Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• allene 14, giving a boryl diene 16. A Cope rearrangement of the boryl diene 16 followed by transborylation gave the dienyl boronic ester 18 and regenerated the catalyst (Scheme 5). Chang reported the alkoxide-promoted hydroboration of N-heteroarenes with HBpin, the first explicit example of a B‒N/B‒H

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

• 14 shares the common [5-8-5] tricyclic framework emblematic of the fusicoccan series, albeit cycloaraneosene (14) does not have any heteroatom (Scheme 1) [16]. Focusing on the B–C bicyclic fragment, they used diene 10, readily available from cyclopentane-1,3-dione (9), as the precursor for installing

• steps from accessible methylcyclopentenone 16 (Scheme 2). The sequence included a Mukaiyama–Michael reaction with silyl enol 15 followed by a Tsuji alkylation. With diene 17 in hands, the RCM reaction was performed by addition of G-II catalyst and furnished the expected C5-C8 bicyclic framework 18 in 95

• protection of the alcohol function as a silyl ether leading to diene 71, the RCM was performed in refluxing hexane and dactylol (72) was isolated in 17% overall yield after silyl ether removal [18][37]. Asteriscanolide (2), isolated in 1985 from the hexane extract of the plant Astericus aquaticus, is a

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

• pristinaespiralis 1 is an intermediate in the cyclisation of farnesyl diphosphate (FPP) to selina-4(15)-7(11)-diene [36]. Several SdS enzyme variants have been constructed by site-directed mutagenesis, including the enzyme variants D83E, E159D and W304L, for which the product spectrum is shifted towards 1 as the

• , and has been isolated from Cryptotaenia japonica [46], Bunium cylindricum [47], an unidentified Pilocarpus sp. [48], and Aristolochia triangularis [49]. Germacrene B (1) is also easily cyclised to selinanes. Percolation of 1 through alumina yields a 1:1 mixture of selina-3,7(11)-diene (9) and γ

• discussed in the following sections. Eudesmanes from I1 The eudesmane sesquiterpenes derived from cation I1 are summarised in Scheme 7. Cation I1 can either be deprotonated to yield selina-3,7(11)-diene (9), (+)-γ-selinene (10) or (+)-selina-4,7(11)-diene (18), or captured by water resulting in juniper

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

• using diethyl (2-methylallyl)phosphonate gave diene ketone S-18 [13]. Here, we envisioned that a Mannich reaction would introduce the required α,β-unsaturated carbonyl system needed for the following intramolecular Diels–Alder reaction, that likely would proceed directly under these conditions. This

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• linkage of several insect pheromones. Cahiez paved the way of this strategy in 2008, showing that (E)-dodeca-9,11-dien-1-yl acetate (2), the sex pheromone of red bollworm moth (Diparopsis castanea), which contains a terminal diene, could be obtained at a laboratory scale (ca. 200 mg) by means of iron

• introduction of the C7–C8 linkage by a key iron-mediated cross-coupling sequence between the suitable α,ω-difunctionalized Grignard reagent and 1-bromopenta-1,3-diene as the electrophile (Scheme 6) [32]. A classic drawback of the use of dienyl halides as coupling partners is their intrinsic thermal instability

• -coupling systems involving this reagent are thus particularly scarce, and few examples are reported, using for some of them Ni-based catalysts [33]. 1-Bromopenta-1,3-diene used in the synthesis of 4 (Scheme 6) is not an exception. The expected (E,E) isomer was easily obtained from sorbic acid, a renewable

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

• helpful when dealing with sensitive dienes. A nice illustration of this is afforded by De Lucchi’s simple synthesis of barrelene (33) from oxepin (29, Scheme 8b) [52]. Oxepin’s equally unstable valence tautomer 30 (benzene oxide) is quite reactive as a diene in Diels–Alder reactions, and can react with 7

• ]. For example, after a first Diels–Alder reaction with furan followed by dehydrochlorination, the resulting dithiin-tetroxide dienophile 38 is reacted with sulfolane (as a buta-1,3-diene precursor), to elaborate a propellane system with a fused cyclohexene ring. Reductive desulfonylation of the dithiane

• -tetroxide ring gives the cyclohexa-1,4-diene intermediate 39. This intermediate can then be easily oxidized to afford the aromatic adduct 40, which is the known cycloaddition product of furan and benzyne. Although this synthetic equivalent of benzyne requires a lengthy work-around, all synthetic operations

