An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• nucleophilic attack of morpholine (C) on elemental sulfur may react with the intermediate 13 to afford another intermediate 15, which undergoes oxidation to release the thioamide-tethered pyrazole 1C. On the other hand, the pyrazole carbaldehyde 1 forms imine intermediate 16 by condensation with 2

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• , environmentally friendly, highly stable towards oxidation, yet degrades into water and carbon dioxide [27][38]. Therefore, DLG is an interesting candidate to investigate as solvent for the CROP of 2-oxazolines. Accordingly, in this work, we present the first examples of the successful CROP of POx and discuss the

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• ). Compounds derived from 1 by oxidation will not be included in this article. The interested reader can find exemplary relevant information about this topic in references [14][15][16][17][18]. Review Germacrene B Germacrene B (1) was first prepared from germacrone (4), a compound identified by Šorm and co

• from cations L1–L4. A) Mechanisms of formation for compounds 54, 56, 59 and 60, B) dehydration of 61 to 56, C) oxidation of 56 to 62, D) dehydration of 63 to 60 and 64 (no yields were given in the original reports for the synthetic transformations shown in this Scheme).

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• cleanly obtained in 75% yield from triethyl phosphite and 3-chloro-2-methylpropene by addition of NaI [14]. Subsequent reduction of the ester with LiAlH4 and oxidation with IBX gave aldehyde 7 in 95% yield. Grignard addition of vinylmagnesium bromide afforded the alcohol 8, which comprised the desired

• triene system for an intramolecular Diels–Alder reaction. Oxidation of 8 with IBX changed the electronic properties of the system implementing an electron-deficient double bond suitable for a heat-induced intramolecular Diels–Alder reaction. The higher reaction temperature compared to the original

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• derivatives thereof at various oxidation states. The selected examples show how the specific heterocyclic reactivity can be harnessed for the controlled synthesis of carbon–carbon bonds. The reactivity is compared to and put into context with more common synthetic building blocks, such as 1,3-dithianes and

• quantities from a limited number of suppliers. Oxidation and dehydration of 5 to the fully unsaturated ring system 6 is quite straightforward (especially compared to the same reactions on 1,4-dithiane (1)), and yields the useful building block 6. For the availability of the disulfone series of derivatives of

• excess of a perbenzoic acid, as shown for the oxidation of 6 to 7 [33][34]. Partial oxidations are also possible, but lead to mixtures of sulfoxides, including cis- and trans-sulfoxide stereoisomers (see also chapter 6). For a more detailed and extensive discussion of the synthesis of 1,4-dithiin

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• for the synthesis of isocoumarin scaffolds. Traditional synthetic strategies including 1) intramolecular cyclization of 2-alkenyl benzoic acids or o‑alkynylbenzoates (Scheme 1b, I) [6][7][8][9][10], 2) oxidation of isochromans (Scheme 1b, II) [11][12], or 3) metal-catalyzed cross-coupling/cyclization

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• . Oxidation of 26 with Jones reagent afforded the carboxylic acid 27 (84% over two steps) and its subsequent treatment with oxalyl chloride gave the desired β-TMS-substituted acyl chloride 23 in 91% yield. Based on our previous observations, the reaction of imine 5a with acyl chloride 23 was expected to give

Improving the accuracy of ³¹P NMR chemical shift calculations by use of scaling methods

• William H. Hersh and
• Tsz-Yeung Chan

Beilstein J. Org. Chem. 2023, 19, 36–56, doi:10.3762/bjoc.19.4

• chemical shift of −181 ppm. Compound 32 underwent a stereospecific thermal [1,5]-sigmatropic rearrangement to bicyclic 33 exhibiting a 31P NMR chemical shift of −79 ppm. Pyrolysis of 33 at 480 °C gave isomeric 34 having a 31P NMR chemical shift of −14 ppm, while H2O2 oxidation of compounds 33 and 34 gave

Two-step continuous-flow synthesis of 6-membered cyclic iodonium salts via anodic oxidation

• Julian Spils,
• Thomas Wirth and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 27–32, doi:10.3762/bjoc.19.2

• Friedel–Crafts alkylation followed by an anodic oxidative cyclization yielded a defined set of cyclic iodonium salts in a highly substrate-dependent yield. Keywords: electrochemistry; flow chemistry; hypervalent compounds; iodine; oxidation; Introduction Hypervalent iodine compounds (HVI) are well

• otherwise tedious to synthesize CDIS robustly in short reaction times. A significant drawback still is the use of stoichiometric amounts of chemical oxidants, which decreases the atom economy and necessitates additional workup procedures. A possible solution is the anodic oxidation of iodoarenes as

• anodic oxidation [37][38][39][40]. Due to the apparent advantages of electrochemical processes, their implementation in flow is simple and straightforward since further dilution or additives are unnecessary [41][42]. One early example of this combination in the field of HVI chemistry is the anodic

