CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• levels of diastereoselectivity (Scheme 48). Further development by Brigaud et al. allowed the synthesis of CF3-substituted pseudoprolines structurally related to oxazolidines 194 and 195 [124]. Viehe et al. also contributed by developing the chloroalkylamino reagent 199, bearing a geminal CF3 group

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

• majority of the substituents on the aryl group of the nitrostyrenes 1. However, a higher diastereoselectivity towards the endo-isomer was observed when strong electron-withdrawing groups (EWGs) were present in the dienophile. For example, in the case of the 4-cyano and the 3-nitro-substituted derivative

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

• ) catalysis of the cyclopropanation reaction, where complex 5a-Au(III) and 6a-Au(III) gave full conversion in 1 hour and 12 hours, respectively (Table 1, entries 4 and 5). The cyclopropyl product 11 was obtained in >90% yield and high cis diastereoselectivity (up to 74% de), similar to our previous studies

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• standard Ugi–azide reaction conditions [35][36][37][38][39] in a one-pot, tandem process. Subjecting glucose-derived lactam 1 to such a procedure gave the desired product in good yield, but with virtually no diastereoselectivity, as shown in Scheme 2. Optimization and scope An initial optimization study

• highest yield and diastereoselectivity, thus were chosen as optimal (Table 1, entry 9.). We also tried to isolate the imine after the reduction step and carry out the second step in a solvent commonly used for the Ugi–azide reaction alone. For this, we observed a significant decrease in overall yield and

Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation

• Alexander P. Molchanov,
• Mariia M. Efremova,
• Mariya A. Kryukova and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218

• investigated using only convection heating. The aim of the current work is to investigate the regio- and diastereoselectivity of the microwave-assisted (3 + 2) cycloaddition of 6-aryldiazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones. Results and Discussion Herein, we report the 1,3-dipolar

Asymmetric Mannich reactions of (S)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimines with yne nucleophiles

• Ziyi Li,
• Li Wang,
• Yunqi Huang,
• Haibo Mei,
• Hiroyuki Konno,
• Hiroki Moriwaki,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2020, 16, 2671–2678, doi:10.3762/bjoc.16.217

• )-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimine. The reactions were conducted under operationally convenient conditions affording the corresponding Mannich adducts with up to 87% yield and 70:30 diastereoselectivity. The isomeric products can be separated using regular column chromatography to

• diastereoselectivity. First, a series of pilot experiments in dichloromethane were performed to scan the base in the reaction. When using LDA and LiHMDS instead of n-BuLi, the yields were noticeably increased to 83% and 87%, respectively (Table 1, entries 2 and 3). In particular, the use of LiHMDS resulted in improved

• diastereoselectivity (69:31 dr, Table 1, entry 3). On the other hand, the solvent was found to show a significant effect on this transformation (Table 1, entries 4–6) and the results indicated dichloromethane was the best choice. Variation of the loading amount of 1-ethynyl-4-methoxybenzene (2a) did not provide any

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

• measurement of the yield and the diastereoselectivity was possible by NMR spectroscopy. The nitro-Michael reaction of 3 equivalents propanal (14) and β-nitrostyrene (15) with 25 mol % of 13a-H2 after 2 days at room temperature resulted in 45% yield of product 16 and a nearly 1:1 diastereomeric ratio (Table 2

• [(13b)1(5)5Ti2], but did not lead to a control of enantioselectivity. A reasonable diastereoselectivity of 60% de was observed for both catalysts. The limited solubility of these complexes caused a significant reduction of the yield at room temperature and due to this the reaction was not performed at

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

• Alexander N. Reznikov,
• Dmitry S. Nikerov,
• Anastasiya E. Sibiryakova,
• Victor B. Rybakov,
• Evgeniy V. Golovin and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174

• conjugated nitroolefins in the presence of a chiral Ni(II) complex to give nitro keto phosphonates with two stereocenters with excellent enantioselectivity and moderate to high diastereoselectivity. These products were used for a reductive cyclization leading to pyrrolidin-3-ylphosphonic acid and for

• to the possibility of creating enantiomerically pure compounds with several stereocenters through the directed regulation of diastereoselectivity in subsequent transformations, which can be realized as stepwise or cascade processes. Due to this reason, the Michael reaction was successfully used over

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