Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• yield and high enantioselectivity (Scheme 7) [15][16]. The Achmatowicz oxidation and ionic reduction generated the enone 58, which is regioisomeric with 53. The 1,4-addition of lithium dimethylcopper gave the desired cis-55 with high a diastereoselectivity (25:1). The cross-metathesis of 55 with 3

• with a 6:1 diastereoselectivity. The Red-Al reduction of 94, protection of the 2° alcohol, and reduction of the enoate to an allylic alcohol were prerequisites for the stereoselective 2,3-sigmatropic selenoxide rearrangement to generate 95. Further protecting group manipulation and Johnson–Lemieux

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• equiv of NMO, yielding bicyclic derivatives 19 in moderate yields and high diastereoselectivity (de > 95%). The observed diastereoselectivity was rationalized considering two transition states of the PKR, and assuming the CF3 group occupies an axial position due to the steric and electrostatic

• )8 followed by the addition of NMO), and starting from the pure anti diastereoisomer of 1,7-enyne 20, the expected bicyclic enone was obtained in good yield and high diastereoselectivity (de > 95%). An attempt to extend the PKR to the formation of a fused tricyclic structure, starting from 1,7-enyne

• -propargyl-N-[2-(trifluoromethyl)allyl]amides 24 were treated with dicobalt octacarbonyl to afford the cobalt alkyne complex, which was then heated in CH3CN. Under these conditions, trifluoromethylated cyclopentenone 25a was obtained in high yield (81%) and diastereoselectivity (anti/syn = 94:6) (Scheme 11

NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

• Alyn T. Davies,
• Mark D. Greenhalgh,
• Alexandra M. Z. Slawin and
• Andrew D. Smith

Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129

• tolerated, giving a consistent diastereoselectivity of ≈75:25 dr (Scheme 2). Following chromatographic purification, the desired products 12–14, respectively, were isolated in 59–71% yield as single diastereoisomers with excellent enantioselectivity (95:5 to >99:1 er). The relative and absolute

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• -one [28] and benzo[a]quinolizin-4-one [27], respectively, in moderate yields. Attempts by Krasavin et al. showed that isoquinoline itself demonstrated modest reactivity and diastereoselectivity in reactions with thiodiacetic anhydride (8) [12]. It can be concluded that due to their stability the

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• both (R) and (S)-isomers, and 1,1-diphenylethene (216c) under UV irradiation. As the products spirothietane-pyrrolidinones 320 were obtained in 65–89% yield. The diastereoselectivity was controlled by the steric effect of the ortho-substituents on the phenyl ring [88] (Scheme 59). The intermolecular

• photochemical [2 + 2] cycloaddition reaction was performed both in benzene solution and in the solid state, affording 78% yield with a ratio of syn/trans 8.7:1 and 61% de for syn-isomers at 15 °C in crystals, while no diastereoselectivity could be observed in benzene solution [16] (Scheme 72). In 2001, they

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• materials, which were accompanied by a decomposition residue. In contrast, maleimides 7b and 7c reacted efficiently to furnish the respective endo/exo adducts 9a–d/10a–d in good to high endo diastereoselectivity and yields (Table 2, entries 1–4). The cycloaddition with 7c led to the best selectivity (vide

• diffraction crystallography of both endo 9m and exo 10m adducts (Figure 2) [43]. In addition, the thermal cycloadditions of 2-vinylpyrroles 8a–j and maleimides 7b,c took place satisfactorily to deliver the expected adducts 9e–p/10e–p, also with high endo diastereoselectivity and good yields (Table 2, entries

• . Accordingly, the R2 substituent in the diene would play an important role in directing the endo/exo orientation of the approach to the maleimide at the transition state (TS). Therefore, the endo diastereoselectivity is apparently not controlled by the presence or the absence of the substituent bonded to the

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

• -hydroxypyrrolidines certainly makes the 4-hydroxyisoxazolidines important and valuable structural fragments in drug discovery. Keywords: 2,3-dihydroisoxazoles; diastereoselectivity; heterocycles; hydroboration–oxidation; isoxazolidin-4-ols; Introduction 2,3-Dihydroisoxazoles (often referred to as 4-isoxazolines

