Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• azido amine intermediate INT-3 can be formed via vinylic substitution of INT-1 with an azide which can cyclize to form INT-4 that subsequently aromatizes to afford product 3 (route B). To demonstrate the applicability of this method, a scale-up reaction was performed using 150 mg of the limiting reagent

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• succeeded in synthesizing various diaryl(alkyl) sulfides 5 through the sulfenylation of unactivated arenes 4 with an electrophilic sulfur reagent in the presence of a palladium catalyst (Scheme 3) [45]. In the second phase, dibenzothiophene derivatives 6 were obtained via subsequent intramolecular arylation

• is noteworthy that the use of diphenyl disulfide as a sulfenylating agent was not effective in this protocol. N-(Aryl/alkylthio)phthalimide as an efficient sulfenylating reagent could also react with indoles to produce 3-thioindoles in the presence of 0.5 mol % of MgBr2, as a Lewis acid [68

• azepane. A possible mechanism was suggested for this Lewis base catalysis system. Methanesulfonic acid (MsOH) activated reagent 14, which coordinated with the Lewis base (S)-E, to form complex I. Then, the transfer of the sulfenium ion to the alkene resulted in chiral thiiranium ion II. Capture of the

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• enolate and a new R• that propagates the radical chain (Scheme 1). Initiation occurs upon oxidation of the dialkylzinc reagent by oxygen. The feasibility of such 1,4-addition reactions is fully reliant on the ease of the intermediate enoxyl radical to undergo alkylzinc-group transfer. Secondary α-carbonyl

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• reagents, are commonly used in conjugate addition reactions. In the presence of Grignard reagents, the NHC-precursor salts do not require an addition of base as the Grignard reagent itself performs this role. In this way, Tomioka and co-workers [57] were able to achieve excellent regio- and

• amidating reagent leading to the isolation of copper–arylcarbamato species and the desired product. The developed amidation protocol works highly efficiently and selectively over a broad range of substrates including polyfluorobenzenes, azoles, and quinoline N-oxides (Scheme 74). 2.10 C(sp2)–H thiolation

One-pot nucleophilic substitution–double click reactions of biazides leading to functionalized bis(1,2,3-triazole) derivatives

• Hans-Ulrich Reissig and
• Fei Yu

Beilstein J. Org. Chem. 2023, 19, 1399–1407, doi:10.3762/bjoc.19.101

• reaction time and the fairly high amount of catalyst employed. As an alternative method, which should be more chemoselective, we examined the reduction with samarium diiodide [60]. This versatile one-electron transfer reagent is known to cleave N–O bonds with high selectivity [61][62] and was applied

Visible-light-induced nickel-catalyzed α-hydroxytrifluoroethylation of alkyl carboxylic acids: Access to trifluoromethyl alkyl acyloins

• Feng Chen,
• Xiu-Hua Xu,
• Zeng-Hao Chen,
• Yue Chen and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2023, 19, 1372–1378, doi:10.3762/bjoc.19.98

• elegant strategies on direct conversion of in situ-activated carboxylic acids for ketone synthesis [27][35][38], we chose dimethyl dicarbonate (DMDC, A1) as the activating reagent. To our delight, the reaction of 1a and 2 in the presence of NiBr2(dtbbpy) (10 mol %), Hantzsch ester (HE) and A1 in DMAc

• -difluoroethoxyphthalimide as the fluoroalkylating reagent failed to afford the desired product. According to our previous work [39] and literature precedent [27][35][38], a possible mechanism is proposed in Figure 2. The interaction between 2 and HE generates an electron donor–acceptor (EDA) complex A, which undergoes a

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• the alcoholate reacted with 1-iodohexadecane to produce 3.3 in 50% yield. The phosphocholine moiety was incorporated by using 2-bromoethyl dichlorophosphate as a key reagent and following a previously reported sequence [67]. The debenzylation by using hydrogenolysis conditions produced 3.5 in 75% to

