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

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• aimed at overviewing the current state-of-art and perspectives of oxidative organocatalysis by redox-active molecules with the emphasis on challenging chemo-, regio- and stereoselective CH-functionalization processes. The catalytic systems based on N-oxyl radicals, amines, thiols, oxaziridines, ketone

Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• Provincial Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, Guangdong 518055, China 10.3762/bjoc.18.173 Abstract An approach to aberrarone, an antimalarial diterpenoid natural product with tetracyclic skeleton is reported. Key to the stereoselective preparation of

• . Impressed by the structural features and biological profiles, our group embarked a project on the total synthesis of this natural product. Herein, we report our stereoselective synthesis of its 6-5-5 tricyclic skeleton. Our retrosynthetic analysis is shown in Scheme 1. For the formation of the D ring with

• stereoselectivity is possible through the conformation of 14 where the OTBS group is in pseudoequatorial position (Scheme 2). Therefore, the Pauson–Khand reaction proceeded to afford 11 containing an α-H at C6. From this intermediate, to our delight, the stereoselective attachment of the requisite methyl group

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• versatility in numerous regio- and stereoselective ring opening and/or expansion reactions, as well as rearrangements [5]. The aziridine structural motif is present in natural products such as mitomycins and azinomycins (Figure 1) [1][5], which exhibit potent biological activities such as antitumor and

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• the synthesis and properties of such BINOL-based chiral MIMs, together with their use in further diastereoselective modifications, their application in asymmetric catalysis, and stereoselective chemosensing. In their minireview, Prodip Howlader and Michael Schmittel [22] highlighted the recent results

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• on the synthesis and the coupling of three main fragments. The central fragment was synthesized via a regio-and stereoselective nitroso Diels–Alder reaction with an enol phosphate, followed by reductive cleavage of the phosphate to the ketone 11b. Coupling studies of this fragment with the lactone

• fragment was accomplished in a stereoselective fashion through a vinyllithium intermediate. An advanced synthetic intermediate was then obtained after functional group transformation. Keywords: cycloaddition; organolithium; stereoselective; total synthesis; Introduction Leustroducsins 1a–c and

• , we have shown that the Wightman reagent 6, a chiral chloronitroso derivative [27], led to a complete regio- and stereoselective reaction with functionalized dienes (Scheme 1). The chiral auxiliary contributes to both regioselectivity and stereoselectivity. After hydrolysis of the chiral auxiliary and

Enantioselective total synthesis of putative dihydrorosefuran, a monoterpene with an unique 2,5-dihydrofuran structure

• Irene Torres-García,
• Josefa L. López-Martínez,
• Rocío López-Domene,
• Manuel Muñoz-Dorado,
• Ignacio Rodríguez-García and
• Miriam Álvarez-Corral

Beilstein J. Org. Chem. 2022, 18, 1264–1269, doi:10.3762/bjoc.18.132

• stereoselective kinetic resolution of allenol 3 via lipase AK-catalyzed acetylation [15]. In this way, unaltered, (−)-hydroxyallene 3 could be separated from (+)-acetyl derivative 9 through standard column chromatography (Scheme 3). Enantiomeric excesses of (−)-3 and (+)-9 were determined by chiral HPLC analyses

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• polycarbonyl compounds such as vic-diketoesters has been investigated in depth by Wasserman, Parr [2] and Gleiter, Rubin [3]. Important contributions for the use of α,β-diketoesters in stereoselective transformations came from Doyle’s group [4][5]. One remarkable example is the diastereoselective

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

• isolated. Moreover, the coupling of benzothiazines with amino acids was realized. In doing so, an enantioselective synthesis of the nonproteinogenic amino acid 2-amino-3-propylhexanoic acid was accomplished. Keywords: amino acid; benzothiazine; oxidative dimerization; peptide coupling; stereoselective

• obtained by DFT calculations (ωB97xD/6-31G*). Conditions applied for the condensation reactions.a Stereoselective catalytic hydrogenation reactions of dehydroamino acid ester 14. Supporting Information Supporting Information File 230: Experimental procedures and characterization data, additional

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• base complexes; stereoselective electrosynthesis; voltammetric testing; Introduction Electrochemistry provides a direct access to highly reactive species by means of harnessing electrons or electron holes as reagents [1][2]. This capacity can be efficiently exploited in organic synthesis for rational

• construction of complex multifunctional molecules [3][4][5][6][7][8]. Recently, we elaborated a versatile electrochemical approach for the stereoselective functionalization of a side chain of amino acids involved in the Ni(II) chiral coordination environment [9][10][11][12][13][14][15]. A combination of redox

• stereoselective functionalization has not been probed as yet. Herein, reductive three-membered ring opening in the chiral α,α-cyclopropanated amino acids involved in the Ni(II)–Schiff base coordination environment is reported. Follow-up transformations of thus formed radical anions will be discussed, including

Electrochemical hydrogenation of enones using a proton-exchange membrane reactor: selectivity and utility

• Koichi Mitsudo,
• Haruka Inoue,
• Yuta Niki,
• Eisuke Sato and
• Seiji Suga

Beilstein J. Org. Chem. 2022, 18, 1055–1061, doi:10.3762/bjoc.18.107

• ]. For instance, they recently reported a stereoselective reduction of alkynes to Z-alkenes using a PEM reactor. The use of a Pd/C cathode catalyst and the appropriate cathode potential realize the selective synthesis of Z-alkenes [22][23][24]. They also reported the stereoselective hydrogenation of α,β

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• stereoselective asymmetric synthetic methods to access 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides, and their fused and spiro derivatives are in high demand and should be developed in the near future. Biologically active 1,2-azaphospholine 2-oxide derivatives. Diverse synthetic strategies for

Efficient production of clerodane and ent-kaurane diterpenes through truncated artificial pathways in Escherichia coli

• Fang-Ru Li,
• Xiaoxu Lin,
• Qian Yang,
• Ning-Hua Tan and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2022, 18, 881–888, doi:10.3762/bjoc.18.89

• cyclase) act on geranylgeranyl diphosphate (GGDP) to perform regio- and stereoselective cyclizations or skeleton rearrangement reactions via carbocation chemistry to form diverse and versatile carbon skeletons; and ii) multiple post-modification enzymes, most often cytochrome P450s, decorate the carbon

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• (2j) and PRP (1) that led to the stereoselective formation of cycloadduct 4 was studied in detail for this purpose (Scheme 8). In analyzing the potential energy surface (PES) of this cycloaddition reaction using the M11 functional together with the cc-pVDZ basis set, we could locate the four

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• reported, by using a metal catalyst or Brønsted-acid catalysis [79][80][81]. However, the efficient regio- and stereoselective installation of the endoperoxide structure is still challenging, because of the increased reactivity of activated oxygen/peroxides and the high sensitivity of peroxide bridges to

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• stereoselective chemosensing. Given the growing importance of mechanically interlocked molecules and the key advantages of the privileged chiral BINOL backbone, we believe that this research area will continue to grow and deliver many useful applications in the future. Keywords: axial chirality; BINOL; catenanes

• towards a large variety of substituted BINOL derivatives [29]. Another big advantage is the commercial availability of both (R)- and (S)-BINOL in enantiomerically pure forms. BINOL and its derivatives have served as a chiral backbone for numerous stereoselective applications, most importantly (but not

• limited to) metal- and organocatalysis [30] and stereoselective chemosensing [31][32]. By introduction of an axially chiral BINOL unit into a MIM, it is possible to combine the unique applicability of the chiral BINOL unit with the special possibilities offered by interlocked molecules. In this minireview