Ring opening of photogenerated azetidinols as a strategy for the synthesis of aminodioxolanes

• Henning Maag,
• Daniel J. Lemcke and
• Johannes M. Wahl

Beilstein J. Org. Chem. 2024, 20, 1671–1676, doi:10.3762/bjoc.20.148

• by Norrish–Yang cyclization, which employs easily accessible α-aminoacetophenones as starting materials [11][12][13][14][15]. Furthermore, ring-opening reactions of azetidines have been recently achieved using sulfur and oxygen nucleophiles [16][17][18][19][20][21][22][23][24][25]. However, methods

• subsequent ring-opening reactions. In this regard, we uncovered a novel entry to dioxolanes by intramolecular ring opening of azetidines using ketones and boronic acids. Results and Discussion Photocyclization We initiated our study by a systematic investigating of the Norrish–Yang cyclization for the

• infra). Thirdly, we wanted to assess substitution α to the nitrogen (R), as this was thought to impact the stability of the intermediary 1,4-biradical 2 [29][30]. To obtain comparable results, all reactions were performed in a LuzChem photoreactor under identical conditions. Deuterated acetonitrile was

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• contrast to ribosomal peptide biosynthesis, many non-proteinogenic amino acids can be incorporated as building blocks. However, RiPP pathways are more flexible and they represent interesting biotechnological production routes. In this review, we will focus on post-translational methylation reactions. A

• single methyl group has the ability to modulate a drug’s efficacy by orders of magnitude; this occurrence is also called the ‘magic methyl effect’ [14][15]. Compared to chemical methylation reactions, a biocatalytic methylation often offers several advantages. MTs exhibit high selectivity and are

• ) as a co-product, which strongly inhibits various MTs [16][17][18][19]. To overcome these limitations, numerous in situ SAM supply and SAM regeneration systems have been developed [4][20][21][22][23][24][25][26], thereby enabling preparative biocatalytic scale methylation reactions [27]. Such

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• are glycoside hydrolases (GHs) that degrade agarose to smaller oligosaccharides [102]. Marine bacteria of diverse genera produce agarases [103][104][105]. Based on the reactions that they catalyze, bacterial agarases are grouped as α- and β-agarases wherein they hydrolyze α-1,3 linkages and β-1,4

• electron transport in the photosynthetic light reactions by interfering with the synthesis of plastoquinone-9 [17]. Global genome sequence analyses confirmed the ubiquitous presence of biosynthetic gene clusters (BGCs) encoding the production of 26 in diverse marine bacterial species, suggesting it to be a

New triazinephosphonate dopants for Nafion proton exchange membranes (PEM)

• Fátima C. Teixeira,
• António P. S. Teixeira and
• C. M. Rangel

Beilstein J. Org. Chem. 2024, 20, 1623–1634, doi:10.3762/bjoc.20.145

• cyanuric chloride (1) with (4-aminophenyl)methylphosphonate 17 also afforded the disubstituted triazine derivative TP2 (Scheme 5). Other reactions were carried out at different conditions, but they did not afford the desired trisubstituted derivative. The spectroscopic data are in agreement with the

• conditions of the previous reaction, including Na2CO3 as base. These reactions afforded the desired trisubstituted triazine derivatives, compounds TP5 and TP6, respectively, in good yields (>70%) (Scheme 6). The TP5 was also prepared using DIPEA as a base, but in low yield (25%). All spectra of these

• reactions between cyanuric acid (1) and compound 11, using Na2CO3 as base, gave a mixture of products, which were not possible to separate. The data obtained from these mixtures suggest that triazine derivatives with different substitutions patterns are obtained, and that the displacement of the chlorine

pKalculator: A pK_a predictor for C–H bonds

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2024, 20, 1614–1622, doi:10.3762/bjoc.20.144

• . Furthermore, we employ our model on 1043 pKa-dependent reactions (aldol, Claisen, and Michael) and successfully indicate the reaction sites with a Matthew’s correlation coefficient (MCC) of 0.82. Keywords: C–H pKa values; pKa predictor; Introduction Over the years, the ability to selectively break a C–H

• section. We also create a dataset from Reaxys that contains 1043 pKa-controlled reactions. These reactions include 584 aldol, 408 Claisen, and 51 Michael reactions. This dataset is used as an out-of-sample dataset to see how well our ML model predicts the reaction site. Additionally, we use six

