Superelectrophilic carbocations: preparation and reactions of a substrate with six ionizable groups

• Sean H. Kennedy,
• Makafui Gasonoo and
• Douglas A. Klumpp

Beilstein J. Org. Chem. 2019, 15, 1515–1520, doi:10.3762/bjoc.15.153

• in the Brønsted superacid CF3SO3H, the substrate undergoes two types of reactions. In the presence of only the superacid, the highly ionized intermediate(s) provide a double cyclization product having two pyrido[1,2-a]indole rings. With added benzene, an arylation product is obtained. A mechanism is

• ), compound 9 undergoes two types of reactions. When the substrate is ionized in the presence of benzene and CF3SO3H, the arylation product 10 is formed as the major product (Scheme 3). Presumably, compound 10 is formed as a mixture of meso and dl stereoisomers. Similar reaction products were observed in our

• providing pentacation 13 then the hexacation 14. The product forming steps occur through either 13 or 14. For the arylation product 10, charge delocalization at the carbocation leads to nucleophilic attack at the para-position of the phenyl group. This SEAr step is followed by protonation at the methine

Different reactivity of phosphorylallenes under the action of Brønsted or Lewis acids: a crucial role of involvement of the P=O group in intra- or intermolecular interactions at the formation of cationic intermediates

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1491–1504, doi:10.3762/bjoc.15.151

• reaction) for selected transformations (1a→13→16→17 for mechanism A, 1a→13→22→23 for mechanism B) was explored. Formation of complex 13 from allene 1a and AlCl3 is exergonic (−26.7 kcal/mol) and thermodynamically favorable. The arylation stage for mechanism A (16→17) is significantly less endergonic (22.6

Synthesis of aryl cyclopropyl sulfides through copper-promoted S-cyclopropylation of thiophenols using cyclopropylboronic acid

• Emeline Benoit,
• Ahmed Fnaiche and
• Alexandre Gagnon

Beilstein J. Org. Chem. 2019, 15, 1162–1171, doi:10.3762/bjoc.15.113

• -cyclopropylation reactions, a transformation which is similar to the Chan [45], Evans [46], Lam [47] arylation reaction of N–H and O–H containing substrates. These seminal reports greatly contributed to the synthesis of cyclopropylated compounds in addition to expanding the scope of copper-catalyzed reactions in

Switchable selectivity in Pd-catalyzed [3 + 2] annulations of γ-oxy-2-cycloalkenones with 3-oxoglutarates: C–C/C–C vs C–C/O–C bond formation

• Yang Liu,
• Julie Oble and
• Giovanni Poli

Beilstein J. Org. Chem. 2019, 15, 1107–1115, doi:10.3762/bjoc.15.107

• [32]. Furthermore, when the newly formed annulation product contains an ortho-haloaryl moiety at the nitrogen substituent, an additional intramolecular keto α-arylation step can be involved in the cascade, thereby forming two new cycles and three new bonds in the same synthetic operation (Scheme 1

Dirhodium(II)-catalyzed [3 + 2] cycloaddition of N-arylaminocyclopropane with alkyne derivatives

• Wentong Liu,
• Yi Kuang,
• Zhifan Wang,
• Jin Zhu and
• Yuanhua Wang

Beilstein J. Org. Chem. 2019, 15, 542–550, doi:10.3762/bjoc.15.48

• aminocyclic compounds. In fact, the synthesis of 1 has always been a challenge [16][17]. Only recently an efficient synthesis method by arylation of cyclopropylamine has been developed and documented by Colacot et al. [16] and Stradiotto et al. [17], which has provided opportunities for further development of

Reusable and highly enantioselective water-soluble Ru(II)-Amm-Pheox catalyst for intramolecular cyclopropanation of diazo compounds

• Hamada S. A. Mandour,
• Yoko Nakagawa,
• Masaya Tone,
• Hayato Inoue,
• Nansalmaa Otog,
• Ikuhide Fujisawa,
• Soda Chanthamath and
• Seiji Iwasa

Beilstein J. Org. Chem. 2019, 15, 357–363, doi:10.3762/bjoc.15.31

• DIBAL-H with benzylamine afforded the desired product 3 in 44% yield with 95% ee (Scheme 2, reaction 1) [52]. We then investigated the arylation of chiral cyclopropylamide 2f with Grignard reagent PhMgBr (Scheme 2, reaction 2). Only 37% of cyclopropyl ketone 4 were observed at room temperature with

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• -isocyanobiphenyls. Ag(II)-mediated oxidative ring-opening/fluorination of cyclopropanols with AgF2. Cu(II)-catalyzed ring-opening/fluoromethylation of cyclopropanols with sulfinate salts. Cu(II)-catalyzed ring-opening/sulfonylation of cyclopropanols with sulfinate salts. Na2S2O8-promoted ring-opening/arylation of

