Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• involvement of a fluorescent intermediate in the cascade synthetic process. Keywords: cascade reactions; copper-catalyzed three-component coupling; gold-mediated 6-endo hydroamination; tandem cyclizations; tetrahydroisoquinoline alkaloids; Introduction The bis-tetrahydroisoquinoline (THIQ) alkaloid family

• led by Corey [23], Myers [24][25], Liu [26][27], and Saito [28] also efficiently exploited PS-type reactions to accomplish the total synthesis of saframycin A (1) (Scheme 1b) [3][4][5][29][30][31][32][33][34][35][36][37][38][39][40][41]. However, PS-type reactions impose constraints due to the

• necessity of electron-donating groups on the aromatic rings to facilitate SEAr reactions. These constraints have stimulated interest in exploring an alternative synthetic approach to achieve greater structural diversification [42]. In this study, to overcome the synthetic limitations inevitably imposed by

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• Gewald three-component reactions. Our focus was to create a representative, diverse and structurally complex library of building blocks, covering a range of shapes and chemical spaces, to facilitate formamide-based heteroannulation for the synthesis of the desired adducts. Thus, we employed aliphatic and

• moiety of the amide group resulted in pyrimidone annulation [41]. This was observed for the first time and completed the reported heteroannulation landscape utilizing the Niementowski reaction [25]. In general, the reactions had a rather broad scope as a great range of cyanoacetamides was compatible. The

• synthesis was efficient and rapid as the final adducts could be isolated only by precipitation. In addition, the reactions were performed in a parallel setup using custom-made metal blocks. Specifically, thienopyrimidine and thienopyrimidone derivatives exhibit a range of biological activities, i.e

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• –N, P–N, and N–H bond-forming reactions. Several studies have proposed copper nitrenoid intermediates originating from dioxazolones, involving an N-acyl nitrene transfer or hydrogen atom transfer process, representing creative synthetic solutions that were previously unachievable using conventional

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• stoichiometric quantities of a copper reagent [3]. This pioneering work, known as the “classical Ullmann reaction”, was extended by Ullmann and Goldberg to enable the C–N and C–O bond formation [4][5][6]. Subsequently, key developments in Cu-catalyzed cross-coupling reactions were achieved, including the

• Rosenmund–von Braun reaction [7], Hurtley’s coupling [8], and the Cadiot–Chodkiewicz reaction [9]. However, these classical reactions often restrict the substrate scope and functional group compatibility due to the harsh conditions required, such as strong bases, high temperatures, and stoichiometric

• amounts of copper reagents. Consequently, investigation into more practical and sustainable reactions remains an area of ongoing research [10]. Conventional cross-coupling reactions typically require C(sp2)-based electrophiles and nucleophiles as coupling partners. Generally, the reaction is initiated

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• coupling reactions of aromatic C–F and C–Br bonds with arylboronic acids. Keywords: arylboronic acid; benzofuran; C–F bond activation; cross-coupling; nickel; Introduction The metal-catalyzed activation of aromatic carbon–fluorine (C–F) bonds is widely recognized as a challenging task in synthetic

• distinct aryl groups onto a benzofuran ring through orthogonal coupling reactions, exploiting the reactivity difference between C–F and C–Br bonds (Scheme 4). Using a palladium catalyst, 5-bromo-2-fluorobenzofuran (1e) was coupled with [4-(trifluoromethyl)phenyl]boronic acid (2g). In this reaction, only

• ]benzofuran (3fa) in 81% yield. Next, we explored the mechanism of the coupling reactions between 2-fluorobenzofurans 1 and arylboronic acids 2. Because these reactions proceed under mild conditions despite involving aromatic C–F bond activation [19], direct oxidative addition of C–F bonds is unlikely (Scheme

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• Venezian 21, 20133, Milano, Italy 10.3762/bjoc.21.7 Abstract This review reports the achievements in copper(II) triflate-catalyzed processes concerning the multicomponent reactions, applied to the synthesis of acyclic and cyclic compounds. In particular, for the heteropolycyclic systems mechanistic

• insights were outlined as well as cycloaddition and aza-Diels–Alder reactions were included. These strategies have gained attention due to their highly atom- and step-economy, one-step multi-bond forming, mild reaction conditions, low cost and easy handling. Keywords: cascade process; copper catalysis

