Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• and the phosphonate 126 leading to the cis-ester 127 in high yield. Reduction of the ester using DIBAL gave the allylic alcohol 114 which was submitted to an Ullmann coupling [59] with isovanillin (80) to give the corresponding diaryl ether 128. Further esterification [60] with S-acetylthioacetic acid

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• azide and alkyne groups in high yield and regioselectivity without using harsh reaction conditions. In recent years, this click protocol has been successfully employed in porphyrin chemistry to synthesize various triazoloporphyrins by attaching an azide or alkyne moiety to the periphery of the porphyrin

• molecular architectures featuring 1,4-disubstituted triazole units with high yield and higher regioselectivity. The click-inspired synthesis and photophysical properties of diverse triazole-linked porphyrin conjugates are discussed in this review. This review includes a number of recent and important

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• reduction steps were compatible to be coupled in one flow system obtaining 6-monoamino-6-monodeoxy-β-cyclodextrin in a high yield. Our flow method developed is safer and faster than the batch approaches. Keywords: azidation; continuous flow; β-cyclodextrin; H-cube; 6-monoamino-6-monodeoxy-β-cyclodextrin

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• ] cyclooctene 27 in very high yield. The final stages of the synthesis corresponded to the elaboration of the second cyclopentenone ring allowing access to ent-fusicoauritone (28) in 24 steps. 1.1.1.2 Strategy 2: Late-stage formation of the 8-membered ring: Ophiobolins belong to the family of sesterterpenoids

• 31 and oxazolidinone 32 (Scheme 5) [26]. Subsequently, compound 33 was converted in four steps into aldehyde 34 which was engaged in a coupling reaction with bromoketone 35 according to Utimoto conditions to furnish the A-C-D adduct 36 as a single stereoisomer in high yield. Of note, the Utimoto

• expected tetracyclic cyclooctane-bearing product 92 in high yield (86%). Of note, this cyclization occurred on a highly functionalized substrate. All the carbons of the cyclooctene ring were stereogenic, except the two of the double bond, and the precursor possesses both a hydrindane and a cyclopentane

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• -azidocholest-5-ene (5) in high yield. The same product was recently obtained by direct dehydroxyazidation of cholesterol upon treatment with N-acetyl azidobenziodazolone (ABZ) and PPh3 in THF [19], Table 1. While synthesizing new potential biologically active probes with cholesterol scaffolds in the Port Said

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• converted to 3 through a 6-step sequence involving reduction of the aromatic ring and oxidation of the enone to a dienone. The resulting dienone 3 underwent a key photoinduced santonin-like rearrangement in the presence of acetic acid, furnishing 4 in high yield. It should be noted that the group of Hiraoka

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• conditions gave the secondary side peracetylated 6 in a high yield. The selective deprotection of silyl groups, yielding compound 7, was also performed standardly using BF3O·Et2O. Our new procedure is based on the methylation of this acetyl-protected β-CD 7 using a DIPEA/methyl tosylate mixture without

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities

• Hongling Shui,
• Yuhong Zhong,
• Renshi Luo,
• Zhanyi Zhang,
• Jiuzhong Huang,
• Ping Yang and
• Nianhua Luo

Beilstein J. Org. Chem. 2022, 18, 1507–1517, doi:10.3762/bjoc.18.159

• Gram-positive bacteria and Candida albicans. Conclusion In summary, we have developed a new route for the efficient synthesis of quinoxaline and its derivatives with high yield and good chemoselectivity via the ADC reaction of 2-aminobenzyl alcohol and aryl aryl/heteroaryl/alkyl secondary alcohols

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• skeleton (Scheme 5, red). Also, hydrazinium dihydrochloride was isolated in this experiment. Deoxygenation of N–OH units in TAAD Bn-8a was also performed by reflux with Zn in water (Scheme 5, green). The Boc group was removed under these conditions producing TAAD 23 in high yield. Structure of N-TAADs and

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• epichlorohydrin and provided α-aryloxy alcohols in an overall high yield and a complete enantioselectivity. Conclusion In summary, we mechanochemically synthesized unsymmetrical salens 1 for preparing metal–salen catalysts 2 for the first time. The use of grinding technology provided salens 1 in an overall higher

Synthesis and electrochemical properties of 3,4,5-tris(chlorophenyl)-1,2-diphosphaferrocenes

• Almaz A. Zagidullin,
• Farida F. Akhmatkhanova,
• Mikhail N. Khrizanforov,
• Robert R. Fayzullin,
• Tatiana P. Gerasimova,
• Ilya A. Bezkishko and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1338–1345, doi:10.3762/bjoc.18.139

• Federation 10.3762/bjoc.18.139 Abstract A novel representative of sodium 3,4,5-triaryl-1,2-diphosphacyclopentadienide containing a chloro substituent in the meta-position of the aryl groups was obtained with a high yield based on the reaction of tributyl(1,2,3-triarylcyclopropenyl)phosphonium bromide and