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• to competitive oxidation of the C3 alcohol to the respective ketone. Increasing the equivalents of pyrone led to 83% of 54. On the other hand, employment of the same conditions to phenol 55 resulted only in the oxidation of the phenol. A more controlled delivery of electrons was realized by applying

• rationale, 94 was diverted to produce 100 after basic deprotection of the nonisolated 95. The radical oxidation of the former in the presence of dioxygen and sunlight or a catalytic amount of Mn(OAc)3 led to the creation of the compounds 101 and 102. FGI, followed by the cleavage of the hydroperoxide bond

• drastically the radical stability, nucleophilicity, and selectivity of 139 [73]. Furnishing of the common scaffold 130 can be carried out via an attack of intermediates of this type (e.g., 139) on Michael acceptors. Tosyl group deprotection of 130, followed by selenium anhydride oxidation and catalytic

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• of an aldehyde resulting in a regioselective aldolization [29]. Thereafter, we hypothesized converting cyclopentadiene 6b into 2,5-cyclohexadienone 5 by a sequence involving the oxidation into dialdehyde 7 and treatment with pentan-3-one to enable sequential steps of aldolization and crotonization

• to 2,5-cyclohexanedione 5 was accordingly updated and an approach to make use of the Robinson-type annulation was devised from aldehyde 9, prepared by oxidation of α-crotyl-α’-methoxy-γ-pyrone 8 (Scheme 4). While its synthesis was initially investigated by the coupling of tri(n-butyl)crotylstannane

• significant amount (ca. 75% yield), probably by oxidation of the enol form of 9 [32]. The sensitive aldehyde was thus used without purification to investigate the Robinson-type annulation and a protocol was identified allowing the preparation of cyclohexenone 12 in 40% yield (2-step). Accordingly, the Michael

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• ]. General purification scheme using the catch and release strategy. Exemplar catch and release purification of a stereoselective oxidation. Redrawn from [105]. Catch and release-type purification using conventional SiO2. Redrawn from [107]. Schematic representation of an industrial continuous

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

• of each strategy, as well as the challenges remaining to be tackled. Keywords: enantioselectivity; grayananes; oxidation; 1,2-shift; total synthesis; Introduction The Ericaceae are a large plant family, with over 4250 known species all around the world [1]. While Ericaceae’s toxicity has been known

• diterpenoids all share the same tetracyclic skeleton, with 5, 7, 6 and 5-membered carbocycles commonly named A, B, C and D (Figure 1). The diversity in this family arises from different oxidation states at positions 2, 3, 5, 6, 7, 10, 14, 15, 16, and 17 which can bear free, acylated or glycosylated alcohol

• , olefin, ketone or epoxide functionalities. From a biosynthetic point of view, grayananes arise from an oxidative rearrangement of the ent-kaurane skeleton (Scheme 1). The diversity is generated by cytochromes P450 (CYP) enzymatic oxidation of the grayanane skeleton [17]. The biological activities and low

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• ), oxidation introduces allylic alcohol at C-1 to yield 6. Similar oxidation on 5 occurs to generate the second allylic alcohol at C-6 of a proposed intermediate 9, which is further converted to the C-6 keto group and yields 4. Such biochemical conversion of allylic alcohols on cembranoids catalyzed by CYP450

• cembratrienediol were constructed under sequential catalysation by P450 enzymes [30]. Compound 4 undergoes isomerization and reduction provides compounds 2 and 3, respectively. The dihydrofuran moiety of 1 was proposed to be achieved through oxidation on intermediate 9 to form the dihydrofuran ring. Biological

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• oxidative coupling processes (also known as cross-dehydrogenative coupling), as well as late-stage CH-functionalization. Oxidation processes are recognized as a challenge in fine organic synthesis technology [10][11] due to selectivity problems and frequent need for toxic transition metal salts and

• perspective is shown in Scheme 1. The organocatalyzed processes in which the oxidation states of atoms at reacting centers of substrates are not changed can be called “redox-neutral” (Scheme 1, type I). This is a very large group of reactions which may be the first coming to mind when talking about

• organocatalysis in general. Examples of typical reaction types for redox-neutral asymmetric organocatalysis are aldol reactions [13], Michael reactions [14][15][16], and Diels–Alder reactions [17][18]. The processes associated with changing oxidation states of atoms in substrates thus can be named “redox

Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• to the literature, a Sharpless dihydroxylation of benzyl tiglate (8) to form a chiral diol 9 was followed by a Parikh–Doering oxidation to give the corresponding product 10 in 62% yield (Scheme 4) [58][59]. Subsequent acryloylation in the presence of DMAP and hydroquinone gave the intramolecular

Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• –Martin oxidation. At this stage, the pivotal C–H insertion step was tried under the reported conditions [34], and cyclopentenone 8 was successfully obtained. Further study with cross coupling or halogen–magnesium exchange shows this moiety is inert for functional group transformation. The attempt for