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

• were formed with complete diastereoselectivity, leading to a single isomer. In order to establish the structure of the isomers, a single crystal obtained for compound 9c was studied by X-ray diffraction analysis which showed, that the Ph(C-2) group and Fc(C-5) substituent were mutually cis-oriented

• (Figure 1). Tentatively, the same configuration was also attributed to all tetrahydrothiophenes 9a,f–l that were formed as single isomers (Table 1). However, the diastereoselectivity changed in reactions that were conducted with alkyl ferrocenyl thioketones 8d–e with 5a. Thus, the reaction with 8d led to

• these observations it was difficult to explain the complete diastereoselectivity of tetrahydrothiophene formation observed in the reactions of aryl ferrocenyl-substituted thioketones 8a,c,f with cyclopropanes 5a–f bearing aryl groups. Tentatively, a repulsive interaction of aryl groups rather than

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

• structures due to the poor diastereoselectivity of the Diels–Alder reaction in this case. Finally, we expect to apply this strategy to complementary reactions like the Pauson–Khand reaction that may be useful to cyclize enyne substrates like 5–7 and expand the spirosteroid diversity. All compounds will be

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• , and could even be extended to functionalized sulfonyl cyanides, though providing lower yields. In every case, the diastereoselectivity was high (dr > 19:1:1) and in favor of the all-trans-product. Conclusion In this review, we summarized the photophysical properties of aromatic aldehydes and the

Efficient synthesis of dipeptide analogues of α-fluorinated β-aminophosphonates

• Marcin Kaźmierczak and
• Henryk Koroniak

Beilstein J. Org. Chem. 2020, 16, 756–762, doi:10.3762/bjoc.16.69

• studies, the Pudovik reaction worked with satisfactory yield and diastereoselectivity [30]. Unfortunately, we were not able to isolate the pure anti-isomer in every case. The latest research shows that this reaction can successfully be carried out under milder conditions, without any solvent and in the

• presence of a weak base [33]. After testing many modifications, it turned out that the use of triethylamine (1 equiv) as a base, and without a solvent, gave the best results with aldehydes 4 (1 equiv) and diethyl phosphite (1 equiv). These conditions not only increased the diastereoselectivity of the

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

Asymmetric synthesis of CF₂-functionalized aziridines by combined strong Brønsted acid catalysis

• Xing-Fa Tan,
• Fa-Guang Zhang and
• Jun-An Ma

Beilstein J. Org. Chem. 2020, 16, 638–644, doi:10.3762/bjoc.16.60

• may bring about a complementary catalytic platform. Encouragingly, the targeted CF2-functionalized aziridine 4a was obtained in up to 51% ee and high diastereoselectivity, albeit in a low yield (Table 1, entries 1 and 2). The difficulty in further improving the conversions might be ascribed to the

• free aziridine 5a in 81% yield while maintaining the ee value. The reduction of the carbonyl moiety with either NaBH4 or LiAlH4 produced hydroxy-substituted CF2-functionalized aziridine 5b in excellent yield with exclusive diastereoselectivity [47]. Furthermore, the ring-opening of 4a under acidic

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

• . Subsequent addition of 2-pyridinecarboxaldehyde (130) afforded the hydroxy intermediate 131 with a high diastereoselectivity bias towards the (Rp,R)-isomer. The racemic mixture could be separated by chromatography. Dehydroxylation of intermediate (Rp,R)-131 by using palladium on carbon as catalyst furnished

Functionalization of the imidazo[1,2-a]pyridine ring in α-phosphonoacrylates and α-phosphonopropionates via microwave-assisted Mizoroki–Heck reaction

• Damian Kusy,
• Agata Wojciechowska,
• Joanna Małolepsza and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 15–21, doi:10.3762/bjoc.16.3

• , high diastereoselectivity, the wide substrate scope and its applicability to smaller (0.11 mmol) and larger scales (1.1 mmol). Substrates used for the Mizoroki–Heck reaction in this study. Structures of the identified side products 4 and 5. Scope of the method for analogs derived from 1 and 2. The

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

• generated from allyl fluoroacetates gave the corresponding α-fluoro-γ,δ-unsaturated acids [14]. The Ireland–Claisen rearrangement of Et3N-solvated enolates showed higher reactivity as well as diastereoselectivity when compared with analogous reactions in THF [15]. The required ester enolates are typically