• combination with an ML model to predict a variety of properties. These properties encompass the site of metabolism [31][33], the strengths of hydrogen bond donors and acceptors [34][35][36], and the regioselectivity of electrophilic aromatic substitution reactions [14]. Building on the methodology from

Generation of multimillion chemical space based on the parallel Groebke–Blackburn–Bienaymé reaction

• Evgen V. Govor,
• Vasyl Naumchyk,
• Ihor Nestorak,
• Dmytro S. Radchenko,
• Dmytro Dudenko,
• Yurii S. Moroz,
• Olexiy D. Kachkovsky and
• Oleksandr O. Grygorenko

Beilstein J. Org. Chem. 2024, 20, 1604–1613, doi:10.3762/bjoc.20.143

• showed biological activity according to the ChEMBL database. Keywords: fused rings; heterocycles; imidazoles; isonitrile; multicomponent reactions; Introduction Multicomponent reactions are widely recognized as a powerful source of biologically active compounds, in particular, for drug discovery

• purposes [1][2][3][4][5][6]. Isonitrile-based multicomponent reactions, such as the Groebke–Blackburn–Bienaymé (GBB) reaction, is an important tool in chemical synthesis providing easy access to a huge compound diversity and complexity [7][8][9][10][11][12][13][14][15][16][17]. Essentially, the GBB

• -component reactions are very effective for the generation of synthetically tractable ultra-large chemical space [30][31][32]. Such virtual but readily accessible (REAL) compound libraries demonstrated excellent performance in early drug discovery programs when combined with modern computational tools such

Supramolecular assemblies of amphiphilic donor–acceptor Stenhouse adducts as macroscopic soft scaffolds

• Ka-Lung Hung,
• Leong-Hung Cheung,
• Yikun Ren,
• Ming-Hin Chau,
• Yan-Yi Lam,
• Takashi Kajitani and
• Franco King-Chi Leung

Beilstein J. Org. Chem. 2024, 20, 1590–1603, doi:10.3762/bjoc.20.142

• specified. All reactions were performed under nitrogen unless otherwise specified. Analytical thin-layer chromatography (TLC) was performed with Macherey-Nagel silica gel 60 UV254 aluminum plates, and visualization was accomplished by UV light (254 nm or 365 nm) or by staining with phosphomolybdic acid and

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

• reactions, we explored different pathways of the reaction mechanisms for the ortho-halogenation using 2-naphthol as a model substrate (Scheme 2). In such a way, we found a reaction pathway that was energetically favored. Based on our successful procedure for chlorination, we also developed an efficient

• influence of PIDA and PIFA in the chlorination and bromination reactions. Interestingly, we found an excellent agreement between the theoretical predictions and the experimental results. Results and Discussion Computational details The equilibrium geometry of reagents and products, the stationary points

• presence of PIDA. Meanwhile, formation of TS3 (ΔG‡ = 21.3 kcal/mol) is the limiting step of the mechanism in the presence of PIFA. Then, in the presence of the PIFA/AlBr3 system, bromination of 2-naphthol is the energetically most favored pathway. Although all these reactions occur through four transition

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• pharmaceuticals, and the reductive syntheses of these heterocycles from pyridines and quinolines have been well studied [12]. Although these transformations have been studied intensively, such reductive reactions usually require harsh reaction conditions such as high reaction temperatures and high pressure of

• reactions. As PEM reactors are flow reactors, they have an advantage over batch reactors in terms of continuous production. Several reductive transformations taking advantage of the characteristics of the PEM reactor have been reported in recent years. For example, Atobe et al. reported the electrocatalytic

• ]. As mentioned above, there have been several reports on reductive reactions using PEM reactors; however, the application of PEM reactors for precise chemical transformations remains limited. To the best of our knowledge, no reports are available on the efficient reduction of cyanoarenes, quinolines

Mining raw plant transcriptomic data for new cyclopeptide alkaloids

• Draco Kriger,
• Michael A. Pasquale,
• Brigitte G. Ampolini and
• Jonathan R. Chekan

Beilstein J. Org. Chem. 2024, 20, 1548–1559, doi:10.3762/bjoc.20.138

• (sodium (2,4-dinitro-5-fluorophenyl)-ʟ-alaninamide) in acetone were added. The reaction mixture was incubated at 40 ºC for 1 h with periodic agitation. The reactions were quenched by adding 10 µL of 2 M HCl and dried under a nitrogen stream. Dried samples were dissolved in 1.7 mL of MeOH and injected both

