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

• prepared in high yield via FeCl3-oxidative coupling of 1,2-dialkoxy-4-bromobenzene (Scholl reaction). The new triphenylene derivatives, F3–F12, were prepared in moderate to high yields (51–73%). In addition, three bitriphenylene derivatives were synthesized in a subsequent annulation step from Fn

• ) for F3 and F4, or two peaks indexed as (11) and (20), respectively, for F10 and F12, confirming unambiguously the hexagonal symmetry (F5, F6, and F8 only show the intense small-angle reflection). In addition, they all show a broad diffuse scattering and a sharp and intense diffraction peak in the wide

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

• . The addition of ligand improved the yield of 2a as shown in Table 1, entries 7–10. Among several ligands, including Buchwald-type phosphines L1–L4 [33] examined, it was found that the use CyJohnPhos (L3) afforded the cyclized product in 90% yield and the reaction with PPh3 (L4) as a ligand was also

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

• , 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

• Michael addition product was obtained with low diastereoselectivity. The mechanism is described in Scheme 4: the bifunctional squaramide activates the azadiene through hydrogen bonding while the malononitrile is deprotonated by the tertiary amine present in the backbone of the catalyst, establishing

• hydrogen bonding with the protonated tertiary amine. Then, a Michael addition of malononitrile to the azadiene takes place to obtain exclusively the (S)-intermediate A. Subsequently an intramolecular nucleophilic addition of the nitrile leads to the intermediate B, which undergoes tautomerization to

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• data analyses. All compounds were assessed for their inhibition on planktonic growth of P. aeruginosa PAO1 in addition to their ability to inhibit the formation of biofilms. None of the tested natural products inhibited planktonic growth or biofilm formation of PAO1 when screened at 50 µM

• new leads against Pseudomonas aeruginosa and supported by numerous reports of favourable activity for ianthelliformisamines A–C [7][12] and their synthetic analogues [8][9][10], we investigated the planktonic and biofilm activity of the new natural products 4–7 in addition to the known metabolite

• ) and diluted to an OD600 of 0.01. Test compounds (15 µL) were loaded prior to the addition of bacteria (135 µL) into 96-well plates. The plates were incubated for 24 h at 37 °C in static conditions. The effects of compounds on bacterial growth and the viability of biofilm bacteria was determined by 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

• extensive scope across a range of benign solvent conditions [7][8][9][10]. In addition, the CuAAC reaction uses inexpensive Cu catalysts [11], is insensitive towards oxygen and water [12][13], and consistently delivers high yields and (where relevant) enantioselectivities [8][9][10][14][15][16][17][18][19

• converted to a mechanistically-required Cu(I) species in situ through the addition of a reductant (e.g., sodium ascorbate, NaAsc) [31][32], or via Glaser–Hay alkyne homocoupling [33][34]. The mild and accessible nature of the CuAAC reaction has allowed the use of azide or alkyne components that bear

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

• ]. The most frequently used involves deprotonating the corresponding sulfoxonium salt with strong base, followed by the addition of an acylating agent (usually an acid chloride or chloroformate). Nevertheless, achieving a wide range of structural variations in sulfoxonium salts or ylides, particularly

• reported the α-alkylation of carbonyl sulfoxonium ylides via a Michael addition approach that occurred without any competition from cyclopropanation [30]. While this reaction represented the first direct alkylation of sulfoxonium ylides, it was nonetheless limited to the more reactive ester ylide variants

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• intramolecular Michael addition. Preliminary conformational studies on tripeptides including this scaffold in the central position show an extended conformation in solution (NMR) and in the solid state (X-ray). Keywords: fluoroalkyl groups; heterocycles; hydrazino acids; peptides; tetrahydropyridazines

• on an intramolecular Michael addition carried out in DMF and catalyzed by 10% of potassium carbonate. As previously observed [37], under these conditions, the 5-endo-trig cyclization was selective and the lactam resulting from the 5-exo-trig cyclization was not observed. Furthermore, in the case of

• strategy, the control of the stereoselectivity of the intramolecular aza-Michael addition could be envisaged with various chiral catalysts in further studies. These heterocyclic hydrazino acids, when incorporated into the peptidic structure, appear to confer an extended conformation. These interesting

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

• [3]. These aspects are aligned with the goal of addressing concerns related to the generation of environmentally hazardous waste [4]. In addition, this type of reaction allows for the efficient discovery of low molecular weight compounds. As a result, most of these compounds are drug-like according

• benzodioxepinones 12 in all cases (Scheme 11). The synthesized compounds demonstrated excellent drug-like features. Parkinson disease (PD) Knoevenagel–Michael addition/cyclization (MCR 3 + 2): Sirtuins, a group of enzymes that rely on NAD+ to function as protein deacetylases, have garnered attention across multiple

