The synthesis of the 2,3-difluorobutan-1,4-diol diastereomers

• Robert Szpera,
• Nadia Kovalenko,
• Kalaiselvi Natarajan,
• Nina Paillard and
• Bruno Linclau

Beilstein J. Org. Chem. 2017, 13, 2883–2887, doi:10.3762/bjoc.13.280

• Robert Szpera Nadia Kovalenko Kalaiselvi Natarajan Nina Paillard Bruno Linclau Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, United Kingdom 10.3762/bjoc.13.280 Abstract The diastereoselective synthesis of fluorinated building blocks that contain chiral fluorine

A Brønsted base-promoted diastereoselective dimerization of azlactones

• Danielle L. J. Pinheiro,
• Gabriel M. F. Batista,
• Pedro P. de Castro,
• Leonã S. Flores,
• Gustavo F. S. Andrade and
• Giovanni W. Amarante

Beilstein J. Org. Chem. 2017, 13, 2663–2670, doi:10.3762/bjoc.13.264

• Brønsted base system for the diastereoselective dimerization of azlactones using trichloroacetate salts and acetonitrile has been developed. Desired products were obtained in good yields (60–93%) and with up to >19:1 dr after one hour of reaction. Additionally, the relative stereochemistry of the major

• dimer was assigned as being trans, by X-ray crystallographic analysis. The kinetic reaction profile was determined by using 1H NMR reaction monitoring and revealed a second order overall kinetic profile. Furthermore, by employing this methodology, a diastereoselective total synthesis of a functionalized

• bond formation, such as a dimerization process. We herein report a diastereoselective dimerization of azlactones using potassium or sodium trichloroacetate salts and acetonitrile as solvent. Besides, a reaction mechanism is proposed based on NMR studies and the relative stereochemistry of the major

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• Boc-Tyr-ψ[(Z)-CF=CH]-Gly using a diastereoselective Reformatsky–Honda condensation, a (E)-selective HWE olefination and a SmI2 reduction as key steps (Scheme 12) [41]. First, Reformatsky–Honda reaction of TIPS-protected phenylacetaldehyde 57 with the chiral auxiliary (L)-phenylglycine derivative 58

• cyclopentanone 90. A HWE olefination converted 90 into (Z)-monofluoroalkene 91 without any significant selectivity. The chiral Ellman’s sulfinylimine 92 was obtained in 3 steps. The diastereoselective addition of isopropyllithium was then possible to afford the (L)-Leu residue with a moderate selectivity (dr

• -ψ[(Z)-CF=CH]-Phe by Dory and co-workers. Diastereoselective addition of Grignard reagents to sulfinylamines derived from α-fluoroenals by Pannecoucke and co-workers. NHC-mediated synthesis of monofluoroalkenes by Otaka and co-workers. Stereoselective synthesis of Boc-Tyr-ψ[(Z)-CF=CH]-Gly by Altman

Synthesis of 1,3-cis-disubstituted sterically encumbered imidazolidinone organocatalysts

• Jan Wallbaum and
• Daniel B. Werz

Beilstein J. Org. Chem. 2017, 13, 2577–2583, doi:10.3762/bjoc.13.254

• accessible from amino acids, are widely used in these kinds of reactions [13][14][15][16][17][18]. More recent examples demonstrate the applicability in various reactions like diastereoselective α-fluorination [19], total syntheses [20][21], cross-dehydrogenative couplings [22], selectivity-reversed Friedel

Diastereoselective Mannich reactions of pseudo-C₂-symmetric glutarimide with activated imines

• Tatsuya Ishikawa,
• Tomoko Kawasaki-Takasuka,
• Toshio Kubota and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 2473–2477, doi:10.3762/bjoc.13.244

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• subsequent Boc protection [21]. Here we report on the diastereoselective synthesis of chiral N-sulfinyl propargylamines with amino acid type “side chains” attached to the propargylic position mediated by Ellman’s auxiliary. Enantiomerically pure amines can be obtained by condensation of aldehydes or ketones