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• compound, carry that functional group through synthesis and also protect any potentially labile group that would otherwise displace during the installation of the fluorine atom [6][7][8]. Therefore, methodologies for the selective C–H fluorination represent a valuable class of reactions [1][9][10], for

• )–H functionalisation reactions in drug-discovery campaigns [17]. Although much is unknown about the precise details, several benzylic fluorides have been reported to be unstable, which is an effect that is apparently dependent on the substitution of the ring. While primary benzylic fluorides are

• predominately considered to be stable to isolation conditions, secondary and tertiary suffer from the elimination of HF, especially in the presence of silica gel or glass vessels. Therefore, benzyl fluorides have been derivatised, for example in C–O, C–N and C–C bond-forming reactions [18][19][20], thereby also

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• -covalent catalysis via bifunctional hydrogen-bonding organocatalysts. The C-4 nucleophilicity of pyrazolin-5-ones was also explored in enantioselective reactions with α,β-unsaturated carbonyl compounds through covalent catalysis with chiral amine-based catalysts; however, it has achieved limited success

• [10][11][12][13][14][15][16][17][18][19][20][21]. Among the developed organocatalyzed enantioselective 1,4-addition reactions of pyrazolin-5-ones, the catalytic asymmetric reactions of pyrazolin-5-ones with α,β-unsaturated ketones are comparatively less studied. In 2009, Zhao’s group were the first

Tetrabutylammonium iodide-catalyzed oxidative α-azidation of β-ketocarbonyl compounds using sodium azide

• Christopher Mairhofer,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1510–1517, doi:10.3762/bjoc.20.135

• accessible starting materials. Our group has a longstanding research interest in α-heterofunctionalization reactions under oxidative conditions [37][38][39] and we [30], as well as others [28][29][31], have recently also explored the use of simple quaternary ammonium iodides for oxidative α-azidations of

• conditions are best-suited. We have recently established the use of dibenzoyl peroxide (DBPO) as a very powerful oxidant for oxidative heterofunctionalization reactions using simple nucleophilic inorganic salts as heteroatom transfer reagents [39][41]. This was successfully demonstrated for the non-catalyzed

• reagent/catalyst system allows indeed for high yielding direct α-azidations of different (cyclic) β-ketocarbonyl derivatives (Scheme 1C), thus resulting in an operationally simple protocol to access α-azidated carbonyl derivatives. In addition, we have also carried out some test reactions using NaNO2

Towards an asymmetric β-selective addition of azlactones to allenoates

• Behzad Nasiri,
• Ghaffar Pasdar,
• Paul Zebrowski,
• Katharina Röser,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1504–1509, doi:10.3762/bjoc.20.134

• -selective manner with moderate levels of enantioselectivities (up to 83:17 er). Furthermore, the obtained products can be successfully engaged in nucleophilic ring opening reactions, thus giving highly functionalized α-amino acid derivatives. Keywords: allenoates; amino acids; azlactones; organocatalysis

• variety of asymmetric α-carbo- and α-heterofunctionalization reactions by utilizing different catalysis strategies [20][21][22]. We have recently carried out systematic investigations concerning the syntheses of advanced β-AA by means of asymmetric α-carbofunctionalization reactions and during these

• derivatives by means of nucleophilic azlactone-opening reactions. Gratifyingly primary amines can be easily utilized under reflux conditions to access the amide derivatives 6a and 6b straightforwardly (Scheme 3), thus demonstrating the versatility of compounds 5 to access more complex acyclic α-AA derivatives

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• -known to be highly susceptible to electroplating on the cathode and thus require the use of ligands to avoid detrimental cathode deposition during electrolysis (Table 1, entry 3). In addition, we discovered that the additional use of DMF as co-solvent is beneficial to the reaction efficiency–reactions

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• binding of one isomer only. Experimental General experimental details. Commercially available solvents and reagents were used without further purification. Reactions carried out under anhydrous conditions are performed under argon in glassware previously dried in an oven. DMF and THF were previously dried

