Determination of formation constants and structural characterization of cyclodextrin inclusion complexes with two phenolic isomers: carvacrol and thymol

• Miriana Kfoury,
• David Landy,
• Steven Ruellan,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2016, 12, 29–42, doi:10.3762/bjoc.12.5

• guest is crucial to allow the formation of a stable inclusion complex. This is mainly controlled by the chemical structure of the encapsulated guest. Kf values generally increase for guests with an isopropyl moiety. Indeed, p-cymene [36] showed higher Kf values than toluene [37]. However, the comparison

• and those of the methyl and isopropyl groups of 1 and 2. This confirmed that, for both guests, the aromatic ring was deeply included in the β-CD cavity and that encapsulation occurred mainly through interactions with their phenyl moiety. But, it also pointed out that other guests’ protons are involved

• correlation peaks with CD protons. NOE cross peaks were observed between the protons of the isopropyl group of the guests and both protons H-3 and H-5. This indicated a partial penetration of the isopropyl group into the CD cavity. Moreover, the H-6 proton of β-CD showed cross peaks only with the protons of

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

• was sufficient and the optimized temperature was 0–25 °C when the reaction was carried out in THF. When other solvents were tested (Table 1, entries 12–14), it was found that diisopropyl ether gave the best result. Finally, the reaction was performed with 0.8 equiv BH3 in isopropyl ether at 0 °C for

• white solid was precipitated and filtered to obtain the crude 1 (2.8 g). The solid was recrystallized from isopropyl alcohol/n-hexane (9 mL:8 mL) to give the product. Yield 2.7 g (80.4%); mp 178–180 °C; 126.4 (c 1, methanol) [lit. [15] mp 180–184 °C; 131.7 (c 1, methanol)]; chiral purity (HPLC): >99

Comparison of the catalytic activity for the Suzuki–Miyaura reaction of (η⁵-Cp)Pd(IPr)Cl with (η³-cinnamyl)Pd(IPr)(Cl) and (η³-1-t-Bu-indenyl)Pd(IPr)(Cl)

• Patrick R. Melvin,
• Nilay Hazari,
• Hannah M. C. Lant,
• Ian L. Peczak and
• Hemali P. Shah

Beilstein J. Org. Chem. 2015, 11, 2476–2486, doi:10.3762/bjoc.11.269

• the base. Yields for Cin and tBuInd are from previous literature results [15]. All yields were determined using GC and are the average of two runs. ORTEP of CpDim at 30% probability. Hydrogen atoms and isopropyl groups of IPr are omitted for clarity. Selected bond lengths (Å) and angles (˚) for: Pd(1

Efficient synthetic protocols for the preparation of common N-heterocyclic carbene precursors

• Morgan Hans,
• Jan Lorkowski,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2015, 11, 2318–2325, doi:10.3762/bjoc.11.252

• 1,3-di(isopropyl)imidazol-2-ylidene. Thus, 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride (IDip·HCl) was obtained following a two-step procedure that first involved the condensation of glyoxal and two equivalents of 2,6-diisopropylaniline into the corresponding diazabutadiene. This intermediate

2-Hetaryl-1,3-tropolones based on five-membered nitrogen heterocycles: synthesis, structure and properties

• Yury A. Sayapin,
• Inna O. Tupaeva,
• Alexandra A. Kolodina,
• Eugeny A. Gusakov,
• Vitaly N. Komissarov,
• Igor V. Dorogan,
• Nadezhda I. Makarova,
• Anatoly V. Metelitsa,
• Valery V. Tkachev,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2015, 11, 2179–2188, doi:10.3762/bjoc.11.236

• ; Introduction Tropolone derivatives represent one of the promising classes of compounds having a wide spectrum of biological activities: in particular, antitumor activity [1][2], barrier properties with respect to various pathogens, insects and microorganisms [3]. The natural compound hinokitiol (4-isopropyl