• ; heteropolycycles; multicomponent reactions; one-pot reaction; Introduction Copper has gained a relevant role in organic synthesis as an alternative to precious metals due to its low toxicity, ease of handling, high catalytic activity, and cost-effectiveness [1][2]. In recent years, Cu(OTf)2 has significantly

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• organocatalytic reactions are discussed according to the dominant catalyst activation mode. For covalent organocatalysis, the typical enamine and iminium modes are presented, followed by N-heterocyclic carbene-catalyzed reactions. The bulk of the review is devoted to non-covalent activation, where chiral Brønsted

• to NHC-catalyzed reactions. The major part is devoted to chiral Brønsted acid catalysis as it seems so far the most widely used activation principle for the generation of axially chiral compounds. Hydrogen-bond-donating catalysts and various other activation modes complete the discussion of recent

• advances in organocatalytic atroposelective syntheses. Review Atroposelective reactions via enamine and iminium activation Iminium activation was utilized in the synthesis of axially chiral styrenes. Tan and co-workers developed an atroposelective strategy toward axially chiral alkenylarenes 3 based on an

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• reduction can be accomplished via catalytic hydrogenation, involving stepwise reactions and workup, use of additional reagents, and reaction time between 3 and 24 hours [11][12]. Most commonly, metal hydrides are employed, typically lithium aluminum hydride [13][14][15][16][17][18], requiring an inert

• (entries 1–6). The isolated product yields were obtained by performing the reactions at 80 °C for the time indicated beside each product. For more details, see the experimental section below. Supporting Information Supporting Information File 68: 1H and 13C NMR spectra of the synthesized compounds, the

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• and Research (A*STAR), 1 Pesek Road, Jurong Island, Singapore 627833, Republic of Singapore 10.3762/bjoc.21.3 Abstract The discovery of the optimal conditions for chemical reactions is a labor-intensive, time-consuming task that requires exploring a high-dimensional parametric space. Historically

• , the optimization of chemical reactions has been performed by manual experimentation guided by human intuition and through the design of experiments where reaction variables are modified one at a time to find the optimal conditions for a specific reaction outcome. Recently, a paradigm change in

• intervention. Herein, we review the currently used state-of-the-art high-throughput automated chemical reaction platforms and machine learning algorithms that drive the optimization of chemical reactions, highlighting the limitations and future opportunities of this new field of research. Keywords: autonomous

Synthesis, structure and π-expansion of tris(4,5-dehydro-2,3:6,7-dibenzotropone)

• Yongming Xiong,
• Xue Lin Ma,
• Shilong Su and
• Qian Miao

Beilstein J. Org. Chem. 2025, 21, 1–7, doi:10.3762/bjoc.21.1

• , expanding its π-skeleton through the Barton–Kellogg and Scholl reactions led to the successful synthesis of a curved polycyclic arene containing three heptagons and two pentagons. Keywords: carbon schwarzites; polycyclic arenes; Scholl reaction; seven-membered carbocycle; Yamamoto coupling; Introduction

• trione 1 in hands, we explored the Scholl reaction and thionation reaction of it (Scheme 1b) because these reactions can potentially allow π-expansion of 1. A variety of Scholl reaction conditions, such as AlCl3/NaCl, AlCl3/CuCl2, FeCl3, and DDQ/TfOH, were tested. However, these reactions either left the

• -layer chromatography (TLC). When other typical conditions for Scholl reactions, such as FeCl3 or DDQ/CH3SO3H, were employed to treat compound 10, product 3 was not isolated. Instead, the starting material either remained unreacted or was converted to a complicated mixture of products. It is worth noting

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• ][27], as well as Friedel–Crafts [28] and Prins-type [29] reactions have been developed to date [2]. However, methods that enable access to the analogous acenaphthylene-fused heteroarenes are less common [30][31][32][33][34][35][36][37][38][39]. In one such study, Würthner and co-workers reported a Pd

• reaction cascade starting from diarylalkynes 8, which involves indole formation/peri-C–H annulation and N-dealkylation reactions to afford acenaphthylene-fused indole products 9 (Scheme 1b) [41]. Recently, Takeuchi and co-workers reported an effective Ir-catalyzed [2 + 2 + 2] cycloaddition between 1,8

