Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

Hierarchically assembled helicates as reaction platform – from stoichiometric Diels–Alder reactions to enamine catalysis

• David Van Craen,
• Jenny Begall,
• Johannes Großkurth,
• Leonard Himmel,
• Oliver Linnenberg,
• Elisabeth Isaak and
• Markus Albrecht

Beilstein J. Org. Chem. 2020, 16, 2338–2345, doi:10.3762/bjoc.16.195

• was observed using the helicate Li4[(13b)1(2)5Ti2] as catalyst. The helicates Li4[(13c)1(2)5Ti2] and Li4[(13d)1(2)5Ti2] with an isopropyl-substituted ethylamine and a cyclic secondary amine ligand as catalytically active unit showed no conversion in the nitro-Michael reaction. Solubility problems were

Lipophilicity trends upon fluorination of isopropyl, cyclopropyl and 3-oxetanyl groups

• Benjamin Jeffries,
• Zhong Wang,
• Robert I. Troup,
• Anaïs Goupille,
• Jean-Yves Le Questel,
• Charlene Fallan,
• James S. Scott,
• Elisabetta Chiarparin,
• Jérôme Graton and
• Bruno Linclau

Beilstein J. Org. Chem. 2020, 16, 2141–2150, doi:10.3762/bjoc.16.182

• Nantes, France Medicinal Chemistry, Oncology R&D, AstraZeneca, Cambridge CB4 0WG, UK 10.3762/bjoc.16.182 Abstract A systematic comparison of lipophilicity modulations upon fluorination of isopropyl, cyclopropyl and 3-oxetanyl substituents, at a single carbon atom, is provided using directly comparable

• isopropyl substituent led to larger lipophilicity modulation compared to fluorination of the cyclopropyl substituent. Keywords: aliphatic fluorination; cyclopropane; isopropyl; isostere; lipophilicity; oxetane; Introduction The introduction of small alkyl groups onto bioactive compounds as space filling

• existing appendages is also commonly employed. For example, an isopropyl and a trifluoromethyl group have very similar volumes, but a very different shape [6]. However, even the introduction of relatively small methyl groups can impart profound consequences (“the magic methyl effect”) [7][8][9] on the

Synergy between supported ionic liquid-like phases and immobilized palladium N-heterocyclic carbene–phosphine complexes for the Negishi reaction under flow conditions

• Edgar Peris,
• Raúl Porcar,
• María Macia,
• Jesús Alcázar,
• Eduardo García-Verdugo and
• Santiago V. Luis

Beilstein J. Org. Chem. 2020, 16, 1924–1935, doi:10.3762/bjoc.16.159

• kinetic plots for this model reaction are represented in Figure 1. The NHC–Pd catalyst 4a showed a rather reduced activity (less than 10% after two hours), while the catalyst bearing isopropyl moieties at the aromatic ring (4b) displayed a significant increase in the catalytic activity, reaching 67% yield

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• , cyclopentaoxasilinone 36a was isolated in 81% yield. A systematic study of the scope showed that unsubstituted enyne 35b only afforded the desired product in 25% yield. In contrast, isopropyl and phenyl substituted enynes yielded cyclopentaoxasilinone 36c,d in 74 and 79% yield, respectively. Furthermore, electron

One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions

• Gui-Feng Kang and
• Gang Zhang

Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120

• substrates, affording the desired products 6wa–ya in 65–81% yields. The possibility of using aliphatic aldehydes in place of aromatic aldehydes was investigated for 2 and 3a. Fortunately, the reactions carried out with isobutyraldehyde (1z) yielded 31% of the isopropyl-functionalized 6-(methylthio)-3,4

Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides

• Mateo Berton,
• Kevin Sheehan,
• Andrea Adamo and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2020, 16, 1343–1356, doi:10.3762/bjoc.16.115

• study, we started selecting some of the most used organomagnesium halides in synthesis. For this purpose, a ranking of the 20 most cited ones, as measured by the citation values obtained from SciFinder, was constructed (Figure 2). Based on our analysis, methyl, ethyl, isopropyl, butyl, benzyl, and

Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration–oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles

• Lívia Dikošová,
• Júlia Laceková,
• Ondrej Záborský and
• Róbert Fischer

Beilstein J. Org. Chem. 2020, 16, 1313–1319, doi:10.3762/bjoc.16.112

• -dichloroethane. Finally, the subsequent basic hydrolysis with 6 M NaOH [39] in isopropyl alcohol [41] to remove the carbamate readily afforded the desired isoxazolidine 12 in good yield (72%). The progress of the reaction was easily followed by TLC (EtOAc), and the N-unsubstituted isoxazolidin-4-ol 12 was