• a multicomponent reaction to obtain SIRT2 inhibitors (Scheme 12). The authors suggest a Knoevenagel condensation approach between isatin derivatives and ethyl cyanoacetate, followed by a Michael addition with C–H activated carbonyl compounds and intramolecular cyclization [50]. They synthesized 45

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

• truncated after incorporation of two bicyclopentane (BCP) units. Synthetic and computational studies suggest this phenomenon can be attributed to alternating radical polarity matching. In addition, single-crystal X-ray diffraction (SC-XRD) data reveal structurally interesting features of the CF3SF4

• bicyclopentyl radical philicities. In addition, we demonstrate that similar reaction conditions can be applied to the synthesis of the analogous CF3SF4-containing [2]staffane (CF3SF4-BCP-BCP-Cl, 3). Finally, we examined compound 3 by SC-XRD and found that it undergoes a phase transition as a function of rate of

• energy profile of the radical chain propagation sequence was computed at the PWPB95-D4/def2-QZVPP//PCM(Et2O)-ωB97X-D/def2-TZVP level of theory [51][52][53][54][55][56][57][58] (Figure 2). Following addition of an SF5 radical to 1 to form INT1, a Cl atom could be abstracted from SF5Cl via TS1 to form 4 or

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

• structures. HVI reagents are characterized by their diverse reactivity as oxidants and electrophilic reagents. In addition, they are inexpensive, non-toxic and considered to be environmentally friendly. An important application of HVI reagents is the synthesis of halogenated cyclic compounds, in particular

• were synthesised in moderate to excellent yields and enantiomeric excesses. In addition to the synthesis of 6-membered rings, 7-membered hexenamines 7 were synthesised. To the authors’ surprise, reaction conditions for the synthesis of β-fluorinated piperidines 6 afforded no product. The reaction

• instead proceeded with addition of dichloro(pyridine-2-carboxylato)gold(III) complex in combination with silver triflimide, AgNTf2. A range of β-fluoroazepanes 7 were successfully synthesised with high enantiomeric purity in good yields. A mechanism for the synthesis of β-fluorinated piperidines was

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

• well as transition and rare-earth metals [32][33]. There are many comprehensive reviews covering these two areas along with the connection of these ligands to supramolecular and medicinal chemistry [34][35][36]. In addition, calix[4]pyrroles, due to the presence of four accessible inner NHs and well

• addition of furan-based silyloxydiene synthons to a variety of achiral aldehydes using four different calix[4]pyrrole macrocycles (3, 4, 11, and 12) as organocatalysts (Figure 3) [38]. These calixpyrrole macrocycles acted as hydrogen-bond donors, activating substrate aldehydes through hydrogen-bonding

• catalytically inactive, but the mixture of CuCl (7 mol %) and calix[4]pyrrole (14 mol %) resulted in a 74% yield of 1-tosyl-2-phenylaziridine (24). Considering the significant shift (from 7.48 to 9.98) in the N–H signal of calix[4]pyrrole after the addition of CuCl, the authors suggested that calix[4]pyrrole

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

• and resource optimization. In addition, all the target compounds were fully characterized using 1H and 13C NMR spectroscopy and HRMS. It is important to mention that this protocol cannot be considered a true one-pot synthesis, as it requires a solvent exchange between reaction steps (e.g., from

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

• , University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146-0431, USA 10.3762/bjoc.20.255 Abstract Distilled propargyltrichlorosilane with >99% isomeric purity was prepared for the first time, and its asymmetric catalytic regiospecific addition reaction to aldehydes was developed through a

• . Accordingly, the development of efficient access to optically active chiral α-allenic alcohols continues to be of significant interest in organic chemistry [11][12][13]. The asymmetric catalytic addition of allenylation reagents to aldehydes provides direct access to chiral α-allenic alcohols in an

• 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

Extension of the π-system of monoaryl-substituted norbornadienes with acetylene bridges: influence on the photochemical conversion and storage of light energy

• Robin Schulte,
• Dustin Schade,
• Thomas Paululat,
• Till J. B. Zähringer,
• Christoph Kerzig and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 3061–3068, doi:10.3762/bjoc.20.254

• elemental analysis. All products showed the characteristic 1H NMR spectroscopic signals of norbornadienes, in particular two signals at ca. 2.10 ppm and 2.20 ppm (7-CH2) and two broad singlets between 3 and 4 ppm (bridgehead 1- and 4-CH). In addition, typical 13C NMR shifts of the aryl-substituted

• derivatives during the photoreaction, whereas the blue-shifted maximum of the photoproduct was formed. In addition, isosbestic points were observed for the derivatives 1h (A), 1i (B), 1k (D), and 1l (E). The irradiations of the derivatives 1h, 1i, 1k, and 1l were stopped once no more changes of the absorbance

