Towards the total synthesis of keramaphidin B

• Pavol Jakubec,
• Alistair J. M. Farley and
• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1096–1100, doi:10.3762/bjoc.12.104

• reported cinchonine-derived bifunctional thiourea catalyst 12 afforded the addition product 13 in high yield with good levels of diastereo- and enantioselectivity (95:5 dr, 90:10 er for the major diastereomer 13). The relative stereochemical configuration of the minor diastereomeric product 14 was

• determined by single X-ray crystallographic analysis of rac-14 (see Supporting Information File 1) and revealed that the major diastereomer 13 indeed possessed the necessary stereochemical configuration [21] for accessing keramaphidin B, assuming the chemoselectivity of the nitro-Mannich lactamisation

• the model system, identical levels of diastereo- and enantiocontrol were observed in the formation of 7 (92% yield). Treatment of the major diastereomeric product 7 with hept-5-yn-1-amine (16) and formaldehyde in boiling methanol afforded the lactam 6 in 56% yield as a single diastereomer in 91:9 er

The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• catalyst (Scheme 27) [102][103]. Again, the formation of a 1,3-dipole (see 127) allows for a cycloaddition, though this example is intermolecular in nature. One of the ethereal ethyl groups in 128 is consequently poised for C–H bond insertion by the tungsten carbene to give 129 as a single diastereomer

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• (Scheme 2, compounds 13–15) proceeded with poor diastereocontrol but the results were improved by changing to catalyst C2 [62]. Nonetheless, in both cases the enantioselectivity for the major diastereomer was excellent. Finally, and starting from the corresponding bicyclic imidazolones, quaternary proline

Scope and mechanism of the highly stereoselective metal-mediated domino aldol reactions of enolates with aldehydes

• M. Emin Cinar,
• Bernward Engelen,
• Martin Panthöfer,
• Hans-Jörg Deiseroth,
• Jens Schlirf and
• Michael Schmittel

Beilstein J. Org. Chem. 2016, 12, 813–824, doi:10.3762/bjoc.12.80

• gallium at 0 °C and Sn(IV) at 25 °C a diastereomer of 5a also formed in 20 and 29% yields, respectively. Generally, with nearly all metals, the yield of 5a increased dramatically when the temperature was raised to 25 °C, but dropped at higher temperatures. The decreased yield at 67 °C may emerge from the

• ligands may simply act as "innocent bystander ligands" in the reaction cascade. Since we have been able to obtain 5a with GaCl3 in a diastereomerically pure form at 25 °C – although at low temperature a sizeable amount of 20% of a second diastereomer was formed – it is reasonable to assume a reversible

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• unwanted diastereomer 22, the synthesis was finished with the desired minor component 23. Boc deprotection followed by reaction with guanidinylation reagent 24 gave bicyclic compound 25. The next steps included a desulfonylation and the reaction with 26 leading to protected epicapreomycidine-containing

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• , when a different derivative of L-diphenylprolinol is used, a different diastereomer of the product is obtained. When along with N-Boc-substituted oxindole 218, substituted derived nitro-alkene 82 and substituted unsaturated aldehyde 154, a bifunctional quinine-derived thiourea 57 and L-diphenylprolinol

• with another derivative of 220, organocatalyst 214, another diastereomer was obtained of the desired product 221 (Scheme 69). This domino Michael–Michael aldol reaction provides the product in an excellent 92% yield, excellent enantiomeric excess (>99%) and good diastereoselectivity (9:2.5:1). Dixon

• McGarrigle, Galan and co-workers (Scheme 77) [96]. In this reaction the reagent is 2,3,4-trisubstituted dihydro-pyran 247 and the product is the corresponding α-galactopyranose 248. This reaction provides exclusively the α-diastereomer in a yield up to 98%. In 2013, Schmidt and co-workers described the use

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• Michael adducts into the benzoin product. The prolinol catalyst 60, on the other hand, mediates the epimerisation of the less reactive diastereomer. This synergy leads to the enrichment of the diastereomeric ratio of the final product 64 (Scheme 38) [55]. Enders developed a closely related iminium-cross

Simple activation by acid of latent Ru-NHC-based metathesis initiators bearing 8-quinolinolate co-ligands

