Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration–oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles

• Lívia Dikošová,
• Júlia Laceková,
• Ondrej Záborský and
• Róbert Fischer

Beilstein J. Org. Chem. 2020, 16, 1313–1319, doi:10.3762/bjoc.16.112

• of N/O-containing heterocycles used as the key intermediates in the synthesis of more complex cyclic and acyclic compounds, including various biologically active molecules. Here, we present a fast and highly stereoselective approach towards both C-3/4-cis and C-3/4-trans isomers of 3-substituted

• isoxazolidin-4-ols. The strategy relies on a highly regio- and trans-stereoselective hydroboration–oxidation reaction of the 4,5-unsubstituted 2,3-dihydroisoxazoles with basic hydrogen peroxide. The consecutive oxidation/reduction route, sequentially employing Dess–Martin periodinane and ʟ-selectride, is used

• hydroxylamines using malonoyl peroxide, providing N-tosylated 3-aryl-substituted 4-hydroxyisoxazolidines in a highly stereoselective manner in favor of the C-3/4-trans isomers [27]. We believe that the 3-substituted isoxazolidin-4-ols, represented by the general structures of the trans and the cis stereoisomer 3

Ferrocenyl-substituted tetrahydrothiophenes via formal [3 + 2]-cycloaddition reactions of ferrocenyl thioketones with donor–acceptor cyclopropanes

• Grzegorz Mlostoń,
• Mateusz Kowalczyk,
• André U. Augustin,
• Peter G. Jones and
• Daniel B. Werz

Beilstein J. Org. Chem. 2020, 16, 1288–1295, doi:10.3762/bjoc.16.109

• present study also demonstrated the growing potential of donor–acceptor cyclopropanes [24][25][26][27][28] as unique building blocks for current organic synthesis and especially for the efficient and highly stereoselective preparation of the relevant five-membered sulfur heterocycles derived from

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• Chemistry Centre, Departament of Chemistry, Faculty of Chemistry and Chemical Engineering, Babeş-Bolyai University, Str. Arany Janos 11, RO-400028 Cluj−Napoca, Romania 10.3762/bjoc.16.98 Abstract The stereoselective synthesis of truxillic bis-amino esters from polyfunctional oxazolones is reported. The

• -face arrangement, which is optimal for their [2 + 2] photocycloaddition. Irradiation of dimers 3 in CH2Cl2 solution with blue light (465 nm) promoted the chemo- and stereoselective [2 + 2] photocycloaddition of the exocyclic C=C bonds and the formation of cyclobutane-containing ortho-palladated

• of the free species [27] and on using Pd complexes as templates [28][29][30]. The latter approach has shown good potential as a synthetic tool because it allows 1,3-diaminotruxillic derivatives to be obtained in a fully regio- and stereoselective way (only the ε-isomer is obtained). The process

Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones

• Valeria Nori,
• Antonio Arcadi,
• Armando Carlone,
• Fabio Marinelli and
• Marco Chiarini

Beilstein J. Org. Chem. 2020, 16, 1084–1091, doi:10.3762/bjoc.16.95

• (Te), Italy 10.3762/bjoc.16.95 Abstract Cascade cyclocarbopalladation of the readily available aryl/alkyl-substituted propargylic amides containing an aryl iodide moiety, followed by Suzuki–Miyaura coupling with arylboronic acids, allowed an efficient regio- and stereoselective synthesis of

• stereoselective formation of carbon–carbon bonds [19]. Intramolecular palladium-catalyzed versions are particularly attractive, since they afford polycarbo- and heterocyclic systems via sequential reactions of the vinylpalladium intermediate [20][21][22][23][24][25]. In this field, a variety of regio- and

• stereoselective Pd-catalyzed cascade reactions, consisting of the addition of in situ-generated arylpalladium complexes over a proximate carbon–carbon triple bond, followed by cross-coupling reactions, have been reported [26][27][28][29][30][31]. Our continuing interest in the palladium-catalyzed reactions of

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

• co-workers also reported the reaction of the CuCF2PO(OEt)2 reagent with α-diazocarbonyl derivatives. Depending on the copper salt used for the generation of the copper reagent, the reaction with α-diazocarbonyl derivatives provided either the α-fluorovinylphosphonate, in a stereoselective fashion, or

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• pentafluoro-ʟ-phenylalanine derivatives 24a–c, respectively [41] (Scheme 5). The stereoselective benzylation of (S)-imidazolidinone ((S)-Boc-BMI) 25 with tetrafluorobenzyl bromides 26a,b afforded the benzylated imidazolidinones 27a,b. The acidic hydrolysis of 27a,b with simultaneous deprotection to release