• cyclopropanols with propiolamides. The ring-opening and [3 + 2]-annulation of cyclopropanols with α,β-unsaturated aldehydes. Cu(II)-catalyzed ring-opening/arylation of cyclopropanols with aromatic nitrogen heterocyles. Ag(I)-catalyzed ring-opening and difluoromethylthiolation of cyclopropanols with PhSO2SCF2H

Organometallic vs organic photoredox catalysts for photocuring reactions in the visible region

• Aude-Héloise Bonardi,
• Frédéric Dumur,
• Guillaume Noirbent,
• Jacques Lalevée and
• Didier Gigmes

Beilstein J. Org. Chem. 2018, 14, 3025–3046, doi:10.3762/bjoc.14.282

• . Parallel to this, 4CzIPN was also used as an organoredox catalyst for the alkylation of heteroarenes [85], the oxidation of silicates [86], the alkylation of imines [87], the α-arylation/heteroarylation of 2-trifluoroboratochromanones [88]. In these different situations, comparisons with reference

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• ], via intramolecular cyclization of a diazomethane group and a nitrile [23], or via our recently reported NH-triazole synthesis starting from 6-methoxyflavanone [24]. Furthermore, 1,4,5-trisubstituted 1,2,3-triazole annulated chromenes have been reported via an intramolecular arylation reaction of 1,2,3

Synthesis of aryl sulfides via radical–radical cross coupling of electron-rich arenes using visible light photoredox catalysis

• Amrita Das,
• Mitasree Maity,
• Simon Malcherek,
• Burkhard König and
• Julia Rehbein

Beilstein J. Org. Chem. 2018, 14, 2520–2528, doi:10.3762/bjoc.14.228

• charge transfer using Cs2CO3 as base [41]. Two recent reports showed the synthesis of C-3 sulfenylated indoles and 3-sulfenylimidazopyridine via C–H functionalization using Rose Bengal as photocatalyst [42][43]. In general, the arylation reactions use the reductive cycle of the photocatalyst and for this

• . When thiophenol was used as the sulfur source, diphenyl disulfide was obtained as a major side product, which in turn hindered the arylation process and resulted in several other oxidized products of thiophenol. So, the readily available diphenyl disulfide was added as the thiolating agent. Addition of

• of the reaction mixture, also when nitrobenzene (PhNO2) was used as oxidant, trace amounts of product were observed along with the formation of aniline, likely arising from the regeneration of the catalyst. Control experiments confirmed that light and photocatalyst were essential for the arylation

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

• Nadia Gruber,
• Jimena E. Díaz and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• by cyclodehydration allowed for a straightforward and efficient synthesis of 3,4-dihydroquinazolines with N-aryl substituents bearing electron-withdrawing groups. The sequence involves an initial SNAr displacement, N-acylation and MW-assisted ring closure. Remarkably, the uncatalyzed N-arylation of 2

• others, and involve a reduction step which would be incompatible with the presence of nitro or cyano groups [5][13][14][39][68][69][70][71]. The synthetic sequence towards compounds 1 requires the chemoselective arylation of the benzylic amino group of the precursor with active haloaryl derivatives. SNAr

• of PPA esters for the optimization of the heterocyclization reaction leading to compounds 1. Results and Discussion The synthetic strategy leading to DHQs 1 is depicted in Scheme 1. The key step of the sequence involves an N-arylation of 2-ABA with active haloaromatics (Scheme 2). As previously

Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine

• Piotr Pomarański,
• Piotr Roszkowski,
• Jan K. Maurin,
• Armand Budzianowski and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2018, 14, 2384–2393, doi:10.3762/bjoc.14.214

• due to electronic reasons, but is strongly disfavoured by steric repulsion (bigger van der Waals radius of the bromine atom compared to the methyl group). This may be the reason for the first arylation to occur at the C-3(5) position in compound 4 and the second one preferably at the C-4 position

• , both in ortho-methoxyphenyl and ortho-chlorophenyl series (Figure 5 and Figure 6). In the former one, however, the successive arylation is additionally affected by apparent O-chelation of the metal at the transition state which results in noticeable diastereoselectivity of this process, leading to a

• acid) in order to visualize the presence of individual enantiomers (see Supporting Information File 1 for details). Based on the current knowledge on the chemistry of palladium complexes with SPhos [42][43][44] we proposed a sequence in the arylation process and the substitution mechanism for the

A challenging redox neutral Cp*Co(III)-catalysed alkylation of acetanilides with 3-buten-2-one: synthesis and key insights into the mechanism through DFT calculations

• Andrew Kenny,
• Alba Pisarello,
• Arron Bird,
• Paula G. Chirila,
• Alex Hamilton and
• Christopher J. Whiteoak

