Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• -surfaces and which are activated for electrophilic aromatic substitution reactions. For the synthesis of W1, we initially prepared tetramethoxybiphenyl 1 (Scheme 1) according to the literature procedure involving the Suzuki coupling between 3,4-dimethoxybromobenzene and 3,4-dimethoxyphenylboronic acid [44

• ]. Next, we performed the oxidative coupling reaction of 1 and W4 in CH2Cl2 catalyzed by anhydrous FeCl3 to give W1 in 35% yield [45]. For the synthesis of W2, we first oxidized triphenylene with CrO3 and 18-crown-6 to give triphenylene-1,4-dione (2) according to Echavarren’s protocol [46]. Triphenylene

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• fluorination attempts. Maintaining some residual solvent allowed for the characterization of compound 13 by NMR spectroscopy. Stereochemical assignment in 13 was based on a large trans-axial coupling constant JH2exo-H3 = 10.6 Hz in the 1H NMR spectrum and interactions between H3endo and H7endo on the

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• radical reaction and can occur either intermolecularly or as an intramolecular cyclization reaction. Radical coupling or combination is a possible transformation that is more feasible when one of the radicals is relatively stabilized (a persistent radical). Trapping a radical with a transition metal is

• one way to convert a free radical to a more stable intermediate, which can subsequently undergo coupling with another radical via an SH2 (bimolecular homolytic substitution) mechanism. Lastly, some noteworthy radical processes proceed through a radical–polar crossover pathway, in which one-electron

• titanium have been employed successfully to catalyze enantioselective radical reactions. Two earth abundant transition metals that have found extensive application in enantioselective radical reactions are copper and nickel. These metals, particularly Ni, can be used in radical–radical coupling reactions

Research towards selective inhibition of the CLK3 kinase

• Vinay Kumar Singh,
• Frédéric Justaud,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Blandine Baratte,
• Thomas Robert,
• Stéphane Bach,
• Chada Raji Reddy,
• Nicolas Levoin and
• René L. Grée

Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172

• series of molecules: the ones without chlorine in meta position on this group (series a) and the others which kept this chlorine, like in DB18 (series b). These syntheses are reported in Scheme 2. A Suzuki-type Pd-catalyzed coupling of 7a with 4-(methoxycarbonyl)phenylboronic acid dimethyl ester (8) gave

• 9a which, after saponification, afforded the first target compound 10a. The second molecule 10b was obtained in the same manner starting from 7b with the chlorine in meta position of the aromatic group. Then, by a similar approach, the targets 13a and 13b were prepared by now using as the coupling

A chiral LC–MS strategy for stereochemical assignment of natural products sharing a 3-methylpent-4-en-2-ol moiety in their terminal structures

• Rei Suo,
• Raku Irie,
• Hinako Nakayama,
• Yuta Ishimaru,
• Yuya Akama,
• Masato Oikawa and
• Shiro Itoi

Beilstein J. Org. Chem. 2025, 21, 2243–2249, doi:10.3762/bjoc.21.171

• typically determined using NMR-based techniques, such as coupling constant analysis and NOE experiments, sometimes with the aid of computational chemistry [3][4][5][6][7]. In contrast, absolute configuration remains more challenging to determine, as it frequently requires chemical degradation or

• ], juniperolide A [21], certonardosterol A4 [22], and sclerketide D [23] remain unresolved due to the limited sample quantity or ambiguous results, even when the modified Mosher’s method is employed; a medium vicinal coupling constant (4–6 Hz) prevents reliable differentiation between threo and erythro

Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• regioselectivity issues, multistep procedures, and limited applicability to tetra-ortho-substituted structures. Herein, we describe a direct, one-pot Pd-catalyzed dehydrogenative C–N coupling between aryl bromides and arylhydrazines to access non-symmetric azobenzenes. The use of bulky phosphine ligands and

• the presence of water, highlighting its robustness. Keywords: azo compounds; cross-coupling; domino catalysis; palladium; phosphine ligands; Introduction Azobenzenes are a widely studied class of compounds known for their distinctive photoresponsive properties, rendering them valuable in a variety

• , most synthetic methods have focused on the preparation of symmetric derivatives [12][13]. Traditional approaches, such as oxidative coupling of anilines [14][15][16][17][18][19], reductive coupling of nitroarenes [20][21][22][23], or cross-coupling between anilines and nitroarenes have proven

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• using widely accepted strategies [46][47]. DMSO-d6 or CDCl3 were used as the solvents and tetramethylsilane (TMS) as the internal standard. Chemical shifts (δ) and coupling constants (J) are given in ppm and in Hz, respectively. High-resolution mass spectra were recorded on an Agilent 2750 GC/Q-TOF mass

A m-quaterphenyl probe for absolute configurational assignments of primary and secondary amines