• acids improved the diastereoselectivity and the reaction rate of silyl ketene acetals of (E)-allylic esters [21]. Chiral bromoboranes were used to form boranyl ketene acetals from ester enolates generated from allyl esters with tertiary amines. The geometry of the enolates depended strongly on the

• , as well as trimethylsilyl ketene acetal 2b generated from 1b, proceeded with similar yields and diastereoselectivity (Table 1, entries 3–6). However, the Ireland–Claisen rearrangement attempted with cinnamyl propionate (1c) did not take place when using LDA as a base (Table 1, entries 7 and 8). Next

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

• derived from (+)-camphor was the most effective one for asymmetric electroreductive hydrocoupling of cinnamates 161 [94][95]. The constant current electrolysis of 161 in an undivided cell resulted in acyclic homodimer 162 (with good yield and excellent diastereoselectivity) along with a certain percentage

• corresponding malonic ester derivatives 166, and the diastereomeric ratio was greatly affected by various electrochemical conditions, and higher yields (88%) were obtained at the expense of diastereoselectivity (dr 61:39) [166a + 166'a]. The authors next modified the chiral auxiliary and obtained the best

• substrates (181a, 181b), the products were formed with 100% diastereoselectivity (183a and 183b), whereas acyclic amines resulted in lower diastereoselectivity (183c and 183d) even though the intramolecular attack of the hydroxy group to the iminium bond in 182 preferentially occurred from the Si-face over

Indium-mediated C-allylation of melibiose

• Christian Denner,
• Manuel Gintner,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2019, 15, 2458–2464, doi:10.3762/bjoc.15.238

• concerning their effects on the conversion rate as well as the diastereoselectivity (Table 1). Concerning the metal species, it is known that indium provides several advantages compared to other allylation-mediating metals such as tin, as it allows the reaction to proceed under very mild conditions without

• -syn. However, the main species, 5-anti-β was obtained in 60% from this mixture (Figure 2). Conclusion For the first time, an indium-mediated allylation reaction was employed with a disaccharide, melibiose (Galpα1-6Glc, 1), as substrate, achieving good diastereoselectivity and excellent yields. Best

Application of chiral 2-isoxazoline for the synthesis of syn-1,3-diol analogs

• Juanjuan Feng,
• Tianyu Li,
• Jiaxin Zhang and
• Peng Jiao

Beilstein J. Org. Chem. 2019, 15, 1840–1847, doi:10.3762/bjoc.15.179

• diastereoselectivity (syn:anti >99:1) during the reduction. To unambiguously determine the diastereomeric ratio, the anti-1,3-diol corresponding to 10 was prepared from 7 by RuCl3–PPh3-catalyzed hydrogenation [63][64]. However, the two diastereomers had identical proton NMR spectra. The terminal hydroxy group of 10

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• diastereoselectivity of the addition of phenyllithium to the aldehyde (2S,1'R)-6 exceeded 80% and the major aziridine alcohol (2S,1'S,1''R)-28 could be separated chromatographically [29]. When (2S,1'S,1''R)-28 was hydrogenated in the presence of Boc2O N-protected (−)-norpseudoephedrine (1S,2S)-(+)-29 was obtained. To

• mixture of diastereoisomeric alcohols (2S,1'R,1''R)-78 and (2S,1'S,1''R)-78 with low (up to 33%) diastereoselectivity readily separable chromatographically. The sphingolipid analogue SG-14 (2S,3S)-84 was obtained from (2S,1'S,1''R)-78 as already described (Scheme 21) and was found to inhibit hSphK2 with

• secured in the starting aldehyde introduction of the two others required cis-dihydroxylation of the Z-alkene 111. The highest diastereoselectivity (99:1) was observed at −10 °C providing the aziridine diol (2S,1'S,2'R,1''R)-112 as a major diastereoisomer. The regioselective aziridine ring opening combined

Enantioselective PCCP Brønsted acid-catalyzed aza-Piancatelli rearrangement

• Gabrielle R. Hammersley,
• Meghan F. Nichol,
• Helena C. Steffens,
• Jose M. Delgado,
• Gesine K. Veits and
• Javier Read de Alaniz