Copper-catalyzed aerobic radical C–C bond cleavage of N–H ketimines

• Ya Lin Tnay,
• Gim Yean Ang and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2015, 11, 1933–1943, doi:10.3762/bjoc.11.209

• , that undergoes β-carbon fragmentation to give p-tolunitrile (5a) and biaryl-2-isopropyl radical B (Scheme 5a). The aerobic oxygenation of C-radical B affords peroxy radical C, that is presumably reduced by Cu(I) species through the Fenton-type mechanism [57] to give alkoxy radical D [58]. Subsequent

Preparation of conjugated dienoates with Bestmann ylide: Towards the synthesis of zampanolide and dactylolide using a facile linchpin approach

• Jingjing Wang,
• Samuel Z. Y. Ting and
• Joanne E. Harvey

Beilstein J. Org. Chem. 2015, 11, 1815–1822, doi:10.3762/bjoc.11.197

• (neat) cm−1: 2958 (m), 2929 (m), 1706 (s), 1625 (s), 1449 (m), 1236 (s), 1172 (s), 997 (m), 689 (m); HRMS (ESI) m/z: [M + H]+ calcd for C17H21O2, 257.1536 found, 257.1529, (Δ = 2.7 ppm). (1′R,2′S,5′R,2E,4E,6E)-2′-Isopropyl-5′-methylcyclohex-1′-yl deca-2,4,6-trienoate (11f). Rf = 0.14 (40:1 pet

A comprehensive study of olefin metathesis catalyzed by Ru-based catalysts

• Albert Poater and
• Luigi Cavallo

Beilstein J. Org. Chem. 2015, 11, 1767–1780, doi:10.3762/bjoc.11.192

• pyridine is roughly 20 kcal/mol, with a small effect of the ligand bulkiness, which only changes for system 8 bearing more sterically demanding isopropyl groups, displaying a value of 15.0 kcal/mol. The pseudo-halide systems, instead, show a remarkably different behavior. The pyridine is quite weakly bound

A facile synthetic route to benzimidazolium salts bearing bulky aromatic N-substituents

• Gabriele Grieco,
• Olivier Blacque and
• Heinz Berke

Beilstein J. Org. Chem. 2015, 11, 1656–1666, doi:10.3762/bjoc.11.182

• isopropyl), 1.33 (d, J = 9 Hz, 12H, CH3-isopropyl), 1.17 (d, J = 9 Hz, 12H, CH3-isopropyl); 13C NMR (CDCl3, 75 MHz) δ 146.80 (N-C1-N), 146.02 (N-C8), 132.21 (N-C2=C7-N), 128.5 (C9, C13, C15, C19), 127.45 (C10, C12, C16, C18), 124.97 (C11, C17), 113.42 (C4=C5), 29.42 (CH3-CH-CH3, isopropyl), 24.73 (CH3

• , isopropyl), 23.10 (CH3, isopropyl); HRMS–ESI (MeOH): calcd for C31H39N2+, 439.31078; found, 439.31042. Synthesis of 1,3-diphenylbenzimidazolium chloride (3-Cl). In a 50 mL two neck round-bottomed flask was weighed N,N’-diphenylbenzene-1,2-diamine (5, 50 mg, 0.19 mmol) and triethyl orthoformate (15 mL) was

• ), 6.66 (dd, J = 5.8 Hz, J = 3.5 Hz, 2H, H-4, H-5), 6.29 (dd, J = 5.8 Hz, J = 3.5 Hz, 2H, H-3, H-6), 5.30 (s, 2H, NH), 3.24 (sept., J = 6.8 Hz, 4H, CH3-CH-CH3 isopropyl), 1.24 (d, J = 6.8 Hz, 12H, CH3-isopropyl), 1.18 (d, J = 6.8 Hz, 12H, CH3-isopropyl); 13C{1H} (CD2Cl2, 75 MHz) δ 145.77 (HN-C1=C2-NH

