropylamine (PIP) as directing group was essential for the formation of a four-coordinate

• from 61–75% across a series of nine benzylic substrates with various substitution patterns on the aromatic ring. In 2018, Yu and co-workers reported a palladium-catalysed enantioselective fluorination of benzylic C(sp3)–H bonds with the use of a transient chiral directing group 6 [43]. This approach

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• 10.3762/bjoc.20.136 Abstract The enantioselective 1,4-addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones catalyzed by a cinchona alkaloid-derived primary amine–Brønsted acid composite is reported. Both enantiomers of the anticipated pyrazole derivatives were obtained in good to excellent

• -covalent catalysis via bifunctional hydrogen-bonding organocatalysts. The C-4 nucleophilicity of pyrazolin-5-ones was also explored in enantioselective reactions with α,β-unsaturated carbonyl compounds through covalent catalysis with chiral amine-based catalysts; however, it has achieved limited success

• [10][11][12][13][14][15][16][17][18][19][20][21]. Among the developed organocatalyzed enantioselective 1,4-addition reactions of pyrazolin-5-ones, the catalytic asymmetric reactions of pyrazolin-5-ones with α,β-unsaturated ketones are comparatively less studied. In 2009, Zhao’s group were the first

Tetrabutylammonium iodide-catalyzed oxidative α-azidation of β-ketocarbonyl compounds using sodium azide

• Christopher Mairhofer,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1510–1517, doi:10.3762/bjoc.20.135

• easily available and cheapest nucleophilic N3 source (for other remarkable approaches using alternative catalysts and oxidants see references [24][25][26]). In addition to the racemic approach, they also showed that this reaction can be rendered enantioselective by using advanced Maruoka-type quaternary

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

• studies we also realized that the masked β-AA derivatives 2 undergo enantioselective β-addition to allenoates 3 under chiral ammonium salt catalysis (Scheme 1B) [18]. Interestingly, hereby we also found that the use of alternative catalyst systems (i.e., tertiary phosphines) allows for a γ-selective

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• invention of cooperative catalysis with electrochemical transition metal catalysis, which generally has mild oxidation potential for the generation of persistent radicals in the form of nucleophile-bound metal complexes. We and other groups have successfully applied this reaction design to enantioselective

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

• enantioselective intramolecular Cannizzaro reaction of aryl and alkyl glyoxals 1a–h and alcohol 2 using trisoxazoline (TOX) ligand (4)/copper catalysts to furnish the requisite mandelic esters 3a–h in good yields (greater than 90%) and high enantioselectivity. This was observed in the wide substrate scope as

• )3 (Scheme 3). They also extended the approach to study enantioselective Cannizzaro reactions of similar substrates using a Cu bisoxazoline (A) [Cu(OTf)2-PhBox] complex as the chiral catalyst, producing the desired enantiomeric compounds in modest yields and up to 33% ee (Scheme 4). The mechanistic

• . developed an asymmetric iron catalyst with the aim of expanding the platform of metal catalysis. Catalysts 14 and 15 proved to be effective in the transformation of glyoxal monohydrates 1a and alcohol 2, to deliver mandelate esters 3a in good yields and enantioselectivities via an enantioselective

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

• herein an enantioselective palladium-catalyzed Heck–Matsuda reaction for the desymmetrization of N-protected 2,5-dihydro-1H-pyrroles with aryldiazonium salts, using the chiral N,N-ligand (S)-PyraBox. This strategy has allowed straightforward access to a diversity of 4-aryl-γ-lactams via Heck arylation

• followed by a sequential Jones oxidation. The overall method displays a broad scope and good enantioselectivity, favoring the (R) enantiomer. The applicability of the protocol is highlighted by the efficient enantioselective syntheses of the selective phosphodiesterase-4-inhibitor rolipram and the

• commercial drug baclofen as hydrochloride. Keywords: desymmetrization; enantioselective Heck–Matsuda reaction; lactam synthesis; N,N-ligands; palladium; Introduction Desymmetrization reactions consist in the modification of a molecule with the loss of one or more symmetry elements, such as those which