• propargylamines by nucleophilic addition. The synthesis of propargylamines by diastereoselective reductive amination requires alkynyl ketones, which are difficult to prepare and are unstable towards reductive conditions. In approach I, organometallic nucleophiles are added to N-sulfinyl propargylimines, derived

• side chains in α-position, which are analogous or similar to amino acid side chains. In general, various aldehydes are condensed with Ellman’s chiral sulfinamide. Diastereoselective re-face addition of (trimethylsilyl)ethynyllithium to the (S)-configured sulfinimines 5 gives the corresponding N

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• proline derivatives. The diastereoselective cyclization, which was clearly supported by DFT calculations is noteworthy. Further developments and applications of these scaffolds are currently underway. Optimized geometries for the two conformers presenting interactions with either Ca (16a) or Cb (16b). H

Enzymatic separation of epimeric 4-C-hydroxymethylated furanosugars: Synthesis of bicyclic nucleosides

• Neha Rana,
• Manish Kumar,
• Vinod Khatri,
• Jyotirmoy Maity and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2017, 13, 2078–2086, doi:10.3762/bjoc.13.205

• ), diisopropyl ether (DIPE), toluene and dioxane. We carried out all ten sets of reactions for diastereoselective acetylation of epimeric mixtures of ribo- and xylotrihydroxyfuranosides 3a,b by using vinyl acetate at 30, 35, 40 and 45 °C and at 250 rpm in an incubator shaker to evaluate the appropriate lipase

• their detailed crystallographic data have been deposited in the Cambridge Crystallographic Data Centre with CCDC No. 1533725, 1533768 and 1532373, respectively. Conclusion A highly efficient and diastereoselective catalyzed Novozyme®-435-catalyzed acetylation methodology has been developed for the

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• phase-transfer catalysis for α-sulfenylation reactions date back almost 20 years, when Wladislaw and co-workers described the diastereoselective α-sulfenylation of chiral β-ketosulfoxides 29 in the presence of achiral and chiral PTCs (Scheme 14, upper reaction) [127][128][129]. In a detailed

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• obtained according to literature procedures [133], thus setting the stereochemistry at C12. The five-step sequence from 20 to vinyl iodide 21 included a (poorly diastereoselective) epoxidation, epoxide opening with a propynyl anion and a hydrozirconation/iodination reaction to generate the vinyl iodide

• iodide 21. As illustrated in Scheme 2, the nine-step synthesis of the latter proceeded via key epoxide 30 and comprised a diastereoselective alkylation of diethyl (S)-malate according to Seebach and Wasmuth [136] to introduce the C12-methyl group (dr = 8:1). Although being longer than the 1st generation

Effect of uridine protecting groups on the diastereoselectivity of uridine-derived aldehyde 5’-alkynylation

• Raja Ben Othman,
• Mickaël J. Fer,
• Laurent Le Corre,
• Sandrine Calvet-Vitale and
• Christine Gravier-Pelletier

Beilstein J. Org. Chem. 2017, 13, 1533–1541, doi:10.3762/bjoc.13.153

• modest diastereoselectivities (65:35) in favor of the 5’R-isomer, whereas O-silyl groups promoted higher diastereoselectivities (up to 99:1) in favor of the 5’S-isomer. A study related to this protecting group effect on the diastereoselectivity is reported. Keywords: diastereoselective alkynylation

• diastereoselective addition of a nucleophile on a carbonyl group. The latter can involve either the reduction of a ketone at C-5’ [12][33][34][35], or the addition on an aldehyde of various nucleophiles such as enolates [15][36][37][38], allylborane [39], dialkyl phosphites [40], TMSCN [41] or Grignard reagents [12