Development of variously functionalized nitrile oxides

• Haruyasu Asahara,
• Keita Arikiyo and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2015, 11, 1241–1245, doi:10.3762/bjoc.11.138

• anion for the hydrolysis was not required, and carboxylic acid 5a was obtained in 81% yield by the addition of only water (Table 3, entry 1). This protocol was applicable to a relatively bulky alcohol to afford isopropyl ester 5k in moderate yield (Table 3, entry 2). Similarly, primary and secondary

New palladium–oxazoline complexes: Synthesis and evaluation of the optical properties and the catalytic power during the oxidation of textile dyes

• Rym Hassani,
• Mahjoub Jabli,
• Yakdhane Kacem,
• Jérôme Marrot,
• Damien Prim and
• Béchir Ben Hassine

Beilstein J. Org. Chem. 2015, 11, 1175–1186, doi:10.3762/bjoc.11.132

• reaction mixture at room temperature [29]. In the light of these results, we also attempted to carry out this process under milder conditions. When (S)-4-isopropyl-2-(naphthalen-1-yl)oxazoline (2) was added to an acetic acid solution of Pd(OAc)2, a yellowish precipitate was obtained and identified as (S,S

• (Pd–N16 distance (1.963 A°), Pd–N1 distance (2.031 A°)) are almost the same (Pd–Cl1 distance (2.281 A°), the Pd–Cl2 distance (2.259 A°)). On the other hand, the addition of (S)-4-isopropyl-2-(naphthalen-1-yl)oxazoline (2) and 3-[(4S)-4,5-dihydro-4-isopropyl-1,3-oxazol-2-yl]propanenitrile (11) to a

• amino acids). (S)-4-Isopropyl-2-(naphthalen-1-yl)oxazoline (2) was isolated in a moderate yield from the condensation of the L-valinol with naphthonitrile under microwave irradiation, while the second ligand 1,2-bis[(S)-4-phenyloxazoline]benzene (7) was synthesized from L-(α)-(+)-phenylglycinol under

Cathodic hydrodimerization of nitroolefins

• Michael Weßling and
• Hans J. Schäfer

Beilstein J. Org. Chem. 2015, 11, 1163–1174, doi:10.3762/bjoc.11.131

• new reaction proceeds through a radical anion of the nitroalkene generated in a catalytic redox process. For ß-isopropyl-nitroethylene the radical anion has been identified by ESR [20]. Results and Discussion Investigation of the cathodic hydrodimerization of nitroalkene 1 to hydrodimer 2 The cathodic

Thiazole formation through a modified Gewald reaction

• Carl J. Mallia,
• Lukas Englert,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 875–883, doi:10.3762/bjoc.11.98

• yields (hydrolysis occurs from generated water) than the corresponding ethyl analogues (entries 1, 2 and 9, 10, Table 4). The isopropyl ester leads to a lower conversion and isolated yield presumably as a consequence of steric interactions (entry 3, Table 4). Changing the electronic character of the

• 13 and 14, Table 4) but an isopropyl group such as in molecule 47 (Figure 2), reproducibly gave no product, indicating the steric limits of the reaction. Although the reaction appears general, certain substrates tested did not generate any product when employing the standard reaction conditions

3α,5α-Cyclocholestan-6β-yl ethers as donors of the cholesterol moiety for the electrochemical synthesis of cholesterol glycoconjugates

• Aneta M. Tomkiel,
• Adam Biedrzycki,
• Jolanta Płoszyńska,
• Dorota Naróg,
• Andrzej Sobkowiak and
• Jacek W. Morzycki

Beilstein J. Org. Chem. 2015, 11, 162–168, doi:10.3762/bjoc.11.16

• amounts of diene 13 and cholesteryl chloride (14) were also formed. In the reactions of i-cholesterol alkyl ethers (methyl 6b, ethyl, 6c, isopropyl 6d, and benzyl 6e), cholesterol glycoconjugate 11 was also formed in 40%, 51%, 41%, and 50% yield, respectively. Glycoconjugate 11 was accompanied by

