Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

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

• fashion similar to that of the dihydropyranone 58 [16], the 1,4-addition of dimethyl copper lithium to 65 gave the desired cis-50 as a single diastereomer [31], allowing for a convergence with the route in Scheme 7. Alternatively, the Wittig methenylation of 63, followed by a silyl ether cleavage gave 66

Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines

• Vladimir Kubyshkin

Beilstein J. Org. Chem. 2020, 16, 1837–1852, doi:10.3762/bjoc.16.151

• diastereomers exhibited some differences. The cis-diastereomer 1 with the C–F bond pointing in the same direction as the carboxymethyl group, appeared more polar compared to the trans-isomer 2, where the direction was opposite (ΔlogPcis/trans ≈ −0.18). The same effect was observed in 4-hydroxyprolines as well

• one considers that the transition state proceeds through the C4-exo conformation, as shown in Figure 9A. In this scenario, the cis-diastereomer 3 1) readily favors the needed conformational state (vide supra), at the same time, 2) the CF3-group dipole is oriented perpendicular to the carbonyl-group

• dipole, and creates no repulsion. As the result, the transition state is energetically favored, and the rotation becomes faster. Conversely, in the other diastereomer 4, both factors disfavor the transition state: 1) the ring should adopt the disfavored C4-exo conformation with an axial CF3 group, and 2

Rearrangement of o-(pivaloylaminomethyl)benzaldehydes: an experimental and computational study

• Csilla Hargitai,
• Györgyi Koványi-Lax,
• Tamás Nagy,
• Péter Ábrányi-Balogh,
• András Dancsó,
• Gábor Tóth,
• Judit Halász,
• Angéla Pandur,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2020, 16, 1636–1648, doi:10.3762/bjoc.16.136

• experiments, and single-crystal X-ray measurement (Figure 3) as diastereomer racemates. When the reaction of 1e was carried out under the same conditions in THF instead of DCM, HPLC–MS analysis of the crude product mixture showed the presence of dimer-like product 23a (25%), the recovered starting material 1e

• possible in case of a RR–SS diastereomer (23b), with only one of the aromatic hydrogen atoms of the isoindoline moiety [H(7)] located in close proximity above the middle of the other aromatic ring. It can be concluded after all that the NMR data also made it possible to assign the RS–SR diastereomeric

Distinctive reactivity of N-benzylidene-[1,1'-biphenyl]-2-amines under photoredox conditions

• Shrikant D. Tambe,
• Kwan Hong Min,
• Naeem Iqbal and
• Eun Jin Cho

Beilstein J. Org. Chem. 2020, 16, 1335–1342, doi:10.3762/bjoc.16.114

• electron density or position of the substituent on the benzylidene moiety. Interestingly, the homocoupling process was highly stereoselective, resulting in the formation of only one diastereomer, probably due to the bulky substitution pattern of the substrates. The structure of the homocoupled 1,2-diamine

Preparation of 2-phospholene oxides by the isomerization of 3-phospholene oxides

• Péter Bagi,
• Réka Herbay,
• Nikolett Péczka,
• Zoltán Mucsi,
• István Timári and
• György Keglevich

Beilstein J. Org. Chem. 2020, 16, 818–832, doi:10.3762/bjoc.16.75

• -diastereomers (cis- and trans-10) were separated by column chromatography, and they were identified by nuclear Overhauser effect (NOE) NMR spectroscopy. In the ROESY spectrum of the cis-diastereomer (cis-10), the phenyl 1H resonances give NOE/ROE crosspeaks with the C(4)H and one of the C(5)H2 1H resonances. By

• contrast, in the spectrum of trans-diastereomer (trans-10), phenyl 1H resonances give NOE/ROE crosspeaks with C(4)-methyl and the other one of the C(5)H2 1H signals (see Supporting Information File 1 for details). Thus, based on the distinctive NOE patterns of phenyl resonances, the two diastereomers (cis