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• ]. It is important to note that we are not aware of any catalytic enantioselective hydrochlorination reactions of alkenes. Conjugate additions of HCl to a complex of α,β-unsaturated acids, incorporated in an α-cyclodextrin, which corresponds to a formal hydrochlorination was reported by Tanaka and co

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

• 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

• ; Introduction The application of chiral metal complexes as enantioselective catalysts is among the fundamental strategies for preparing compounds in non-racemic forms [1][2][3][4]. These complexes typically comprise a chelating chiral ligand capable of coordinating with a metal ion; otherwise, a metal atom

• -(pyridin-2-yl)imidazolidin-4-one, differentiated by various substitutions at the imidazolidine ring [5][6][7]. Their copper(II) complexes were evaluated as efficient enantioselective catalysts, particularly in asymmetric Henry reactions (Scheme 1). Subsequent research has led to the development of various

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

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

• substrate is the most active. In 2012, Kojima and Mikami utilized bimetallic tropos BIPHEP [bis(phosphino)biphenyl]–digold complexes for enantioselective intramolecular hydroamination of N-alkenylureas [9], and they hypothesized that N-alkenylureas could be activated through bimetallic coordination not only

• mechanism in Scheme 2). Solvent effects: Michon and co-workers reported the beneficial assistance of water on enantioselective hydroamination, with the perchlorate being the best performing counterion. They propose that the anion is acting as a salting-in agent to contribute to better solvation of catalyst

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• . With this mechanistic blueprint as a backdrop, Phipps and co-workers developed an enantioselective Minisci-type addition, under dual photoredox and chiral Brønsted acid catalysis [44] (Scheme 5A). In their proposed mechanism, the activation of the NHPI ester radical precursor was proposed to occur via

• the phthalimidyl anion within the chiral pocket of the phosphate catalyst to form complex 55, before enantioselective addition to the iminium ion affords product 56. NHPI esters can also engage in π–π interactions with electron-rich species to generate charge-transfer complexes that can absorb light

• enantioselective cross-electrophile coupling between NHPI esters and alkenyl bromides [100] (Scheme 26A). In addition, Jolit and Molander disclosed the decarboxylative arylation of NHPI esters derived from bicyclo[1.1.1]pentanes (BCPs) by combining Ni-catalysis and photoinduced EDA complex activation [101] (Scheme

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• through concerted or stepwise mechanisms. An enantioselective palladium-catalyzed three-component reaction of glyoxylic acid, sulfonamides, and aryltrifluoroborates toward synthetically useful α-arylglycine compounds is described by the Manolikakes group [11]. Moreover, Šebesta and co-workers report a

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• isostere of polar functional groups [5][6]. Chiral indoline is an important member of the class of nitrogen-containing heterocyclic compounds that often exhibits various pharmaceutical activities and exists in many natural products [7][8]. The enantioselective synthesis of chiral indolines has received

• relatively strict reaction conditions (up to 150 bar H2). In 2022, Liu’s group reported an asymmetric hydrogenation of 3H-indoles catalyzed by a chiral Mn complex, which showed good yield and enantioselectivity [25]. In addition to metal catalysis for the enantioselective reduction, asymmetric

• organocatalysis using chiral phosphoric acids has also been studied (Scheme 1b) [26][27][28]. In 2010, Magnus Rueping and his co-workers developped an enantioselective Brønsted acid-catalyzed transfer hydrogenation of 3H-indoles [29]. In 2020, Song and Yu successfully applied a new chiral Brønsted acid

A novel recyclable organocatalyst for the gram-scale enantioselective synthesis of (S)-baclofen

• Gyula Dargó,
• Dóra Erdélyi,
• Balázs Molnár,
• Péter Kisszékelyi,
• Zsófia Garádi and
• József Kupai

Beilstein J. Org. Chem. 2023, 19, 1811–1824, doi:10.3762/bjoc.19.133

• organocatalysts has been a major breakthrough in the realization of enantioselective transformations. Stereoselective synthesis is essential in the pharmaceutical industry, as the development of drugs often requires the production of enantiomerically pure chiral compounds [6][7][8]. The application of