• ratio (Table 2, entry 15). The three attempts of C-5’ alkynylation of N-3-allylated uridine aldehydes, did not revealed marked influence on the diastereoselective ratio (Table 2, entries 3, 8, 15). To explain the diastereoselective outcome of the reaction, we first considered Cram chelated models

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• isolate several exclusively β-glycosyl sulfonohydrazide (GSH) donors in very high yields (Figure 6) [92][93]. Furthermore, both C2–OH and 2-deoxy-2-NHAc saccharides were compatible with their conditions. Their initial study [92] focused on the diastereoselective glycosylation of 2-deoxy-2-NHAc sugars

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• Scheme 9. After reduction the alcohol was protected with TIPS and the TBS ether was cleaved by acetic acid to get to the primary alcohol 43. The reduction with (S)-alpine borane was highly diastereoselective (dr > 20:1). Following this sequence over 6 steps the two stereogenic centers at C7 and C8 were

A concise and practical stereoselective synthesis of ipragliflozin L-proline

• Shuai Ma,
• Zhenren Liu,
• Jing Pan,
• Shunli Zhang and
• Weicheng Zhou

Beilstein J. Org. Chem. 2017, 13, 1064–1070, doi:10.3762/bjoc.13.105

• key step was the diastereoselective synthesis of pivaloyl-protected 5 (Scheme 2). Thus, this reaction was studied in more detail to screen the best conditions, and the results were presented in Table 1. On the basis of literature [12], 2-[(5-bromo-2-fluorophenyl)methyl]-1-benzothiophene (4b) [9] was

Phosphazene-catalyzed desymmetrization of cyclohexadienones by dithiane addition

• Matthew A. Horwitz,
• Elisabetta Massolo and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2017, 13, 762–767, doi:10.3762/bjoc.13.75

• base organocatalyzed addition (Scheme 1). This reaction would lead to bicyclic systems with the salient attribute of having a convex-concave facial differentiation, allowing subsequent diastereoselective transformations. With the aim of using a dithiane nucleophile, we selected 1,3-dithiane-2

• appreciable enantioselectivity was observed. To investigate the feasibility of a convex-facial addition, we subjected 2a to Luche reduction conditions (Scheme 3). We found this transformation to be completely diastereoselective, and an X-ray diffraction study [58] of the product confirmed our hypothesis

• to undergo diastereoselective convex-facial additions. The carbonyl deprotection was unsuccessful and we hope that our efforts can serve as a cautionary tale for future synthetic planning involving related structures. Chiral iminophosphorane catalysts surveyed. Desymmetrization of cyclohexadienone by

Continuous-flow processes for the catalytic partial hydrogenation reaction of alkynes

• Carmen Moreno-Marrodan,
• Francesca Liguori and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2017, 13, 734–754, doi:10.3762/bjoc.13.73

• wall and minimize diffusion limits (Figure 2). Without bubbles, the yield of 4a would have been ca. 57% at the same residence time. The catalyst was used for weeks without significant deactivation. 1-Cyclohexyl-2-methyl-3-butyn-1-ol In the course of their studies on diastereoselective chain-elongation

Synthesis of new pyrrolidine-based organocatalysts and study of their use in the asymmetric Michael addition of aldehydes to nitroolefins

• Alejandro Castán,
• Ramón Badorrey,
• José A. Gálvez and
• María D. Díaz-de-Villegas

Beilstein J. Org. Chem. 2017, 13, 612–619, doi:10.3762/bjoc.13.59

• organocatalysts with a bulky substituent at C2 were synthesized from chiral imines derived from (R)-glyceraldehyde acetonide by diastereoselective allylation followed by a sequential hydrozirconation/iodination reaction. The new compounds were found to be effective organocatalysts for the Michael addition of

• obtained by the addition of allylmagnesium bromide to imines derived from (R)-glyceraldehyde acetonides A (Figure 1) according to our previously described methodology [15]. The configuration at C2 of the pyrrolidine ring would be determined in the diastereoselective allylation of the starting chiral imines