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

• different mesh numbers. Single crystals of both were obtained by slow evaporation from diethyl ether. The less polar, minor material gave ice-white needles, and an X-ray single crystal structure determination revealed the product to be cholesta-3,5-diene (9, Figure 3). The 1H NMR data of 9 are in full

• these results, the mechanistic interpretation depicted in Scheme 2 can be provided. Under Appel conditions with a combination of CBr4 and PPh3, 3β-hydroxycholest-5-ene (1) leads to two products, cholesta-3,5-diene (9) and 3β-bromocholest-5-ene (4). Both 9 and 4 result from intermediate 10, in which the

• C3 hydroxy of 1 is activated. Deprotonation of 10 at C2 with bromide as base provides diene 9 as the minor product. Bromide 4 is formed via cyclopropyl cation 11, which is generated from 10 by loss of triphenylphosphine oxide being supported by involvement of the Δ5 π-bond electrons from the α-face

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

• led to common scaffolds 47 and diene 48 after subsequent elimination. Those molecules serve as templates for Ni-based radical-based sp3–sp2 coupling and single-electron transfer (SET)-based [3 + 2] coupling, respectively (Scheme 4). Initial attempts to realize the [3 + 2] radical coupling with CAN led

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

• diastereoselectivity in 58% on a 3 g scale. Subsequently, vinyl halide 48 was converted to diene 50 by Suzuki coupling with potassium vinyltrifluoroborate (49) in 90% yield (Scheme 8). The C7–C8 bond formation from a bridgehead carbocation was a real challenge to close the 7-membered ring. To achieve this, the

• oxygen ene reaction involving the electron-rich olefin allowed the formation of an aldehyde, which was directly cleaved by an iridium-catalyzed deformylation, affording 52 in one-pot [36]. Deprotonation with KHMDS allowed the formation of an electron-rich diene which could again react with singlet oxygen

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• Talaromyces wortmannii ATCC 26942. Heterologous expression reveals that TadA catalyzes the formation of a new fusicoccane-type diterpene talaro-7,13-diene. D2O isotope labeling combined with site-directed mutagenesis indicates that TadA might employ a different C2,6 cyclization strategy from the known

• fusicoccane-type diterpene synthases, in which a neutral intermediate is firstly formed and then protonated by an environmental proton. In addition, we demonstrate that the associated cytochrome P450 enzyme TadB is able to catalyze multiple oxidation of talaro-7,13-diene to yield talaro-6,13-dien-5,8-dione

• Talaromyces wortmannii ATCC 26942, in which TadA is identified to be a new FC-type DTS responsible for the formation of talaro-7,13-diene, and the associated P450 enzyme TadB is characterized to be a multifunctional enzyme, converting talaro-7,13-diene to highly oxygenated talaro-6,13-dien-5,8-dione. Results

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• –O bond from an 1,2-oxazine, itself obtained by a nitroso Diels–Alder reaction from a chiral nitroso derivative and a functionalized diene (Figure 3). The nitroso Diels–Alder cycloaddition reaction has been well studied and has been used as a powerful tool for synthesis [19][20][21][22]. We have

• reported extensive studies on the regio-and stereoselectivity of nitroso Diels–Alder reactions between various nitroso derivatives and functionalized dienes [23]. These studies led to the selection of enol phosphates as ketone precursors for the diene functionalization. Enol phosphates display several

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• cycloaddition delivered the advanced intermediate 43 in an efficient and elegant way. Jatropha-5,12-diene Towards the total synthesis of natural and unnatural jatrophane diterpenes, Hiersemann et al. used a highly efficient, intramolecular carbonyl-ene reaction of α-ketoester 49 (Scheme 8) [22]. The ketoester

Dienophilic reactivity of 2-phosphaindolizines: a conceptual DFT investigation

• Nosheen Beig,
• Aarti Peswani and
• Raj Kumar Bansal

Beilstein J. Org. Chem. 2022, 18, 1217–1224, doi:10.3762/bjoc.18.127

• reaction with an electron-rich diene such as DMB. However, in the case of compound 1 (R1 = R2 = CO2Me), the EWG at the 1-position functions as electron-sink between the nitrogen lone-pair and the >C=P– functionality. As a result, the latter retains its electron-deficient character and undergoes DA reaction