• )-catalyzed [2 + 2 + 2] cycloaddition reactions with 1,8-dialkynylnaphthalenes to access azafluoranthenes and 2-pyridone-fused naphthalenes [27]. In 2017, we reported a Pd-catalyzed cascade reaction that involves a sequential Suzuki–Miyaura cross-coupling and a subsequent intramolecular C–H arylation between

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• as strong oxidizing agents [1], during the last decades HIRs have been investigated as group-transfer reagents, useful in several bond-forming reactions, such as in C–C, C–N, and C–O [2][3][4][5]. The benziodoxol(on)e family, cyclic iodine(III) reagents, stands out for their thermal stability and

• in electrophilic transfer reactions, with emphasis on umpolung reactivity of usually nucleophilic functional groups. Thus constituting a powerful synthetic tool, opening room for new synthetic disconnections [10]. Within the benziodoxol(on)e class, a range of HIRs featuring nitrogen-containing groups

• first report from Zhdankin and co-workers in 1994, described the preparation of azidobenziodoxolone, ABX (I), a reagent widely used in oxidative azide transfer reactions [21]. Years later, Zhdankin’s group also reported the synthesis of amidobenziodoxolone (II) [14]. Other examples of N-containing

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• functionalization (LSF) of peptide scaffolds. α,β-Unsaturated amino acids like dehydroalanine (Dha) derivatives have emerged as particularly useful structures, as the electron-deficient olefin moiety can engage in late-stage functionalization reactions, like a Giese-type reaction. Cheap and widely available

• by Chatgilialoglu et al. [22] under non-photoredox conditions, MacMillan et al. [23] sparked renewed interest in silanes as XAT reagents by generating a tris(trimethylsilyl)silyl radical through photoredox catalysis for arylation reactions [22][23]. In 2018, Balsells et al. [24] reported a similar

• modification potential by means of polar, metal-, or organo-catalyzed and radical additions [29][30][31][32][33][34][35][36]. As such, Dha derivatives make an excellent candidate for exploring a photochemical Giese-type reaction [37]. To foster a physiological reaction environment, reactions can be conducted

Efficient synthesis of fluorinated triphenylenes with enhanced arene–perfluoroarene interactions in columnar mesophases

• Yang Chen,
• Jiao He,
• Hang Lin,
• Hai-Feng Wang,
• Ping Hu,
• Bi-Qin Wang,
• Ke-Qing Zhao and
• Bertrand Donnio

Beilstein J. Org. Chem. 2024, 20, 3263–3273, doi:10.3762/bjoc.20.270

• commercial perfluoroarene chemical blocks and reagents, involving catalyzed C–F-bond activation and cross-coupling reactions, usually requiring precious transition-metal catalysts and tedious synthetic routes [28][29][30][31][32][33][34]. Therefore, low-cost and facile synthetic strategies are desired to

Intramolecular C–H arylation of pyridine derivatives with a palladium catalyst for the synthesis of multiply fused heteroaromatic compounds

• Yuki Nakanishi,
• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2024, 20, 3256–3262, doi:10.3762/bjoc.20.269

• ; phosphine ligand; pyridine amides; Introduction Transition-metal-catalyzed synthetic reactions have recently attracted much attention in synthetic organic chemistry [1][2]. C–H Arylation reactions catalyzed by a transition metal are of particular interest because these reactions involve rather superior

• reaction of the corresponding heteroaromatic carboxylic acids with thionyl chloride followed by treatment with N-octyl-2-bromoaniline [15]. The reactions proceeded smoothly affording products 1a–c in good yields as shown in Scheme 1. We then studied the reaction of quinoline amide 1a under several

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• -heterocycles using various catalytic systems such as chiral metal catalysts, chiral Lewis acids or chiral organocatalysts. This review presents an overview of the recent advances in enantioselective cyclization reactions of 1-azadienes catalyzed by non-covalent organocatalysts. Keywords: α,β-unsaturated

