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

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

• enantioselective aza-Friedel–Crafts addition. In the first step, the DDQ-promoted oxidation of 3-indolinonecarboxylate 22 generated indolenines that performed as the potential electrophiles towards indoles 4. The chiral catalyst effectively assembled the reacting partners in a chiral transition state through H

• )methanamines 41 with high enantioselectivities. In this case, P14 was identified as the optimal catalyst (Scheme 11b) [36]. In 2019, Kim and co-workers reported a phosphoric acid-catalyzed enantioselective aza-Friedel–Crafts reaction between N-substituted indoles 4 and indol-3-ylsulfamidates 42. The dual

• anthracenyl group of the catalyst framework and aromatic rings of both substrates was also responsible for the stereoselective addition (Scheme 14) [39]. In 2019, Akiyama and co-workers developed a simple enantioselective aza-Friedel–Crafts process using unprotected pyrroles 9 and indoles 4 mediated by BINOL

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• correlates also with the slightly lower yields for the tandem products obtained with Zn enolates from acylimidazoles. Conclusion Enantioselective conjugate additions of dialkylzinc reagents afford chiral zinc enolates. These reactive species were trapped with several highly electrophilic onium compounds to

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• imines 25 (Scheme 6). The authors also demonstrated the enantioselective aminoalkylation, using chiral diamines as ligands. The introduction of chiral diamines in the metal complex produced the aminoalkylated products enantioselectivity with good ratio of enantiomeric excess. The plausible mechanism

• metals inhibits the metal–chiral ligand coordination, thus making the C–H alkylation of pyridine substrates challenging. In addition, transition-metal-catalyzed enantioselective C–H alkylation reactions of pyridine still remain a great challenge. In this regard, in 2022, Ye and co-workers [60] reported

• for the first time an enantioselective C-2 alkylation of pyridine using a chiral phosphine oxide-ligated Ni–Al bimetallic catalyst system and the protocol was found effective for a wide range of pyridines including unsubstituted pyridines, C2, C3 and C4-substituted pyridines and complex pyridines

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• Bastian Jakob Nico Schneider Luca Gengenbach Georg Manolikakes Department of Chemistry, RPTU Kaiserslautern-Landau, Erwin-Schrödinger-Str. Geb. 54, D-67663 Kaiserslautern, Germany 10.3762/bjoc.19.52 Abstract A palladium-catalyzed enantioselective three-component reaction of glyoxylic acid

• these transformations to a palladium-catalyzed enantioselective synthesis of α-arylglycine bearing a free carboxylic acid functionality directly from the parent glyoxylic acids (Scheme 1c) [22]. We could show that the desired arylglycine can be synthesized in good to excellent enantioselectivities

• sterically hindered arylboronic acids. Herein, we report an improved version of this palladium-catalyzed enantioselective three-component reactions using aryltrifluoroborates as replacement of the arylboronic acid building block (Scheme 1d). The broader scope of this 2nd generation protocol is exploiting a

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

• imines or their synthetic equivalents. Furthermore, we wanted to develop an enantioselective and diastereoselective process without adding chirality elements within the reagents. For our initial studies, we have selected the well-studied cyclic enones as substrates and the Taniaphos ligand (L14) that has

• developed a Lewis acid-promoted conjugate addition to unreactive Michael acceptors such as amides or vinyl heterocycles [60]. Trimethylsilyl triflate or boron trifluoride-activated unsaturated amides underwent highly efficient and enantioselective addition of Grignard reagents. When this methodology was

• enantioselective tandem borylation/intramolecular aldol cyclization procedure (Scheme 37) [78]. The desymmetrization process of cyclic diones 147 gave the densely functionalized bicyclic products 148 with four contiguous stereocenters usually in a highly diastereoselective fashion. Presumably, the difference in

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

• whole steric construction of a molecule and give rise to additional interactions which would increase the stereocontrolling properties. This idea efficiently works in the enantioselective extraction of the unprotected amino acids [38][39]. In the case of the Ni–Schiff base complexes, the t-Bu group may

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• investigated the Cu-catalyzed borylacylation of bicyclic alkenes 1 (Scheme 11) [45]. Like the previous borylative difunctionalization reactions, it was found the reaction generated a single exo,exo diastereomer. A brief investigation into an enantioselective variant of the borylacylation was investigated

• reaction to afford the naphthalene product 88a. Inspired by Zhao’s seminal report on the racemic carboamination of bicyclic alkenes [53], the Cramer laboratory studied the Co-catalyzed enantioselective carboamination of bicyclic alkenes 1 via C–H functionalization in 2021 (Scheme 17) [54]. The authors