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• formed in situ from the corresponding aminothiols [9][10][11][12][13]. Green chemistry methods for benzo-1,4-thiazine synthesis have also been described in the literature. 2,3-Disubstituted-1,4-benzothiazines were prepared in high yield (83–96%) by oxidative cyclocondensation of 2-aminobenzenethiols and

• , three-component procedure was also explored for the preparation of 3-aryl-4H-benzo-1,4-thiazin-2-amines [18]. 3-Aryl- and 3-alkyl-4H-benzo[b][1,4]thiazine-4-carbonitriles 2 (Figure 1) were synthesized in high yield from the corresponding 2-aminobenzothiazoles using the copper–organic framework Cu–MOF-74

• intramolecular amination of aryl bromides [27]. Recently, Nguyen and Retailleau introduced a TFA-catalyzed umpolung strategy with 2-aminothiophenols, preparing several 2H-benzo-1,4-thiazine derivatives 5 in high yield [28]. 3-Phenyl-2H-benzo-1,4-thiazine, an earlier representative of this family, was found to

Lewis acid-catalyzed Pudovik reaction–phospha-Brook rearrangement sequence to access phosphoric esters

• Jin Yang,
• Dang-Wei Qian and
• Shang-Dong Yang

Beilstein J. Org. Chem. 2022, 18, 1188–1194, doi:10.3762/bjoc.18.123

• desired 3aa being obtained at a temperature lower than 80 °C, but 4aa was produced in a high yield (Table 1, entries 7−9). When the reaction was performed at 120 °C, the yield of 3aa was slightly lower than that at 100 °C. With the high-yielding reaction conditions established (Table 1, entry 5), we

• formaldehyde or ketone groups could also be transformed into the desired diphosphination products 3bm and 3bn in moderate to good yield. The generality of the system was further showcased by tolerating quinoline and isoquinoline groups, and the desired products 3bp and 3bq were afforded in a high yield

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• proceeds smoothly at room temperature giving rise to cyclopropane 4 in excellent diastereoselectivity (de = 92%) and high yield. The optical purity of the starting compounds was confirmed by comparison of the optical rotation data with previously published values (see Supporting Information File 1

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• [17] gave (Z)-4 as a single diastereomer through anti elimination. Overall, TDD was obtained from ʟ-tryptophan in a high yield of 37% over eight linear steps. HPLC analysis on a chiral stationary phase showed that 4 obtained through this second route was enantiomerically enriched (80% ee by peak

• temperature. Also the addition of base (NEt3) did not promote the reaction. Therefore, the mode of action of TDD towards glutathione S-transferase needs further investigation. Conclusion We have established an efficient synthesis of TDD that makes this compound available from ʟ-tryptophan with a high yield of

Electrogenerated base-promoted cyclopropanation using alkyl 2-chloroacetates

• Kouichi Matsumoto,
• Yuta Hayashi,
• Kengo Hamasaki,
• Mizuki Matsuse,
• Hiyono Suzuki,
• Keiji Nishiwaki and
• Norihito Kawashita

Beilstein J. Org. Chem. 2022, 18, 1116–1122, doi:10.3762/bjoc.18.114

• was 44% in the case of 0.90 F/mol (Table 2, entry 2). However, using 1.1 F/mol resulted as well in a lower yield of 2 (<35%, Table 2, entry 3). Thus, 0.90 F/mol or 1.0 F/mol of electricity for the current reaction was found to be sufficient to obtain the product in high yield, and we choose 1.0 F/mol

Electrochemical formal homocoupling of sec-alcohols

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masashi Shiota,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2022, 18, 1062–1069, doi:10.3762/bjoc.18.108

• 2a in a high yield, and we chose 125 μL of H2O as the optimal volume for the present transformation (Table 1, entries 11–13). The reaction under inert atmosphere did not improve the yield of 2a (Table 1, entry 14). With the optimized conditions in hand, the substrate scope of the present

Electrochemical hydrogenation of enones using a proton-exchange membrane reactor: selectivity and utility

• Koichi Mitsudo,
• Haruka Inoue,
• Yuta Niki,
• Eisuke Sato and
• Seiji Suga

Beilstein J. Org. Chem. 2022, 18, 1055–1061, doi:10.3762/bjoc.18.107

• . Linear enone 1f gave the desired ketone 2f in high yield (88%, 97% selectivity). Reduction with the PEM reactor also proceeded smoothly with enone 1g, which has a cyclohexene moiety, to give the corresponding ketone 2g in 87% yield (91% selectivity). As shown so far, several kinds of enones 1 could be

• subjected to electroreduction using the PEM reactor to afford ketones in high yield and selectivity. Electroreduction of enones to saturated alcohols We next examined the electrochemical reduction of several enones 1 to saturated alcohols 3 using an Ir/C catalyst for the cathode (Scheme 3). Full conversion