• hydrolysis of the corresponding N-Troc intermediate was successfully exemplified on the 3-isopropyl-substituted derivative. We believe that the presented method will provide a fast and highly stereoselective approach towards both C-3/4-cis and C-3/4-trans isomers of 3-substituted isoxazolidin-4-ols as

• -isoxazolidine 11 (120 mg, 0.29 mmol) in isopropyl alcohol (1.2 mL), and the mixture was stirred at rt for 1 h. After the disappearance of the starting material (TLC, hexanes/EtOAc, 5:1), the solution was neutralized with HCl (6 M). Afterwards, a saturated aq NaHCO3 solution (2 mL) and solid NaCl were added, and

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• hand, Wade et al. reported that ester 138b (R = iPr) afforded the isopropyl 3-fluorophenylalaninate (139b) as racemate in 45–50% yield [70] under similar reaction conditions (Scheme 31). 2.6. Fluorination and reductive amination of phenylpyruvate A direct fluorination of the ester derivatives of

Towards triptycene functionalization and triptycene-linked porphyrin arrays

• Gemma M. Locke,
• Keith J. Flanagan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2020, 16, 763–777, doi:10.3762/bjoc.16.70

• [C11 to C16, centroid···centroid distance of 3.755(3) Å and shift distance of 1.593(5) Å] involved in a head-to-head slip plane π-stacking interaction with another triptycene molecule either side, while the third face ring iii of the triptycene exhibits C23–H23B···π interactions between the isopropyl

• three methyl groups on the TMS moiety was modelled over two position in a 55:45% occupancy. Two of the isopropyl group carbon atoms C24 and C26 were two positions in a 50:50% occupancy (see Supporting Information File 2 for full details). Crystal data for 16: C100H90N8NiZn (M =1527.87 g/mol): triclinic

Regioselectively α- and β-alkynylated BODIPY dyes via gold(I)-catalyzed direct C–H functionalization and their photophysical properties

• Takahide Shimada,
• Shigeki Mori,
• Masatoshi Ishida and
• Hiroyuki Furuta

Beilstein J. Org. Chem. 2020, 16, 587–595, doi:10.3762/bjoc.16.53

• : triisopropylsilyl group; Mes: 2,4,6-trimethylphenyl group. Top and front views of the crystal structures of (a) 4a and (b) 6b with 50% thermal ellipsoid probabilities. The isopropyl groups on the silicon atom are omitted in the front view for clarity. Partial 1H NMR spectra of (a) 1a, (b) 3a, (c) 4a, (d) 5a, and (e

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• in an aqueous medium under aerobic conditions at 70 °C (Scheme 20). In another example, GO was effectively modified with CuO nanoparticles through a facile pathway that can be seen below [83]. In the next step, GO was sonicated in isopropyl alcohol for 0.5 h to produce a black dispersion. After

Copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters with chiral phenol–carbene ligands

• Shohei Mimura,
• Sho Mizushima,
• Yohei Shimizu and
• Masaya Sawamura

Beilstein J. Org. Chem. 2020, 16, 537–543, doi:10.3762/bjoc.16.50

• affected the stereoselectivities: Lower enantioselectivities were observed with benzyl ester 2g (Table 2, entry 8, >99% yield, 70% ee) and isopropyl ester 2h (Table 2, entry 9, >99% yield, 83% ee). In addition to the α,β-unsaturated esters, an α,β-unsaturated Weinreb amide 1i afforded the corresponding

Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin

• Anna R. Bockman and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2020, 16, 509–514, doi:10.3762/bjoc.16.46

• amines to be adequately reassessed on their ease of amidation (Table 2). It was found that the reaction was most affected by an α-substitution on the amine (Table 2; products 11–13). This is in agreement with known Taft parameters which show steric effects are more pronounced for an isopropyl group

Synthesis of a dihalogenated pyridinyl silicon rhodamine for mitochondrial imaging by a halogen dance rearrangement

• Jessica Matthias,
• Thines Kanagasundaram,
• Klaus Kopka and
• Carsten S. Kramer

Beilstein J. Org. Chem. 2019, 15, 2333–2343, doi:10.3762/bjoc.15.226

• of the ester group in 2’-position, an isopropyl ester derivative; another one might be the effects of the fluorine atoms and the ester group on the HOMO energy level of the benzene moiety. Since our group is interested in PET-active near-infrared (NIR) dyes for bimodal medical imaging (PET/optical