Beilstein J. Org. Chem. 2019, 15, 1569–1574, doi:10.3762/bjoc.15.160

• a trans relationship between the C4 and C5 substituents [13][14][15]. It is believed that the 4π conrotatory electrocyclization step that converts the pentadienyl cation 5 into the corresponding cyclopentenone adduct 6 is responsible for controlling the relative diastereoselectivity in this cascade

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

• Alexander N. Reznikov,
• Anastasiya E. Sibiryakova,
• Marat R. Baimuratov,
• Eugene V. Golovin,
• Victor B. Rybakov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2019, 15, 1289–1297, doi:10.3762/bjoc.15.127

• catalytic Michael reaction itself was carried out with high diastereoselectivity, but the Michael adducts may epimerize at the C-2 position at a significant rate. Conditions for the preparation of individual diastereomers were found. Keywords: asymmetric catalysis; chiral diamine ligands; ketosulfones

• that the reaction of β-keto phosphonates with nitroalkenes in the presence of Ni(II) complexes with chiral vicinal diamines was carried out not only with excellent enantioselectivity, but also diastereoselectivity [55]. Moreover, β-keto sulfoxides react with nitroalkenes under catalysis by Ni(II

• -ketosulfone 5a was carried out with moderate to high enantioselectivity but low diastereoselectivity and led to the formation of two diastereomers (2R,3S)-8a and (2S,3S)-9a. Since we did not succeed in growing a crystal that was suitable for X-ray determination of the absolute configuration of 8а, we defined

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• , the authors found a high diastereoselectivity in the Ugi-4CR conducted with a carbonyl linked at C-17, a sterically crowed position very close to the axial methyl group placed of C-13. This step was implemented as part of the synthetic route toward steroidal 2,5-diketopiperazine 6, based on a strategy

• carbonyl is far away from the rigid chiral steroid, the Ugi reaction shows no significant diastereoselectivity, while the carbonyl component directly linked to the bulky steroidal nucleus – especially in α-position of a stereocenter – provides a very good diastereocontrol in the MCR. Dar et al. [18

• displaying biological activities such as antimicrobial, antiviral and anti-inflammatory, among others. Scheme 3 exemplifies the reaction of cholestan-6-one 7 with 2-aminopyridine and phenyl isocyanide to afford the heterocycle–steroid hybrid 8 in good yield and diastereoselectivity, whereas different

Ugi reaction-derived prolyl peptide catalysts grafted on the renewable polymer polyfurfuryl alcohol for applications in heterogeneous enamine catalysis

• Alexander F. de la Torre,
• Gabriel S. Scatena,
• Oscar Valdés,
• Daniel G. Rivera and
• Márcio W. Paixão

Beilstein J. Org. Chem. 2019, 15, 1210–1216, doi:10.3762/bjoc.15.118

• polyfurfuryl alcohol-supported catalysts for applications in heterogeneous enamine catalysis. The utilization of the polymer-supported catalysts in both batch and continuous-flow organocatalytic procedures proved moderate catalytic efficacy and enantioselectivity, but excellent diastereoselectivity in the

• amine and the enantio- and diastereoselectivity of the catalytic process. In this case, furfuryl derivatives – used either as amine or isocyanide component – were ligated [16] to the peptide skeleton aimed at assessing whether the position of the polymerizable handle was important for the

• ) due to the lack of the catalytic pyrrolidine moiety. On the other hand, PFA-supported catalysts 3 and 4 gave moderate to good yields depending on the solvent used. In general, polymeric catalyst 3 provided a better yield, enantio- and diastereoselectivity in the Michael adduct than 4 in all tested

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids

• Herman O. Sintim,
• Hamad H. Al Mamari,
• Hasanain A. A. Almohseni,
• Younes Fegheh-Hassanpour and
• David M. Hodgson

Beilstein J. Org. Chem. 2019, 15, 1194–1202, doi:10.3762/bjoc.15.116

• alkylating agent, which leads to the improved diastereoselectivity [43]. The trans stereochemistry assignment for the dialkylated products 34 follow from the observed equivalence of the acetonide methyl groups in all their proton and carbon NMR spectra. In Seebach's original studies, which established