• , they can be attacked by a nucleophile and undergo a 1,2-addition or conjugate addition leading to the production of allylic amines or aliphatic imines, respectively. They can also behave as C4 synthons in cycloaddition reactions such as the aza-Diels–Alder reaction, giving access to nitrogen-containing

• , respectively. Additionally, the most common cyclic α,β-unsaturated imines involve benzofuran or saccharin-derived azadienes (Figure 1). Cycloaddition reactions, especially Diels–Alder reactions, have attracted a lot of attention since their discovery as one of the most powerful methodologies for the

Germanyl triazoles as a platform for CuAAC diversification and chemoselective orthogonal cross-coupling

• John M. Halford-McGuff,
• Thomas M. Richardson,
• Aidan P. McKay,
• Frederik Peschke,
• Glenn A. Burley and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2024, 20, 3198–3204, doi:10.3762/bjoc.20.265

• further diversification of the triazole products, including chemoselective transition metal-catalysed cross-coupling reactions using bifunctional boryl/germyl species. Keywords: chemoselectivity; click chemistry; copper; germanium; triazole; Introduction Since its inception, click chemistry has been

• established as a powerful approach for molecule synthesis. Strategies within click chemistry include several widely used reactions such as the (hetero-)Diels–Alder reaction [1][2], alkene hydrothiolation [3], and an array of amide-bond-forming chemistries [4]. However, by virtue of the access to alkyne and

• of borylated functional groups, allowing orthogonal cross-coupling, whilst also offering excellent stability compared to boron-based reagents [57][58][59][60][61][62][63][64][65][66][67]. Based on their utility and stability, germanium units could therefore be useful within CuAAC reactions and offer

Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives

• Anastasiya V. Agafonova,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264

• derivatives [1]. In particular, the catalytic isomerization of 5-chloroisoxazoles allows the generation of azirine-2-carbonyl chlorides, which can be easily converted into a variety of azirine-2-carboxylic acid derivatives by reactions with nucleophilic reagents. Using this approach, numerous 2-(1H-pyrazol-1

• separate impurities. In these cases, as well as in reactions giving low aldehyde yields in the first step (4b,d), the second developed reaction sequence turned out to be more effective. In the second approach, the oxidation of aldehydes 4 with Oxone to acids 5 occurs with yields close to quantitative, and

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• versatile intermediates in organic synthesis due to their unique reactivity and ability to participate in a wide range of chemical transformations. In this scenario, sulfoxonium ylides are excellent substrates for bifunctionalization reactions, due to the ambiphilic character in their ylidic carbon [16

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• . Diagonal 643, E-08028 Barcelona, Spain 10.3762/bjoc.20.261 Abstract The ongoing quest to discover effective treatments for diseases remains a significant challenge for the scientific community. Multicomponent reactions (MCRs) have emerged as powerful tools in accelerating drug discovery, enabling the

• to the authors whose important contributions may not be included. By concentrating on these pivotal studies, we strive to offer a clear and concise perspective on current research trends and breakthroughs in this field. Keywords: Alzheimer; depression; epilepsy; multicomponent reactions; Parkinson

• ; schizophrenia; Introduction Multicomponent reactions Due to efforts to develop new drug arsenals faster to overcome the difficulties of medicinal chemistry (multistage and highly wasteful processes), multicomponent reactions (MCRs) have emerged as a plausible solution. MCRs are convergent reactions in which

Controlled oligomerization of [1.1.1]propellane through radical polarity matching: selective synthesis of SF₅- and CF₃SF₄-containing [2]staffanes

• Jón Atiba Buldt,
• Wang-Yeuk Kong,
• Yannick Kraemer,
• Masiel M. Belsuzarri,
• Ansh Hiten Patel,
• James C. Fettinger,
• Dean J. Tantillo and
• Cody Ross Pitts

Beilstein J. Org. Chem. 2024, 20, 3134–3143, doi:10.3762/bjoc.20.259

• established that [1.1.1]propellane participates in radical-chain reactions (i.e., oligomerization) at room temperature in solution to form unsubstituted [n]staffanes. The origin of this innately controlled oligomerization was then investigated through density functional theory (DFT) calculations. The free