Characterization of two new degradation products of atorvastatin calcium formed upon treatment with strong acids

• Jürgen Krauß,
• Monika Klimt,
• Markus Luber,
• Peter Mayer and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2085–2091, doi:10.3762/bjoc.15.206

• /dehydration process in the side chain), treatment with conc. aqueous hydrochloric acid gave a complex, bridged molecule under C–C-bond formation of the lactone moiety with the pyrrole, migration of the isopropyl group and loss of the carboxanilide residue. The novel degradation products were characterized by

• isopropyl residue, originally located at C-2 of the pyrrole, is shifted to C-3, rendering the annulated, tetrasubstituted pyrrole 6. The structure of 6 was confirmed by X-ray crystal structure analysis. However, most likely cleavage of the carboxanilide moiety (compare formation of 7 from atorvastatin with

• , which is formed via initial acid-mediated electrophilic attack of the unsaturated lactone at C-2 of the pyrrole ring. The resulting carbenium ion should be stabilized as shown in Scheme 3 (B ↔ B’). Subsequent shift of the isopropyl group from C-2 to C-3 then would give carbenium(-iminium) ion C, which

Bipolenins K–N: New sesquiterpenoids from the fungal plant pathogen Bipolaris sorokiniana

• Chin-Soon Phan,
• Hang Li,
• Simon Kessler,
• Peter S. Solomon,
• Andrew M. Piggott and
• Yit-Heng Chooi

Beilstein J. Org. Chem. 2019, 15, 2020–2028, doi:10.3762/bjoc.15.198

• ) showed 15 distinct carbon signals, while 13C and 1H NMR data (Table 1) indicated an isopropyl unit (δC 28.3, 29.2 and 73.1; δH 1.20 and 1.24), one tertiary methyl (δC 20.1; δH 1.25), a disubstituted olefin (δC 105.7 and 155.2; δH 5.12 and 4.89) and four methines (δC 39.6, 51.1, 51.6 and 54.0; δH 1.73

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

• -phenylethylamine (49) to generate key tricyclic intermediates 51 and 52, a Pd(II)-catalyzed carbonylation–lactonization reaction of 9 to construct the butenolide (D-ring), and a Friedel–Crafts isopropylation to install the C-13 isopropyl group. Still, the construction of the C-5 trans junction A-/B-ring was

• 18.5% overall yield. Importantly, by late-stage installation of the C-13 isopropyl group, this synthesis also provided a useful approach for the synthesis of other structurally relevant derivatives of triptolide such as C-15 and C-16 modified derivatives of triptolide. In 1980, van Tamelen and co

• form the A- and D-ring. The second one involves the reaction of the bicyclic intermediate 13 and 2-isopropyl-1,4-benzoquinone (14) to form the B- and C-ring. Finally, a regio- and stereoselective reduction, methylation and dehydration procedure and a selenylation, oxidation and elimination procedure

Analysis of sesquiterpene hydrocarbons in grape berry exocarp (Vitis vinifera L.) using in vivo-labeling and comprehensive two-dimensional gas chromatography–mass spectrometry (GC×GC–MS)

• Philipp P. Könen and
• Matthias Wüst

Beilstein J. Org. Chem. 2019, 15, 1945–1961, doi:10.3762/bjoc.15.190

• )-(+)-germacrene D, that includes two consecutive 1,2-hydride shifts [33]. In all terpenes in Scheme 3, TOF–EIMS measurements showed that a deuterium atom is located in the isopropyl group. This can be explained by the assumption that in Vitis vinifera L. all sesquiterpenes are formed via the (S)-germacradienyl

• ). The signal with m/z = 161 [M]+ corresponds to the fragment after abstraction of the isopropyl group (marked blue). Feeding experiments using d2-DOX showed that according to the biosynthesis pathway demonstrated in Scheme 3, a maximum of 6 deuterium atoms are incorporated into α-cubebene. The presence

• isopropyl group leads to the fragment with m/z = 166. At this point it becomes obvious why it can be assumed that the tricyclic sesquiterpene hydrocarbon α-cubebene is synthesized via (S)-(−)-germacrene D and not via (R)-(+)-germacrene D. Assuming the biosynthesis of α-cubebene takes place via (R

Inherent atomic mobility changes in carbocation intermediates during the sesterterpene cyclization cascade

• Hajime Sato,
• Takaaki Mitsuhashi,
• Mami Yamazaki,
• Ikuro Abe and
• Masanobu Uchiyama