• Yuka Takeuchi,
• Mutsumi Kobayashi,
• Yuuka Gotoh,
• Mari Ikeda,
• Yoichi Habata,
• Tomohiko Shirai and
• Shunsuke Kuwahara

Beilstein J. Org. Chem. 2025, 21, 2211–2219, doi:10.3762/bjoc.21.168

• polarized along the long axes of the methoxybiphenyl chromophores. The CD spectrum of (S)-2a shows Cotton effects arising from exciton-coupling between the two methoxybiphenyl chromophores; λext = 278 nm (Δε1 = −0.6 dm3 mol−1 cm−1) and λext = 258 nm (Δε2 = +1.7 dm3 mol−1 cm−1). The amplitude of exciton

• the quaternary ammonium salts (S)-2f,g and (R)-2h exhibit CD Cotton effects due to the exciton-coupling between the two methoxy-biphenyl chromophores (Figure 1b). Compound (R)-2f exhibited the mirror image of the CD spectrum of (S)-2f (Figure S19 in Supporting Information File 1). The direction of

• clarity. The relationship between the ACD values and excess of P conformer. Excess of P conformer (%) = ([P] − [M])/([P] + [M]) × 100, where [P] and [M] are the amounts of P and M conformers calculated by B3LYP/6-31G*, respectively. Coupling reaction of 1 and chiral primary and secondary amines. The

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• characteristics. Electrochemical construction of five-membered rings from alkynes attracted increasing attention due to the notable advantages of electrochemical transformations and facile access of alkynes. Indole skeletons were constructed successfully through electrochemical intramolecular coupling of ethynyl

• ]. Besides, electrochemical cyclization of alkynes is also an important access towards indoles. In 2016, Xu reported the electrochemical intramolecular coupling of urea derivatives to form substituted indoles (Scheme 1) [162]. Using [Cp2Fe] (5 mol %) as the redox catalyst, the intramolecular coupling of

• . Indole skeletons were obtained successfully through electrochemical coupling of urea derivatives, dehydrogenative annulation of alkynes with anilines, annulation of o-arylalkynylanilines, cyclization of 2-ethynylanilines, selenocyclization of diselenides with 2-ethynylanilines, and enantioselective

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• production of jet fuel precursors through the electrocatalytic highly selective coupling reaction of furfural and levulinic acid. The Ni2+ species serves as the active site for the coupling process (Scheme 53) [181]. A similar strategy involving phenolic compounds and furfural allowed the production of

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• and transformations of 43 produced hydroxyketone 44. Due to the steric hindrance of this substrate, the subsequent Suzuki cross coupling reaction with 3-boronophenol proceeded in low yield. To address this issue, Han′s group employed a novel palladacycle catalyst 45, previously developed by their

• group [35][36][37]. This catalytic system efficiently overcame the challenge and furnished the coupling product 46 in high yield. Oxidative cleavage of the double bond in 46 followed by Mg(II)-mediated chelation-controlled Friedel–Crafts cyclization delivered secondary alcohol 47, which was elaborated

• -catalyzed Suzuki cross-coupling reaction of sterically hindered substrates developed by Han [35][36][37], the coupled product 57 was obtained in a satisfactory yield (72%) from 55 and pinacol boronate 56, along with trace amounts of the double bond migrated side product 58 (57:58 = ca. 15:1). Demethylation

Further elaboration of the stereodivergent approach to chaetominine-type alkaloids: synthesis of the reported structures of aspera chaetominines A and B and revised structure of aspera chaetominine B

• Jin-Fang Lü,
• Jiang-Feng Wu,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2025, 21, 2072–2081, doi:10.3762/bjoc.21.162

• generation of our synthetic strategy to chaetominine-type alkaloids featuring two modifications of the last step of our 4 to 6-step approach. Firstly, by employing EDCI/HOBt as the coupling system for the last step of the one-pot O-debenzylation–lactamization reaction, the overall yield of our previous total

• Improved five-step total synthesis of (–)-isochaetominine A In our recent communication on the synthesis of versiquinazoline H (11) [65], we uncovered that the employment of EDCI/HOBt as the coupling system for the last step, namely, the O-debenzylation–lactamization reaction, afforded much higher yields

• our third-generation strategy featuring the employment of benzyl ʟ-valinate as the coupling component [63], tripeptide derivative 28 was synthesized in three steps. Exposure of 28 to DMDO in acetone followed by treating the resulting intermediates with Na2SO3 produced the proposed structure of aspera

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• position 12 [23]. The most straightforward synthetic strategy for formation of an carboxamide group at position 12 of the indolo[1,2-c]quinazolin-6(5H)-one (1) scaffold involved a two-step sequence: (1) carboxylation of the nucleophilic C12 position, followed by coupling with appropriate amines. To