• catalytic amination of (E)-cinnamic acid The enzyme phenylalanine aminomutase (PAM) from Taxus chinensis catalyzes the stereoselective isomerization of α-phenylalanine to β-phenyalanine 111a–c. Mechanistic studies showed that (E)-cinnamic acid is an intermediate in this transformation [63]. Accordingly

• formation [64]. 2.2. Stereoselective benzylic fluorination of N-(2-phenylacetyl)oxazolidin-2-one using NFSI Treatment of oxazolidinone 122 with N-fluorobenzenesulfonimide (NFSI) in the presence of NaHMDS afforded the fluorinated oxazolidinone derivative 123. The reductive removal of the chiral auxiliary

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• group publication [74] on new antimalarial drugs can be highlighted (Scheme 29). The authors report a 3.4 gram-scale preparation of ascaridole, in this case a synthetic intermediate, using TPP as photocatalyst. Another example of a scaled-up endoperoxide approach involves the stereoselective singlet

Diversity-oriented synthesis of 17-spirosteroids

• Benjamin Laroche,
• Thomas Bouvarel,
• Martin Louis-Sylvestre and
• Bastien Nay

Beilstein J. Org. Chem. 2020, 16, 880–887, doi:10.3762/bjoc.16.79

• enyne substrates, the one-pot reaction manifold enabled the anchorage of non-steroidal spirocyclic moieties at C-17. The procedure proved efficient and stereoselective with mestranol and lynestrenol derivatives incorporating a 2-tetrahydrofuranyl spirocycle at C-17. It was more difficult with 2-oxepanyl

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• and technologies [21][22][23][24][25][26][27][28][29][30]. Thus, numerous multistep total syntheses of organic compounds, including bioactive molecules [31][32][33][34][35] and natural products [36][37], have been performed in a highly chemo- and stereoselective manner through metathesis routes [38

• subsequent Eu(fod)3-catalyzed intermolecular Diels–Alder cycloaddition and epoxidation reactions (Scheme 5) [69]. In this stereoselective synthesis, the last biomimetic step was critical to obtain the proper enantiomer of the tetracyclic core of nanolobatolide. Amphidinolide macrolides Amphidinolides

• metathesis in tandem with a diene cross-metathesis as the crucial steps were reported by Lee in the total synthesis of (−)-amphidinolide E (3) (Scheme 6) [70]. It is noteworthy that the second-generation Grubbs catalyst was quite active and stereoselective for both the enyne and cross-metathesis steps

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• )- and (E)-alkenes 311 afforded the (E)-alkene 312 as the major product. The targeted γ-borylated compounds (relative to the leaving group) were formed, each with high enantioselectivity, which can be used for further stereoselective C–C and C–X (X = heteroatom) bond formation. Catalytic Cu(NHC)-mediated

• )boronates 320–322. High functional group tolerance and enantioselectivities are characteristics of this reaction. The stereoselective formation of a 3,3-disubstituted cyclopentene scaffold (e.g., 331), containing three contiguous asymmetric centers, was also developed starting from an achiral cyclic acetal

• conditions, a rare cross-coupling takes place (Scheme 62) [115]. The cooperative effect of a catalytic system consisting of Cu/Ni (e.g., Ni(acac)2, CuCl, and PCy3) was also reported by Nakao et al. leading to regio- and stereoselective arylboration of 1-arylalkenes with aryl chlorides or tosylates. The

Towards the total synthesis of chondrochloren A: synthesis of the (Z)-enamide fragment

• Jan Geldsetzer and
• Markus Kalesse

Beilstein J. Org. Chem. 2020, 16, 670–673, doi:10.3762/bjoc.16.64

• Hannover, Germany 10.3762/bjoc.16.64 Abstract The stereoselective synthesis of the (Z)-enamide fragment of chondrochloren (1) is described. A Buchwald-type coupling between amide 3 and (Z)-bromide 4 was used to generate the required fragment. The employed amide 3 comprising three chiral centers was

• provided alcohol 11 in an excellent yield which was subjected to aminolysis to provide amide 3 in seven steps and an overall yield of 16% [16][17][18][19][20]. Synthesis of (Z)-bromide 4 For the synthesis of (Z)-bromide 4 we chose a palladium-catalyzed, stereoselective dehalogenation as the key step

• ][19][20], whereas the (Z)-bromide 4 can be generated in a four-step sequence with a 39% overall yield, including a palladium-catalyzed, stereoselective dehalogenation [21][22][23][24][25]. Retrosynthetic analysis of chondrochlorene A (1). Synthesis of amide 3 [16][17][18][19][20]. TIPDSCl2 = 1,3