• through alumina or molecular sieves-containing cartridges using a solvent purificator MBRAUN SPS-800. All the reactions with azobenzene-containing substrates were carried out in the dark. Reactions were monitored by TLC on Silica Gel 60F-254 plates with detection by UV (254 nm or 365 nm) or by spraying

• melting point capillary apparatus. Specific optical rotations were measured in solution using sodium light at 589 nm where no absorption occurred for all compounds. Absorption spectra were recorded on a Cary-5000 spectrophotometer from Agilent Technologies. Photochromic reactions were induced in situ by a

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• are not always readily accessible. Typically, the preparation methods involve SNAr reactions with N-centered nucleophiles [5], nitroarene reduction [6] and transition metal (e.g., Pd, Cu)-catalyzed C–N cross coupling of aryl halides, aryl sulfonates or arylboronic acid reagents with ammonia or NH

• -cyclohexenones with nucleophilic nitrogen sources like ammonia, amines and hydrazine [14]. The reactions were regarded as via simple nucleophilic addition along with Pd-catalyzed dehydrogenative aromatization in these elegant works (Scheme 1, (1)). The Semmler–Wolff reaction is often implemented in the synthesis

• of 3-cyclohexanones caused by the strong electron-withdrawing effect, which made 3a as a base rather than a nucleophile under such conditions. The location of substituents was found to affect the product yield greatly, considering that the reactions worked better with 3-cyclohexenones bearing a para

Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• of Arts and Sciences, Amasya University, Amasya, Turkey 10.3762/bjoc.20.129 Abstract Herein, we report the first environmentally friendly systematic fluoroalkoxylation reactions in bicyclic systems. New oxyfluorination products were obtained with excellent yields (up to 98%) via Wagner–Meerwein

• used as nucleophiles. First, optimization experiments were carried out for fluoroalkoxy reactions with benzonorbornadiene (1a, Table 1). As a result of experiments conducted in six different solvents at room temperature with 1.0 equivalent of selectflor and 1.0 equivalent of methanol, it was observed

• benzonorbornadiene (1a), the reactions of benzonorbornadiene (1a) with selectfluor and 10 different alcohol derivatives were examined (Scheme 1). Under optimum conditions, fluoroalkoxy compounds 3a–j were obtained in excellent yields (91–98%) by the reaction of benzonorbornadiene (1a) with selectfluor and alcohols

Synthesis of 4-functionalized pyrazoles via oxidative thio- or selenocyanation mediated by PhICl₂ and NH₄SCN/KSeCN

• Jialiang Wu,
• Haofeng Shi,
• Xuemin Li,
• Jiaxin He,
• Chen Zhang,
• Fengxia Sun and
• Yunfei Du

Beilstein J. Org. Chem. 2024, 20, 1453–1461, doi:10.3762/bjoc.20.128

• no significant influence on the outcome of the reactions of various N-aryl-substituted pyrazoles with a methyl group at the ortho-, meta- or para- positions of the phenyl group. Next, N-arylated substrates bearing electron-withdrawing groups (-F, -Cl, -Br, -I, -CF3, -NO2) were tested, and the desired

Predicting bond dissociation energies of cyclic hypervalent halogen reagents using DFT calculations and graph attention network model

• Yingbo Shao,
• Zhiyuan Ren,
• Zhihui Han,
• Li Chen,
• Yao Li and
• Xiao-Song Xue

Beilstein J. Org. Chem. 2024, 20, 1444–1452, doi:10.3762/bjoc.20.127

• hypervalent iodine(III) reagents has been developed [12][13][14][15][16][17] (Figure 1), including the well-known Zhdankin reagents [13] and Togni reagents [14]. These reagents are popularly used as electrophilic group transfer reagents [18][19] in a variety of reactions, such as C–H functionalization [20][21

• applications [27][28][29][30]. For example, hypervalent bromine(III) reagents enable C–H amination and alkene aziridination reactions without the need for additional Lewis acid activation [31][32][33]. However, challenges in the synthesis and stabilization of cyclic hypervalent bromine and chlorine reagents

Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction

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

Beilstein J. Org. Chem. 2024, 20, 1436–1443, doi:10.3762/bjoc.20.126

• been known as indispensable building blocks in modern organic chemistry. Many isocyanide-based carbon–carbon and carbon–heteroatom bond forming reactions have been developed in fascinating ways over the past decades [4][5][6]. The famous multicomponent reactions such as Passerini reaction, Ugi reaction