• trifluoroacetic acid affords intermediate compound 6, bearing a trifluoroacetyl group on the indole moiety. Treatment of 6 with the base yielded the acid 3 in high yield (Scheme 2). The carboxyl group of 3 was converted to the corresponding amides via coupling with mono-N-Boc-protected C2–C4 diamines using PyBOP

• as the activating agent under standard peptide coupling conditions. Cleavage of the Boc-protecting group with TFA afforded the target 6-oxoindolo[1,2-c]quinazoline-12-carboxamides 7a–c (Scheme 2). 3-Aminomethylindole derivatives represent a well-established class of compounds with diverse biological

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• evidences of chemical transformations. Thus, a bioinspired total synthesis was investigated (Scheme 1b). Synthetically, we did not start from trans-nerolidol (1) to construct a C–C bond cleavage. Instead, a convergent coupling approach was selected to quickly access the aldehyde precursor. Phenyl sulfide 5

• -dithiane linchpin coupling (Scheme 3b). To our delight, using DDQ as the optimal oxidizing reagent, the expected THF-containing product 23 was generated as a sole diastereoisomer, suggesting the pQM 22 underwent oxa-Michael addition only with the C10 alcohol. The free C12 alcohol did not affect this

• divergent coupling approaches, and the stereocontrol with Evans oxazolidinone was always reliable to obtain an sole diastereomer (Scheme 6d). Bioinspired concise and scalable total synthesis sarglamides In 2023, Yue and co-workers investigated the ingredients of the Chinese folk medicine Sarcandra glabra

Solar thermal fuels: azobenzene as a cyclic photon–heat transduction platform

• Jie Yan,
• Shaodong Sun,
• Minghao Wang and
• Si Wu

Beilstein J. Org. Chem. 2025, 21, 2036–2047, doi:10.3762/bjoc.21.159

• investigated their solar thermal energy storage performance [46]. Key parameters governing the performance of azobenzene–RGO hybrid solar thermal fuels include hydrogen-bonding interactions, intermolecular distances between adjacent azobenzene groups, and electronic coupling effects. Conjugated azobenzene

• development of azobenzene-based solar thermal fuels and demonstrated their potential applications. Nanocarbon-integrated azobenzene polymers: Their energy storage efficiency (up to >200%) and cycle life are primarily modulated by template confinement effects and electronic coupling. However, high costs and

Measuring the stereogenic remoteness in non-central chirality: a stereocontrol connectivity index for asymmetric reactions

• Ivan Keng Wee On,
• Yu Kun Choo,
• Sambhav Baid and
• Ye Zhu

Beilstein J. Org. Chem. 2025, 21, 1995–2006, doi:10.3762/bjoc.21.155

• are assigned following the 3-step procedure for all types of strategies including cyclization, biaryl coupling, and desymmetrization, irrespective of the chemical identity of the newly established chiral axis including C–C [10][11] (Scheme 3C and 3D), C–N [12] (Scheme 3B), N–N [13] (Scheme 3A), and C

• –B [14] (Scheme 3E) bonds. In the case of an asymmetric cross-coupling reaction (Scheme 3C) [10], both sets of the substituents on individual aryl groups are considered because neither is involved in the bond formation/cleavage. Accordingly, the catalyst-controlled atroposelective Suzuki–Miyaura

• coupling of biaryls is designated as [30 20]. In addition to biaryls, axially chiral allenes are popular targets for asymmetric synthesis. Three examples of asymmetric reactions that form axially chiral allenes are shown in Scheme 4. For example, the enantioselective nucleophilic substitution to yield

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• propargylsilane 7d halogenation–cyclization cascade and Suzuki–Miyaura cross-coupling in the second step [22]. Thus, we have developed a faster and palladium-free route towards tetrahydrofurans 8. The latter can still be modified further through silicon–halide exchange followed by cross-coupling chemistry as

• can arylate propargylsilanes and induce a 1,2-silyl shift to generate β-Si-stabilized allyl cations. Compared to the previously employed two-step halocyclization–cross-coupling sequence [22], this approach offers a shorter, [Pd]-free synthetic sequence to the modified styryl-containing tetrahydrofuran

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• manifold with carboxylic acid derivatives, numerous coupling processes affording ketone products have been developed. Since the initial report from Scheidt and co-workers using 4-alkyl-substituted Hantzsch esters as coupling partners [31][32][33][34][35][36], several alkyl radical sources have been

• contrast to these numerous reports with carbon-based alkyl radicals, dual NHC/photoredox-mediated coupling processes between carboxylic acid derivatives and other classes of radical are lacking [22][23][24][25][26][27][28][29][30]. In particular, to the best of our knowledge, formal reduction reactions of