Synthesis of disparlure and monachalure enantiomers from 2,3-butanediacetals

• Adam Drop,
• Hubert Wojtasek and
• Bożena Frąckowiak-Wojtasek

Beilstein J. Org. Chem. 2020, 16, 616–620, doi:10.3762/bjoc.16.57

• Adam Drop Hubert Wojtasek Bozena Frackowiak-Wojtasek Institute of Chemistry, Opole University, ul. Oleska 48, 45-052 Opole, Poland ZWP EMITOR S.C., ul. Olimpijska 6, 45-681 Opole, Poland 10.3762/bjoc.16.57 Abstract 2,3-Butanediacetal derivatives were used for the stereoselective synthesis of

Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction

• Svetlana V. Amosova,
• Andrey A. Filippov,
• Nataliya A. Makhaeva,
• Alexander I. Albanov and
• Vladimir A. Potapov

Beilstein J. Org. Chem. 2020, 16, 515–523, doi:10.3762/bjoc.16.47

• a regio- and stereoselective manner affording 1,3-thiaselenol-2-ylmethyl vinyl selenides in high yields predominantly with Z-configuration. Not a single representative of the 1,3-thiaselenol-2-ylmethyl selenide scaffold has been previously described in the literature. Keywords: 2-(bromomethyl)-1,3

• -thiaselenole; nucleophilic addition; nucleophilic substitution; rearrangement; seleniranium intermediate; Introduction The regio- and stereoselective synthesis of organoselenium compounds based on selenium-centered electrophilic reagents has been one of the most important and effective directions in

• did not occur (Scheme 2). The high anchimeric assistance effect of the selenium atom in thiaselenole 1 is the driving force for the generation of the seleniranium intermediate 2. A fundamental approach to the regio- and stereoselective synthesis of unsaturated functionalized organoselenium compounds

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• usually lead to stereoselective reduction products, hence, they are used for the synthesis of chiral phosphines from chiral oxides [53]. Lithium tetrahydridoaluminate is used for the reduction of achiral phosphines because its action on optically active phosphine oxides leads mainly to the optically

• precursors. However, asymmetric synthesis can be used as strategy to introduce stereogenic P-atoms into the ligand’s backbone. The borane complexation approach is a unique stereoselective way for introducing a P-stereogenic center. Benoit et al. [2] reported on the synthesis of 2-phenyl-1,3,2

• steric properties, use of low-priced and easily available reagents, mild and expedient reaction conditions, and few reaction steps. The motifs can also be chiral, and this is helpful in stereoselective synthesis. The introduction of different moieties can bring about enhanced properties like fluorescence

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• possessing a Z geometry, as evinced by a NOE interaction between Hd and the methyl group. The cis relationship between the OH group and the pyrrolidine ring, resulting from the chemo- and stereoselective syn reduction of the carbonyl group, was evinced by NOESY-1D experiments showing intense NOE effects

Efficient method for propargylation of aldehydes promoted by allenylboron compounds under microwave irradiation

• Jucleiton J. R. Freitas,
• Queila P. S. B. Freitas,
• Silvia R. C. P. Andrade,
• Juliano C. R. Freitas,
• Roberta A. Oliveira and
• Paulo H. Menezes

Beilstein J. Org. Chem. 2020, 16, 168–174, doi:10.3762/bjoc.16.19

• there are several stereoselective methods described for the reaction of propargyl or allenyl organometallics with carbonyl compounds [8][9][10][11][12][13][14], the control of the regioselectivity is still a major concern. This is mainly due to the metallotropic rearrangement of propargyl and allenyl

Convenient synthesis of the pentasaccharide repeating unit corresponding to the cell wall O-antigen of Escherichia albertii O4

• Tapasi Manna,
• Arin Gucchait and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2020, 16, 106–110, doi:10.3762/bjoc.16.12

• intermediates, it was decided to proceed through a step-economic block synthetic strategy to achieve the target pentasaccharide derivative. Accordingly, stereoselective glycosylation of a ᴅ-galactosamine derivative 2 with a ᴅ-galactose thioglycoside derivative 3 in the presence of a combination [26][27] of N

• disaccharide acceptor 9 and the disaccharide thioglycoside donor 10, a stereoselective glycosylation between them was attempted in the presence of a combination [26][27] of NIS and HClO4/SiO2 as thiophilic activator. Unfortunately, the required tetrasaccharide derivative 11 was obtained in a poor yield (22

• %, Scheme 3). It was decided to follow a sequential glycosylation strategy to achieve a significant quantity of compound 11. Accordingly, a stereoselective glycosylation was carried out using compound 9 with ʟ-fucose thioglycoside derivative 6 in the presence of a combination [26][27] of NIS and HClO4/SiO2

[1,3]/[1,4]-Sulfur atom migration in β-hydroxyalkylphosphine sulfides

• Katarzyna Włodarczyk,
• Piotr Borowski and
• Marek Stankevič

Beilstein J. Org. Chem. 2020, 16, 88–105, doi:10.3762/bjoc.16.11

• stereoselective manner, given that corresponding chiral substrates were used for the cyclization. The chiral compounds suitable for cyclization could be obtained by desymmetrization of phosphine sulfides (Scheme 3) [58]. In order to gain insight into the cationic cyclization of β-hydroxyalkylphosphine sulfides, a

Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?