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

• addition of benzylic–Cu intermediates to imines proceeds through a flexible linear transition state which is sensitive to the steric environment surrounding the copper catalyst. This observation provided the opportunity to achieve either diastereomer depending on the choice of the ligand L45 or L46. Based

Ultrasonic-assisted unusual four-component synthesis of 7-azolylamino-4,5,6,7-tetrahydroazolo[1,5-a]pyrimidines

• Yana I. Sakhno,
• Maryna V. Murlykina,
• Oleksandr I. Zbruyev,
• Anton V. Kozyryev,
• Svetlana V. Shishkina,
• Dmytro Sysoiev,
• Vladimir I. Musatov,
• Sergey M. Desenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2020, 16, 281–289, doi:10.3762/bjoc.16.27

• 2D NMR experiments), and X-ray diffraction analysis. The signals in the 1H and 13C NMR spectra of some of the compounds 4 were duplicated. This could have been caused by two reasons, namely by free rotation of the azolyl fragment in the position 7 or by the presence of a second diastereomer. To

• pyrimidine NH group and cross-peaks of the NH group with protons of the aromatic system, thus excluding structure B (Figure 1). Eventually, the structure of tetrahydropyrimidines 4 was proven by X-ray analysis carried out for a single crystal of one diastereomer of compound 4g, which allowed assignment of

Unexpected one-pot formation of the 1H-6a,8a-epiminotricyclopenta[a,c,e][8]annulene system from cyclopentanone, ammonia and dimethyl fumarate. Synthesis of highly strained polycyclic nitroxide and EPR study

• Sergey A. Dobrynin,
• Igor A. Kirilyuk,
• Yuri V. Gatilov,
• Andrey A. Kuzhelev,
• Olesya A. Krumkacheva,
• Matvey V. Fedin,
• Michael K. Bowman and
• Elena G. Bagryanskaya

Beilstein J. Org. Chem. 2019, 15, 2664–2670, doi:10.3762/bjoc.15.259

• hydrogens in the azepine ring: electrocyclization proceeds via a conrotatory mechanism due to the antisymmetry of the HOMO (Figure 2). The selective formation of a single diastereomer in the 1,3-dipolar cycloaddition reaction is likely a result from secondary interactions of orbitals of the π-systems of the

• : the electrocyclization proceeds via a conrotatory mechanism due to the antisymmetry of the HOMO. Selective formation of a single diastereomer in the 1,3-dipolar cycloaddition reaction. X-ray structure of compound 6 (one of the two enantiomers present in the crystal). A, B) Temperature dependence of

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

• optimization procedures (Scheme 2). The overall yield of the isolated epimers was 92%. According to Binder et al. [17] and our own experience [18], we expected the syn-product (2-syn) to be the main diastereomer. However, the determination of the configuration is not possible by NMR analysis. Consequently, the

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• 88. Ester exchange of 88 with (+)-8-phenylmenthol gave the key cyclization precursor 16. Oxidative radical cyclization of 16 in the presence of Mn(OAc)3 and Yb(OTf)3·H2O afforded the major tricyclic diastereomer 89 (dr = 38:1). Then the construction of the unsaturated lactone was performed by

• epoxide as a single diastereomer via in situ-generated methyl(trifluoromethyl)dioxirane and the reduction of the C-14 ketone in the presence of Eu(fod)3 to give triptolide (47%) together with its C-14 α-hydroxy epimer epi-triptolide (47%). In 2014, Li’s group reported a divergent synthesis for triptolide

Host–guest interactions in nor-seco-cucurbit[10]uril: novel guest-dependent molecular recognition and stereoisomerism

• Xiaodong Zhang,
• Wei Wu,
• Zhu Tao and
• Xin-Long Ni

Beilstein J. Org. Chem. 2019, 15, 1705–1711, doi:10.3762/bjoc.15.166

• and Discussion We took advantage of the two novel identical cavities and the simple formation of ternary diastereomer complexes with NS-CB[10]-based host-1 and host-2. The size of each cavity of host-1 is similar in size to Q[7], and the cavity size of host-2 is close to that of Q[6]. We first

