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

Enantioselective Diels–Alder reaction of anthracene by chiral tritylium catalysis

• Qichao Zhang,
• Jian Lv and
• Sanzhong Luo

Beilstein J. Org. Chem. 2019, 15, 1304–1312, doi:10.3762/bjoc.15.129

• α-ketoesters 4 was subjected to the reaction with anthracene (3a) to give the desired cycloadducts 5a–n in moderate to good yields and with up to 93% ee. The bulkier isopropyl ketoester resulted in a lower yield and enantioselectivity (Table 2, entry 3 vs 1 and 2). Variations on the aromatic group

An efficient synthesis of the guaiane sesquiterpene (−)-isoguaiene by domino metathesis

• Yuzhou Wang,
• Ahmed F. Darweesh,
• Patrick Zimdars and
• Peter Metz

Beilstein J. Org. Chem. 2019, 15, 858–862, doi:10.3762/bjoc.15.83

• ylide 21 [8] followed by alkyne generation [23] with butyllithium in a one-pot process, trienyne 3 was obtained as a 1.6:1 mixture of E and Z olefin isomers. Due to the presence of the isopropyl group at the disubstituted alkene [24] of 3, 30 mol % of the second generation Grubbs catalyst 22 were

An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• wondered if alkylation of adenine with advanced intermediate 14 might represent a facile route to 6 (Figure 3). Holý and co-workers have previously utilised a similar alkyl chloride reagent to access adefovir analogues, but found that recourse to an isopropyl ester intermediate was necessary as the

Hoveyda–Grubbs catalysts with an N→Ru coordinate bond in a six-membered ring. Synthesis of stable, industrially scalable, highly efficient ruthenium metathesis catalysts and 2-vinylbenzylamine ligands as their precursors

• Kirill B. Polyanskii,
• Kseniia A. Alekseeva,
• Pavel V. Raspertov,
• Pavel A. Kumandin,
• Eugeniya V. Nikitina,
• Atash V. Gurbanov and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2019, 15, 769–779, doi:10.3762/bjoc.15.73

• pyridine group (Figure 1) recently released to the market. It has been experimentally established that the catalysts with an O-isopropyl group in their structure usually show the best combination of stability and activity. However, the oxygen atom having only one site for modification (i.e., the alkyl

Tuning the stability of alkoxyisopropyl protection groups

• Zehong Liang,
• Henna Koivikko,
• Mikko Oivanen and
• Petri Heinonen

Beilstein J. Org. Chem. 2019, 15, 746–751, doi:10.3762/bjoc.15.70

• reported were 10 minutes in an acetate buffer at pH 4.18 and approximately 4 minutes at pH 3.22. These values are close to an order of magnitude longer than what we determined for MIP 4a, and two orders of magnitude longer than those of the cyclohexyl and isopropyl analogs 4c, 4d (Table 1). It must be

• , d: R = isopropyl, e: R = CH2CF3. Proposed acetal hydrolysis pathways. Half-lives of 5’-acetal (4a–e) and 3’-acetal-protected (7a,c–e) 2’-deoxythymidines, and 2’-deoxy-3’-O-propen-2-ylthymidine (8b) in acetate (pH 4.94), citrate (pH 5.61) and phosphate (pH 6.82) buffers at 25.0 °C. The ionic strength

Selective benzylic C–H monooxygenation mediated by iodine oxides

• Kelsey B. LaMartina,
• Haley K. Kuck,
• Linda S. Oglesbee,
• Asma Al-Odaini and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2019, 15, 602–609, doi:10.3762/bjoc.15.55

• decatungstate [58]. Substrates containing tertiary C–H bonds, such as 1-isopropyl-4-methylbenzene (6b), were essentially unreactive under the developed conditions, returning starting alkyl arene with only a trace of acetoxylated product 7b (see Supporting Information File 1, Figure S11) [59]. Previous work on

LCST phase behavior of benzo-21-crown-7 with different alkyl chains

• Yan Deng,
• Xing Li,
• Qiao Zhang,
• Zheng Luo,
• Chengyou Han and
• Shengyi Dong

Beilstein J. Org. Chem. 2019, 15, 437–444, doi:10.3762/bjoc.15.38

• mg/mL (44.2 °C). It is demonstrated that, the longer the alkyl chain is the lower Tcloud becomes. We also found that the presence of a propyl substituent (3a) and an isopropyl group (3b) results in a quite different critical transition temperature, with Tcloud at 62.1 °C and 41.5 °C, respectively

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• that observed for 7a/7’a. Other substituents were tolerated on the phosphorus atom including an isopropyl or a cyclohexyl group and the corresponding phosphine oxides 7h/7’h and 7i/7’i were isolated in good yields. Increasing the steric hindrance around the phosphorus atom resulted in a higher

• diastereoselectivity. However, the sigmatropic rearrangement of the highly hindered di(tert-butyl)phosphinite 6j and tetra(isopropyl) phosphorodiamidite 6k did not occur (Scheme 7) [37]. The mechanism proposed by Rubin et al. involves a reversible addition of the Lewis base (DBU) on the cyclopropene double bond at C2

A novel and efficient synthesis of phenanthrene derivatives via palladium/norbornadiene-catalyzed domino one-pot reaction

• Yue Zhong,
• Wen-Yu Wu,
• Shao-Peng Yu,
• Tian-Yuan Fan,
• Hai-Tao Yu,
• Nian-Guang Li,
• Zhi-Hao Shi,
• Yu-Ping Tang and
• Jin-Ao Duan