• point of comparison, we examined the reactivity of 1 with CF3SF4Cl. This reagent is known to behave comparably to SF5Cl in radical chain reactions [17][59][60][61] and can also be prepared conveniently in house [62]. In an analogous equivalents screen, we found that the 5:3 product ratio shifts from 7.7

• [81]. This unexpected observation suggests that CF3SF4-containing [2]staffanes, in particular, warrant additional studies and may be of interest, e.g., in liquid crystal design. Conclusion Suppressing [n]staffane formation beyond n = 1 in radical chain reactions involving [1.1.1]propellane (1) tends

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• , we have collected and described the HVI-mediated halocyclisation reactions reported in the literature for each halide. We have organised the examples firstly by the halide nucleophile, and then secondly by the internal heteroatom nucleophile involved in the cyclisation. The selectivity (chemo-, regio

• aza-heterocycles were synthesised in good yields. The authors proposed a mechanism for the fluorocyclisation reactions (Scheme 6), which relies on the activation of the fluoro-iodane reagent 12 with the zinc catalyst. The activation enables better orbital overlap to occur with the π bond of the alkene

• system was used due to concerns with the long-term stability of iodosylbenzene and unwanted reactions of BF3·Et2O with other reagents. In addition, a catalytic system was reported that employed 20 mol % iodotoluene with 1 equivalent of m-CPBA as terminal oxidant. The authors proposed that

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• interactions and accelerating aldol reactions. In the absence of a catalyst, no reaction between 2-(trimethylsilyloxy)furan (TMSOF, 13) and benzaldehyde (14) was observed, whereas all the tested macrocyclic compounds were found catalytically active, with 11 being the most efficient providing erythro/threo (15

• , Ballester and co-workers reported on the preparation of an octapyridinium-based water-soluble superaryl-extended calix[4]pyrrole molecular container and used it as a capsule for desymmetrization reactions [41], where the reported compound acts both as sequestering and supramolecular protecting group. All of

• activation of both substrates via hydrogen-bonding interactions. Additionally, these macrocycles showed excellent activity for sulfa-Michael additions, as well as a moderate activity for Henry and aza-Henry reactions. These results are consistent with the observation reported by Senge and co-workers

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• affinity compared to their drug parents and by using powerful synthetic tools such as multicomponent reactions (MCRs) [11][12][13]. Among these, isocyanide-based multicomponent reactions (I-MCRs), such as the Ugi-azide reaction, have demonstrated the highest biological-synthetic relevance [1][14][15][16

• ]. In this regard, a relatively unexplored field within MCRs comprises high-order multicomponent reactions, which involve reacting at least five or even more components in a single operational step. These reactions are highly convergent, efficient, and have superior atom economy, producing high

• structural diversity and complexity compared to classical 3- or 4-CRs [17][18][19]. In the same context, the hybridization of 1,5-disubstituted tetrazoles with an indole moiety using I-MCRs such as the Ugi-azide reaction as a key step, is very limited. To our knowledge, only three reactions have been

Enantioselective regiospecific addition of propargyltrichlorosilane to aldehydes catalyzed by biisoquinoline N,N’-dioxide

• Noble Brako,
• Sreerag Moorkkannur Narayanan,
• Amber Burns,
• Layla Auter,
• Valentino Cesiliano,
• Rajeev Prabhakar and
• Norito Takenaka

Beilstein J. Org. Chem. 2024, 20, 3069–3076, doi:10.3762/bjoc.20.255

• enantioenriched form [11][12]. However, such metal/metalloid reagents and the corresponding metal catalyst-bound intermediates often equilibrate between possible regioisomeric forms and can undergo both, SE2 and SE2’ addition reactions, resulting in a mixture of homopropargylic alcohols and α-allenic alcohols [14

• aldehyde allylation reaction with allyltrichlorosilane [47], it has been routinely employed in analogous chlorosilane reactions [48][49][50][51][52][53][54][55]. However, a mechanistic basis of its role on the observed rate acceleration remains elusive while it certainly functions as a scavenger of HCl

• as an acid scavenger. The reactions with catalyst 3 in the presence of either N,N-diisopropylethylamine or 4 Å molecular sieves gave identical results (99% yield, 78:22 er), and thus we decided to proceed with molecular sieves (Scheme 4). It is often the case that the narrower the chiral pocket of a