Genomics-inspired discovery of massiliachelin, an agrochelin epimer from Massilia sp. NR 4-1

• Jan Diettrich,
• Hirokazu Kage and
• Markus Nett

Beilstein J. Org. Chem. 2019, 15, 1298–1303, doi:10.3762/bjoc.15.128

• . A compound which was found to be predominantly produced under iron deficiency was subsequently isolated. Its structural characterization by spectroscopic and bioinformatic analyses revealed a previously not known diastereomer of the cytotoxic alkaloid agrochelin. The structure of this natural

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

• . The study of the solvent effect on the reaction are summarized in Table 2. As can be seen from Table 2, the dr value decreases when using more polar solvents. An individual diastereomer 8a is formed when toluene is used as a solvent (Table 2, entry 1). The highest reaction rate and enantioselectivity

• are also achieved in toluene. Considering these factors, toluene was chosen as the best solvent for this reaction. The obtained experimental data show that in some cases the formation of diastereomer (2R,3S)-8a or diastereomer (2S,3S)-9a as the major one is observed depending on the type of catalyst

• have shown, during the first 12 hours, one diastereomer (2R,3S)-8a was formed predominantly (dr 8a:9a of more than 14:1). During this time, the conversion reached 71%. Only after this period, the appearance of the significant amount of second diastereomer (2S,3S)-9a was recorded. After 24 hours, the dr

Bambusuril analogs based on alternating glycoluril and xylylene units

• Tomáš Lízal and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2019, 15, 1268–1274, doi:10.3762/bjoc.15.124

• in favor of 1a-1 which remained constant at even lower temperature. By application of the Boltzmann distribution to the conformer population, we have calculated that 1a-1 is more stable by 0.13 kcal mol−1 than 1a-2. Conformer 1a-1 is preferred probably due to its higher symmetry. Diastereomer 1b was

• the orientation of one glycoluril unit were obtained. The building blocks within the macrocycles connected via methylene bridges are flexible giving rise to two preferred conformers for each diastereomer. These conformers were identified by molecular modelling and also by low-temperature NMR

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

• protocol provided a small library of steroidal 2,5-diketopiperazines 6 obtained as a single diastereomer, thus proving the high diastereoselection of the initial Ugi-4CR with the steroidal carbonyl substrate. In the 2,5-diketopiperazine ring, the configuration of the new asymmetric center C-3’ was S, a

• (3CR) developed by Barluenga et al. [35] to steroids. The original Barluenga’s 3CR comprises the reaction of salicylaldehyde with an alkyl orthoformate and 4-pentyn-1-ol to obtain a 4-alkylchroman spiroketal as a single diastereomer. However, as shown in Scheme 10, the employment of alkynyl-4,5

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

• (≈80:20 dr) with reactive organohalides (Scheme 4) [17]. The process was valuable, because it allowed direct elaboration of a chiral pool building block that was readily available as either antipode [22][23], with the major alkylated diastereomer 15 being generated in 97:3 er [18]. The study was also

• separable 76:24 mixture of alkylated tartrates 17 and 18, respectively. The relative stereochemistry was assigned by analogy with Seebach’s findings for substituted tartrates: that the diastereomer with the ring methine cis to the ester group (i.e., 17) always displays the higher chemical shift (≈5 ppm vs

• ≈4.5 ppm in CDCl3) [18], and was further supported by 1D NOESY experiments on both alkylated tartrates 17 and 18. The use of DMPU as co-solvent [18][25] reversed the ratio, with the currently undesired diastereomer 18 becoming favoured (37:63, 17:18). However, with HMPA the proportion of 17 improved

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

• :19 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 31 (c 1, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 7.41–7.24 (m, 20H), 4.97 (d, J = 9.2 Hz, 1H), 4.94 (d, J = 8.4 Hz, 1H), 4.78 (d, J

• , 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

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

• can be partly separated. Their diastereoselectivities can be further enhanced by slow evaporation of the corresponding diastereomers from acetonitrile and the absolute configuration of one diastereomer was confirmed with X-ray crystal structure (Supporting Information File 1, Figure S2). After