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• , desulfenylation of VI by anion CF3CO2, afforded 2-thioindole 107 (Scheme 45). The enantioselective synthesis of a broad spectrum of 3-thio-3-pyrrolyloxindoles 109 and 3-seleno-3-pyrrolyloxindoles 110 via sulfenylation and selenenylation of 3-pyrrolyloxindoles 108 was described by Yuan′s research group in 2015

• attack of the aromatic ring on the thiiranium ion moiety furnished products 137 and reproduced the selenide catalyst (Scheme 59). Zhao and co-workers found that N-thiosuccinimides are also suitable promoters for the enantioselective hydrothiolation of alkenes at low temperatures (Scheme 60) [91]. The

• stereogenic carbon centers bearing a sulfur atom. Although, significant efforts have been made to form enantioselective C–S bonds, the direct sulfenylation with more green, economical, and environmentally friendly sulfenylating reagents remains a challenge for organic chemists. N-(Sulfenyl)succinimides

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

• -workers [61] extended the application of NHC–copper catalysts to the conjugate addition of boronates to acyclic α,β-unsaturated carboxylic esters, ketones, and thioesters leading to the enantioselective formation of boron-substituted quaternary carbon stereogenic centers (Scheme 43). All transformations

• similar approach, Sawamura, Ohmiya and co-worker [62] accomplished the enantioselective conjugate addition of alkylboranes to α,β-unsaturated ketones in the presence of NHC–Cu(I) catalyst generated in situ from a chiral imidazolium salt and PhOK. A variety of functional groups are tolerated in the

• -hydroboration products. Furthermore, the presence of 2,6-dimethylphenyl-derived N-substituents on the NHC were optimal for the catalysis. Hoveyda and co-workers [87] reported the NHC–Cu(I)-catalyzed site- and enantioselective hydroboration of 1,1-disubstituted aryl olefins to obtain α-alkyl-β-pinacolatoboranes

Visible-light-induced nickel-catalyzed α-hydroxytrifluoroethylation of alkyl carboxylic acids: Access to trifluoromethyl alkyl acyloins

• Feng Chen,
• Xiu-Hua Xu,
• Zeng-Hao Chen,
• Yue Chen and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2023, 19, 1372–1378, doi:10.3762/bjoc.19.98

• reaction scope and development of related enantioselective photoinduced nickel-catalyzed radical cross-coupling reactions are currently underway in our laboratory. Experimental General procedure for the visible-light-induced nickel-catalyzed cross coupling of alkyl carboxylic acids with N

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• copper is to activate the 1,3-dicarbonyl compounds through complexation that leads to a highly diastereoselective nucleophilic addition. Scheidt et al. reported an enantioselective Cu-catalyzed intramolecular cross-dehydrogenative coupling approach to substituted tetrahydropyrans with excellent yields

• and stereoselectivity (Scheme 8) [58]. The mechanism of this reaction differs from the previously reported ones and proceeds through the in situ generation of nucleophilic and electrophilic partners which provides new opportunities for enantioselective oxocarbenium ion-driven CDC processes. Due to an

• electron-deficient position of the pyridine ring in complex B to obtain pyridine radical C, which aromatizes through tert-butoxyl radical-mediated extraction of hydrogen to afford the desired 2-substituted pyridine and regenerate Sc(OTf)3. In 2019, Liu et al. first reported an enantioselective CDC of

Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

• Alessandro Brusa,
• Debora Iapadre,
• Maria Edith Casacchia,
• Alessio Carioscia,
• Giuliana Giorgianni,
• Giandomenico Magagnano,
• Fabio Pesciaioli and
• Armando Carlone

Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92

• single operation and from readily available substrates. Their combination with asymmetric aminocatalysis [4][6][7][8] has recently led to innovative approaches for the one-step enantioselective preparation of stereochemically dense molecules. Nowadays, organocatalytic cascade processes provide a powerful

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• much more efficiently in decarboxylative RLT reactions than aliphatic acids [42]. Outside of decarboxylation, X. Peter Zhang recently reported the enantioselective synthesis of allylic amines through coupled HAT and RLT on allylic C–H bonds [45], using a bulky cobalt porphyrin complex developed and

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81