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

• , acetonitrile, with 91–100% efficiency, and the catalyst was reused in five reaction cycles without the loss of activity and selectivity. Keywords: baclofen; catalyst recovery; lipophilic cinchona squaramide; organocatalysis; stereoselective catalysis; Introduction In today’s chemical industry, catalytic

• 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

• cinchona squaramide organocatalyst. Its catalytic activity and recyclability were examined in a new stereoselective synthesis of baclofen, which is used to treat muscle spasms [30]. Finally, the catalyst was easily recycled by centrifugation over five reaction cycles without significant loss of activity

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• active natural products. The direct functionalization of C–H bonds in enamides offers a convenient and versatile approach to access a wide range of functionalized enamides. In 2021, Fu and his colleagues successfully developed a novel method for the stereoselective alkylation of enamides 14 using iodine

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• =N motif within hydrazones gives them both electrophilic and nucleophilic character. In 2005, Brigaud et al. developed a highly stereoselective method for the synthesis of α-trifluoromethylamines with organometallic reagents to extend the asymmetric methodologies of trifluoroacetaldehyde hydrazones

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• Ar and CF3 groups can localize the negative charge and also provide steric effects to afford stereoselective cycloaddition products with 3:1 to 6:1 dr. The steric hindrance also prevents products 9 from undergoing a second cycloaddition. The control reactions of methyl ketone or benzaldehydes gave

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

• tetrahydropyrans 88 (Scheme 36) [70]. In this protocol, by controlling acid catalyst (camphorsulfonic acid (CSA) or trifluoromethanesulfonic acid (TfOH)), two different products were achieved and tetrahydrofurans 87 could be converted to tetrahydropyrans 88 by stereoselective rearrangement. In the same year, Zhu

One-pot nucleophilic substitution–double click reactions of biazides leading to functionalized bis(1,2,3-triazole) derivatives

• Hans-Ulrich Reissig and
• Fei Yu

Beilstein J. Org. Chem. 2023, 19, 1399–1407, doi:10.3762/bjoc.19.101

• the alkynyl-substituted 1,2-oxazin-4-ol derivative 19 which is smoothly available from the corresponding ketone 6 by highly stereoselective reduction with sodium borohydride [53]. Starting from 1,3- (8) or 1,4-bis(bromomethyl)benzene (16), respectively, the approved conditions in the presence of TBTA

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

• NaH, DMF) were applied to prepare enantiopure (R)-6.1 or (S)-6.1 from commercially available enantiopure solketal [75][76][78]. For the protected secondary alcohol of the glycerol derivative 6.6a (Figure 6B), a stereoselective synthesis, starting from either ᴅ- or ʟ-tartaric acids, produced first the

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

• process which involves two consecutives stereoselective reactions. The control of the diastereomeric ratio is, however, difficult to attain as demonstrated by an extensive screening and is always near 50:50 without significant deviations changing the reaction conditions. On the contrary, the use 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

• acyclic, carbocyclic, heterocyclic, and polycyclic molecular architectures with high molecular complexity. In particular, asymmetric organocatalysis plays a pivotal role in the construction of optically active, bioactive, and natural products. The main advantages of organocatalyzed stereoselective

• categorized into two major divisions: 1) covalent bonding and 2) noncovalent bonding catalysts. A covalent bonding organocatalyst reacts with a substrate to form an activated chiral intermediate which undergoes a stereoselective reaction with another reagent. A noncovalent bonding catalyst usually assembles

• the reaction partners in a highly ordered three dimensional transition state through noncovalent interactions (like H-bonding, π–π interactions) thus promoting the stereoselective reaction. Examples of covalent bonding organocatalysts are amines [6][7], N-heterocyclic carbenes [8][9], phosphines [10

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

• 10.3762/bjoc.19.65 Abstract We present here a stereoselective tandem reaction based on the asymmetric conjugate addition of dialkylzinc reagents to unsaturated acylimidazoles followed by trapping of the intermediate zinc enolate with carbocations. The use of a chiral NHC ligand provides chiral zinc

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

• . Except lately, in 2020, Chen and group [82] reported a Pd/Cu-catalyzed regio- and stereoselective synthesis of C2-alkenylated pyridines starting from internal alkynes 84 and pyridinium salts in a stereodivergent manner (Scheme 17a). The interesting part of this work was the switching of the alkene

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

• construction of the rings. However, the synthetic methods are still limited, especially for asymmetric synthetic methods. Thus, it is clear that highly stereoselective asymmetric synthetic methods to access various medium and large phostam, phostone, and phostine derivatives are in high demand and should be

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

• stereocenters were isolated in excellent yields and high diastereoselectivity. The authors have shown that catalyst loadings as low as 0.5 mol % can still be sufficient to promote the highly stereoselective reaction. Similarly to aldol reactions, Mannich-type additions are also suitable to trap the metal

• stereoselective methodologies have been published that demonstrate the Cu- or Ni-catalyzed conjugate addition of organozincs to α,β-unsaturated ketones 14 followed by the reaction of the metal enolate with a nitroolefin (20) (Table 1) [30][31][32][33]. These reactions were facilitated by different ligand families

• stereoselective conjugate borylation of cyclobutene 1-carboxyester 175 (Scheme 45A) [87]. As a result, the cis-β-boronyl cyclobutylcarboxyester 176 was prepared on a gram scale with 80% yield and an excellent 99% ee (dr >20:1). Subsequent transformation to the corresponding trifluoroborate salt 177 resulted in a