• method was developed for the incorporation of the phosphocholine polar head group that makes use of the phosphoramidite 8.2 which is a weakly air sensitive reagent [85]. This method was applied for the synthesis of PAF as illustrated in Figure 8 [86]. The alcohol 8.1 reacted with 8.2 in the presence of

• incorporation of a phenyl group between the glycerol and the lipid chain. The lipid chain was bonded to the aromatic ring in either ortho-, meta-, and para-position [91]. The incorporation of a phenyl moiety starts with the reaction of the Grignard reagent formed from 4-bromoanisole (10.1, the other isomers 2

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

• 5a [27] as the model substrate bearing a good leaving group, with imidazole (2a, 2 equiv) as a powerful nucleophilic reagent. The reaction was achieved with no need of a catalyst or any additive in toluene at reflux affording within 24 h the SN2-type product 6a in 82% yield (Table 1, entry 1

Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

• Alessandro Brusa,
• Debora Iapadre,
• Maria Edith Casacchia,
• Alessio Carioscia,
• Giuliana Giorgianni,
• Giandomenico Magagnano,
• Fabio Pesciaioli and
• Armando Carlone

Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92

• as a reagent has always been challenging. The low boiling point and high volatility pose a problem with its handling and safety. The small steric hindrance gives rise to a high reactivity both as an electrophile and as a pro-nucleophile, hampering chemoselectivity (further to side reactions such as

• nitroalkene derivatives with low reagent excess and high enantioselectivity; this reaction represents the first step in the Enders triple cascade catalytic cycle. The use of acetaldehyde in a two-component cascade reaction was previously reported by Enders [27]; however, the scope of this reaction is limited

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

• paradigm with photocatalytic ATRA to enable the modular difunctionalization of alkenes under reagent control (Scheme 3). In Stephenson’s photocatalytic ATRA reports, the C–X bond in the product was proposed to be formed through both direct quenching of a transient alkyl radical by halogen atom transfer

• (XAT) from the alkyl halide reagent and further oxidation of the transient radical to a carbocation by radical polar crossover (RPC), providing two mechanistic pathways to form the ATRA products [32]. While powerful, this approach is inherently incompatible with introducing alternative functionality

• instead of the halide included in the alkyl halide reagent, limiting the ability to form different difunctionalization products. Taking inspiration from Groves’ bio-inspired manganese tetradentate manganese catalysts, we found we could instead functionalize the transient alkyl radical via RLT from a

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

• selection of hypervalent iodine compounds have also been assessed in silico to determine the strengths of their σ-holes (Figure 3). Togni’s CF3-benziodoxole reagent (I-5, 0.029 e) possessed the weakest σ-hole from among those analyzed, consistent with monovalent iodobenzene (I-2) [72]. Difluoroiodobenzene

• appreciation and understanding of σ-holes in iodonium ylides, many examples exist where inter- or intramolecular halogen bonding has been invoked to provide a meaningful explanation of unexpected reactivity, of reagent stability, or as a reaction control element. Examples of these include spontaneous

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

• products (e.g., 7) whereas irradiation with blue light (λ = 455 nm) provided disubstituted products 8 (Figure 5A). Additionally, adding a different trapping reagent before switching from green to blue light allows for a sequential and controlled substitution in a one-pot reaction (Figure 5B). 2,4,6

• the single electron reduction of aryl halides while simultaneously generating S4•−. Upon C(sp2)–X bond cleavage, an aryl radical is formed and trapped by a trapping reagent such as N-methylpyrrole, yielding the open-shell species 4•. Upon irradiation of S3•−, the excited species *[S3•−] oxidizes 4• to

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

• categorized into two major divisions: 1) covalent bonding and 2) noncovalent bonding catalysts. A covalent bonding organocatalyst reacts with a substrate to form an activated chiral intermediate which undergoes a stereoselective reaction with another reagent. A noncovalent bonding catalyst usually assembles