• generated by addition reaction of isocyanides to electron-deficient alkynes, which were sequentially trapped by various electrophiles and nucleophiles to give versatile acyclic and heterocyclic compounds [15][16][17][18][19][20][21][22][23][24][25][26]. In recent years, many multicomponent reactions based

• can act as an activated enamino unit and electron-rich dienophile to take part in some synthetic reactions [36][37][38][39]. In recent years, 5,6-unsubstituted 1,4-dihydropyridines have been recognized as the reactive electron-rich dienophiles, which proceeded several Povarov reactions with various 1

A comparison of structure, bonding and non-covalent interactions of aryl halide and diarylhalonium halogen-bond donors

• Nicole Javaly,
• Theresa M. McCormick and
• David R. Stuart

Beilstein J. Org. Chem. 2024, 20, 1428–1435, doi:10.3762/bjoc.20.125

• Discussion This study evolved from a parallel exploration of reactions involving unsymmetrical phenyl(mesityl)halonium salts, i.e., Ph(Mes)X+. DFT analysis revealed similar structural trends to our previous work [21] when we expanded the halogens to include astatine (At). Due to its radioactivity and short

Synthesis of cyclic β-1,6-oligosaccharides from glucosamine monomers by electrochemical polyglycosylation

• Md Azadur Rahman,
• Hirofumi Endo,
• Takashi Yamamoto,
• Shoma Okushiba,
• Norihiko Sasaki and
• Toshiki Nokami

Beilstein J. Org. Chem. 2024, 20, 1421–1427, doi:10.3762/bjoc.20.124

• polymerization of organic molecules is an important strategy for the preparation of functional materials, such as conducting polymers [1][2][3][4][5]. Electrochemical reactions can be controlled by electric potential or current, electrodes, and electrolytes, which are not available in conventional chemical

• reactions. Therefore, electrochemical polymerizations can be utilized for selective synthesis. Cyclic oligosaccharides are an important class of host molecules, and some natural cyclic oligosaccharides are produced by enzymatic processes. However, the corresponding chemical syntheses are still primitive [6

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• intermediates through selective FeCl3-catalyzed intramolecular N-annulation. Keywords: α-aminoacetals; fused-ring systems; heterocyclic hemiaminals; heterocyclic N,O-aminals; multicomponent reactions; Introduction N-Fused heterocycles are ubiquitous within crucial molecules, including biologically active

• was incremented with respect to 6a (entry 4, Table 1). Rising the amount of FeCl3 to 30 mol %, the reaction was complete in 2 hours, enhancing the yield of 5a (73%) and minimizing the yield of 6a (8%) (entry 5, Table 1). In reactions carried out in acetonitrile (ACN) or tetrahydrofuran (THF) the yield

• dissolved in DCM (10 mL), FeCl3 (30 mol %) added and magnetically stirred at room temperature. Within 2–30 h, the reactions went to completion (TLC monitoring), affording, at last, N,O-aminals 5a–r (42–82%) and the corresponding hemiaminals 6a–p (4–35%) after column chromatography (Scheme 3). An increased

Hypervalent iodine-catalyzed amide and alkene coupling enabled by lithium salt activation

• Akanksha Chhikara,
• Fan Wu,
• Navdeep Kaur,
• Prabagar Baskaran,
• Alex M. Nguyen,
• Zhichang Yin,
• Anthony H. Pham and
• Wei Li

Beilstein J. Org. Chem. 2024, 20, 1405–1411, doi:10.3762/bjoc.20.122

• .20.122 Abstract Hypervalent iodine catalysis has been widely utilized in olefin functionalization reactions. Intermolecularly, the regioselective addition of two distinct nucleophiles across the olefin is a challenging process in hypervalent iodine catalysis. We introduce here a unique strategy using

• tethered with a nucleophile to avoid the lack of regiochemical additions (Scheme 1a) [21][22][23][24][25][26][27][28]. Intermolecular hypervalent iodine-catalyzed olefin difunctionalizations have been realized for olefin dihalogenation, dioxygenation and diamination reactions, where often the same type of

• electrophilicity of the halogen source could be modulated to render different classes of nucleophiles for additions onto olefins in various olefin difunctionalization reactions [48][49][50][51][52]. In particular, we demonstrated that addition of either a Lewis acid or a base could activate amides to couple with