Metal catalyst-free N-allylation/alkylation of imidazole and benzimidazole with Morita–Baylis–Hillman (MBH) alcohols and acetates

• Olfa Mhasni,
• Jalloul Bouajila and
• Farhat Rezgui

Beilstein J. Org. Chem. 2023, 19, 1251–1258, doi:10.3762/bjoc.19.93

• Toulouse, France University of Tunis El Manar, Laboratory of Organic Chemistry, Faculty of Sciences, Campus, 2092 Tunis, Tunisia 10.3762/bjoc.19.93 Abstract A highly α-regioselective N-nucleophilic allylic substitution of cyclic MBH alcohols and acetates with imidazole or benzimidazole, in toluene at

• various nucleophiles, including C- and heteronucleophiles, such as compounds bearing –OH, –SH, and –NH groups [4][5][6][7]. Among them, the carbon–nitrogen bond formation through N-nucleophilic substitution reactions plays a central role for the synthesis of numerous compounds exhibiting various

• precursors in nucleophilic allylic substitution reactions with amines, presumably due to the perceived poor leaving group ability and low reactivity of the hydroxy group. Interestingly, the direct nucleophilic substitution of the corresponding alcohols has drawn much attention because of the availability of

Selective construction of dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] via three-component reaction

• Ziying Xiao,
• Fengshun Xu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1234–1242, doi:10.3762/bjoc.19.91

• , the nucleophilic addition of the amino anion to the carbonyl group in the of 1,3-cyclohexanedione scaffold resulted in cyclic intermediate C. Thirdly, the elimination of water from intermediate C gave the isolated product 3. In the case of the intermediate B2 with a benzoyl group, there are two kinds

Radical ligand transfer: a general strategy for radical functionalization

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

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

• indicative of a carbocationic pathway are not observed, suggesting that RPC does not occur. Further, the inability of ATRA products to undergo SN2 with the added nucleophiles under our reaction conditions is inconsistent with a tandem ARTA/nucleophilic displacement alternative mechanism. Finally, a

• proposed to follow one of two pathways: formation of a carbocation through RPC followed by nucleophilic attack or direct RLT from a redox-active metal complex. Preliminary evidence for a radical decarboxylation/RLT cascade was reported in 1965, when Kochi demonstrated decarboxylative chlorination of

• various acids with lead(IV) tetraacetate in the presence of lithium chloride (Scheme 4) [40][41]. Nucleophilic lithium chloride was used as the chlorine atom source for this transformation. In the representative scope of this transformation, primary and secondary chlorides could be formed in relatively

Cyanothioacetamides as a synthetic platform for the synthesis of aminopyrazole derivatives

• Valeriy O. Filimonov,
• Alexandra I. Topchiy,
• Vladimir G. Ilkin,
• Tetyana V. Beryozkina and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2023, 19, 1191–1197, doi:10.3762/bjoc.19.87

• the data given in the current work. The formation of 3,5-diaminopyrazoles 4a–c occurs, presumably, as a result of a sequential attack of electrophilic carbon atoms of the cyano- and thioamide groups of thioamides 1a–c by nucleophilic nitrogen atoms of hydrazine (3a) and is accompanied by the

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

• Carlee A. Montgomery and
• Graham K. Murphy

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

• literature to-date has shown that the vast majority of reactions follow the reductive elimination pathway to produce 4. However, a clear exception to this is in reactions with nucleophilic fluoride or [18F]fluoride, which reductively eliminate to exclusively generate fluoroarenes (e.g., 5). The rationale for

• previously proposed for hypervalent iodine compounds [9][117][118][119], Moriarty proposed a carbene-free mechanism for the formation of 11 [113]. In this, the nucleophilic olefin first attacked the electrophilic iodine center to form zwitterion 15, which closed to produce iodocycle 16 and then underwent

• intramolecular cyclopropanation of iodonium ylides (left); and, stepwise intermolecular cycloadditions with olefins (right). Concerted cycloaddition pathway for the metal-free, intramolecular cyclopropanation of iodonium ylides. Nucleophilic (top) and electrophilic (bottom) addition pathways proposed by Koser