Beilstein J. Org. Chem. 2018, 14, 2366–2374, doi:10.3762/bjoc.14.212

• molecule to the initial metallocycle, the conversion is more challenging and therefore requires harsher reaction conditions. This competitive binding (Int 2substrate vs RS 2) is similar to that proposed by Bergman and Ellman for Cp*Rh(III)-catalysed arylation of imines [27]. Additionally RS 1, resulting

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

DFT calculations on the mechanism of copper-catalysed tandem arylation–cyclisation reactions of alkynes and diaryliodonium salts

• Tamás Károly Stenczel,
• Ádám Sinai,
• Zoltán Novák and
• András Stirling

Beilstein J. Org. Chem. 2018, 14, 1743–1749, doi:10.3762/bjoc.14.148

• the basis of the mechanism the origin of the stereoselectivity is ascribed to the interaction of the Cu ion with the oxazoline oxygen driving the ring-closure step selectively. Keywords: catalysis; DFT calculation; iodonium salts; reaction mechanism; tandem arylation–cyclisation; Introduction

• ][20][21][22][23][24][25][26][27][28]. In particular, the arylation–cyclisation reactions promoted by the highly electrophilic Cu(III)–aryl intermediates 3 can allow access to aryl-functionalised carbocyclic and heterocyclic molecules 8 with valuable functionalities [9][29][30][31][32][33][34][35][36

• before the C–O bond formation in the ring closing step (see Scheme 1). As an example of the catalytic arylation–cyclisation strategy, an efficient procedure to form substituted oxazoline derivatives from alkyl and aryl propargylamides has been developed. The process involves a 5-exo-dig cyclisation and

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• phenanthrenes 54 in moderate to good yields (Scheme 19) [59]. Indoles also are relevant substrates for the tandem arylation with cyclic diaryl-λ3-iodanes, allowing the preparation of dibenzocarbazoles 55 in moderate yields (Scheme 20) [60]. The reaction is catalyzed simply by Pd(OAc)2 in the absence of any

• reductive elimination. Starting from the ortho-N-(acyl)diaryl-λ3-iodanes 57, a combination of copper and palladium catalysis, in the presence of a phosphine ligand, induces the internal O-arylation of the proximal amide moiety, followed by a subsequent metal-catalyzed coupling-reaction with the resulting Ar

• high yielding N-arylation of 1H-1,2,3-benzotriazole (BTA), utilizing symmetrical diaryl-λ3-iodanes as two-fold aryl donors has been reported in the presence of Pd(OAc)2 and TPPTS as a water-soluble ligand, and copper(II) phenylcyclopropylcarboxylate (Scheme 35) [74]. Noteworthy, it is mentioned that Ar

Metal-free formal synthesis of phenoxazine

• Gabriella Kervefors,
• Antonia Becker,
• Chandan Dey and
• Berit Olofsson

Beilstein J. Org. Chem. 2018, 14, 1491–1497, doi:10.3762/bjoc.14.126

• a high-yielding O-arylation of a phenol with an unsymmetrical diaryliodonium salt to provide an ortho-disubstituted diaryl ether. This species was cyclized to acetylphenoxazine in moderate yield. The overall yield in the three-step sequence is 72% based on recovered diaryl ether. An interesting

• , unusually stable iodine(III) intermediate in the O-arylation was observed by NMR and could be converted to the product upon longer reaction time. Keywords: arylation; cyclization; diaryl ether; diaryliodonium salt; phenol; Introduction Phenoxazine (1) is a tricyclic compound consisting of an oxazine ring

• [17][19][20]. A Pd-catalyzed double N-arylation using di(2-bromoaryl) ethers and primary amines was recently developed (Scheme 1c) [21]. Furthermore, N-functionalization of the phenoxazine core can be performed under metal-free conditions [22]. Our research group has reported highly efficient O

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• arylation protocols [18][19][20][21][22]. While in solid state they clearly have a T-shaped pseudotrigonal bipyramid structure, the common structural motif for λ3-iodanes, recent theoretical investigations revealed a potential role of the cationic, normal valent tetrahedral form, in atom transfer processes

• waste. Examples for their atom-economical utilization, in which at least both aryl ligands are transferred, are still rare. A general approach would involve at first a metal-catalysed or metal-free arylation step of a suitable substrate A with the diaryliodonium salt 1 to give monoarylated intermediate

• –boron bond formation gives one equivalent of arylboronic ester 4 and an iodoarene 2 through a metal-free boron arylation. Subsequent cross coupling under Suzuki conditions affords symmetrical biphenyls 3’ in good yields. Due to the temporary introduction and cleavage of the boron moiety the formal atom