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

• base chiral template is a fairly versatile “tool” that can be adapted to a specific task. A relatively new approach to functionalization of amino acids is a combination of a stereoselective synthesis in a metal-coordination environment with electrochemical activation [31]. It increases the reactivity

• be shown below, this is not necessary since the isomeric Schiff base template proved efficient in stereoselective modification of amino acids. The products of the oxidative dimerization via the phenylene ring were not detected for both isomeric templates. The subsequent reaction with (S

• characterized using spectral methods (for HRMS, 1H, 13C NMR, including 2D techniques, see Supporting Information File 1). To obtain the serine derivative (SerNi)L7, the recently developed electrochemical approach for the stereoselective hydroxyalkylation [32] was used. The reaction protocol is operationally

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

• , the authors noted the reaction was stereoselective for the trans-addition product. Mechanistically, the authors proposed the reaction begins with the Cu-mediated substitution reaction of iodobenzene (66a) with KSCN to afford phenyl thiocyanate (70). The Cu complex can then undergo oxidative addition

• after dissociation. Alternatively, 205 can undergo a ring closure followed by a subsequent C–P-bond cleavage causing a ring opening resulting in 207. Intramolecular SN2’ and elimination of the phosphine oxide generates the final product 202e which the authors propose is stereoselective due to

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• the literature all target similar disconnections, especially an aldol strategy involving a recurrent 4-acetyl-1,3-thiazolidin-2-one ketone partner. Herein, we describe an alternative disconnection and subsequent stereoselective transformations to construct a stereopentade amenable to latrunculin and

• analogue synthesis, starting from (+)-β-citronellene. Key stereoselective transformations involve an asymmetric Krische allylation, an aldol reaction under 1,5-anti stereocontrol, and a Tishchenko–Evans reduction accompanied by a peculiar ester transposition, allowing to install key stereogenic centers of

• precluded the installation of the pyran ring – and the use of its well-known isomerization to set up important stereocenters [6][9] –, thus imposing the anticipated construction of key asymmetric centers. The following discussion will deal with the stereoselective synthesis of a stereopentade amenable to

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• -benzyl group with the Cbz group, trityl ether hydrolysis, oxidation of the liberated OH group, and stereoselective addition of MeMgBr to the resulting aldehyde functionality. Hydrogenolysis of the Cbz protecting group in 13 followed by N-alkylation afforded pyrrolidines 14–16 which after acidic

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

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• substituents in the one-pot reaction and showed that regardless of the substitution pattern, the reactions lead to the stereoselective formation (≥95% (2E,4E)) of the respective dienones under mild conditions. It was found that enynes with alkyl chains gave higher yields than the corresponding aryl-substituted

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• issues for living organisms [25][26]. Additionally, the classic stereoselective synthesis of dienol phosphates requires cryogenic temperatures (−78 °C) as well as NMP-based methodologies [27]. Therefore, motivated by those considerations, we sought a suitable efficient and non-toxic additive which would

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• should be noted that the three-step strategy (dithiolane protection, oxidative rearrangement, and hydrodesulfurization) can be used to treat carbonyl functional groups as synthetic equivalents of cis-alkenes (Scheme 10c), as is shown by the highly stereoselective conversion of α-phenylacetophenone (60

• -fused dihydrodithiin ring is first hydrodesulfurized and then dehydroxylated in a stereospecific and stereoselective manner [62]. The dihydrodithiin building block 66 thus acts as a synthetic equivalent of an allyl alcohol anion and serves as a versatile synthon for de novo carbohydrate synthesis [63

• expected allyl cation (3 + 2) cycloaddition reactivity is not operating under gold(I) catalysis, but instead it behaved as a reliable and quite stereoselective vinylgold carbenoid species, affording exclusively cyclopropanation products with a wide range of olefin substrates (Scheme 18c). The carbene-type

Organophosphorus chemistry: from model to application

• György Keglevich

Beilstein J. Org. Chem. 2023, 19, 89–90, doi:10.3762/bjoc.19.8

• newly prepared thiophosphorus acids were not efficient in the asymmetric transfer hydrogenation of 2-phenylquinoline. However, they may find application in other model reactions. These days, stereoselective syntheses incorporating “green" chemical considerations are of utmost importance in medicinal

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• the radical formation of the tetracyclic core of 130 in 75% yield as a mixture of two diastereoisomers (dr = 3:2) that were both used to access natural products. Impressively, the protocol allowed the installation of three rings and the stereoselective introduction of chiral centers at C2 and C21 for

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• ]. General purification scheme using the catch and release strategy. Exemplar catch and release purification of a stereoselective oxidation. Redrawn from [105]. Catch and release-type purification using conventional SiO2. Redrawn from [107]. Schematic representation of an industrial continuous

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

• the PMB protecting group, Dess–Martin oxidation, and SmI2-induced cyclization. This last step was highly selective, giving solely the intermediate 17. The synthesis was then pursued by the hydroboration–oxidation of the monosubstituted alkene, followed by stereoselective epoxidation of the 1,1

• , obtaining excellent selectivity in all cases. Alternatively, the same year, the authors published a vinyl radical cyclization occurring in presence of n-Bu3SnH, providing a stereoselective access to the bicyclo[3.2.1]octane unit corresponding to the CD rings [25]. Newhouse’s synthesis of principinol D In

• compound 60 was employed to form an α,β-epoxyketone intermediate which underwent SmI2 reduction at −78 °C, giving access to the desired syn diastereomer with good selectivity (dr = 8.5:1). The free alcohol was then protected with an ethoxymethyl ether (EOM). Finally, Peterson olefination, stereoselective