• -cyclocholestan-6β-yl isopropyl ether (6d). See the Supporting Information File 1 for full experimental data. Cyclic voltammograms registered in 0.2 M tetrabutylammonium tetrafluoroborate (TBABF4) in dichloromethane on a platinum electrode (area, 0.008 cm2) of (a) the supporting electrolyte (black), (b) 1,2:3,4

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• synthesized also from aromatic aldehydes, α,β-unsaturated aldehydes, or allylic alcohols in the presence of the DDQ (2,3-dichloro-5,6-dicyanobenzoquinone)/amberlyst-15 system in a methanol/toluene mixture under microwave irradiation [171]. Methyl, ethyl, and isopropyl benzoates were prepared from benzaldehyde

A study on the inhibitory mechanism for cholesterol absorption by α-cyclodextrin administration

• Takahiro Furune,
• Naoko Ikuta,
• Yoshiyuki Ishida,
• Hinako Okamoto,
• Daisuke Nakata,
• Keiji Terao and
• Norihiro Sakamoto

Beilstein J. Org. Chem. 2014, 10, 2827–2835, doi:10.3762/bjoc.10.300

• C18 (4.6 mm × 150 mm, Nihon Waters, Tokyo, Japan). The column temperature was 40 °C. The mobile phase was a mixture of acetonitrile and isopropyl alcohol (8:2, v/v). The flow rate was 0.6 mL/min. UV detection was carried out at 208 nm. A limit of detection of 0.15 μg mL−1 was obtained at a signal-to

Stereoselective synthesis of perillaldehyde-based chiral β-amino acid derivatives through conjugate addition of lithium amides

• Zsolt Szakonyi,
• Reijo Sillanpää and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2014, 10, 2738–2742, doi:10.3762/bjoc.10.289

• synthesis of β-peptides and 1,3-heterocycles in three steps. The steric effects of the isopropyl group at position 4 and of the α-methyl substituent of (R)-N-benzyl-N-α-methylbenzylamine on the reactivity were also studied and, upon application of a chiral amine, excellent stereoselectivity of the conjugate

• -based chiral β-amino acid derivatives derived from commercially available (−)-perillaldehyde (1). These 4-isopropyl-substituted analogues of ACHC (2-aminocyclohexanecarboxylic acid) might serve as promising building blocks for the synthesis of chiral 1,3-heterocycles and foldamers [7][11][23][35

• subsequently converted to the tert-butyl ester (3) [37]. In order to study the steric effect of the more bulky isopropyl group on the Michael addition, (4S)-tert-butyl phellandrate (6) was prepared via (4S)-phellandral (4) and (4S)-phellandric acid (5) (Scheme 1) [38][39][40]. The asymmetric Michael addition

Autonomous assembly of synthetic oligonucleotides built from an expanded DNA alphabet. Total synthesis of a gene encoding kanamycin resistance

• Kristen K. Merritt,
• Kevin M. Bradley,
• Daniel Hutter,
• Mariko F. Matsuura,
• Diane J. Rowold and
• Steven A. Benner

Beilstein J. Org. Chem. 2014, 10, 2348–2360, doi:10.3762/bjoc.10.245

• inserted gene encoding kanamycin resistance (or, for that matter, any insert at all). To assess whether the assembly had produced a gene able to confer kanamycin resistance, these cells were subcultured in shaken growth medium containing kanamycin and isopropyl β-D-1-thiogalactopyranoside (IPTG). Continued

• incubated with shaking at 37 °C until OD reached 1.4. Volumes (25 and 50 µL) of this culture were then plated (with appropriate serial dilutions) on agar containing ampicillin alone (to count cells that had been transformed regardless of the success of the OligArch assembly), kanamycin and isopropyl β-D

(CF₃CO)₂O/CF₃SO₃H-mediated synthesis of 1,3-diketones from carboxylic acids and aromatic ketones