• that the triplet energy of 1i is significantly lower than 2.4 eV and even triplet sensitizers with lower triplet energies than that of [Ru(phen)3](PF6)2 could be employed for this reaction, which might even allow red light-driven switching. In addition to these kinetic studies, the photoisomerization

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• substitution/addition reactions became the standard for end-capping reactions, although a transition metal–catalyzed cross-coupling reaction has also been used to synthesize CD-based rotaxane. Typically, water-soluble components are prepared, after which the Suzuki coupling reaction in water is used to

• depended on the cavity size, the same as small-molecule inclusion. For example, PEG forms stable pseudopolyrotaxane structures with α, β, and γ-CDs, although polypropylene glycol (PPG) only forms a stable pseudopolyrotaxane structure with β-CD [41]. In addition to these linear polymer chains, various types

• synthesis, Harada and co-workers reported the end-capping reaction based on nucleophilic substitution by the amino groups on axle ends (Scheme 2) [43]. Similarly, other highly efficient reactions have been performed as end-capping reactions to produce polyrotaxane [13][14][15]. In addition to the simple

Tunable full-color dual-state (solution and solid) emission of push–pull molecules containing the 1-pyrindane moiety

• Anastasia I. Ershova,
• Sergey V. Fedoseev,
• Konstantin V. Lipin,
• Mikhail Yu. Ievlev,
• Oleg E. Nasakin and
• Oleg V. Ershov

Beilstein J. Org. Chem. 2024, 20, 3016–3025, doi:10.3762/bjoc.20.251

• caused a blue shift of the maximum at 511 nm, and a new maximum in the region of 380–400 nm appeared in the absorption spectra. The intensity of the short-wavelength band also increased upon addition of trifluoroacetic acid. At the same time, a second band centered at 440 nm also appeared in the emission

Tailored charge-neutral self-assembled L₂Zn₂ container for taming oxalate

• David Ocklenburg and
• David Van Craen

Beilstein J. Org. Chem. 2024, 20, 3007–3015, doi:10.3762/bjoc.20.250

• positively charged or charge-neutral, is their metal-driven self-assembly. Unfortunately, this can also be their Achilles' heel, as the underlying coordination bonds are fragile compared to covalent bonds. For example, metallocages can easily break apart by the addition of competitive anions which are highly

• determined by NMR (see Supporting Information File 1, Figures S7, S9, S11, S13, S15, and S17). 1H NMR dicarboxylate binding studies were carried out with oxalate (C22−) and longer variants C(2+n)2− up to adipate (with n = 4). Oxalate addition to [L2Zn2] results in an intermediate exchange with broadened NMR

• guests and competition experiments. 1H NMR titrations with malonate, succinate, glutarate, and adipate showed no clean binding (formation of mixtures) upon addition of these guests as TBA salt to [L2Zn2], with broad regions and multiple sets of signals persisting even after the addition of a large excess

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• range of polymers [1]. They are also applied as curing, hardening and crosslinking agents [2]. Global demand for organic peroxides is expected to increase as the use of engineered plastics increases and production capacity is expanded. In addition, the need for polymers is expected to increase due to

• mainly include: nucleophilic addition or nucleophilic substitution with H2O2 or ROOH [17][18], autoxidation with O2, pericyclic reactions of unsaturated bonds with O3 or O2, and metal-catalyzed peroxidation (Isayama–Mukaiyama hydrosilylperoxidation [19][20], for example) [21][22][23]. As the topic is

• and tert-butylperoxy moiety (Scheme 33) [89]. The mechanism of the process is probably based on the formation of radical species A and B, which disproportionate to form the intermediate C. Sequential addition of sulfonyl and tert-butylperoxy radicals to the double bond of intermediate C leads to

gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• , we observed a striking illustration of this phenomenon. A Michael addition involving gem-difluorovinyl and trifluorovinyl acceptors was successfully achieved, demonstrating high stereoselectivity. This selectivity was further elucidated through theoretical calculations. Using this methodology, a

• series of new α,β-unsaturated amides, both fluorinated and nonfluorinated, were synthesized. Keywords: gem-difluorovinyl Michael acceptors; Michael addition; trifluorovinyl Michael acceptors; α,β-unsaturated amides; Introduction The Michael reaction, characterized by the addition of stable carbon

• advancements have broadened the scope of Michael donors and acceptors to encompass fluorine-containing compounds, enhancing the reaction's utility in synthesizing fluorinated derivatives [7][8]. Shibata and colleagues pioneered the use of fluorinated Michael donors, notably achieving enantioselective addition

4,6-Diaryl-5,5-difluoro-1,3-dioxanes as chiral dopants for liquid crystal compositions