Retraction: One-pot odourless synthesis of thioesters via in situ generation of thiobenzoic acids using benzoic anhydrides and thiourea

• Mohammad Abbasi and
• Reza Khalifeh

Beilstein J. Org. Chem. 2023, 19, 1170–1170, doi:10.3762/bjoc.19.85

• Mohammad Abbasi Reza Khalifeh Chemistry Department, Faculty of Sciences, Persian Gulf University, Bushehr 75169, Iran Department of Chemistry, Shiraz University of Technology, Shiraz, Iran 10.3762/bjoc.19.85 Keywords: benzoic anhydride; Michael addition; nucleophilic displacement; thioester

Selective and scalable oxygenation of heteroatoms using the elements of nature: air, water, and light

• Damiano Diprima,
• Hannes Gemoets,
• Stefano Bonciolini and
• Koen Van Aken

Beilstein J. Org. Chem. 2023, 19, 1146–1154, doi:10.3762/bjoc.19.82

• nucleophilic attack by water. The superoxide first abstracts a proton to form the perhydroxyl radical VII followed by hydrogen atom abstraction from intermediate VIII to yield sulfoxide IX. The generated hydrogen peroxide decomposes into water and oxygen. The novel proposed pathway can either be dominant or

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• ). Nucleophilic addition of the amine to the acyl radical and amine-assisted intermolecular proton transfer [84] generates the α-hydroxy radical 24 from which formation of the amide 25 proceeds either via i) oxidation by [Ir2]+ and deprotonation or ii) radical chain propagation [85]. Electron-deficient, electron

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

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

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

• ]. The well-known Huisgen 1,4-dipoles have a special kind of zwitterionic intermediates and are usually prepared by a nucleophilic addition of pyridine, quinoline, isoquinoline and other aza-arenes to electron-deficient alkynes [4][5][6][7][8]. The reactive Huisgen 1,4-dipoles have been widely employed

• -configured. For explaining the formation of the various cyclic compounds, a plausible reaction mechanism was proposed on the base of the previously reported works [41][42][43][44] and the present experiments (Scheme 2). Initially, the nucleophilic addition of isoquinoline to dimethyl acetylenedicarboxylate

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• -bonding interactions to facilitate a highly face-selective nucleophilic attack by π-nucleophile to the cyclic imine (see transition state 22’ in Scheme 7a). The BINOL-derived chiral phosphoric acid P8 was employed as the asymmetric organocatalyst for this transformation to construct the heterodimerized

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

• Dileep Kumar Singh and
• Rajesh Kumar

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

• the ability of MgI2 etherate to act as a Lewis acid activator. The iodine counterion is coordinated to the Lewis basic oxygen atom of the acetal group to give the more Lewis acidic cataonic Mg-coordinated intermediate A. Intermediate A upon nucleophilic reaction with amines 20 yields B, which upon

• hydrolysis of 2,5-DMTHF (2), which provide intermediate C after the removal of methanol in the presence of CuCl2. In the next steps, nucleophilic addition reaction of amines 34 with intermediate C, dehydration, and intramolecular aromatization affords N-substituted pyrroles 35. In 2018, Patil and Kumar [70

• by a water molecule to form intermediate B. Further, dehydration and protonation leads to the formation of intermediate E. Nucleophilic attack of amine 36 on E then affords intermediate F. Finally, protonation, cyclization, and dehydration afford N-substituted pyrrole 37. The authors also

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• easily generate reactive open-shell radical species and/or intermediates. The substrate is consequently activated for bond cleavage, atom abstraction, or nucleophilic or electrophilic attack. After quenching, the oxidized or reduced photocatalyst regains or loses an electron to return to the starting

• the importance of steric effects [99]. Indeed, while the addition of the nucleophilic α-amino radical to the α-styrenyl position affords the 6-membered ring (kinetic product via intramolecular 6-exo-trig ring closure) [100] the resulting radical is unstabilized, the 7-membered ring (obtained via