• formation of a new C–C bond [21]. The reaction requires an electrophilic reagent/intermediate present in the reaction system on which an electrophilic attack by the π-electron cloud of the aromatic ring can occur spontaneously to form a dearomatized species. The latter is rearomatized in a succeeding step

• 2004. In this methodology, a 1,1’-bi-2-naphthol (BINOL)-derived chiral phosphoric acid P1 was used as the catalytic reagent to couple 2-methoxyfuran (1) and N-Boc-protected aldimines 2 to incorporate an aza-tertiary stereocenter into the 2’ position of the heteroaromatic products 3 (Scheme 1) [24

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• min. Subsequently, 1.2 M dimethylzinc reagent in toluene (0.31 mL, 0.38 mmol, 1.5 equiv) was added dropwise to the solution and the resulting mixture was also stirred for 10 min. The acylimidazole (0.25 mmol, 1.0 equiv) dissolved in anhydrous THF (0.5 mL) was added dropwise to the mixture. The

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

• yields (Scheme 28). In this reaction, Grignard reagent 148 was used as arylation source in excess amount as the reagent underwent homocoupling leading to the formation of biaryl systems under the reaction conditions. 1,2-Dichloro-2-methylpropane (149) was found to be an effective oxidant under the

Facile access to 3-sulfonylquinolines via Knoevenagel condensation/aza-Wittig reaction cascade involving ortho-azidobenzaldehydes and β-ketosulfonamides and sulfones

• Ksenia Malkova,
• Andrey Bubyrev,
• Stanislav Kalinin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 800–807, doi:10.3762/bjoc.19.60

• of the secondary quinoline-3-sulfonamide synthesis, the increase of reagent excesses in relation to ketosulfonamide resulted in the conversion and an increase of the yield as observed by TLC (see GP2 in Supporting Information File 1). Chromatographic purification afforded compounds 5a–q mostly in

• target products (Scheme 3, 5e and 5g). The drop was especially dramatic for the nitro group containing reagent 1f. Indeed, the transformation was accompanied by a number of side reactions according to TLC. To our delight, the protocol turned out to be suitable for α-sulfonyl-substituted alkyl acetates

• carbonyl group deactivation. Furthermore, while implementing the protocol for 2-azidoquinoline-3-carbaldehyde (1t), a low conversion of this reagent was detected, which can be explained by the fact that 1t tends to exist in the inactive tetrazole form. In addition, our attempt to involve Boc-protected

Synthesis of substituted 8H-benzo[h]pyrano[2,3-f]quinazolin-8-ones via photochemical 6π-electrocyclization of pyrimidines containing an allomaltol fragment

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky,
• Mikhail E. Minyaev and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2023, 19, 778–788, doi:10.3762/bjoc.19.58

• 9a was obtained in 15% yield (Table 1, entry 1). Next, we repeated the above-mentioned reaction under similar conditions without a basic reagent and the exclusion of the base led to a significant increase in the yield of the target product 9a (Table 1, entry 2). Next, we tested the reaction in

• to 2 h did not affect the yield of pyrimidine 9a (Table 1, entry 8). It is important to emphasize that the use of bases essentially impaired the efficiency of the method (Table 1, entries 9 and 10). Apparently, the addition of a basic reagent does not influence the main process and the decrease in

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

• persulfate (K2S2O8) as the exclusive reagent [14]. The mechanistic study revealed that an initial oxidation to an iminium ion could be the key intermediate in the intramolecular cyclization step. In sharp contrast, when N-aryl(benzyl)amines that do not have an ortho-substituted nucleophile in aniline ring

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• compound 12. Meanwhile, Campaña, Morcillo, and co-workers converted the eight-membered ring 11 to nonagon-containing carbohelicene 14 through a single ring expansion reaction by treating 11 with TMSCHN2 (Scheme 2). By reacting with Tebbe’s reagent, compound 14 could be converted to all-carbon analogue 15