Radical cation Diels–Alder reactions of arylidene cycloalkanes

• Kaii Nakayama,
• Hidehiro Kamiya and
• Yohei Okada

Beilstein J. Org. Chem. 2022, 18, 1100–1106, doi:10.3762/bjoc.18.112

• reaction is a typical example of this activation mode since both the original diene and dienophile are electron-rich and thus not an effective combination of reactants [1][2][3][4][5][6][7][8][9][10][11]. Single-electron transfer makes the construction of six-membered ring systems possible. In general

• , single-electron oxidation of an electron-rich dienophile generates its radical cation which is then trapped by the diene (Figure 1). Since the forming cyclohexene remains in the radical cation state as well, one electron reduction is required to complete the net redox neutral transformation. Therefore, a

• there is some correlation between these arylidene cycloalkane cycloadditions. Control studies are summarized in Table 1. LiClO4, TiO2, and light were crucial for the reaction (Table 1, entries 1–4) and the equivalents of the diene 2 was also key (entries 5 and 6 in Table 1). The reaction was sensitive

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• -hydroxy-4-(4-methoxyphenyl)cyclopent-2-ene-1-carboxamido)-5-(4-methoxyphenyl)cyclopenta-2,4-diene-1,2-dicarboxylate (4a): yellow solid, 62%; mp 182–184 °C; 1H NMR (400 MHz, CDCl3) δ 8.92 (s, 1H, NH), 7.46 (d, J = 8.4 Hz, 2H, ArH), 7.34 (d, J = 8.4 Hz, 2H, ArH), 6.90 (s, 1H, CH), 6.88–6.84 (m, 4H, ArH

Understanding the competing pathways leading to hydropyrene and isoelisabethatriene

• Shani Zev,
• Marion Ringel,
• Ronja Driller,
• Bernhard Loll,
• Thomas Brück and
• Dan T. Major

Beilstein J. Org. Chem. 2022, 18, 972–978, doi:10.3762/bjoc.18.97

• ) precursor erogorgiaene and (1R)-epoxyelisabetha-5,14-diene (EED), respectively [6][7]. Ps, marine amphilectane-type diterpenoids from the gorgonian coral Antillogorgia elisabethae, feature superior anti-inflammatory properties which render them innovative target compounds for drug development [8][9]. Hence

Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• isomerized to nerolidyl diphosphate (NPP), followed by the 6,7-bond formation to generate carbocation intermediate I (Scheme 1, II) [31]. Sequential 1,3-hydride shift and 1,6-cyclization occurred to afford cadinyl cation (J). Further 1,3-hydride shift and deprotonation on J resulted in cadina-1(6),4-diene (L

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

• ]. Therefore, Roberge, Fogg, and co-workers investigated the advantages of continuously stirred tank reactors (CSTR) and tube reactors in comparison to the corresponding batch reaction for the ring-closing metathesis of diene 58, producing macrocyclic olefin 60 (Scheme 14) [52]. Although, macrocycle 60 is not

• min. When diene 58 and catalyst 59 are pre-mixed and pumped through a tube reactor, the ethylene released from the reaction results in a segmented flow. Therefore, the formed ethylene is not released from the tube reactor, hampering the reaction to reach full conversion as observed under batch

• and with a Z-selectivity of >98% [54]. In contrast, Amorelli, Collins, and co-workers performed a ring-closing metathesis for the synthesis of macrocycle 72 from diene 70 at high temperatures of 150 °C in only 5 min without removal of formed ethylene (Scheme 17) [55]. Under these conditions, the

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• reported on the syntheses of a wide range of diverse substance classes applying this useful starting material. In the course of our studies concerning polyhalogenated nitrodienes, in many cases 2-nitroperchlorobuta-1,3-diene (1) [8][9][10] or nitrotrichloroethylene [11][12][13] have proved as appropriate

• precursors for a diverse variety of synthetically and/or physiologically interesting chemical compounds. Recently, we have developed an efficient method for the synthesis of persubstituted nitropyrazoles from diene 1 [14]. In this paper we are describing the formation of uniquely persubstituted 1H-pyrazoles