• Maurice Médebielle,
• Peer Kirsch,
• Jérémy Merad,
• Carolina von Essen,
• Clemens Kühn and
• Andreas Ruhl

Beilstein J. Org. Chem. 2024, 20, 2940–2945, doi:10.3762/bjoc.20.246

• from neat chiral mesogens, or through the addition of a chiral dopant to an achiral nematic liquid crystal [5][6]. The ability of the dopant to induce chirality in the nematic phase is defined as the helical twisting power [HTP; β = (pc)−1; with p the helical pitch and c the molar concentration]. The

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• formation of the Nu–Ar product and aryl iodide [21]. Second, the arylation can take place in the presence of a metal catalyst via oxidative addition, followed by reduction elimination [48][49]. Thirdly, it proceeds through a ligand-coupled arylation which involves a five-membered transition state to yield

• additives. An efficient conversion was detected when the substrate contains electron-rich functionalities. In contrast, the yield dropped notably when the amines were substituted with electron-deficient functionalities. In addition, asymmetric diaryliodonium salts were examined, and the transfer of the aryl

• compounds (Scheme 16) [68]. The novel iodine(III) intermediate was generated through nucleophilic substitution of a heteroatom nucleophile, which initiated the reaction. A subsequent aryl migration from the iodine to the heteroatom resulted in the formation of the arylated nucleophile. In addition to

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• morpholine hydrazone derived from 4-nitrobenzaldehyde was selected as a model substrate (Table 1). The latter was engaged in a two-step process: 1) halogenation to provide the corresponding N,N-hydrazonoyl bromide, which will then undergo an anion metathesis upon the addition of AgSCF3 to the reaction

• mixture. When the reaction was conducted in the presence of NBS in acetonitrile for 10 min, followed by the addition of AgSCF3, the desired product was isolated in 91% yield. A total selectivity for the formation of the Z isomer was observed as ascertained by 2D NMR (for more details, see Supporting

Synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives via isocyanide-based multicomponent reactions

• Marzieh Norouzi,
• Mohammad Taghi Nazeri,
• Ahmad Shaabani and
• Behrouz Notash

Beilstein J. Org. Chem. 2024, 20, 2870–2882, doi:10.3762/bjoc.20.241

• addition to the application of isocyanides in a variety of MCRs, one of the unique reactions involves the formation of zwitterions from isocyanides upon reaction with acetylene and active olefin compounds such as alkyl acetylenedicarboxylates and gem-diactivated olefins. Due to having nucleophilic and

• increase and the electron-donating substituents led to a decrease in the reaction efficiency (Scheme 3, 4a–k). In addition, benzothiazepine was used in this protocol and the corresponding pyrrole-fused benzothiazepine was obtained with a yield of 73% (Scheme 3, 4l). Also, various isocyanides were suitable

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• [12][13]. In addition, there are more and more applications in the field of medicinal chemistry, especially for the treatment of cancer [14][15]. In the course of the renewed interest in the chemistry of indigo, indirubin, and isoindigo in the field of cancer research, N-glycosides of these compounds

• steps from indigo (1a). The reaction of 1a with potassium permanganate afforded product 12 which was transformed to dehydroindigo (13) by pyridine-mediated elimination of acetic acid. The reaction of 13 with tetra-O-trimethylsilyl-ʟ-rhamnopyranose (4b) in the presence of trimethylsilyl iodide, addition

• of n-propyl mercaptane with subsequent addition of acetic anhydride, pyridine and KHF2 afforded indigo-N-rhamnoside 5c as a 2:1 mixture of α/β-anomers. The relatively low yield is a result of side reactions and decomposition, due to the rather unstable nature of the product. The reaction of 5c with

Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides

• Baptiste Leroux,
• Alexis Beaufils,
• Federico Banchini,
• Olivier Jackowski,
• Alejandro Perez-Luna,
• Fabrice Chemla,
• Marc Presset and
• Erwan Le Gall

Beilstein J. Org. Chem. 2024, 20, 2834–2839, doi:10.3762/bjoc.20.239

• alkyl iodides [24]. It was indeed noticed that the reactivity of primary iodides in the multicomponent carbonyl alkylative amination (CAA) reaction was quite sluggish compared to the secondary counterparts. In addition, primary alkyl bromides were found to be almost inactive in the process. Therefore

• . In addition, whereas tert-butylzinc iodide was efficient in the multicomponent coupling (99% yield), tert-butylzinc bromide led to a very low yield (16% 5kaa). The coupling presented some other limitations. It was not possible to carry out the reaction when a primary amine was employed. In addition

• significant assets associated to the use of alkyl bromides, which are more easily prepared (or commercially available), less costly, and more stable than the corresponding alkyl iodides. In addition, the reaction can be conducted in commercial THF or 2-MeTHF and without special precautions. We also found a