• JungKeun Kim,
• Elvira Shokova,
• Victor Tafeenko and
• Vladimir Kovalev

Beilstein J. Org. Chem. 2014, 10, 2270–2278, doi:10.3762/bjoc.10.236

• (indanones, tetralone, acetophenones, 2-acetylthiophene and methyl benzyl ketone) with alkanoic acids RCOOH 1d–h (where R = 1-adamantylmethyl, neopentyl, isopropyl, methyl, phenyl) gave the corresponding β-diketones 3c–t in 37–86% yields (Table 2). In most cases reactions were carried out at the molar ratios

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• structure. The excellent regioselectivities and enantioselectivities resulted from the existence of the two isopropyl substituents in the chiral phosphine A2, which effectively controlled the approach of the acrylate toward the plausible phosphine/allenoate zwitterionic intermediate. Although the yields

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

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

• stereochemistry of the AT reaction was reported by Reiff and Aaron [29]. They used enantiopure O-isopropyl methylphosphonite 7-1 (Scheme 7-i) as a substrate. This substrate was purified by distillation with no racemization. However, rapid racemization was observed when 7-1 was treated with sodium methoxide in

Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

• Oliver Ries,
• Martin Büschleb,
• Markus Granitzka,
• Dietmar Stalke and
• Christian Ducho

Beilstein J. Org. Chem. 2014, 10, 1135–1142, doi:10.3762/bjoc.10.113

• derivative with limited stability, which was immediately converted into alcohol 4 by diastereoselective Felkin–Anh type Grignard addition with isopropyl magnesium chloride (50% yield over 2 steps from 3, dr > 95:5). However, we could not confirm that the use of diethyl ether as co-solvent in the Grignard

• acyclic D-serinal derivatives for the addition of nucleophiles to amino acid-derived aldehydes [33][34]. However, Zhu and co-workers have pointed out that Garner’s aldehyde surprisingly furnishes the syn diastereomer as the major product from its reaction with isopropyl magnesium chloride [32], thus

Synthesis of zearalenone-16-β,D-glucoside and zearalenone-16-sulfate: A tale of protecting resorcylic acid lactones for regiocontrolled conjugation

• Hannes Mikula,
• Julia Weber,
• Dennis Svatunek,
• Philipp Skrinjar,
• Gerhard Adam,
• Rudolf Krska,
• Christian Hametner and
• Johannes Fröhlich

Beilstein J. Org. Chem. 2014, 10, 1129–1134, doi:10.3762/bjoc.10.112

• protection of the more nucleophilic 4’-phenol and subsequent glucosylation or sulfation should lead to the desired products. For the development of a reliable protective group strategy and subsequent reaction optimization, 2,4-dihydroxybenzoic acid isopropyl ester (9) [29] was used as a RAL mimic. For

Consecutive isocyanide-based multicomponent reactions: synthesis of cyclic pentadepsipeptoids

• Angélica de Fátima S. Barreto,
• Otilie E. Vercillo,
• Ludger A. Wessjohann and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2014, 10, 1017–1022, doi:10.3762/bjoc.10.101

• its structure five side chains attached to the α carbon atoms: one isopropyl, one benzyl and three isobutyl groups. To generate the pentapeptoid analogues of San A, the side chain groups isobutyl, isopropyl and benzyl linked to the α carbon atom present in the peptide were moved to the nitrogen atoms

• . It was decided to keep at least one benzyl group in the structure of the peptoids and vary the isopropyl and isobutyl groups, thus maintaining a greater similarity with the structure of the San A depsipeptide. The retrosynthetic analysis of the depsipeptoids (Scheme 1) shows that the proposed

• added under pseudo-high dilution conditions (addition rate: 0.6 mL/h; addition time: 83 h; concentration: 0.80 mmol/L) to a suspension of paraformaldehyde 4, triethylamine, sodium sulfate and isopropyl/isobutyl/tert-butyl isocyanide 12a–c in methanol to yield the target cyclic pentadepsipeptoids 2a–f