Diastereoselective anodic hetero- and homo-coupling of menthol-, 8-methylmenthol- and 8-phenylmenthol-2-alkylmalonates

• Matthias C. Letzel,
• Hans J. Schäfer and
• Roland Fröhlich

Beilstein J. Org. Chem. 2017, 13, 33–42, doi:10.3762/bjoc.13.5

• Matthias C. Letzel Hans J. Schafer Roland Frohlich Organisch-Chemisches Institut der Westfälischen Wilhelms- Universität, Corrensstraße 40, D-48149 Münster, Germany 10.3762/bjoc.13.5 Abstract Diastereoselective radical coupling was achieved with chiral auxiliaries. The radicals were generated by

• intermolecular diastereoselective radical coupling reactions [10][11][12][13][14][15][16]. There are some examples of high diastereoselectivity in the coupling of radicals generated from azo compounds [10][11], in intramolecular coupling of radicals, that are obtained by photochemical activation [12][13][14

cis-Diastereoselective synthesis of chroman-fused tetralins as B-ring-modified analogues of brazilin

• Dimpee Gogoi,
• Runjun Devi,
• Pallab Pahari,
• Bipul Sarma and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2016, 12, 2816–2822, doi:10.3762/bjoc.12.280

• Abstract We have synthesized a series of cis-6a,7,8,12b-tetrahydro-6H-naphtho[2,1-c]chromen-6a-ols as B-ring-modified analogues of (±)-brazilin. A completely regio- and cis-diastereoselective intramolecular Friedel–Crafts epoxy–arene cyclization of 1-tetralone-derived glycidyl ethers catalyzed by Brønsted

• been reductively removed by a diastereoselective method which should be useful in future for preparing libraries of chroman-fused tetralins with trans-stereochemistry at the ring junction. Keywords: brazilin; chroman; epoxy-arene cyclization; natural-product-like molecules; tetralin; Findings The

• diastereoselective synthesis of 5. In this communication, we describe our synthetic study along this line. We envisioned that compounds 5 could be achieved from tetralin-based epoxy ethers 6 via the IFCEA cyclization strategy (Scheme 1). Compounds 6 could be synthesized from tetralin-based epoxy alcohols 7 and

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

• Ilya V. Efimov,
• Marsel Z. Shafikov,
• Nikolai A. Beliaev,
• Natalia N. Volkova,
• Tetyana V. Beryozkina,
• Wim Dehaen,
• Zhijin Fan,
• Viktoria V. Grishko,
• Gert Lubec,
• Pavel A. Slepukhin and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2016, 12, 2390–2401, doi:10.3762/bjoc.12.233

• was observed by Pokar et al. [34] in 1980 and diastereoselective formation of fused isoxazolines was recently reported by Jelizi et al. [35]. Their structures are assigned as trans-isomers which are deduced from coupling constants of 4.0 and 4.2 Hz for the C4–H and C5–H in the NMR spectra (see

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• enduracididine Although several synthetic approaches to enduracididine and its derivatives have been published, the discovery of teixobactin (17) has reignited interest in the synthesis of this unnatural amino acid. Synthesis of enduracididine by Shiba et al.: The first diastereoselective synthesis of

• with isothiourea 33 followed by mesyl chloride afforded cyclic guanidine 72 in 70% yield. Silyl deprotection, Swern oxidation and Still–Gennari olefination afforded Z-alkene 73. Diastereoselective dihydroxylation of 73 followed by treatment with 1,1'-thiocarbonyldiimidazole (TCDI) and sodium azide

Highly chemo-, enantio-, and diastereoselective [4 + 2] cycloaddition of 5H-thiazol-4-ones with N-itaconimides

