Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• simplified manganese salen complex I, allowing for the identity of the carbon–heteroatom bond to be controlled based on added nucleophile and enabling C–Cl, C–N, and C–S bonds to be formed directly while completely suppressing traditional ATRA products [9]. In mechanistic studies, rearrangement products

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• , where the byproducts typically associated with free carbene formation (e.g., dimerization or rearrangement) were not observed (Scheme 2). In 1988, Hadjiarapoglou was investigating transition metal- and photocatalyzed intermolecular cyclopropanations between ylide 8 and norbornene, and found indane 9 was

• which the expected product of a free carbene-derived Wolff-type rearrangement was not observed (Scheme 2b). Likewise, Gallos et al. were investigating the intramolecular cyclopropanation of ylide 12, and found that the metal-free reaction proceeded with identical yield and diastereoselectivity as did

• intermediate was not viable under such mild conditions. The initially proposed ionic pathway (Figure 5, left) was abandoned as solvent effects had little influence on the reaction rate, and since no Wagner–Meerwein rearrangement products were detected with bicyclic olefin precursors. Radical-based pathways

Synthesis of imidazo[4,5-e][1,3]thiazino[2,3-c][1,2,4]triazines via a base-induced rearrangement of functionalized imidazo[4,5-e]thiazolo[2,3-c][1,2,4]triazines

• Dmitry B. Vinogradov,
• Alexei N. Izmest’ev,
• Angelina N. Kravchenko,
• Yuri A. Strelenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2023, 19, 1047–1054, doi:10.3762/bjoc.19.80

• [2,3-c][1,2,4]triazines was synthesized via a cascade sequence of hydrolysis and skeletal rearrangement of imidazo[4,5-e]thiazolo[2,3-c][1,2,4]triazin-7(8H)-ylidene)acetic acid esters in methanol upon treatment with excess KOH. Imidazo[4,5-e]thiazolo[3,2-b][1,2,4]triazin-6(7H)-ylidene)acetic acid

• rearrangement; 1,3-thiazines; thiazolidine-4-ones; Introduction Nitrogen- and sulfur-containing heterocyclic compounds are widely represented in nature and used for the synthesis of biologically active substances. Among the 1,3-thiazine derivatives, promising compounds as antimicrobial and antiviral drugs

• derivatives undergo rearrangement into the corresponding isomeric derivatives of imidazo[4,5-e]thiazolo[2,3-c]-1,2,4-triazine [18][21] (Scheme 1A). In the present study, we report a new base-induced recyclization of functionalized imidazothiazolotriazines 1 and 2 resulting in derivatives of the new

Synthesis of tetrahydrofuro[3,2-c]pyridines via Pictet–Spengler reaction

• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2023, 19, 991–997, doi:10.3762/bjoc.19.74

• rearrangement to a more stable benzhydryl-type cation resulting in the formation of isomeric products. In an alternative group of methods, more accessible 2-substituted furans are used as starting compounds. For example, a construction of tetrahydrofuro[3,2-c]pyridines based on the Pictet–Spengler reaction [17

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition

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

Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73

• refluxing acetonitrile gave unique 2-azabicyclo[4.2.0]octa-3,7-dienes as major products and 1,3a,4,6a-tetrahydrocyclopenta[b]pyrroles as minor products via further rearrangement. Keywords: 1,4-dihydropyridine; electron-withdrawing alkyne; formal [2 + 2] cycloaddition; Huisgen's 1,4-dipole; isoquinoline

• -tetrahydrocyclopenta[b]pyrrole derivatives 6, it was found that the 1,4-dihydropyridinyl ring of the substrate was converted to a fused pyrrole ring, which might be a result from a rearrangement process of the formed 2-azabicyclo[4.2.0]octa-3,7-diene-7,8-dicarboxylates 5a–o at elevated temperature. The chemical

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• proposed by Wang [55] (Scheme 2b), 2,5-dimethoxytetrahydrofuran (2) is first protonated with acetic acid, followed by ring opening to form carbocation B. In the following step, primary amine 1 nucleophilically attacks carbocation B to produce intermediate C, which, after proton rearrangement and the

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• -dihydroisoquinolin-3(2H)-one (2a) that represents the homoanalogue of the parent 3-bromoxindole (1; R1, R5: H). The starting 1,4-dihydroisoquinolin-3(2H)-one was prepared from commercially available 2-indanone by Schmidt rearrangement with azoimide [28]. Unfortunately, its bromination using various agents (NBS

Bromination of endo-7-norbornene derivatives revisited: failure of a computational NMR method in elucidating the configuration of an organic structure

• Demet Demirci Gültekin,
• Arif Daştan,
• Yavuz Taşkesenligil,
• Cavit Kazaz,
• Yunus Zorlu and
• Metin Balci