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

• electrochemical synthesis of axially chiral biaryls. Reaction conditions: undivided cell, 2 (0.3 mmol), H2O (1 mL), MeCN (9 mL), 3.5 F mol−1. aIsolated yield of the major diastereomer. bDetermined by 1H NMR analysis of crude reaction mixture. cCombined yield of the two diastereomers. Proposed reaction mechanism

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

• ) Photocatalytic oxyamination, b) photocatalytic diamination, and c) proposed mechanism for photocatalytic oxyamination using copper(II) as a terminal oxidant. Scope studies for dual-catalytic alkene difunctionalization using 2.5 mol % 3, 30 mol % Cu(TFA)2, and a 15 W blue flood lamp. Diastereomer ratios >20:1

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

• phosphinite 6a which afforded a 73:27 mixture of the diastereomeric phosphine oxides 7a/7’a (86%). The major diastereomer 7a corresponds to a sigmatropic rearrangement occurring on the most hindered face (cis to the aromatic group) of the cyclopropene which was somewhat surprising. Substitution at the para

• -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

• (7d/7’d = 52:48) were present. An inversion of the face selectivity was detected in favor of diastereomer 7’e (7e/7’e = 43:57) arising from the rearrangement of phosphinite 6e possessing a p-trifluoromethylphenyl substituent. Replacement of the acetal protecting group of the hydroxymethyl substituent

Systematic synthetic study of four diastereomerically distinct limonene-1,2-diols and their corresponding cyclic carbonates

• Hiroshi Morikawa,
• Jun-ichi Yamaguchi,
• Shun-ichi Sugimura,
• Masato Minamoto,
• Yuuta Gorou,
• Hisatoyo Morinaga and
• Suguru Motokucho

Beilstein J. Org. Chem. 2019, 15, 130–136, doi:10.3762/bjoc.15.13

• their characteristic signals. Keywords: cyclic carbonate; diastereomer; diol; limonene; NMR; Introduction (R)-Limonene (LM) is a naturally occurring terpene, and therefore a very attractive and renewable resource [1]. Its derivatives have versatilely and widely been studied [1][2][3][4]. Otherwise

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• the syn diastereomer 18 in high stereoselectivity (93:7). After silylation of the free hydroxy group, the cleavage of the PMB ether with DDQ led to alcohol 20 in 77% yield for the two steps. Ring-closing metathesis of diene 21, obtained by O-vinylation of 20, gave the dihydropyran 22 in 53% overall

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

• Gisela V. Saborit,
• Carlos Cativiela,
• Ana I. Jiménez,
• Josep Bonjoch and
• Ben Bradshaw

Beilstein J. Org. Chem. 2018, 14, 2597–2601, doi:10.3762/bjoc.14.237

• . Gratifyingly, treatment of 4 with TiCl4 in the presence of commercially available 1-methyl-1-(trimethylsilyl)allene at −78 °C for 1 h afforded the desired cis-6,5-bicylic core 5 in 63% yield as a single diastereomer. The desilylated product 6 was also obtained as a mixture of diastereomers. The high

Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety

• Alex Frichert,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222

• conversion to the diastereomer by oxidation and reduction. Conformational analysis of some of the resulting diols obtained under McMurry conditions was complicated by the presence of several conformers of similar energy. The pinacol coupling appears to start at the ketone, as indicated by the selective

• , those conformations are within 10 kJ/mol range of each other. However, only one of those conformations shows the required short distance between 14-H and 3-CH3, making the configuration (2R,3S,14R) probable for diastereomer 18. In the preferred conformation of 18, all non-sp3-hybridized carbon atoms of

• the ring system and the adjacent atoms are located almost in plane, whereas the isopropyl group and ring carbons C3 and C4 are located on opposite sides of that plane. Since the oxidation/reduction sequence has affected the configuration at C2, diastereomer 19 is assigned the configuration (2S,3S,14R