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• more effective chiral iodonium salts 16 which were used for the α-arylation of β-ketoester 86 to deliver α-arylated β-ketoesters 87 with moderate enantioselectivity (Scheme 17) [63]. This was the first example of an asymmetric α-arylation of β-ketoesters using hypervalent iodine reagents. A more

• different stereoelectronic properties by using aliphatic alcohols as a sole source of chirality [64]. Olofsson and Wirth et al. also jointly reported the synthesis of new structurally distinct chiral reagents 20 considering their interest towards asymmetric metal-free arylation [65]. In 1997, Wirth et al

• diamination of alkenes. Stereoselective oxyamination of alkenes reported by Wirth et al. Enantioselective and regioselective aminofluorination by Nevado et al. Fluorinated difunctionalization reported by Jacobsen et al. Aryl rearrangement reported by Wirth et al. α-Arylation of β-ketoesters. Asymmetric α

A selective removal of the secondary hydroxy group from ortho-dithioacetal-substituted diarylmethanols

• Anna Czarnecka,
• Emilia Kowalska,
• Agnieszka Bodzioch,
• Joanna Skalik,
• Marek Koprowski,
• Krzysztof Owsianik and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2018, 14, 1229–1237, doi:10.3762/bjoc.14.105

• -coupling reactions of substrates containing an 1,3-dithiane moiety are feasible, like in the case of the 2-arylation of 2-aryl-substituted 1,3-dithianes. However, in the case of 2-benzyl-substituted 1,3-dithianes, a tandem elimination/1,3-dithiane ring opening followed by a Pd-catalyzed C−S bond formation

Imide arylation with aryl(TMP)iodonium tosylates

• Souradeep Basu,
• Alexander H. Sandtorv and
• David R. Stuart

Beilstein J. Org. Chem. 2018, 14, 1034–1038, doi:10.3762/bjoc.14.90

• -deficient and sterically encumbered aryl groups. Keywords: arylation; C–N coupling; diaryliodonium; hypercoordinate iodine; metal-free; Introduction Imides are important structural units in a range of approved pharmaceuticals and agrochemicals (Scheme 1a) [1]. Despite the general prevalence of imides, N

• Discussion We initiated our optimization of the arylation of the potassium phthalimide nucleophile with diaryliodonium electrophiles by surveying several reaction conditions: dummy ligand (Aux), counter anion, solvent and volume, reaction temperature, and stoichiometry (Table 1). Consistent with an

Polysubstituted ferrocenes as tunable redox mediators

• Sven D. Waniek,
• Jan Klett,
• Christoph Förster and
• Katja Heinze

Beilstein J. Org. Chem. 2018, 14, 1004–1015, doi:10.3762/bjoc.14.86

• syntheses [17][18][19][20][21][22][23][24][25][26][27][28]. Tuning of the electrochemical potential of substituted ferrocenium salts promoted a selective oxidative bicyclization reaction under mild conditions (Scheme 1a) [27]. Ferrocene and decamethylferrocene act as redox catalysts in Meerwein arylation

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• the presence of X-Phos or BINAP as ligands. The literature data influenced the selection of the base. The arylation of anilines, escpecially of unsubstituted ones with o-bromoanisoles requires stronger bases such as NaOt-Bu or KOt-Bu [34][35][36][37][38]. This is due to the deactivated, electron-rich

Cobalt-catalyzed directed C–H alkenylation of pivalophenone N–H imine with alkenyl phosphates

• Wengang Xu and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2018, 14, 709–715, doi:10.3762/bjoc.14.60

• alkenes and alkylation/arylation using organic halides [29][30]. These previous studies have prompted us to expand the scope of cobalt catalysis for the C–H alkenylation and thus to develop an ortho C–H alkenylation reaction of pivalophenone N–H imine with alkenyl phosphates using a new cobalt–NHC

• , the NHC precursor featuring a cyclohexane backbone and 2,6-diethylphenyl groups (L1·HBr), which proved to be the optimal ligand for the C–H arylation of pivalophenone N–H imine as well as for the C–H alkenylation of N-arylimine (Scheme 1a, b) [28][29], was not particularly effective for the present

• reaction (Table 1, entry 8). To our delight, we observed a remarkable improvement in the reaction efficiency using the benzofused analogue of IPr·HCl (L2·HCl), affording 3aa in 88% yield without any trace of a dialkenylation product (Table 1, entry 9). It should be noted that, unlike the C–H arylation of

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• -receptor agonists [8][9][10][11][12][13][14][15][16]. Indeed, the copper-catalyzed N-arylation of (3S)-26 was performed in dioxane with N,N-dimethylethylenediamine as ligand [27] to deliver the targeted pazinaclone analogue (3S)-27 in a fair yield (66%) without significant loss in enantiomeric purity