• Shuai Qiu,
• Choon-Hong Tan and
• Zhiyong Jiang

Beilstein J. Org. Chem. 2016, 12, 2293–2297, doi:10.3762/bjoc.12.222

• class of sulfur-containing pro-nucleophiles in a highly enantio- and diastereoselective conjugate addition to nitroalkenes, providing α,α-disubstituted α-mercapto carboxylic acids [5]. Since then, several asymmetric variants using 5H-thiazol-4-ones as nucleophiles have been disclosed; such as amination

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

• Alexei N. Izmest’ev,
• Galina A. Gazieva,
• Natalya V. Sigay,
• Sergei A. Serkov,
• Valentina A. Karnoukhova,
• Vadim V. Kachala,
• Alexander S. Shashkov,
• Igor E. Zanin,
• Angelina N. Kravchenko and
• Nina N. Makhova

Beilstein J. Org. Chem. 2016, 12, 2240–2249, doi:10.3762/bjoc.12.216

• regio- and diastereoselective one-pot method for the synthesis of new polynuclear dispiroheterocyclic systems with five stereogenic centers (dispiro[imidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazine-6,3′-pyrrolidine-2′,3′′-indoles]) comprising pyrrolidinyloxindole and imidazo[4,5-e]thiazolo[3,2-b]-1,2,4

• generated from isatins and sarcosine to benzylidene derivatives of the same imidazothiazolotriazine will proceed from the less sterically hindered side [41] (anti attack). Herein, we report a regio- and diastereoselective one-pot method for the synthesis of a novel class of polynuclear dispiroheterocyclic

• phase (see Supporting Information File 1). Thus, the cycloaddition of azomethine ylides was found to be highly regioselective, as the electron-rich carbon of the dipole adds to the β-carbon of the α,β-unsaturated moiety of dipolarophile 1. Further the reaction is diastereoselective, as only one

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• protocols using the three different d0-metals are highly diastereoselective (vide infra) and have been shown over the past decades to be applicable to a broad range of starting materials. Mechanistic aspects, stereochemistry and substrate scope of the direct oxidative diene cyclization Intrigued by the

• for divalent cations. It is commonly used to both modify intracellular Ca2+ concentrations and to investigate Ca2+ transport across biological membranes [58]. In 2011, Kocienski and co-workers reported on a formal synthesis of ionomycin using an auxiliary-directed, diastereoselective permanganate

• -solamin A (29) and B using the diastereoselective, auxiliary-controlled, permanganate-promoted type A oxidative cyclization of 1,5-dienes to create the THF diol backbone and to introduce four of the five stereogenic centers present in these mono-THF acetogenins (left, Scheme 8) [76][78]. Starting from

Diastereoselective synthesis of 3,4-dihydro-2H-pyran-4-carboxamides through an unusual regiospecific quasi-hydrolysis of a cyano group

• Mikhail Yu. Ievlev,
• Oleg V. Ershov,
• Mikhail Yu. Belikov,
• Angelina G. Milovidova,
• Viktor A. Tafeenko and
• Oleg E. Nasakin

Beilstein J. Org. Chem. 2016, 12, 2093–2098, doi:10.3762/bjoc.12.198

• University, Leninskie gory 1, Moscow, Russia 10.3762/bjoc.12.198 Abstract An efficient diastereoselective approach for the synthesis of functionalized 3,4-dihydro-2H-pyran-4-carboxamides with variable frame was developed based on the reaction of available 4-oxoalkane-1,1,2,2-tetracarbonitriles (adducts of

• TCNE and ketones) with aldehydes in an acidic media. An unusual process of quasi hydrolysis of the cyano group was observed in the course of the described regio- and diastereoselective transformation. Keywords: diastereoselectivity; 3,4-dihydro-2H-pyran-4-carboxamide; nitriles; pyran; quasi-hydrolysis

• diastereoselective cascade reaction [23]. The crucial stage of the described transformation is the formation of a pyran-4-carboxamide intermediate. A trace amount of it was isolated accidentally and we could not repeat this procedure and characterize the compound by spectra. Results and Discussion In continuation of