• Julia Wappel,
• Roland C. Fischer,
• Luigi Cavallo,
• Christian Slugovc and
• Albert Poater

Beilstein J. Org. Chem. 2016, 12, 154–165, doi:10.3762/bjoc.12.17

• ). The minor isomer 2a (28% yield) was identified as the OC-6-14 diastereomer featuring the two oxygen atoms in trans disposition (and the nitrogen atom trans to the benzylidene ligand). The major isomer 2b (57% yield) is the OC-6-32 diastereomer bearing the two oxygen ligands in cis disposition (and one

Diastereoselective Ugi reaction of chiral 1,3-aminoalcohols derived from an organocatalytic Mannich reaction

• Samantha Caputo,
• Andrea Basso,
• Lisa Moni,
• Renata Riva,
• Valeria Rocca and
• Luca Banfi

Beilstein J. Org. Chem. 2016, 12, 139–143, doi:10.3762/bjoc.12.15

• and NMR analogies suggest that the main diastereomer was always the same, with one notable exception: product 6f obtained in the absence of Lewis acid. In this case, it was necessary to carry out the reaction in THF/iPrOH because the isocyanide was poorly soluble in MeOH, and thus the unexpected

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• . Therefore, the product was isolated as alcohol 15 after a one-pot reduction of the ketone moiety (60% in four steps from 6), along with the minor diastereomer at C1 position (dr > 18:1). These results mean that the stereochemistry at the C2 position was fully controlled, presumably due to hydride attack

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• acetylide to the carbonyl group of 69, followed by desilylation under basic conditions gave rise to (±)-ethynylcarbinol, which was separated by chiral HPLC. The desired diastereomer was then transformed to benzene sulfinate ester 70. A palladium-catalyzed [2,3]-sigmatropic rearrangement formed an isomeric

• synthesized in four steps. Esterification with (R)-(+)-citronellic acid (127) yielded a single diastereomer of ester 128. Addition of lithium diisopropylamide to a mixture of 128, trimethylsilyl chloride and triethylamine initiated an Ireland–Claisen rearrangement [63] which gave carboxylic acid 129 in 85

Bromotyrosine-derived alkaloids from the Caribbean sponge Aplysina lacunosa

• Qun Göthel,
• Thanchanok Sirirak and
• Matthias Köck

Beilstein J. Org. Chem. 2015, 11, 2334–2342, doi:10.3762/bjoc.11.254

• proposed to be the same as of 19, chemical fragmentation of 5 releasing from the sponge Aplysina spp. after induction by tissue damage (Figure 4). However, the conversion from 5 to 19 has not been confirmed. A single data set in the 13C NMR spectrum supported the presence of one diastereomer of 1. Compound

• diastereomer of 2 was confirmed by a single data set in the 13C NMR spectrum. Compound 3 was isolated together with N-methylaerophobin-2 (15) as a mixture (approximate ratio 1:5). The ESIMS spectrum exhibited a 1:2:1 ion cluster at m/z 457/459/461, indicating the presence of two bromine atoms. The HRMS–ESI

Synthesis of D-fructose-derived spirocyclic 2-substituted-2-oxazoline ribosides

• Madhuri Vangala and
• Ganesh P. Shinde

Beilstein J. Org. Chem. 2015, 11, 2289–2296, doi:10.3762/bjoc.11.249

• spiro 2-substituted-2-oxazolines were stable and obtained as a single diastereomer. To assign the relative stereochemistry at the anomeric center, compounds 11a and 17a were subjected to 2D NMR analysis. In the NOESY spectra of compounds 11a and 17a, the cross peaks between C1–H, C1–H’ and CH3 groups of

• as a single diastereomer in good yield. In the absence of the nucleophile, the oxacarbenium-ion intermediate of protected D-psicofuranose derivatives underwent spiroketalization to give di-D-fructose dianhydrides. Given the established, pharmacological applications of riboside derivatives, these

Investigation of the role of stereoelectronic effects in the conformation of piperidones by NMR spectroscopy and X-ray diffraction

