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

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• mixture of starting material 6, the conjugate addition product 14, and a trace of the denitration product 15. The structure of both compounds was confirmed by single X-ray crystallography (Figure 4 and Figure 5). The addition of methanol is stereoselective with only a single diastereomer of 14 being

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• -pavettamine rather than pavettamine. Chain extension and stereoselective ketone reduction were achieved using the (R)-methyl p-tolyl sulfoxide chiral auxiliary to give the desired 1,3-syn-diol C5 unit. A protecting-group strategy was also developed for the orthogonal protection of the alcohol and amine

• addition of the chiral auxiliary. Our attention then turned to the stereoselective reduction of 8. Chelation-controlled reduction of 8 using ZnCl2 and DIBALH allowed for the successful formation of 16 as a single diastereomer (Scheme 4), as evidenced by 1H NMR spectroscopy [18]. TBS deprotection furnished

• compound 9. Stereoselective reduction of intermediate 8 as key step towards intermediate 4. Reaction conditions: a) i) ZnCl2, rt, 2 h; ii) DIBALH, THF, −78 °C to rt, 2 h, 87%; b) TBAF, THF, 0 °C, 4 h, 87%; c) 5% p-TsOH, 2,2-dimethoxypropane, acetone, rt, 1 h, 86%. Synthesis of the C5 fragments from

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• % from benzyl alcohol (16), alongside 50% of the trifluoroacetate 18. Carrying out the same process via a flow-based protocol allowed for the formation of benzaldehyde (17) in 91% yield with only 8% of the accompanying side product 18 [88]. Similarly, a stereoselective alkylation of an Evans’ type

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• ligands [52][53][54][55] and as chiral auxiliaries [56]. The most widely used synthetic methods to form the aziridine ring [57][58][59][60][61] include intramolecular cyclizations in amines bearing potential leaving groups. Stereoselective syntheses of aziridines have been successfully carried out by

• determined following a single-crystal X-ray analysis (Scheme 11). The stereoselective synthesis of diastereomeric 2-chloro-2-aroylaziridines 36 and 32 was successfully accomplished through a three-component cascade coupling reaction of silyldichloromethanes 33, arylnitriles 34 and chiral N-tert

• through a cyclic transition state to the Si face of the imine (RS)-14. In this way, both cis-aziridines diastereoisomers 36 and 32 were formed from the same chiral imine 14 and arylnitriles 34 (Scheme 12). Chiral sulfinyl imines have been also used in the stereoselective synthesis of aziridines. The

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• donors for the installation of a 1,2-cis-linked multifluorinated GlcNAc and GalNAc moiety. Results and Discussion Our approach to the synthesis is summarized in Scheme 1. Challenging regio- and stereoselective introduction of fluorine at C3 and C4 of the pyranose ring, together with azide installation at

Nitroalkene reduction in deep eutectic solvents promoted by BH₃NH₃

• Chiara Faverio,
• Monica Fiorenza Boselli,
• Patricia Camarero Gonzalez,
• Alessandra Puglisi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2021, 17, 1041–1047, doi:10.3762/bjoc.17.83

• also demonstrated. A wide variety of alkyl- and aryl-substituted nitroalkenes were reduced with high chemoselectivity, including β-substituted nitroolefins, and thus paving the way to the study of innovative, sustainable and stereoselective reductive methods to synthesize enantiopure nitroalkanes

Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols

• Ákos Bajtel,
• Mounir Raji,
• Matti Haukka,
• Ferenc Fülöp and
• Zsolt Szakonyi

Beilstein J. Org. Chem. 2021, 17, 983–990, doi:10.3762/bjoc.17.80

• synthesised in a stereoselective manner. Isopinocarveol prepared from (−)-α-pinene was converted into condensed oxazolidin-2-one in two steps by carbamate formation followed by a stereoselective aminohydroxylation process. The relative stereochemistry of the pinane-fused oxazolidin-2-one was determined by 2D

• -2-one; stereoselective; tautomerism; Introduction The best known 2-amino-1,3-diol derivative sphingosine (1) plays a crucial role in intracellular signaling as second messenger, and its derivatives called sphingolipids are also critical for cell growth, cell differentiation, cell recognition, and

• the lack of a readily available natural sources and the high biological importance of sphingolipid analogues, their synthesis has been the subject of numerous studies [16]. The key step for the synthesis is the stereoselective construction of the 2-amino-1,3-diol moiety of the molecules. Generally

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• glycoconjugates [1][2][3][4]. Due to the large diversity of glycosyl donors and acceptors there is no general glycosylation method developed so far. To ensure high yielding, as well as regio- and stereoselective glycosidic bond formation, a proper combination of glycosyl donor and acceptor, protecting and leaving

• [27]) and coupling partners [28], great attention has been paid to a stereoselective glycosylation by sterically fixed glycosyl fluorides as glycosyl donors [29][30][31]. The enhanced stability of glycosyl fluorides has also allowed to develop a straightforward protecting-group-free strategy towards