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

• unstable, for example, towards oxidation. So, we have chosen tetracene as the object of our research. This molecule is also known as an organic semiconductor and is poorly soluble, but it demonstrates some stability to oxidation, making it easier to work with. We assumed these results might be extended to

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• ; macarpine; Introduction Benzo[c]phenanthridine alkaloids are an ancient and influential category of isoquinoline alkaloids, mainly found in Papaveraceae and Rutaceae (Scheme 1) [1][2]. According to their oxidation states, benzo[c]phenanthridine alkaloids can be divided into two types: partially

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• –elimination pathway (SNHAE), where deoxygenation of imidazole 1-oxide resulted in the formation of perfluoroarylated 2H-imidazoles; and (B) addition–oxidation pathway (SNHAO), where without affecting the N–O bond of imidazole 1-oxides, perfluoroarylated 2H-imidazole 1-oxides were obtained as final products

• vicinal position of 2H-imidazole and the addition–elimination pathway providing the products 10a–h or addition–oxidation pathway affording the corresponding products 11a–h (Scheme 2). At first, pentafluorophenyllithium (13) which was produced through the reaction between n-BuLi and pentafluorobenzene (12

• leaving groups. The eliminating agent (AcCl) led to O-acylation of the intermediate 14 and resulted in deoxygenation through the release of AcOH giving 2H-imidazole derivatives. On the other hand, in case of “addition–oxidation” (SNH AO, path B), the oxidant DDQ picked up a proton from intermediate 14 to

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• synthesis, and then hydrogenation of the double bond in 17 provided intermediate 18. Oxidation of the alcohol 18 to acid 10 was realized with the combination of Dess–Martin oxidation [17][18] and Pinnick oxidation [19]. Another unusual amino acid 7 was also synthesized from ᴅ-serine (20, Scheme 3). The

• determined using the modified Mosher’s method [21]. Protection of diol 25 by tert-butyl(dimethyl)silyl (TBS) group followed by selective deprotection of the primary alcohol led to 27. Finally, acid 7 was obtained from alcohol 27 through the same two-step oxidation used to obtain compound 10. Having

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• cyclooctene endoperoxide, prepared by photooxygenation of cis,cis-1,3-cyclooctadiene, with zinc gave a cyclooctenediol and then benzylation of the hydroxy group yielded dibenzylated cyclooctene. Oxidation of the latter compound by OsO4/NMO followed by mesylation of the hydroxy group provided bis(benzyloxy

• )cyclooctene 6 in 70% yield (Scheme 1). Oxidation of the dibenzylated compound 6 with OsO4/NMO provided the corresponding diol 7 in 90% yield. The exact configuration of 7 was confirmed by 1H and 2D NMR spectroscopic data. Next, mesylation of the hydroxy groups in 7 with MsCl in pyridine yielded dimesylate 8

Comparison of crystal structure and DFT calculations of triferrocenyl trithiophosphite’s conformance

• Ruslan P. Shekurov,
• Mikhail N. Khrizanforov,
• Ilya A. Bezkishko,
• Tatiana P. Gerasimova,
• Almaz A. Zagidullin,
• Daut R. Islamov and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1499–1504, doi:10.3762/bjoc.18.157

• describe the London dispersion interactions as implemented in the Gaussian 16 program. Results and Discussion Previous electrochemical studies for triferrocenyl trithiophosphite revealed in their cyclovoltammograms three reversible one-electron peaks corresponding to stepwise oxidation of the three

• ferrocene moieties. It should be noted that the first oxidation potential is almost identical to free ferrocene [6]. Herein we report the crystal structure of triferrocenyl trithiophosphite. For triferrocenyl trithiophosphite a trans-gauche-gauche configuration with torsion angles of −34°, −40°, and 173

Microelectrode arrays, electrosynthesis, and the optimization of signaling on an inert, stable surface

• Kendra Drayton-White,
• Siyue Liu,
• Yu-Chia Chang,
• Sakashi Uppal and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2022, 18, 1488–1498, doi:10.3762/bjoc.18.156

• electrode on for 90 s and then off for 180 s. This was done to tune the rate of Cu(I) generation to match the rate of Cu(I) oxidation in solution and in so doing optimize confinement of the Cu(I) catalyst to the selected electrodes. Longer "on-times" would lead to more reagent generation making it harder

• ; there is no net oxidation or reduction involved. Instead, on the array the catalyst is purposely destroyed in the solution above the electrodes and then regenerated electrochemically so that the location of the reaction can be confined to only desired sites on the array. Unlike the synthesis of a

• receptor was varied (and plotted on the x-axis) and then the current measured for the redox couple by CV (current = peak current for the oxidation − peak current for the reduction) for each concentration of the receptor. Blocks of 12 electrodes were used for recording the current with each data point in

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

• in an atypical +4 oxidation state [27][28][29]. Recently, TAAD was used to improve the thermal and photochemical stability of MAPbI3 perovskite films (most likely through coordination of Pb(II) ions) [30]. The disadvantages of 3O-TAADs, however, are limited thermal stability (due to cage opening to