Beilstein J. Org. Chem. 2023, 19, 764–770, doi:10.3762/bjoc.19.56

• , and assigned our product the structure (1R,2S,3R,4S,7r)-2,3,7-tribromobicyclo[2.2.1]heptane. To fit their revised structure, they proposed an alternative mechanism featuring a skeletal rearrangement without the intermediacy of a carbocation. Herein, we are not only confirming the structure originally

• bromonium ion 10, which is sterically feasable. However, after the backside attack by the bromide in 10, the resulting tribromo compound 3 undergoes an unprecedented skeletal rearrangement without a carbocation intermediate to give compound 7, their proposed alternative structure to 6. Wagner–Meerwein

• show any tendency to undergo a skeletal rearrangement, in fact with 75% it is the major product at 77 °C [4]. It is somewhat astonishing that the authors have overlooked this fact. Based on the detailed NMR arguments and experiments we presented above, supported by a sound mechanistic pathway we

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• Ring expansion through rearrangement Several methods utilise ring expansion to prepare the required 7-membered azepine and oxepine rings of 1a and 1b. 2.1 Ring expansion of acridin-9-ylmethanols In 1960, Bergmann and Rabinovitz [43] reported a simple ring expansion of acridin-9-ylmethanol (23) to 1a in

• good yield (80%) by heating 23 in polyphosphoric acid (Scheme 5). Independently, in an effort to synthesise phenothiazine isosteres, Craig et al. [39] prepared 1a via a Wagner–Meerwein rearrangement of 23 with P2O5 (Scheme 5) the following year. The method was used to successfully synthesise

• unsubstituted as well as chloro-substituted derivatives of 1a. Storz et al. [44] have reported on an analogous method to prepare dibenzo[b,f]oxepines 1b through the rearrangement of 9-(α-hydroxyalkyl)xanthenes. 2.2 Ring expansion of 2-(9-xanthenyl)malonates Oxidative ring expansion of 2-(9-xanthenyl)malonates

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• 1-(2-thiophenyl)pyrroles (Scheme 4). It includes intramolecular cationic π-cyclizations in 3-hydroxy-2-(2-sulfanylphenyl)-2,3-dihydro-1H-isoindol-1-ones (Scheme 4, entry 14) [9] and intramolecular cyclizations of 1-(2-(methylsulfinyl)phenyl)-1H-pyrroles under «interrupted Pummerer rearrangement

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

•  56B) [103]. These complex natural compounds exhibit strong pharmacological activities like anti-inflammatory, antituberculosis, analgesic properties, etc. The key reaction steps included a highly stereoselective gold-catalyzed or thermally activated Cope rearrangement and a gold-catalyzed 6-endo-dig

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• the bicyclic alkene followed by migratory insertion affords intermediate 12 which undergoes β-oxygen elimination to form 13. Rearrangement of 13 via β-hydride elimination and enolization generates a 1-naphthol species which undergoes intramolecular cyclization with the ester to form the final product

• final ring-opened adduct 37. Copper-catalyzed reactions In 2009, Pineschi and co-workers explored the Cu-catalyzed rearrangement/allylic alkylation of 2,3-diazabicyclo[2.2.1]heptenes 47 with Grignard reagents 48 (Scheme 8) [41]. The reaction is thought to proceed via the Lewis acid-catalyzed [3,4

• ]-sigmatropic rearrangement of the diazabicycle 47 to form the allylic carbazate intermediate 51. Nucleophilic attack of an organomagnesium, or organocuprate, in an anti SN2’ fashion on 52 furnish the final ring-opened product 49. The authors note the use of a carbamate protecting group was crucial for the

Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33

• with nucleophilic deoxyfluorinating reagents often does not lead to the expected products with a fluorine atom in place of the –OH group. They usually undergo rearrangement, and intramolecular cyclization leading to products that are constitutional isomers [15]. The solvolysis reaction of phosphonates

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• between the two olefinic parts. After protection of the secondary alcohol as a para-methoxybenzyl (PMB) ether (78% yield of 14), the ketone (15) was installed in two steps from the epoxide (direct rearrangement attempts of the epoxide to form the ketone were unsuccessful). Thus, the epoxide was first

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

• their anti-inflammatory activity (see Section 3). Reaction of compounds 166 and 167 gave the corresponding diaryl ether 168, which was converted to phenol 169 using a Baeyer–Villiger oxidation reaction followed by hydrolysis. Subsequent phenol allylation reaction followed by Claisen rearrangement led to

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

• ‒N/B‒H transborylation with HBpin to regenerate BH3 and give the N-Bpin-indoline product 27; 2) two molecules of H2B-N-indoline underwent rearrangement to regenerate BH3 and gave a bisindolinylborane 28. The bis-N-indolinylborane then underwent B‒N/B‒H transborylation with HBpin to regenerate H2B-N