• yields. Mono- and disubstituted bridgehead variants were applicable, but with reduced efficacy with the former producing a dihydronaphthofuran 107i as the major product. In 2019, the Cramer group continued studying this reaction and developed an enantioselective variant utilizing a chiral Cp* derivative

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• and co-workers demonstrated for transannular Diels–Alder cycloaddition reactions of symmetrically tethered large systems (10–18-membered rings) [29]. In this context, we have recently reported the transannular enantioselective (3 + 2) cycloaddition of cycloalkenone hydrazones under Brønsted acid

• also carried out an analysis of the electron localization function (ELF) [31][32] and the charge transfer along the reaction coordinate to determine the different stages and the polarity of the reaction. Results and Discussion The enantioselective intermolecular cycloaddition between hydrazones and

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• largely underexplored to date. Furthermore, the development of enantioselective transformations allowing the synthesis of enantioenriched fluorine-containing compounds by transition-metal-catalyzed C–H bond activation will have a significant impact as for instance an access to pharmaceutically relevant

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• combretastatin D-1 (1) in 23% overall yield after 16 steps. Later, the same authors performed the enantioselective synthesis of 1 in an attempt to review its absolute configuration [41]. Thus, acetylation of compound 2 followed by the use of Jacobsen’s catalyst [42] to perform the epoxidation of the double bond

• synthesis of combretastatin D-2 (2) by Rychnovsky and Hwang [36]. Divergent synthesis of (±)-1 form combretastatin D-2 (2) by Rychnovsky and Hwang [36]. Enantioselective synthesis of 1 by Rychnovsky and Hwang employing Jacobsen catalyst [41]. Synthesis of fragment 57 by Couladouros and co-workers [43][45

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• a B‒O/B‒H transborylation in catalysis was the catalytic Midland reduction of propargylic ketones developed by Thomas to give enantioenriched propargylic alcohols (Scheme 10) [74]. The reaction was proposed to occur by enantioselective reduction of the propargylic ketone 42 by myrtanyl borane 43 to

• to give aldol-type products 61. Thomas reported the borane-catalysed diastereo- and enantioselective allylation of ketones with allenes and HBpin to give diastereo- and enantioenriched allylic alcohols, after workup (Scheme 15) [78]. The mechanism was investigated by single-turnover experiments and

• first example of Al‒O/B‒H exchange in catalysis was reported by Woodward, in the enantioselective catalytic hydroboration of ketones with HBcat as the terminal reductant (Scheme 23) [103]. A mixture of 1,1′-bi-2-naphthol (BINOL), 1,1'-binaphthalene-2,2'-dithiol (DTBH2), or 2-hydroxy-2'-mercapto-1,1

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• -workers reported in 2011 the first enantioselective total synthesis of (+)-ophiobolin A (8), involving a RCM approach to form the central eight-membered ring [24]. In this way, their total synthesis involved the enantioselective preparation of the C-D spiro bicyclic ring system 33 in 21 steps from diester

• instead of 100 °C) to avoid C-7 epimerization, and two equivalents of the Pd complex. The cycloadduct 129 was obtained in very high yield and could be converted to cotylenin A (130) in 5 steps. This work constituted an enantioselective total synthesis of cotylenin A (130) (Scheme 25). 3.2 Intramolecular

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• [112][113][114][115][116], no enantioselective synthesis is available. Full 1H and 13C NMR data of 53 (including 14 carbon signals) have been published [113]. The guaiane sesquiterpenes that are potentially derived from cationic intermediates L1–L4 are summarised in Scheme 16A. trans-β-Guaiene (54) can

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• chromatography; enantioselective synthesis; GC/MS; semiochemicals; Introduction Hyperolius cinnamomeoventris (Figure 1) is one of the largest species of reed frogs (Hyperoliidae), which are commonly found in Africa, south of the Sahara. Males of the Hyperoliidae possess a characteristic yellow gular patch on

• , such a synthetic approach would shorten the synthesis from eight to four steps and allow access to both enantiomers of the compounds 12–14. The synthesis started with an enantioselective Michael addition of aldehyde 1 to methyl vinyl ketone (15) catalyzed by (S)-Jørgensen’s organocatalyst S-16, to

• absolute configuration of the sesquiterpene A was elucidated by enantioselective gas chromatography. The enantiomers of the alcohols could be separated on a Hydrodex β-6TBDM phase (Figure 5). This allowed to determine the absolute configuration of the sesquiterpene A. A coinjection of a gland extract with