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

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• chiral amines, very low diastereoselectivity was obtained, probably due to the harsh reaction conditions employed. In addition to carbonyl and carboxyl derivatives, pyridine was also used successfully as an electron-withdrawing group (EWG) in the Michael acceptor 105. A simple control experiment allowed

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• dichloromethane (3 × 150 mL) after which the organic phases were pooled, dried with anhydrous sodium sulfate, filtered, and evaporated. The crude was purified with column chromatography (heptane/ethyl acetate 1:1) to give 3 (3.38 g, 89%) as a clear, viscous oil. The diastereoselectivity was determined to be α:β 1

• , 78%) as a clear, viscous oil. The diastereoselectivity was determined to be α:β 1:99 by HPLC, using the same protocol as is used for purity determinations. The stereochemistry of the β diastereomer, the only one isolated, was assigned using NOESY. [α]D20 −37 (c 0.1, CH3CN); 1H NMR (400 MHz, CDCl3) δ

• mg of 7 α/β-mixture as clear and viscous oils. The diastereoselectivity was determined to be α:β 1:2.3 by HPLC using the same protocol as is used for purity determinations. The stereochemistry was assigned using NOESY. Data for α-7: [α]D20 52 (c 0.2, CH3CN); 1H NMR (400 MHz, acetone-d6) δ 7.44–7.24

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• Information File 1). Homo-coupling of (S)-b with Ni(COD)2 was achieved with very high diastereoselectivity and only a single atropisomer was formed. The X-ray crystal structure showed that it is (M)-(S,S)-3 (Figure 1). This high atropstereoselectivity is believed to be due to the energetically unfavorable

An efficient synthesis of the guaiane sesquiterpene (−)-isoguaiene by domino metathesis

• Yuzhou Wang,
• Ahmed F. Darweesh,
• Patrick Zimdars and
• Peter Metz

Beilstein J. Org. Chem. 2019, 15, 858–862, doi:10.3762/bjoc.15.83

• olefin 14 delivered aldehyde 4 with considerably higher efficiency compared to the known six-step preparation of ent-4 from (−)-menthone [21]. Asymmetric Michael addition [7][8][10] of aldehyde 4 to methyl vinyl ketone (15) proceeded with high catalyst-controlled diastereoselectivity (dr = 23:1) to yield

A diastereoselective approach to axially chiral biaryls via electrochemically enabled cyclization cascade

• Hong Yan,
• Zhong-Yi Mao,
• Zhong-Wei Hou,
• Jinshuai Song and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2019, 15, 795–800, doi:10.3762/bjoc.15.76

• imidazopyridine-containing biaryls via central-to-axial chirality transfer (Scheme 1). Results and Discussion The substituents on the phenyl ring (R1) and at the propargylic position (R2) of carbamate 2 were varied to study their effects on the diastereoselectivity (Table 1). The electrolysis was conducted under

• imidazopyridine-based biaryl 3a in 68% yield with good diastereoselectivity (14:1 dr). Replacing the t-Bu group at the propargylic position with iPr (Table 1, entry 2) or on the phenyl ring with Ph (Table 1, entry 3) or OiPr (Table 1, entry 4) all resulted in low diastereoselectivity (2:1 to 3:1). The scope of

• tolerated albeit with reduced diastereoselectivity. The t-Bu group on the phenyl ring and at the propargylic position could be replaced with other bulky tertiary substituents to afford a range of functionalized biaryl products (3p–w). The electrochemical conditions were compatible with several functional

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• achieve good diastereoselectivity during the carbometalation reaction, few conditions needed to be fulfilled in the design of the starting cyclopropenyl ring (Figure 1): The presence of a coordinating group (such as an oxygen) at the C3 position is crucial for the selective facial addition of the incoming

• different types of cyclopropene precursors. We concentrated our efforts on the reaction of diversely substituted 3-methyl-3-arylcyclopropenes 6. In this case, as there is no coordinating functionality to dictate the facial selectivity, the control of the diastereoselectivity may be more challenging

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• -alcohol [53]. However, unlike in our case, the reaction proceeded with poor diastereoselectivity irrespective of the dihydroxylating agent used. To confirm the 1,3-anti diol stereochemistry of 7a, it was debenzylated using DDQ/CH2Cl2–H2O to furnish the trihydroxy compound 7a'. The 1H and 13C NMR spectra

Tandem copper and photoredox catalysis in photocatalytic alkene difunctionalization reactions

• Nicholas L. Reed,
• Madeline I. Herman,
• Vladimir P. Miltchev and
• Tehshik P. Yoon

Beilstein J. Org. Chem. 2019, 15, 351–356, doi:10.3762/bjoc.15.30

• ]. Subsequent oxidation of radical 7 by Cu(II) affords a formally cationic intermediate that is trapped by the carbamoyl oxygen to afford oxonium 8. The loss of the tert-butyl cation provides the oxyamination product 2, which can be isolated in good yields with excellent diastereoselectivity. Turnover of the

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• -position of the aromatic group at C3 significantly affected the diasteomeric ratio with an increase observed with the mesomeric donor methoxy group in favor of diastereomer 7b (7b/7’b = 78:22) compared to 7a/7’a, and a drop of diastereoselectivity when a fluorine atom (7c/7’c = 60:40) or a hydrogen atom

• diastereoselectivity. However, the sigmatropic rearrangement of the highly hindered di(tert-butyl)phosphinite 6j and tetra(isopropyl) phosphorodiamidite 6k did not occur (Scheme 7) [37]. The mechanism proposed by Rubin et al. involves a reversible addition of the Lewis base (DBU) on the cyclopropene double bond at C2

• activation barriers of the reactions leading to 8 and 8’, regardless of the aromatic substituent. Since 8 and 8’ were in rapid equilibrium with phosphinite 6, the diastereoselectivity should depend on the relative stabilities of the transition states TS1 and TS’1. An electron-donating group at the para

Synthesis of 1,2-divinylcyclopropanes by metal-catalyzed cyclopropanation of 1,3-dienes with cyclopropenes as vinyl carbene precursors

• Jesús González,
• Alba de la Fuente,
• María J. González,
• Laura Díez de Tejada,
• Luis A. López and
• Rubén Vicente

Beilstein J. Org. Chem. 2019, 15, 285–290, doi:10.3762/bjoc.15.25

• proceeded in reasonable yields while the diastereoselectivity strongly depends on the structure of the diene. An example of an intramolecular process as well as the use of furan and 1,4-cyclohexadiene as dienes are also reported. Keywords: cyclopropanation; cyclopropenes; dienes; divinylcyclopropanes