Characterization of the synthetic cannabinoid MDMB-CHMCZCA

• Carina Weber,
• Stefan Pusch,
• Dieter Schollmeyer,
• Sascha Münster-Müller,
• Michael Pütz and
• Till Opatz

Beilstein J. Org. Chem. 2016, 12, 2808–2815, doi:10.3762/bjoc.12.279

• and comparison of the data with DFT calculations, while ECD spectroscopy was found to be inconclusive in this case. The enantiomeric purity of samples from test purchases and police seizures was assessed by a self-developed chiral HPLC method. Keywords: chiral HPLC; ECD spectroscopy; NPS; synthetic

• samples. For this purpose, we used analytical methods such as NMR, tandem mass spectrometry, vibrational and electronic circular dichroism spectroscopy (VCD and ECD), as well as chiral HPLC. Results and Discussion Pure MDMB-CHMCZCA (3) was obtained as a so-called “research chemical” (RC) from an online RC

• (pure substances as well as designer drug products) was assessed by chiral HPLC after base-induced racemization of a sample of (S)-3. Experimental Isolation of MDMB-CHMCZCA from Spice products In analogy to the procedure described in [9], hashish-like resin (20 mg) was cut in small pieces, soaked in

Biomimetic synthesis and HPLC–ECD analysis of the isomers of dracocephins A and B

• Viktor Ilkei,
• András Spaits,
• Anita Prechl,
• Áron Szigetvári,
• Zoltán Béni,
• Miklós Dékány,
• Csaba Szántay Jr,
• Judit Müller,
• Árpád Könczöl,
• Ádám Szappanos,
• Attila Mándi,
• Sándor Antus,
• Ana Martins,
• Attila Hunyadi,
• György Tibor Balogh,
• György Kalaus (†),
• Hedvig Bölcskei,
• László Hazai and
• Tibor Kurtán

Beilstein J. Org. Chem. 2016, 12, 2523–2534, doi:10.3762/bjoc.12.247

• Dracocephalum rupestre, have been synthesized in a one-pot reaction. The separation of 2a–d and 3a–d was achieved by preparative HPLC. The four stereoisomers of each natural product were separated by analytical chiral HPLC and their absolute configuration was studied by the combination of HPLC–ECD measurements

• and B showed good agreement with those of the isolated flavonoid alkaloids [2]. Similarly to the natural route, no diastereoselectivity occurred in this sequence, as proven by the separation of the stereoisomers by chiral HPLC and by the integration or deconvolution of NMR signals of Hy-3 recorded in

• CD3OD. The separation of the stereoisomers of dracocephins A (±)-2a–d could be achieved by chiral HPLC using an analytical Chiralpak IC column with the eluent MeCN/2-propanol/TFA 97:3:0.1 (Figure 2). Four peaks with alternating signs of the ECD signal in the HPLC–UV and –ECD traces were observed, the

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

• , followed by gradient elution with DCM/MeOH mixture (500:1−200:1 ratio). Removing the solvent in vacuo, afforded product 3a. Substrate scope of the [4 + 2] annulation. Reaction conditions: 1 (0.1 mmol), 2 (0.15 mmol), V (0.01 mmol), CHCl3 (1.0 mL) at −10 °C. All drs are >20:1; ees were determined via chiral

• HPLC analysis. a20 mol % of V was used, T = 0 °C. Transformation of adduct. Optimization of reaction conditionsa. Supporting Information Supporting Information File 356: Experimental information and spectroscopic data. Acknowledgements Financial support from the National Science Foundation of China

Determination of the absolute stereostructure of a cyclic azobenzene from the crystal structure of the precursor containing a heavy element

• Reji Thomas and
• Nobuyuki Tamaoki

Beilstein J. Org. Chem. 2016, 12, 2211–2215, doi:10.3762/bjoc.12.212

• found that the spectrum completely matches with the previously reported compound (E)-2 [46]. To confirm the formation of compound (E)-2 we have carried out chiral HPLC studies on a Chiralpak IA column using a mixture of ethyl acetate and hexane (10:90) as the eluent to characterize the nature of the

• , 35.9. Schematic representation of the steps to enantiomer (E)-2A. Chromatogram (Chiral HPLC) obtained for (a) racemic mixture of (E)-1 (b) sample used for reductive debromination (second eluted enantiomer S-(−)-(E)-1) (c) recorded after the LiAlH4 reduction of S-(−)-(E)-1 and (d) the chromatogram of