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• compounds to give diarylated (oxoalkyl)malonates [6]. In the reaction using tin(II) chloride as the Lewis acid, the ring opening and nucleophilic attack of the nitro group occur, to produce functionalized isoxazolines (reaction d) [7]. In contrast, denitration under basic conditions generates highly

• ) halogenation, and 3) ring closure (Scheme 2). β-Nitrostyrene 2 serves as an appropriate acceptor for conjugate addition by diethyl malonate (3a) to afford adduct 4a, in which the methine group flanked by two carbonyl groups is readily halogenated, and the subsequent intramolecular nucleophilic substitution by

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• involves the initial formation of π-complex A via activation of the alkyne by Pd. Then, in case of N-methylpyridinium salt 82, in presence of CuBr the pyridine–Cu(I) complex 87 is formed through C–H activation that further undergoes nucleophilic attack to the coordinated alkyne in a trans-manner to give Pd

• plays a role as an activator and is subsequently eliminated via deoxygenative elimination furnishing the C-2-functionalized pyridines 167. The reaction mechanism (Scheme 32b) involves the initial C–H-cupration of 166 producing an oxazolyl–copper intermediate 168. Nucleophilic addition followed by C–H

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

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

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

• nitrogen and carbonyl oxygen, generating both nucleophilic and electrophilic centers, i.e., a free amino group and protonated carbonyl group, which is much more prone to nucleophilic attack than a carbonyl group itself. Quantum calculations (see the left side of Figure 2) show that the relative stabilities

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• their unique stability, defined reactivity, and versatility in organic synthesis [2]. Leveraging their electron-deficient nature, N-arylsulfonylimines are widely used in organic transformations including nucleophilic addition, cycloaddition, imino-aldol reaction, ene reactions, aza-Friedel–Crafts

• nucleophilic addition and as a result the corresponding cyclized product is not formed. The synthesis of these nitrogen heterocycles signifies the innate ability of in situ-generated N-arylsulfonylimines in a variety of reactions with various ortho-substituted anilines without the need for pre-isolation or

• -arylsulfonylimine 2, generated in situ from the corresponding N-(arylsulfonyl)benzylamine 1, undergoes transimination with the ortho-substituted aniline 3 to form imine 3ab via 3aa. Subsequent intramolecular nucleophilic addition in imine 3ab produces intermediate 3ac, which upon oxidation delivers the desired N

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• reaction (pathway A) via ate complex 11a [10] of the electron-rich, more nucleophilic (p-methoxyphenyl)boronic acid (2b), which outcompetes the palladium-catalyzed pathway B (Scheme 2b). In turn, suppression or at least a significant deceleration of the uncatalyzed background reaction should lead to an

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• yields with moderate to good diastereoselectivities via Michael addition and nucleophilic addition–elimination (Scheme 17) [39]. The synthesis is a [5 + 2] annulation fashion. The reactions of 2-phenyl/alkoxy-4H-benzo[d][1,3,2]dioxaphosphinin-4-ones 82 and dialkyl 2-benzylidenemalonates 78 produced

• '-carboxylates 83 in 5–10% yield as byproducts. The major products 84 were generated via Michael addition and the nucleophilic addition–elimination of the carbanion of the generated enolate moiety, while the oxyanion of the enolate moiety attacked the phosphorus to form the byproducts 83 (Scheme 18) [40][41

• ]. 2.2 Synthesis via [6 + 1] and [7 + 1] annulations The reactions of cyclohex-2-enone (87) and cyclohept-2-enone (88) with dimethyl phosphonate yielded dimethyl bicyclic phostone-phosphonates 89 and 90 under basic conditions in 59% yield via Michael addition, the nucleophilic hydrophosphonylation, and

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

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

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

• direction of nucleophilic addition of alcohols to FPD species was observed earlier on the example of 5-oxa-FPDs II and was found to be reversible [33][53][54]. We isolated products 5a,b,e to study their chemical behavior in solutions. We found that when compounds 5a,b,e were dissolved in anhydrous solvents