• facilitating for the synthesis of 2-deoxy glucoside 20 from corresponding fluoride α-19 in 91% yield and good α-selectivity at −10 °C (Scheme 5). Due to the absence of a neighboring group at C2 position, the stereoselective synthesis of 2-deoxy glycosides is challenging [72][73][74]. We hypothesize that the

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• important building blocks and ubiquitous scaffolds in many natural products and active pharmaceutical ingredients (API). Among various established methods, the Prins reaction has emerged as a powerful technique in the stereoselective synthesis of the tetrahydropyran skeleton with various substituents, and

• ; Prins cyclization; stereoselective; tetrahydropyran; Introduction 6-Membered saturated oxygen heterocycles, known as tetrahydropyran (THP), are recognized as privileged scaffolds, present in a variety of biologically important natural products, such as polyether antibiotics, marine toxins, pheromones

• , and pharmaceutical agents. These structural motifs are frequently used as synthons and as key intermediates for natural product synthesis. Therefore, the development of stereoselective synthetic methods for the substituted THP subunit has long been the area of fundamental research in organic chemistry

Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions

• Dat Phuc Tran,
• Yuki Sato,
• Yuki Yamamoto,
• Shin-ichi Kawaguchi,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 866–872, doi:10.3762/bjoc.17.72

• reactivities. The method using V-40 as an initiator is successfully investigated for the regio- and stereoselective phosphinylphosphination of terminal alkynes giving the corresponding trans-isomers of 1-diphenylphosphinyl-2-diphenylthiophosphinyl-1-alkenes in good yields. The protocol can be applied to a wide

• variety of terminal alkynes including both alkyl- and arylalkynes. Keywords: (E)-1,2-bis(diphenylphosphino)ethylene derivative; radical addition; stereoselective phosphinylphosphination; terminal alkyne; tetraphenyldiphosphine monoxide; Introduction Organophosphorus compounds are an essential class of

• A1. Radical A1 is captured by Ph2P(O)PPh2 to provide A2, regio- and stereoselectively [62]. Conclusion In conclusion, a highly regio- and stereoselective phosphinylphosphination of alkynes with Ph2P(O)PPh2 has been successfully developed. The radical initiator V-40 can be used to selectively generate

Stereoselective syntheses of 3-aminocyclooctanetriols and halocyclooctanetriols

• Emine Salamci and
• Yunus Zozik

Beilstein J. Org. Chem. 2021, 17, 705–710, doi:10.3762/bjoc.17.59

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• naturally occurring cinchona alkaloids have shown remarkable performance as organocatalysts for stereoselective synthesis in the past decade [1][2][3][4][5][6]. Among them, quinine-derived organocatalysts make a noteworthy appearance in the formation of new stereogenic centres, which can serve as valuable

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• phosphonodepsipeptides in the future. However, highly stereoselective asymmetric synthetic methods of phosphonodepsipeptides are of high demand and need to be developed in the near future. Phosphonopeptides, phosphonodepsipeptides, peptides, and depsipeptides. The diverse strategies for phosphonodepsipeptide synthesis

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• might be thought to be theoretically possible [18][19], via a late-stage addition to an intact pyrrolizidine core. The molecules are isolated as their racemates and, by analogy to the clazamycins, even if the LgnC-mediated hydroxylation is fully stereoselective, the C(7a) center is expected to be

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• one of the most widely used fluorine-containing building blocks [48][49]. Recently, we have developed an efficient stereoselective synthesis of β-fluoro-β-nitrostyrenes 1 based on the radical nitration of 2-bromo-2-fluorostyrenes [50]. This process takes place with simultaneous elimination of bromine

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

• stereoselective methods for the synthesis and transformations of cyclopropane derivatives. These investigations gained a significant interest, because cyclopropane and cyclopropene fragments are present in the structures of many biologically active substances, such as antibiotics, anticancer, and antimycotic

• intermediate allylic cation which was the electrophile in a Friedel–Crafts reaction with 159. The subsequent desilylation of the Friedel–Crafts product gave an α-fluorinated ketone intermediate which then reacted with a second equivalent of 159 in a (Z)-stereoselective, chelation-controlled process. Fu et al

A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach

• Michael Andresini,
• Leonardo Degannaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2021, 17, 203–209, doi:10.3762/bjoc.17.20

• preparation of 2H-azirines and their stereoselective transformation into highly functionalized NH-aziridines, starting from vinyl azides and organolithium compounds. The protocol has been developed using cyclopentyl methyl ether (CPME) as an environmentally benign solvent, resulting into a sustainable, safe