• this helical aza-NG was achieved by introducing a chiral auxiliary reagent at the nitrogen site [40], and the racemization barrier of one enantiomer was measured as 26.2 kcal/mol by monitoring the changes of CD spectra at 60–80 °C. The synthesis started with the Diels−Alder reaction of 5H-dibenzo[b,f

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• underwent intramolecular Ullmann-type coupling catalysed by CuBr·DMS to form the fused dihydro[b,f]oxepine ring system in 89% yield, whereafter hydrogenation afforded 105 in almost quantitative yield (Scheme 22). The method is a sequence of 12 steps, the majority of which are to prepare Wittig reagent

• from 2-bromostyrene (116) via halogen–lithium exchange and quenching with the appropriate heteroatom source (SiR2Cl2, SnMe2Cl2, GeR2Cl2, BBr3). P-Tethered dienes were synthesised via quenching of a 2-vinylphenyl Grignard reagent with phenylphosphonic dichloride (PhPOCl2). O-Tethered dienes were

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

• the iodinium agent. However, the corresponding 7-bromomethyl product 50b was not isolated with bromo(biscollidine) hexafluorophosphate as the brominium reagent. The reactants were further extended to functionalized hydrogen methyl 1,3-dioxolane-fused pent-4-en-1-ylphosphonate 51 with bromo

• (biscollidine) hexafluorophosphate as the brominium reagent, leading to the corresponding 3-benzyloxy-6-bromo-1,2-oxaphosphepane 2-oxide 52 in 64% yield. The reaction of hydrogen methyl 1,3-dioxolane-fused hex-5-en-1-ylphosphonate 53 with bromo(biscollidine) hexafluorophosphate produced the corresponding 4

• ) hexafluorophosphate as the reagent, while they generated mixtures of 7-(1-iodoalkylidene)-1,2-oxaphosphepane 2-oxides 60 and 8-alkyl-7-iodo-2-methoxy-3,4,5,6-tetrahydro-1,2-oxaphosphocine 2-oxides 59b with iodo(biscollidine) hexafluorophosphate as the reagent (Scheme 12) [32]. 1.3 Synthesis via P–C bond formation The

Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• from academia and industry. Herein, we report a direct C-3 acetoxymalonylation of imidazo heterocycles using relay C–H functionalization enabled by organophotocatalysis starring zinc acetate in the triple role of an activator, ion scavenger as well as an acetylating reagent. The mechanistic

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

• APBTT 1a with methanol (2a) were optimized. The best yield of PBTA 3aa was observed when methanol was used both as a solvent and a reagent and heated at 65 °C for 1 h (entry 7, Table 1). It is useful to note that, under these conditions, an increase in the heating time (up to 6 h) did not affect the

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

• years of development. The effort of our group to broaden possibilities to engage metal enolates in reactions with new electrophiles is described. The material is divided according to the organometallic reagent employed in the conjugate addition step, and thus to the particular metal enolate formed

• high diastereoselectivity and good to excellent yields. In most cases, the authors detected only a single diastereomer in the crude reaction mixture (NMR). Using the enantiomeric form of the ligand or the chiral sulfoximine reagent, four diastereomeric β-aminoketones can be produced in excellent

• –Jung vinylsilane reagents 33. Kawamura et al. performed zinc enolate trapping reactions using ligand L10, a chiral quinoline-based N,N,P-ligand (Scheme 8A) [35]. The authors have concluded that the strict control of the amount of organozinc reagent added is essential to avoid side-product formation

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• with pyrenecarboxylic acid in the presence of triethylamine (TEA), N,N,N’,N′-tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (HBTU) as the coupling reagent, and 1-hydroxybenzotriazole (HOBT) as a coupling additive to give the products Phen-Py-1 and Phen-Py-2 (Scheme 2) in 56% and 84