• isolated yield of compound 3aa was 50%. However, under such conditions, a longer reaction time was required (about 3 h, UPLC–UV–MS monitoring). Then, to expand the scope of the developed approach to PBTAs, we examined several more groups of nucleophilic reagents. For these purposes, we carried out a test

• room temperature for 24 h), a mixture of unidentified substances was formed. Interestingly, in the reaction of APBTT 1a with morpholine, we succeeded to isolate the product 10a (Scheme 15) [56]. Product 10a was formed in a result of a nucleophilic attack of morpholine on the C1 position of APBTT 1a

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

• Péter Kisszékelyi and
• Radovan Šebesta

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

• , and Mannich-type reactions, Michael addition, nucleophilic substitutions, cyclopropanations, and reactions with carbocations. The field of asymmetric conjugate addition with its extension into enolate trapping reactions began to develop approximately in 1996. In this review article, we analyze more

• addition with Grignard reagents Feringa and co-workers realized the tandem conjugate addition of Grignard reagents to 4-chlorocrotonates 46 [42]. The enolate 47, which was formed in this process, underwent an intramolecular nucleophilic substitution to form cyclopropane derivatives. Thioesters, esters as

• structurally different Michael acceptors were successfully applied. Their work also included a 3 mmol scale-up (62%, 87% ee, dr >20:1) and various derivatizations of the Mannich products. Furthermore, they have also attempted a multi-electrophile cascade reaction, which harnesses the nucleophilic nature of the

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• as the starting platform for the modification of an amino acid moiety by nucleophilic substitution and addition reactions, including electrochemically induced processes [5][16][17][18][31]. The electrochemical behavior of the new complexes was investigated to get an experimental support for their

• oxidative stability. The reactivity of the glycine and dehydroalanine complexes in the nucleophilic functionalization of amino acids was compared to the corresponding derivatives of the parent ligand L1. The results clearly demonstrated the advantages of the new complexes as stereocontrolling templates

• techniques; for details, see Supporting Information File 1); [α]D20 = 2127 (MeOH). To test the stereocontrolling efficiency of the new ligand L7 and to obtain new cysteine Ni–Schiff base derivatives (RCysNi)L7 which are of practical interest, complex (ΔAlaNi)L7 was involved in a nucleophilic addition as

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

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

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

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

• coordinate to the bicyclic alkene forming 91. Migratory insertion of the olefin affords 92 which undergoes intramolecular nucleophilic addition followed by protodemetalation and elimination of MHP to afford 94. Base-mediated ring opening of the bridging ether generates 95 which undergoes an elimination

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• trifluoromethylthiolation of azacalix[1]arene[3]pyridines by C–H bond activation using a complex of Cu(ClO4)2·6H2O and the shelf-stable Me4NSCF3 [115][116] as a nucleophilic source of SCF3 (Scheme 3) [100]. Within these conditions, a set of six azacalix[1]arene[3]pyridines bearing electron-donating groups, halogens or

• the presence of an electrophilic source or an oxidation/ligand exchange in the presence of a nucleophilic source (i.e., AgSCF3) and an oxidant (B in Scheme 4). Finally, after a reductive elimination step, the expected functionalized product 6 is obtained and the palladium catalyst is regenerated. In

• year, the group of Huang reported an elegant and straightforward palladium(II)-catalyzed ortho-selective trifluoromethylthiolation of arenes bearing various directing groups using the nucleophilic trifluoromethylthiolating source AgSCF3 in combination with Selectfluor® as oxidant (Scheme 6, 29 examples

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

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

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

• ]. Based on its structure, many other inhibitors have been developed, such as vinyl sulfones, fluoromethyl ketones, and semicarbazides [8][9]. These inhibitors covalently bind to the nucleophilic thiol group of Cys234 in the active site of cathepsin C via a thioether bond. Phosphonates have been identified

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

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• hydroalumination of the alkyne 1, followed by Al‒C/B‒H exchange with HBpin, to give the alkenylboronic ester 3 and regenerate the aluminium hydride 81 (Scheme 19c). Single-turnover experiments and a lack of observable H2 production supported this hypothesis. It should also be noted that nucleophilic bases