Au(III) complexes with tetradentate-cyclam-based ligands

• Ann Christin Reiersølmoen,
• Thomas N. Solvi and
• Anne Fiksdahl

Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18

• trans product. Thus, the proper choice of the gold catalyst allows highly stereoselective formation of either cis or trans cyclopropanation products and facilitates the isolation of pure isomers. Despite the chiral nature of these ligands, no enantioselectivity was observed in the test reactions

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• . Therefore, the synthesis of inthomycin A was advanced in the racemic form. Treatment of compound (rac)-17 with aqueous ammonia gave the corresponding amide (rac)-18 in 96% yield. Heck coupling between (rac)-18 and vinylboronate pinacol ester [31] using Pd(PPh3)4/Et3N conditions provided stereoselective

• (rac)-13 in a stereoselective manner, attention was then focused on the development of an analogous strategy towards the (Z,Z,E)- and (Z,E,E)-triene systems present in oxazolomycin A (5a) and oxazolomycin C (5c), respectively. The key steps were i) synthesis of dienyl halides, ii) synthesis of the

• mixture of (Z,E)/(E,E)-36a, respectively). Aldehyde 35 was then converted into dibromide 37 using PPh3/CBr4 followed by stereoselective palladium-catalyzed monoreduction according to the literature available protocol [41] to give vinyl bromide 38 in 76% yield (Z/E as 99:1 mixture). Iodide 15a [42] was

Silver-catalyzed synthesis of β-fluorovinylphosphonates by phosphonofluorination of aromatic alkynes

• Yajing Zhang,
• Qingshan Tian,
• Guozhu Zhang and
• Dayong Zhang

Beilstein J. Org. Chem. 2020, 16, 3086–3092, doi:10.3762/bjoc.16.258

• stereoselective manner under mild reaction conditions. This reaction is operationally simple and offers an excellent functional group tolerance as well as a broad substrate scope that includes both terminal and internal alkynes. The reaction proceeded through the oxidative generation of a P-centered radical and

• others concerning the silver-catalyzed phosphonofluorination of alkenes [24][25][26], we herein present a general silver-catalyzed regio- and stereoselective phosphonofluorination of alkynes using Selectfluor® and phosphonates as reactants (Scheme 1). This new silver-catalyzed approach to fluorinated

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• selectively attacked the C-8 ketone moiety of 47 to give alcohol 49 in β-configuration in 80% yield [32]. Chemoselective and stereoselective reduction of the C-9 ketone of 49 was accomplished by treatment with NaBH(OAc)3 [33] and produced 50 after a two-step synthesis. Removal of the sulfoximine group in 50

• ] cycloadditions, which are usually under substrate-control. Remarkable innovation of the stereoselective palladium-catalyzed trimethylenemethane cycloaddition reported by Trost’s group, which makes use of catalytic amounts of palladium and chiral phosphine ligand 74, was applied successfully in the

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• for E-alkenes in medicinal chemistry. Keywords: Alzheimer's disease; bioisostere; conformational analysis; gauche effect; stereoselective synthesis; Introduction Piperine (1, Figure 1) is a well-known natural product that is derived from peppercorns [1][2][3]. Many biological studies of 1 have been

• . Stereoselective fluorination is an emerging strategy for controlling the conformations of organic molecules. The highly polarized C–F bond tends to align in predictable ways with adjacent functional groups, due to a combination of hyperconjugative and/or dipolar interactions [18][19][20][21]. This knowledge led

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

• Fujita et al. [9][10][11] or stereoselective nucleophilic substitutions by Raymond et al. [12] are important examples in this context. Recently, we described the use of hierarchically assembled helicates as templates for stereoselective Diels–Alder reactions via a post-functionalization process [13

• off the stereoselectivity [13]. Herein we investigated the induction pathway and significantly optimized the stereoselectivity of the reaction. Furthermore, a catalytic approach was introduced which paves the way to the final goal of supramolecular stereoselective catalysis with hierarchical helicates

• as homogeneous catalysts. Results and Discussion Stereoselective Diels–Alder reactions in the periphery of hierarchically assembled helicates Elucidating the induction pathway of the Diels–Alder reaction is vital for the optimization of the system described above and for the development of future

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

• sumanene (2), it is not only gifted with three benzylic positions stapled between the benzene rings of the triphenylene system but also possess the bowl-curvature which enables stereoselective functionalization at these valuable positions. Taking the advantage of these benzylic positions, two years later

• the trideuteriosumanene 33 in a stereoselective manner from the same trianion 31 just by trapping it with CD3OD/CH3OD (Scheme 5). In the same paper, they have also reported the hexaallylated sumanene 34 as well as hexa-p-methoxybenzylsumanene 35 by reacting sumanene (2) with allyl bromide and 4

• mono-substituted sumanene derivatives 49b–d in a stereoselective manner as can be inspected from Scheme 10 [41][42]. In another event, Amaya, Ito, Katoh and Hirao reported a vital building block 53 to extend the π-conjugation bidirectionally through regioselective functionalization (Scheme 11) [43]. To