• Dominika Krištofíková,
• Juraj Filo,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2019, 15, 2948–2957, doi:10.3762/bjoc.15.290

• difficult due to their rather nonpolar transition states, which are difficult to be addressed by catalysts [29]. Several stereoselective [3,3]-sigmatropic rearrangements are realized with chiral Brønsted acids [30][31][32][33][34]. Jacobsen reported guanidinium-catalyzed enantioselective Claisen

Progress in metathesis chemistry

• Karol Grela and
• Anna Kajetanowicz

Beilstein J. Org. Chem. 2019, 15, 2765–2766, doi:10.3762/bjoc.15.267

• been made over these years. For example, a number of new highly stereoselective Ru and Mo catalysts have been introduced, solving the problem of E- and Z-selectivity. Some tagged Ru catalysts can be applied in water and even in biological systems, while Mo and W alkylidenes packed into innovative wax

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• stereoselective organic electrochemical reactions along with the synthetic accomplishments achieved with these methods. Keywords: chiral auxiliary; chiral catalyst; chiral electrode; chiral electrolyte; chiral mediator; electroorganic chemistry; Introduction Electric current-assisted exchange of electrons

• 169 substituted with chiral auxiliaries to methyl vinyl ketone for stereoselective construction of the quaternary carbon centers in 170 (Scheme 54). While screening a number of chiral auxiliaries, the authors found that upon electrolysis under galvanostatic conditions at low temperature, the

• transformations, Feroci and Inesi developed a stereoselective carboxylation of cinnamic acid derivatives 171 substituted with chiral auxiliaries [99]. The substrate 171 was subjected to galvanostatic reduction under CO2 atmosphere in an undivided cell. Carboxylation followed by treatment with diazomethane

Synthetic terpenoids in the world of fragrances: Iso E Super^® is the showcase

• Alexey Stepanyuk and
• Andreas Kirschning

Beilstein J. Org. Chem. 2019, 15, 2590–2602, doi:10.3762/bjoc.15.252

• of the oxime derivative of (−)-(1R,2S)-Georgywood® ((−)-35) [33][34]. Corey´s asymmetric synthesis of Iso E Super Plus® ((+)-34) is initiated by a stereoselective Diels–Alder cycloaddition utilizing the CBS catalyst (36) to yield the cyclohexene derivative 42 with good facial selectivity [33

Safe and highly efficient adaptation of potentially explosive azide chemistry involved in the synthesis of Tamiflu using continuous-flow technology

• Cloudius R. Sagandira and
• Paul Watts

Beilstein J. Org. Chem. 2019, 15, 2577–2589, doi:10.3762/bjoc.15.251

• suitable azidating agent undergoes a highly regio- and stereoselective nucleophilic substitution of allylic O-mesylate at the C-3 position affording azide compound 5 (Scheme 3). Nie and co-workers [19] reported the treatment of mesyl shikimate 4 with NaN3 (4 equiv) in aqueous acetone (Me2CO/H2O 5:1) at 0

• stereoselective to the C-3 position [9][19][20][23]. The two OMs groups at C-4 and C-5 remaining intact as reported in batch [9][19][20]. The highly selective C-3 azidation is reasonable and easily understood because the C-3 position is much more reactive (allylic position) and less hindered (Figure 6). The

Chemical synthesis of the pentasaccharide repeating unit of the O-specific polysaccharide from Escherichia coli O132 in the form of its 2-aminoethyl glycoside

• Debasish Pal and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2019, 15, 2563–2568, doi:10.3762/bjoc.15.249

• manipulations on the commercially available monosaccharides and stereoselective chemical glycosylations. The 2-aminoethyl glycoside at the reducing end will facilitate further glycoconjugate formation without hampering the stereochemistry of the anomeric center. We have used similar glycosides in case of other

• stereochemistry of the reducing end sugar. The challenging stereoselective glycosylation with the galactofuranosyl unit was achieved through a chemoselective glycosylation approach depending on the higher reactivity of the furanose derivative over the pyranose system. Structure of the target pentasaccharide

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218