• Cesar Garcias-Morales,
• David Ortegón-Reyna and
• Armando Ariza-Castolo

Beilstein J. Org. Chem. 2015, 11, 1973–1984, doi:10.3762/bjoc.11.213

• , only the diastereomer with the phenyl groups in the cis orientation was obtained. This is because in the transition state (TS) for the cis compounds the energy of the 1H,3H-allylic strain (A1,3) is lower in comparison with the TS trans,1Ar,3H-allylic strain [57], which is caused by the hindrance effect

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• compound 269 was obtained from oxabicyclo adduct 268 by a domino metathesis sequence in the presence of catalyst 2. Moreover, compound 269 was obtained as a single diastereomer and constitutes the core structure of phelligridin G (Scheme 55). In 2009, Hanson’s group reported [56] the synthesis of

Synthesis of novel N-cyclopentenyl-lactams using the Aubé reaction

• Madhuri V. Shinde,
• Rohini S. Ople,
• Ekta Sangtani,
• Rajesh Gonnade and
• D. Srinivasa Reddy

Beilstein J. Org. Chem. 2015, 11, 1060–1067, doi:10.3762/bjoc.11.119

• the desired azido alcohol (±)-3 as an 8:1 regioisomeric mixture. However, we could neither purify nor isolate compound (±)-3 in pure form, which was always accompanied by an undesired isomeric compound. To confirm whether it is a diastereomer or regioisomer, we performed two derivatization reactions

• literature and the data were compared with that reported [34]. The structure of the minor diastereomer (±)-4’ was assigned based on 2D NMR correlations. Secondly, the azido alcohol (±)-3 was subjected to a click reaction with phenylacetylene under standard conditions and the resulting two compounds, (±)-5

• and our initial designs. ORTEP plot of triol (±)-12. The Aubé reaction and its selected applications. Top: synthesis of azido alcohol derivative 3 and bottom: structural elucidation of the minor diastereomer. Aubé reaction of cylopentenyl azido alcohol 3 with cyclohexanone. Substrate scope of the

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• reactions focused on the development of diastereoselective CA reactions. These reactions were achieved by performing conjugate additions to chiral Michael acceptors that blocked one face of the double bond from the incoming nucleophile, thus preferentially producing one diastereomer over the other. The

• performing DCA reactions using chiral substrates is that the overall stereochemistry of the Michael acceptor may either produce the undesired diastereomer in high yield or a low diastereoselectivity may be observed. Due to the complex nature of the chiral starting material, structural changes that would

• ). The authors were able to execute the conjugate addition of 26 using a Gilman reagent in high yield. The diastereoselectivity was not determined for the CA product. Instead, the authors converted the product to 3-methylglutamic acid 28 and they were able to observe only one diastereomer. DCA reactions

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• available. Fortunately, a partial, and simple, solution is available through the facile conversion of trans-4-hydroxy-L-proline to its diastereomer cis-4-hydroxy-D-proline, a conversion that has been studied and modified for more than 60 years [72]. Treatment of trans-4-hydroxy-L-proline with acetic

The reactions of 2-ethoxymethylidene-3-oxo esters and their analogues with 5-aminotetrazole as a way to novel azaheterocycles

• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess and
• Viktor I. Saloutin

Beilstein J. Org. Chem. 2015, 11, 385–391, doi:10.3762/bjoc.11.44

• heterocycle 10. Compound 10 was isolated as one diastereomer, but the relative configuration of its stereogenic centers was not determined. Moreover, we studied the reaction of ethyl 2-ethoxymethylidenecyanoacetate (1f) with 5-AT. It has been found that this reaction does not occur either in refluxing ethanol

Attempts to prepare an all-carbon indigoid system

• Şeref Yildizhan,
• Henning Hopf and
• Peter G. Jones

Beilstein J. Org. Chem. 2015, 11, 363–372, doi:10.3762/bjoc.11.42

• cannot take place because of steric hindrance by the gem-dimethyl group. Intermediate 15 is a vinylcarbene that, in principle, has several options to react further. It could dimerize to the intended product 14 (or its diastereomer), cyclize to a cyclopropene derivative or react via its resonance

Anionic sigmatropic-electrocyclic-Chugaev cascades: accessing 12-aryl-5-(methylthiocarbonylthio)tetracenes and a related anthra[2,3-b]thiophene