Catalytic Chan–Lam coupling using a ‘tube-in-tube’ reactor to deliver molecular oxygen as an oxidant

• Carl J. Mallia,
• Paul M. Burton,
• Alexander M. R. Smith,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1598–1607, doi:10.3762/bjoc.12.156

• , unfortunately, gave a poor isolated yield of 26% and also underwent some epimerisation (25, 53% ee determined by chiral HPLC, Scheme 2). Additionally, a small amount of the product (25) reacted further with phenylboronic acid through the phenol to give 26 in 3% isolated yield. In the case of L-leucine methyl

• ester an isolated yield of 60% was realised, but this substrate also underwent partial epimerisation (27, 71% ee determined by chiral HPLC, Scheme 2). Using N-heterocyclic substrates as the nucleophilic partner with a range of different phenylboronic acids generally gave good isolated yields (19, 20, 28

Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals

• Haipan Zhu,
• Peile Du,
• Jianjun Li,
• Ziyang Liao,
• Guohua Liu,
• Hao Li and
• Wei Wang

Beilstein J. Org. Chem. 2016, 12, 1340–1347, doi:10.3762/bjoc.12.127

• albeit a relatively low yield (Table 3, 46%, entry 13). It is noteworthy that although aliphatic enals also can engage in this [3 + 2] annulation reaction. Unfortunately, we could not separate them on chiral HPLC column for the determination of the enantioselectivity by all means we have attempted (data

One-pot synthesis of enantiomerically pure N-protected allylic amines from N-protected α-amino esters

• Gastón Silveira-Dorta,
• Sergio J. Álvarez-Méndez,
• Víctor S. Martín and
• José M. Padrón

Beilstein J. Org. Chem. 2016, 12, 957–962, doi:10.3762/bjoc.12.94

• treatment. Although we have demonstrated earlier that no loss of enantiomeric purity was observed in the synthesis of anti-β-amino alcohols [16], we submitted commercially available DL-alanine to the aforementioned one-pot procedure to give rac-2a. Both rac-2a and 2a were analyzed by chiral HPLC. The

Supported bifunctional thioureas as recoverable and reusable catalysts for enantioselective nitro-Michael reactions

• José M. Andrés,
• Miriam Ceballos,
• Alicia Maestro,
• Isabel Sanz and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2016, 12, 628–635, doi:10.3762/bjoc.12.61

• or by staining with phosphomolybdic acid solution. Specific rotations were measured on a digital polarimeter using a 5 mL cell with a 1 dm path length, and a sodium lamp, and the concentration is given in g per 100 mL. Chiral HPLC analysis was performed by using Daicel Chiralcel OD or Chiralpak AD-H

Spiro-fused carbohydrate oxazoline ligands: Synthesis and application as enantio-discrimination agents in asymmetric allylic alkylation

• Jochen Kraft,
• Martin Golkowski and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 166–171, doi:10.3762/bjoc.12.18

• as a benchmark for new chiral ligands and examined in great detail [9][10][11][12][13][14][27][28]. In all cases investigated here, the alkylated product 14 was isolated after purification by chromatography and its enantiomeric excess was determined via chiral HPLC using a Reprosil chiral-NR column

A novel and practical asymmetric synthesis of dapoxetine hydrochloride

• Yijun Zhu,
• Zhenren Liu,
• Hongyan Li,
• Deyong Ye and
• Weicheng Zhou

Beilstein J. Org. Chem. 2015, 11, 2641–2645, doi:10.3762/bjoc.11.283

• . Experimental All solvents and reagents were of reagent grade and used without further purification. 1H and 13C NMR spectra were recorded using a Bruker 400 MHz spectrometer with TMS as an internal standard. HPLC analyses were recorded with on a Dionex Ultimate 3000 chromatograph and chiral HPLC analyses were

• , 13C NMR and ESIMS spectra of compounds 1, 4, 5, 5”, 6 and 7 and chiral HPLC diagrams of 1 and 7.

Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones

• Antonia Di Mola,
• Maximilian Tiffner,
• Francesco Scorzelli,
• Laura Palombi,
• Rosanna Filosa,
• Paolo De Caprariis,
• Mario Waser and
• Antonio Massa

Beilstein J. Org. Chem. 2015, 11, 2591–2599, doi:10.3762/bjoc.11.279

• after crystallization overnight at −20 °C, the solid was filtered off and the solution containing the enantioenriched compound was evaporated and analyzed by chiral HPLC. The resulting enantioenriched product was obtained as a colourless oil in 77% overall yield (400 mg, 1.51 mmol, 95% ee). The

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

Synthesis of racemic and chiral BEDT-TTF derivatives possessing hydroxy groups and their achiral and chiral charge transfer complexes

• Sara J. Krivickas,
• Chiho Hashimoto,
• Junya Yoshida,
• Akira Ueda,
• Kazuyuki Takahashi,
• John D. Wallis and
• Hatsumi Mori

Beilstein J. Org. Chem. 2015, 11, 1561–1569, doi:10.3762/bjoc.11.172

• of enatiopure donors 1 and the preparations of their charge transfer complexes are under way. Moreover, enantiopure (S,S)-2 and (R,R)-2 were also synthesized as shown in Scheme 2. Chiral HPLC was performed using a JAIGEL-OA7500 column on a JAI LC-908 recycling preparative system using the solvent

The enantioselective synthesis of (S)-(+)-mianserin and (S)-(+)-epinastine

• Piotr Roszkowski,
• Jan. K. Maurin and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2015, 11, 1509–1513, doi:10.3762/bjoc.11.164

• , desmethylmianserin (10) was obtained in 81% yield by reduction of the carbonyl groups using a 1.0 M solution of lithium aluminum hydride in THF. Finally, the reaction between derivative 10 and methyl iodide led to optical pure (S)-(+)-mianserin (1) (as confirmed by chiral HPLC) in 67% yield. In order to obtain

Chiroptical properties of 1,3-diphenylallene-anchored tetrathiafulvalene and its polymer synthesis

• Masashi Hasegawa,
• Junta Endo,
• Seiya Iwata,
• Toshiaki Shimasaki and
• Yasuhiro Mazaki

Beilstein J. Org. Chem. 2015, 11, 972–979, doi:10.3762/bjoc.11.109

• of 3. Synthesis of chiral (R)-PTDPA and (S)-PTDPA. Redox potentials of 3 and PTDPA.a Absorption maxima of 3, 10 and PTDPA.a Supporting Information Supporting Information File 216: Experimental procedures, characterization data, copies of 1H and 13C NMR charts, recyclable chiral HPLC chart and DFT

First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

• Paweł Borowiecki,
• Daniel Paprocki and
• Maciej Dranka

Beilstein J. Org. Chem. 2014, 10, 3038–3055, doi:10.3762/bjoc.10.322

• subsequently followed by chiral HPLC. As a first attempt, Novozym 435-catalyzed KR of racemic alcohol (±)-3 was carried out (Table 1, entries 1–6). After series of experiments, the influence of various co-solvents could be summarized as the following row orders in terms of enzyme activity: pentane > n-hexane

• and the enantiomeric elution order from chiral HPLC, which were opposite to those corresponding to the appropriate products obtained when toluene was applied as a solvent (see Supporting Information File 1). This phenomenon was also confirmed by isolation of byproducts characteristic for this reaction

Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction

• László Tóth,
• Yan Fu,
• Hai Yan Zhang,
• Attila Mándi,
• Katalin E. Kövér,
• Tünde-Zita Illyés,
• Attila Kiss-Szikszai,
• Balázs Balogh,
• Tibor Kurtán,
• Sándor Antus and
• Péter Mátyus

Beilstein J. Org. Chem. 2014, 10, 2594–2602, doi:10.3762/bjoc.10.272

• iminium carbon of intermediate A occurred with trans-diastereoselectivity to the C-2 phenyl group. The formation of the diastereomeric cis-7a,b could not be detected. The chiral HPLC analysis of the products 7a,b also confirmed that the reaction took place diastereoselectively and enantiomers of trans-7a

• uncorrected. The NMR spectra were recorded on Bruker-AMX 500 (1H: 500 MHz; 13C: 125 MHz) and Bruker Avance II 400 (1H: 400 MHz; 13C: 100 MHz) spectrometers using TMS as internal standard. Chemical shifts were reported as δ in ppm and 3JH,H coupling constants in Hz. Chiral HPLC separation of 7a,b were

Oligomerization of optically active N-(4-hydroxyphenyl)mandelamide in the presence of β-cyclodextrin and the minor role of chirality