• 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN), which has been commonly employed in dual NHC/photoredox-catalyzed coupling reactions, cleanly provided the fully reduced species in 50% 1H NMR yield (Table 1, entry 19). Comments on the reaction mechanism At this stage of the study, our

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• triflate 46, alkylation with sulfone 47 via treatment with butyllithium and hexamethylphosphoramide (HMPA) yielded the coupling product 48 as a mixture of diastereoisomers in 60% yield. Ultimately, single-electron reduction removed both the sulfone and benzyl groups of 48, furnishing (S)-α-tocotrienol (49

• produced coupling product 69 in 84% yield. Finally, a six-step sequence completed the synthesis of (18S)-variabilin (70). In 2010, Kawasaki and co-workers reported the asymmetric synthesis of both (S)-Rosaphen and (R)-Rosaphen to evaluate their odor profiles (Scheme 12) [44]. Diol 72 was prepared from

• with 99% ee. The TBS protection was crucial to prevent the potential racemization by intramolecular transesterification. Ester 79 was then prepared from 78 in eight steps. To complete the dimerization, fragments 80 and 81 were independently prepared from 79. An intermolecular Suzuki–Miyaura coupling

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• -diazoamides 1. Finally, Pd-catalysed cross-coupling with warhead-substituted phenyl iodides gave, in low to moderate yield, the required α-diazoamide substrates 2 (referred to individually as D1–5 below). Whilst the Pd-catalysed arylation of α-diazoamides and esters is known [15][16][17][18][19], its

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• through circular dichroism (CD) and circularly polarized luminescence (CPL) spectroscopy. Results and Discussion The syntheses of N-doped macrocycles MC1–3 are shown in Scheme 1. Diamines 1a and 1b were synthesized by double Pd-catalyzed C–N coupling reaction of 4,6-dichlorobenzene-1,3-diamine with phenyl

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• Margherita Gazzotti Fabrizio Medici Valerio Chiroli Laura Raimondi Sergio Rossi Maurizio Benaglia Dipartimento di Chimica, Università degli Studi di Milano, via Golgi 19, IT-20133 Milano, Italy 10.3762/bjoc.21.147 Abstract The stereoselective electroreductive intramolecular coupling of chiral

• applications in the preparation of chiral ligands. Keywords: chiral piperazines; electrosynthesis; flow chemistry; green chemistry; imino-pinacol coupling; Introduction Vicinal diamines represent a highly valuable class of compounds that, over the past decades, have found widespread application in natural

• represent the most established approach to imino-pinacol coupling (Scheme 1), with zero-valent metals traditionally employed as reductants and various strategies extensively explored [2]. The use of alkali metals [3][4][5], as lithium and sodium, and alkaline earth metals [6], as magnesium, are

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• to one another and cis to the ring junction NC–H. The relative stereochemistry of the oxindole quaternary stereocentre was less obvious from this method, but the coupling constants of the aliphatic ring protons in the 1H NMR spectrum had similar values to those in the adduct 5a, suggesting that the

• are reported. 1H NMR spectra were recorded on a Bruker AC400 (400 MHz) instrument. Chemical shifts are reported in ppm with respect to the residual solvent peaks, with multiplicities given as s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad. Coupling constants (J values

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• with poor diastereoselectivity while maintaining high enantioselectivity for both diastereomers (see 76d–g). Furthermore, the authors have investigated the asymmetric condensation using other seven-membered cyclic ketones (see 77a) as well as the coupling with alkylhydroxylamine (see 77b

• synthesis of planarly chiral macrocycles via CPA-catalyzed coupling of carboxylic acids with alcohols via ynamide mediation. Kinetic resolution of substituted amido[2.2]paracyclophanes via CPA-catalyzed asymmetric electrophilic amination. Enantioselective synthesis of inherently chiral calix[4]arenes via

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• be synthesised through oxidation of aminoheteroarenes 12 (Scheme 4A) or reduction of nitroheteroarenes 13 (B). Bayer–Mills coupling (Scheme 4C) is suitable for both symmetric and asymmetric targets, usually in acidic conditions. Basic conditions [14] are more effective with very electron-poor

• aromatic amines. Another strategy for both symmetric and asymmetric targets is the azo coupling of a diazonium salt 15 (Scheme 5A) with a nucleophile, which can be a (hetero)aromatic 16 [29] (B), a lithiated ring 19 [39] (C), or a precursor 20a,b [29][32][40] (D). In case of more than one reactive position

• reductive cross-coupling of benzyl halides when substituents prone to reduction (CN, esters) are present (Scheme 12C). The Ullman–Goldberg coupling of 41b with Boc-hydrazine followed by deprotection and oxidation then affords 35 [55]. Asymmetric diazocines can be synthesised by Sonogashira cross-coupling