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

• construction of the 8-membered ring from an appropriate cyclopentane precursor. The proposed strategies include metathesis, Nozaki–Hiyama–Kishi (NHK) cyclization, Pd-mediated cyclization, radical cyclization, Pauson–Khand reaction, Lewis acid-promoted cyclization, rearrangement, cycloaddition and biocatalysis

• iterative addition of geranyl (C10) or farnesyl (C15) building blocks derived from isoprene as starting unit and further structure rearrangement and functionalization [1]. This ubiquitous distribution highlights their pivotal role in living systems such as cell wall structural agent or ecological mediator

• precursor. The proposed strategies include metathesis, Nozaki–Hiyama–Kishi (NHK) cyclization, Pd-mediated cyclization, radical cyclization (including SmI2), Pauson–Khand reaction, Lewis acid-promoted cyclization, rearrangement, cycloaddition, and biocatalysis. In particular, the purpose will focus on the

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

• rearrangement [57]. Although, these protocols are useful and have exhibited wide applications in organic synthesis (Figure 2), the scope of these reported methods may suffer from drawbacks such as harsh reaction conditions, use of expensive reagents, prolonged reaction times, low product yields, and cumbersome

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

• conformers [26][38][39][40][41], pointing to a higher energy barrier between their conformers in comparison to the barriers between the conformers of 1. Like observed for germacrene A [40] and hedycaryol [41][42], 1 readily undergoes a Cope rearrangement to γ-elemene (5) above 120 °C (Scheme 3C), while the

• structure was subsequently secured by preparation from 1 through Cope rearrangement [20] and through dehydration of elemol (7) with POCl3 in pyridine yielding 5 and β-elemene (8) (Scheme 3D) [45]. Compound 5 has also frequently been reported from natural sources especially after heat treatment of the sample

• dehydration of (−)-1(10)-valencen-7β-ol (35) (Scheme 10C) [92], but has not been isolated from natural sources. Compound 22 could be formed from I1a by Wagner–Meerwein rearrangement to I1c and deprotonation (Scheme 7). This hydrocarbon ([α]D22 = +26, c 0.06) has been obtained as a dehydration product of

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• condensation of enals 6 with aldehydes 7a or ketones 7b [6][7][8][9][10][11], isomerization of alkynones 8 [12][13][14][15], Horner–Wadsworth–Emmons reaction of unsaturated phosphonates 9 and aldehydes 10 [16][17], and dehydrogenation of enones 11 [18]. Further, Claisen rearrangement of vinyl propargylic

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

• amorph-4-en-10β-ol (14) from a natural source. Alcohol 14 has been isolated before [17][18] or obtained by rearrangement from (+)-α-ylangene [25]. In the latter case the (4S)-stereoisomer of 14 was formed, as the isopropyl group is not affected by the rearrangement (see Figure S3 in the Supporting

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

• of this heterocycle is quite challenging due to the ease of the β-fragmentation pathway of lithiated derivatives (Scheme 2). Chlorination or oxygenation of the ring sulfur atom(s) in 1, followed by Pummerer-type rearrangement and elimination, affords a straightforward access to the more useful

• access to building block 2. The benzannelated series of 1,4-dithiane heterocycles 5–7 can in principle be obtained using Parham’s α-halocarbonyl condensation and rearrangement approach, starting from benzene-1,2-dithiol. More conveniently, however, ethanedithiol and cyclohexanone can be condensed, and

• synthesis starts from a carbonyl compound, wherein an aldehyde can undergo ‘umpolung’ into a cis-vinyl anion equivalent via a 1,3-dithiolane-to-1,4-dithiane rearrangement (Scheme 10b). The potential of the method is demonstrated by the synthesis of (Z)-9-tricosene or muscalure (59), which is the natural sex

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

• at C3 [12]. In this way, substitutions at the stereogenic homoallylic carbon atom can proceed with retention of configuration. Concurrently, a so-called i-steroid rearrangement leads, for instance, to 6β-azido-3α,5-cyclo-5α-cholestane by 6β-face attack of the steroidal substrate by the nucleophile

Organophosphorus chemistry: from model to application

• György Keglevich

Beilstein J. Org. Chem. 2023, 19, 89–90, doi:10.3762/bjoc.19.8

• . elaborated a Lewis acid-catalyzed one-pot synthesis of phosphinates and phosphonates staring from pyridinecarboxaldehydes and diarylphosphine oxides [2]. This protocol is the analogy of the Pudovik reaction, followed by the phospha-Brook rearrangement applied mainly for the synthesis of phosphoric ester

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

• rearrangement of Equation 1 and Equation 2 to give Equation 4, where the intercept b1 in Equation 4 simply incorporates the calculated shielding and chemical shift of the reference as shown. Calculation of the absolute shielding of the reference is therefore irrelevant if one is using a scaling method, and

• 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