• Helmut Ritter,
• Antonia Stöhr and
• Philippe Favresse

Beilstein J. Org. Chem. 2014, 10, 2361–2366, doi:10.3762/bjoc.10.246

• conversion of the enantiomers of 1 during the enzymatic oligomerization has been studied using chiral HPLC. Accordingly, the racemate of 1 was oligomerized three times with each enzyme in the absence of RAMEB-CD or in the presence of RAMEB-CD, respectively to evaluate the reproducibility. The isolated

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• chiral HPLC or CPG. In a recent study, Montchamp et al. used the AT reaction for the determination of the ee of P-chiral H-phosphinates by the formation of diastereoisomers (Scheme 33) [108]. The ee determined by this method, which can be achieved directly in the NMR tube before recording 31P NMR spectra

• , was consistent with those determined by other methods (e.g., chiral HPLC). 4.2 Flame retardants Since the early age of the development of synthetic fibers, the production of flame retardants became an industrial and academic challenge aiming to identify efficient compounds for this purpose but also to

Stereocontrolled synthesis of 5-azaspiro[2.3]hexane derivatives as conformationally “frozen” analogues of L-glutamic acid

• Beatrice Bechi,
• David Amantini,
• Cristina Tintori,
• Maurizio Botta and
• Romano di Fabio

Beilstein J. Org. Chem. 2014, 10, 1114–1120, doi:10.3762/bjoc.10.110

• intermediate 16. The two most abundant diastereoisomers were isolated in pure form by semi-preparative chiral HPLC and their stereochemistry was elucidated by NOE studies [40]. In principle, as shown in Figure 2, the attack of the carbene intermediate to the olefin moiety 18 can occur at both the re and si

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• alkenylphosphine 81c was formed. The highest enantiomeric excess measured by chiral HPLC was 56%. No reaction was observed without the palladium catalyst [165]. Gillaizeau and co-workers have demonstrated the use of α-amido enol phosphates 88 as vinylic coupling partners in the palladium-catalyzed C–P cross

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• nonsymmetric ketones. Moreover, an optical active compound could be generated during the reaction process since a chiral catalyst (proline) is used in the reactions. However, enantioselectivity was not observed by chiral HPLC analysis, and 3-pentanone gives rise to a mixture of diastereoisomers. Following this

Organocatalytic asymmetric fluorination of α-chloroaldehydes involving kinetic resolution

• Kazutaka Shibatomi,
• Takuya Okimi,
• Yoshiyuki Abe,
• Akira Narayama,
• Nami Nakamura and
• Seiji Iwasa

Beilstein J. Org. Chem. 2014, 10, 323–331, doi:10.3762/bjoc.10.30

• was converted via the Barton–McCombie deoxygenation [13] into a simple ester 10, which was then reduced to the primary alcohol 4a by treatment with LiAlH4. Comparison of the optical rotations and retention times on chiral HPLC clearly showed that the asymmetric fluorination of 2a catalyzed by (S)-1

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• recorded on Bruker Avance (300, 400, 500 and 600 MHz) instruments. High resolution mass spectra were conducted at the mass spectrometry facility of the Institute for Organic Chemistry of the University of Cologne. Enantiomeric excess was determined by chiral HPLC. We employed the LaChrom elite unit by

Total synthesis of (+)-grandiamide D, dasyclamide and gigantamide A from a Baylis–Hillman adduct: A unified biomimetic approach

• Andivelu Ilangovan and
• Shanmugasundar Saravanakumar

Beilstein J. Org. Chem. 2014, 10, 127–133, doi:10.3762/bjoc.10.9

• enantiopure ester (+)-16 in 71% yield, after purification (Scheme 4). Chiral HPLC analysis of (+)-16 showed that the enantiomeric ratio is 99.7:0.3 in favour of the (+)-isomer. Further chemistry was carried out as described earlier in Scheme 3, to get (+)-grandiamide D (5) in almost the same yield. The

• enantiomeric purity of (+)-grandiamide D (5) was found to be 98.6%, as determined from chiral HPLC analysis. (observed [α]D25 = +4.7 (c 0.5, CHCl3); reported [7] [α]D20 = +2.0 (c 0.5, CHCl3). Synthesis of dasyclamide Since Baylis–Hillman adduct (±)-18 was considered as the common intermediate, we decided to

• synthetic product. The overall yield for the synthetic route was found to be 2.3%. Chiral HPLC analysis revealed that it is a racemic compound which was further confirmed by the optical rotation ([α]D23= 0 (c, 0.5, CHCl3); reported for the enatio-pure compound: [α]D20= −10 (c, 0.3, CHCl3)). Further attempt