Beilstein J. Org. Chem. 2019, 15, 291–298, doi:10.3762/bjoc.15.26

• . Therefore, it is speculated that the intrinsic electronic properties of aryl iodides makes no difference in this process. The reaction of methoxy-, 2-ethyl-, 2-isopropyl, and 2-phenyliodobenzenes in this procedure afforded the desired products in excellent yields (y-3, y-5, y-6 and y-4), while 1

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• biosynthesis of this polymer. The presence of aromatic rings, such as the 4-methoxyphenyl group at the anomeric position, should be avoided because these groups can significantly modify the binding mode between the CS and the enzymes. For this reason, we introduced an isopropyl group in β-position of the

• anomeric center of the glycosyl acceptor. We hypothesized that the isopropyl moiety would not affect the CS–enzyme interaction. Trichloroacetimidate 12 was obtained by oxidative removal of the 4-methoxyphenyl group with CAN at 0 ºC and further treatment with trichloroacetonitrile and catalytic amounts of

• DBU. The glycosylation reaction with 2-propanol using TMSOTf as Lewis acid at 0 ºC cleanly provided the β-isopropyl glycoside 13 in 65% yield. Interestingly, no α-anomer was detected in the reaction mixture. Finally, cleavage of the levulinyl group using hydrazine monohydrate in pyridine/acetic acid

Ruthenium-based olefin metathesis catalysts with monodentate unsymmetrical NHC ligands

• Veronica Paradiso,
• Chiara Costabile and
• Fabia Grisi

Beilstein J. Org. Chem. 2018, 14, 3122–3149, doi:10.3762/bjoc.14.292

• . Catalyst 154 containing an N-isopropyl group (Figure 29), which is considered to be sterically equivalent to the N-trifluoromethyl group, disclosed a substantially lower selectivity in both alternating copolymerization and ethenolysis reaction, underlining that the electronic effect determined by the

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• molecules 8–10, in 60%, 53% and 49% yields, respectively. Such well-known π-nucleophiles as phenols could be used for the reaction, though 3-methoxyphenol and 3,5-dimethoxyphenol gave inseparable mixtures of regioisomers 11a and 11b (NMR, LCMS). The reactions with p-isopropyl- and p-tert-butylphenols gave

The activity of indenylidene derivatives in olefin metathesis catalysts

• Maria Voccia,
• Steven P. Nolan,
• Luigi Cavallo and
• Albert Poater

Beilstein J. Org. Chem. 2018, 14, 2956–2963, doi:10.3762/bjoc.14.275

• with ortho-methyl and isopropyl groups at both ortho positions of their phenyl ring. DFT results highlight the more sterically demanding indenylidenes have to undergo a more exothermic first phosphine dissociation step. Overall, the study emphasises advantages of increased steric hindrance in promoting

• or isopropyl groups at the ortho positions of the phenyl substituent, compared to the unsubstituted 1 and 2. Comparing IMes vs SIMes, the activation is about 1 kcal/mol more favoured for the unsaturated system [42][43]. The absolute difference of 1 kcal/mol is maintained throughout the mechanism

• , however, we must point out that the opening of the metallacycle requires only 0.6 kcal/mol for the SIMes system versus 1.7 kcal/mol for the unsaturated system. The methyl and isopropyl-substituted indenylidene moieties reveal a different performance between the SIMes and the IMes congeners. When the

Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety

• Alex Frichert,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222

• the ring system and the adjacent atoms are located almost in plane, whereas the isopropyl group and ring carbons C3 and C4 are located on opposite sides of that plane. Since the oxidation/reduction sequence has affected the configuration at C2, diastereomer 19 is assigned the configuration (2S,3S,14R

• ). For diastereomer 19, 2-H did not show a NOESY correlation to 5-Hβ, but instead a correlation to 14-H, to the isopropyl methine hydrogen, and to 3-CH3. In addition, 3-CH3 correlates with both methylene hydrogens at C4. We found only two conformers of the (2S,3S,14R) diastereomer that meet those

• carbon following the ethoxycarbonylation. The 3JHH coupling constant proved that the isopropyl and ethoxycarbonyl groups both assume an equatorial position in a chair conformation. We were not able to obtain an X-ray analysis of cyanohydrin 22, but of one diastereomer (30) of an analog where the OTBS was

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• pyrones 44a–g in good-to-high yields within 1 h (Scheme 40). Ester, ketone, and hydroxy groups were tolerated in the reaction. In the case of an unsymmetrical diyne bearing methyl and isopropyl groups (43g), a mixture of regioisomers 44g + 44g′ was obtained in high yield with high regioselectivity. For

A novel and practical asymmetric synthesis of eptazocine hydrobromide

• Ruipeng Li,
• Zhenren Liu,
• Liang Chen,
• Jing Pan,
• Kuaile Lin and
• Weicheng Zhou

Beilstein J. Org. Chem. 2018, 14, 2340–2347, doi:10.3762/bjoc.14.209

• Bruker 400 MHz spectrometer with TMS as an internal standard. Mass spectra were recorded with a Q-TOF mass spectrometer using electrospray positive ionization (ESI+). Enantiomeric ratios were determined by HPLC using a chiral column (Chiralpak AY-H) with hexane/isopropyl alcohol 50:50 as eluents

Coordination-driven self-assembly of discrete Ru₆–Pt₆ prismatic cages

• Aderonke Ajibola Adeyemo and
• Partha Sarathi Mukherjee

Beilstein J. Org. Chem. 2018, 14, 2242–2249, doi:10.3762/bjoc.14.199

• moiety in 3a and 3b were slightly shifted downfield while the isopropyl and methyl protons of the p-cymene moiety in all the cages remained almost unchanged as compared to the arene–ruthenium(II) clips 1a,1b(NO3)2. Additionally, the protons of naphthacenedione in 3a and naphthaquinone in 3b were not