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• the usefulness of the current protocol for quick access to these halo derivatives. Encouraged by this, we attempted monochlorination with selected phenols and anilines. The first attempt with 2-naphthol afforded the desired chloro derivative 2ah in high yield within 2 min. However, unlike in the case

• used (Scheme 4). The formation of the corresponding monobromo products was not observed. Similarly, p-cresol (1a) was converted to the corresponding diiodo derivative 3i in high yield by using 2.1 equiv of NIS indicating the generality of this synthetic protocol. Next, the attempted dihalogenation of

Morita–Baylis–Hillman reaction of 3-formyl-9H-pyrido[3,4-b]indoles and fluorescence studies of the products

• Nisha Devi and
• Virender Singh

Beilstein J. Org. Chem. 2022, 18, 926–934, doi:10.3762/bjoc.18.92

• ester 4a–e in high yield (83–87%) and ester functionality reduction with LiAlH4 in dry THF yielded the alcohols 5a–e in excellent yield (90–98%). The required 3-formyl-9H-β-carbolines 6a–e were obtained in 73–88% yield by oxidizing the alcohol derivatives 5a–e with MnO2 in dry DCM. The present

Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications

• Sadanobu Iwase,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2022, 18, 872–880, doi:10.3762/bjoc.18.88

• 1,1-diphenylethylene as a more electron-rich olefin compared to α-methylstyrene was carried out similarly. As expected, the adduct 6 was formed in a high yield of 90% as shown in Scheme 10. Isopropanol can serve as both a proton and a hydrogen radical source while cumene serves only as a hydrogen

• -methylstyrene consumed less than 2 F/mol of electricity to provide protonated and deuterated adducts 4/4D in almost same yields. Similar indirect electrolysis of compound 1 in iPrOH/MeCN in the presence of 1,1-diphenylethylene consumed much more than 2 F/mol of electricity to afford adduct 6 in high yield

Palladium-catalyzed solid-state borylation of aryl halides using mechanochemistry

• Koji Kubota,
• Emiru Baba,
• Tamae Seo,
• Tatsuo Ishiyama and
• Hajime Ito

Beilstein J. Org. Chem. 2022, 18, 855–862, doi:10.3762/bjoc.18.86

• smoothly and provided the desired product 3f in high yield (84%). Also, the reaction of (4-chlorophenyl)(phenyl)methanone (1r) afforded the corresponding product 3q in good yield. To demonstrate the practical utility of the developed protocol, the solid-state borylation reaction was investigated on a gram

• afforded the borylation product 3a in high yield, which was comparable to the yield obtained at the 0.3 mmol scale. We confirmed by thermography that the internal temperature after the reaction was approximately 100 °C. Conclusion In summary, we have developed the first protocol for the solid-state

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• reaction. After filtration through activated aluminum, (S)-α-phellandrene (30) is obtained in a high yield of 88% over three steps on a 30 g scale corresponding to a productivity of 0.887 mol/day [36]. The smell of leaves and freshly cut green grass can mainly be traced back to (Z)-hex-3-en-1-ol (32) (so

An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2022, 18, 738–745, doi:10.3762/bjoc.18.74

• )-one 14 in 89% yield. The reaction of pyridone 2e with PBr3 afforded methyl 4-bromo-6-(4-fluorophenyl)-2-phenylnicotinate (15) in 80% yield. The latter was employed in the Suzuki reaction in the high-yield synthesis of 2,4,6-triaryl-substituted nicotinate 16. The nitrogen of 2,3,4,6-tetrasubstituted

• rearrangement of methyl 2-(isoxazol-5-yl)-3-oxopropanoates 1. High yield transformations of compound 2 provide easy access to 2,4,6-triaryl-substituted and 1,2,5,6-tetrasubstituted nicotinates. Approaches to the synthesis of alkyl 4-oxo-1,4-dihydropyridine-3-carboxylates. Synthesis of 4-oxo-1,4-dihydropyridine

Rapid gas–liquid reaction in flow. Continuous synthesis and production of cyclohexene oxide

• Kyoko Mandai,
• Tetsuya Yamamoto,
• Hiroki Mandai and
• Aiichiro Nagaki

Beilstein J. Org. Chem. 2022, 18, 660–668, doi:10.3762/bjoc.18.67

• with good operational stability, evaluated by a constant high yield of cyclohexene oxide, to obtain the desired product with high productivity. Keywords: air; continuous flow; cyclohexene oxide; flow epoxidation; rapid gas–liquid reaction; Introduction From the past to the present, organic synthesis

• achieved by using a flow technique (Scheme 1). Cyclohexene oxide was selectively produced with high yield in our flow oxidation system using air and within only 1.4 min. The fast epoxidation of cyclohexene without added catalyst in the solution was achieved since the solution of cyclohexene and aldehyde in

• . Conclusion In the present study, we developed the continuous flow system for the aerobic cyclohexene oxide production based on appropriate temperature and residence time control. Moreover, the production of cyclohexene oxide with high yield and selectivity was achieved under the conditions of a very short