• -bisazolylbutadienes 2a–c with up to 98% yield (Scheme 1). The regiospecificity is caused by the fact that the LUMO of diene 1 is located preferentially at the dichloronitrovinyl fragment, and to an extent of 67% (by using MINDO/3 as semi-empirical method for the quantum calculation of the molecular electronic

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• 2002, an interesting methodology for menadione synthesis was reported by Kacan and Karabulut (Scheme 5). The authors studied a Diels–Alder reaction, using LiClO4-diethyl ether (LPDE) as a catalyst, 1-ketoxy-1,3-butadiene 28 as a diene and 2-methyl-1,4-benzoquinone (29) as dienophile. By this method

• demethoxycarbonylating annulation of methyl methacrylate (33) with 3-cyanophthalide (32), in the presence of lithium tert-butoxide as catalyst (64% yield) (Scheme 7) [91]. Recently, Dissanayake and co-workers tested the stability of furans to be used as a diene in Diels–Alder reactions for the synthesis of p

• -benzoquinones and p-hydroquinones or the synthesis of menadione (10). The furan derivative 34 was used as a diene and 2-iodophenyltrifluoromethanesulfonate (35) as a dienophile, in the presence of n-butyllithium, forming 10 in 55% yield (Scheme 8) [92]. In the same year, Gogin and and co-workers developed a

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• catalyzed by rhodium/diene to afford the 1,2,4-trisubstituted naphthalene framework 8 with complete regio- and stereocontrol (Scheme 1) [62][63]. In 2015, the Nishimura group reported the first iridium-catalyzed addition of salicylaldehydes 14 to bicyclic alkenes 11 (Scheme 1) [64]. Although a variety of

• this field. Potential energy profile of the PCM solvation model for the hydrometalation/reductive elimination pathway of the Ir/diene-catalyzed hydroacylation of MeOBD with salicylaldehyde (14) in 1,4-dioxane, as evaluated by DFT calculation (M06 [69]/def2SVP [70]/PCM [72]//M06 [69]/def2TZVP [70]/PCM

• PCM solvation model for the carbometalation/reductive elimination pathway of the Ir/diene-catalyzed hydroacylation of MeOBD with salicylaldehyde (14) in 1,4-dioxane, as evaluated by DFT calculation (M06 [69]/def2SVP [70]/PCM [72]//M06 [69]/def2TZVP [70]/PCM [72]). Calculated Gibbs free energies (in

Diametric calix[6]arene-based phosphine gold(I) cavitands

• Gabriele Giovanardi,
• Andrea Secchi,
• Arturo Arduini and
• Gianpiero Cera

Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21

• scavenger [37]. After 4 h, NMR analysis of the crude reaction mixture revealed high conversion of the starting material with the formation of the 6-endo-dig rearranged diene 2a and the parental regioisomer 2b in a 1:1 ratio. Noteworthy, this latter is formed by an initial 5-exo-dig cyclization step (entry 1

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• Cheng investigated the cascade cyclization of dienes 119 with alkyl carbazates 117 for the synthesis of fused nitrogen heterocyclic compounds 120 (Scheme 25) [117]. Diene substrates possessing EDGs reacted smoothly under the optimized conditions while their electron-deficient counterparts delivered the

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• ionised substrate [9]. The structure of bacterial selina-4(15),7(11)-diene synthase (SdS) and its comparison to other TPS structures revealed that this helix break motif is a general feature of type I TPSs [11]. Furthermore, hydrogen bondings of the substrate’s diphosphate to a highly conserved Arg

Efficient synthesis of polyfunctionalized carbazoles and pyrrolo[3,4-c]carbazoles via domino Diels–Alder reaction

• Ren-Jie Fang,
• Chen Yan,
• Jing Sun,
• Ying Han and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2021, 17, 2425–2432, doi:10.3762/bjoc.17.159

• active diene, indole-substituted chalcones. Then, the p-TsOH-catalyzed Diels–Alder reaction of indole-chalcones with second chalcones and sequential aromatization through DDQ dehydrogenation resulted in the polyfunctionalized carbazoles 6a–l in good yields (Table 2). Additionally, the similar reaction

• 3-(indol-3-yl)-1,3-diphenylpropan-1-one gave the expected indole-substituted chalcone A, which comprises the desired 3-vinylindole scaffold as the reactive diene. In the meantime, the carbonyl group of the chalcone is protonated to give the activated dienophile in the presence of p-toluenesulfonic