Beilstein J. Org. Chem. 2019, 15, 1890–1897, doi:10.3762/bjoc.15.184

• the counterclockwise rotation of the isopropyl moiety is necessary for 1,5-hydrogen shift to occur (TS_2-3a in quiannulatene biosynthesis and TS_2-3 in sesterfisherol biosynthesis) [19]. Phase II: conformational changes and hydrogen shifts In phase II, different trends of inherent mobility are seen

Application of chiral 2-isoxazoline for the synthesis of syn-1,3-diol analogs

• Juanjuan Feng,
• Tianyu Li,
• Jiaxin Zhang and
• Peng Jiao

Beilstein J. Org. Chem. 2019, 15, 1840–1847, doi:10.3762/bjoc.15.179

• triisopropylsilyl nitronate. Then, the catalytic asymmetric cycloaddition gave the 2-isoxazolidine cycloadduct 1 in a high yield. In the light of our previous ligand screening results [49], two bisoxazolines with an isopropyl (ligand B) or tert-butyl group (ligand A) were tested. Optimization of the conditions

Complexation of 2,6-helic[6]arene and its derivatives with 1,1′-dimethyl-4,4′-bipyridinium salts and protonated 4,4'-bipyridinium salts: an acid–base controllable complexation

• Jing Li,
• Qiang Shi,
• Ying Han and
• Chuan-Feng Chen

Beilstein J. Org. Chem. 2019, 15, 1795–1804, doi:10.3762/bjoc.15.173

• complex H1·G1 was obtained by vapor diffusion of isopropyl ether into acetone. As shown in Figure 4, G1 was encapsulated in the cavity of H1 to form a 1:1 complex, in which G1 is distorted by the dihedral angle between the pyridinium rings of 33.19°. There exist multiple CH···π interactions between the

• diffusion of isopropyl ether into a chloroform/acetone 1:1 (v/v) solution of the 1:1 mixture of H3 and G1, we only obtained a single crystal of H3 instead of the host–guest complex. The steric hindrance of the n-butoxy groups in H3 (Supporting Information File 1, Figure S90) might lead to weak complexation

• of H3 with the tested guests in solution. However, we obtained a single crystal of complex H5·G1 by vapor diffusion of isopropyl ether into an acetone solution. As shown in Figure 5, we found that G1 was encapsulated in the cavity of H5 to form a 1:1 complex, and the complex molecules are stacked

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• [16][18][19], isopropyl 5c [16] and tert-butyl 5d [16][20] as well as for 4-methoxyphenyl ester 5e [21]. However, the corresponding (−)-menthyl esters (2R,1'R)-5f and (2S,1'R)-5f were separated by solvent-driven selective crystallization at low-temperature from ethanol and hexane, respectively. The

An azobenzene container showing a definite folding – synthesis and structural investigation

• Abdulselam Adam,
• Saber Mehrparvar and
• Gebhard Haberhauer

Beilstein J. Org. Chem. 2019, 15, 1534–1544, doi:10.3762/bjoc.15.156

• reduction of the distance between the two isopropyl groups. As further example the chiral foldable container 5 should be mentioned [49]. Here, two imidazole-containing macrocycles are linked to each other by two azobenzene units (Figure 2). Irradiation with UV light causes two consecutive trans→cis

• , whereas platform 3a possesses two oxazole rings. Overall, both macrocycles feature four amino acid side chains (isopropyl groups), whereby all of them are of the same configuration (S). Therefore, they are presented on one face of the macrocycle in a convergent manner. Platform 3a was synthesized in a few

• macrocycles: In the elongated trans,trans-isomer this distance shows a value of 14.1 Å, in the more compact cis,cis-isomer the distance amounts to 11.3 Å. The replace of the isopropyl groups by recognition units and the enlargement of the two linkers, which makes a shielding of a guest from the environment

Formation of an unexpected 3,3-diphenyl-3H-indazole through a facile intramolecular [2 + 3] cycloaddition of the diazo intermediate

• Andrew T. King,
• Hugh G. Hiscocks,
• Lidia Matesic,
• Mohan Bhadbhade,
• Roger Bishop and
• Alison T. Ung

Beilstein J. Org. Chem. 2019, 15, 1347–1354, doi:10.3762/bjoc.15.134

• -arylsulfonyl fluoride 3 was 95% intact in rat plasma after 120 min at 37 °C [5]. This indicated that the combination of electron-donating effects and steric hindrance of isopropyl groups provide greater stability to a sulfur–fluorine bond than groups that can only provide the steric hindrance in the molecule