• Laurence Burroughs,
• John Ritchie,
• Mkhethwa Ngwenya,
• Dilfaraz Khan,
• William Lewis and
• Simon Woodward

Beilstein J. Org. Chem. 2015, 11, 273–279, doi:10.3762/bjoc.11.31

• ). Only the meso diastereomer of 1c is predicted by Woodward–Hoffman analyses [18] to deliver anti-6 that is required for facile E2 elimination leading to the desired tetracene 7 under thermal conditions. However, the initially required 1c are typically attained as ca. 1:1 rac/meso mixtures and this might

• either the rac or meso diastereomer could be realised. The meso enriched diastereomer of 8a could be realised by treating rac/meso mixtures of bis-lithium alkoxide of 8a with freshly prepared anhydrous NBu4F (2 equivalents) [23] (Scheme 3). Acid quench of the resultant purple dianion leads to ca. 5:1

• chiral diastereomer while no equivalent splitting in 1H NMR samples of 8a prepared from purple 11 (in line with it being the meso diastereomer). These assignments are in line with the finding of Saá [15]. The chemical shifts of the methine CHOH proton in rac-8a (δH 6.20) and meso-8a (δH 6.33) reflect an

Synthesis of dinucleoside acylphosphonites by phosphonodiamidite chemistry and investigation of phosphorus epimerization

• William H. Hersh

Beilstein J. Org. Chem. 2015, 11, 184–191, doi:10.3762/bjoc.11.19

• linker. This results in the formation of an enormous number of diastereomers that may have different properties, such as nuclease stability and RNase H interactions. Some [5][10] but not all [11][12] of the non-phosphorothioate antisense reagents avoid the diastereomer problem, but the extensive study of

• separated and continuous fractionation of the phosphorus epimers that occurred during repeated chromatographies. However, 10 was ultimately obtained as a white foam. Samples of the fast-moving diastereomer and of a mixture of the two diastereomers of 10 were fully characterized. They exhibited the

• diastereomeric mixtures occurred. Due to the sensitivity of the acyls, chromatography on long columns of silica (with or without 1% NEt3 to deactivate the silica) gave rise to the loss of acyls, without any improvement in diastereomer separation. However, the individual samples of fractionated diastereomers of

Electrochemical selenium- and iodonium-initiated cyclisation of hydroxy-functionalised 1,4-dienes

• Philipp Röse,
• Steffen Emge,
• Jun-ichi Yoshida and
• Gerhard Hilt

Beilstein J. Org. Chem. 2015, 11, 174–183, doi:10.3762/bjoc.11.18

• cyclisation in moderate to good yields. The products were generated in diastereoselective fashion and the configuration of the formed diastereomer could be identified by 1H NMR experiments comparing a mixture of both diastereomers, synthesised by conventional selenoalkoxylation, with the electrochemically

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• intermediate 90 was treated with a Lewis acid and vinylmagnesium bromide to afford the trans-diastereomer after column chromatography. Coupling of 91 and 92 (prepared using conventional chemistry) resulted in the peptide-turn inducing compound 93. The Moeller research group has carried out extensive research

Inherently chiral calix[4]arenes via oxazoline directed ortholithiation: synthesis and probe of chiral space

• Simon A. Herbert,
• Laura J. van Laeren,
• Dominic C. Castell and
• Gareth E. Arnott

Beilstein J. Org. Chem. 2014, 10, 2751–2755, doi:10.3762/bjoc.10.291

• reported with diastereoselective ratios of greater than 100:1 in some instances. Notably, it has been found that the opposite diastereomer can be accessed via this approach merely through the choice of an alkyllithium reagent. The inherently chiral oxazoline calix[4]arenes have also been preliminarily

• ortholithiation conditions varying the solvent, alkyllithium and ligand. The results are reported in Table 1, which for the purposes of comparison, also includes data from our previously published work on the isopropyloxazoline calix[4]arenes 1a and 1b [27][28]. The conversion values and diastereomer ratios were

• ortholithiation study.a Results of the Tsuji–Trost reaction. Supporting Information Experimental details and characterization data for all products; determination of enantiomeric ratios and determination of major calix[4]arene diastereomer. Supporting Information File 480: Synthetic procedures and spectral data