Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• nucleophilic addition reactions using isatin-derived imines 50 as electrophiles was reported by Tan, Shi and co-workers in 2020. Enantioenriched 3,3'-bisindoles with a biologically essential chiral 3-aminooxindole unit can be readily prepared by these methods. CPA 9 utilizes hydrogen bonding to activate both

• accelerating imine formation (I-19), and under the catalysis of a chiral phosphoric acid, intramolecular nucleophilic addition occurs to form I-20, followed by oxidative dehydrogenation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). In the presence of 10 mol % chiral phosphoric acid CPA 7, the axially

• -yl)methanols 87 as electrophile and 2-naphthols 88 or phenols 90 as nucleophile (Scheme 29) [45]. The (3-alkynylindol-2-yl)methanol 87 is expected to convert to the allene-iminium intermediate I-24 by accepting a proton from CPA 14. Then, the CPA anion activates the nucleophilic addition between 2

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• photoexcitation the CuI acetylide A undergoes a SET process to form the CuII phenylacetylide species B and a superoxide radical anion. In parallel, under irradiation the homolytic S–S-bond cleavage in 2-aminothiophenol dimer 38 forms thiol radicals 40. The nucleophilic addition of the amino group in radical 40 to

• , the imine 60 transferred a single electron to the CuII ion, thereby providing intermediate II [CuI-N•+]. [CuI-N+•] was equal to CuI and N+• of the imine, which is activated for the nucleophilic addition. With the help of O2, CuI regenerates CuII to complete the catalytic cycle (Scheme 27). A series of

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• Petasis–Ferrier-type cyclization, and finally nucleophilic addition of mercuric enolate to iminium results in the formation of azaspiro structure. Conclusion In conclusion, this review summarizes Hg(II)-salt-mediated cyclization reactions either for direct synthesis of cyclized products or as a part of

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• these types of reactions. The first thiourea-catalyzed asymmetric intermolecular reaction with N-acyliminium chlorides was then also realized by the same group in 2009. Therein, nucleophilic addition of indoles 17 to the N-acyliminium chlorides was achieved with excellent enantiomeric excess (Scheme 4b

• , that Reissert dearomatizations of N-heteroarenes, especially of isoquinolines [36], and nucleophilic addition to 1-chloroisochromanes [38] have become benchmark reactions in the context of anion-binding catalysis. Besides reports of thiourea-catalyzed reactions with different nucleophiles [39][40], the

• have been provided by the group of Jacobsen in the nucleophilic addition of indoles 17 to pyranones 62 (Scheme 14a) [71], as well as in the enantioselective synthesis of α-allyl amino esters 67 by the reaction of α-chloro amino acid derivatives 65 with allyltin and allylsilane 66 nucleophiles [72

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• nucleophilic addition of the hydroxycoumarin. The procedure allowed obtaining products 34 with excellent yields and enantiomeric excesses (Scheme 11). Zhu et al. described the asymmetric Michael addition of substituted 4-hydroxycoumarins (1) to cyclic enones 36, using an in situ formed organocatalyst [44]. The

• half-thioesters 67 to coumarins 66 using a sulphonamide organocatalyst 69 was reported by Nakamura et al. [55]. The hydrogen bond between the secondary amine and the coumarin carboxyl provides a nucleophilic addition on the Re face, and therefore resulting in products 68 with R absolute configuration

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• corresponding triazole products in moderate yield (Scheme 8) [42]. The authors proposed a reaction mechanism in which the β-thioenaminone 18 tolerates deprotonation to afford anionic intermediate 21 through the tautomer 20 in the presence of a base. In the next step, the nucleophilic addition of 21 to the azide

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• after the nucleophilic addition as a stable bis-5,5-palladacycle (A), thereby preventing the β-hydride elimination step and allowing its further reaction with a proton to yield intermolecular hydroalkylation products (Scheme 5) [35]. In that work, the authors considerably expanded the scope of suitable

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• 5, which undergoes nucleophilic addition with another molecule of aldehyde 1 to furnish the iminoalcohol intermediate 6. The iminoalcohol 6 undergoes dehydration under the reaction conditions to give E-imine/Z-enamine 7a or Z-imine/E-enamine 7c intermediates irreversibly, which plays a decisive role

Fritsch–Buttenberg–Wiechell rearrangement of magnesium alkylidene carbenoids leading to the formation of alkynes

• Tsutomu Kimura,
• Koto Sekiguchi,
• Akane Ando and
• Aki Imafuji

Beilstein J. Org. Chem. 2021, 17, 1352–1359, doi:10.3762/bjoc.17.94

• -tolyl sulfoxides 2, 5–7 and 1-unsubstituted sulfoxide 8 were prepared from carbonyl compounds 1 (Scheme 3). The 2,2-bis(4-methoxyphenyl)-substituted sulfoxides 2a, 5, and 8 were prepared via the nucleophilic addition of [(p-tolylsulfinyl)methyl]lithiums to 4,4'-dimethoxybenzophenone, acylation of the

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• imines derived from tert-butanesulfinamide. These imines are versatile chiral auxiliaries and have been extensively used as eletrophiles in a wide range of reactions. The electron-withdrawing sulfinyl group facilitates the nucleophilic addition of organometallic compounds to the iminic carbon with high

• -containing heterocycles; N-tert-butanesulfinyl imines; Intoduction Chiral imines derived from tert-butanesulfinamide have been extensively used as electrophiles in a wide range of reactions. The presence of the chiral electron-withdrawing sulfinyl group facilitates the nucleophilic addition of

• Re-face of the imine (Scheme 4) [1][36]. The nucleophilic addition reactions to N-tert-butanesulfinyl imines were also described by Ellman and co-workers who reported the addition of allylmagnesium bromide to ketimines. The employment of Grignard reagents showed greater diastereoselectivity than

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• -methyl-2H-pyran-2-one and arylglyoxal to form intermediate A. Michael addition of amine to intermediate A gives B which further undergoes an intramolecular nucleophilic addition reaction to yield C which on cyclization and with subsequent loss of water from D produce the desired products 34. Meshram and

• mechanism describes the synthesis by the formation of an intermediate A from the condensation between compounds 33 and 32 in presence of an acid undergoing nucleophilic addition with 93 resulting in intermediate B. This intermediate undergoes an intramolecular cyclization C aided by an acid to give

• under microwave conditions delivered the desired product in better yields than the reflux strategy. Scheme 33 depicts the most probable pathway for the desired products 89 and 90. Initially, an acid-catalyzed reaction between arylglyoxal and amino uracil yields intermediate A. Nucleophilic addition of

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• excellent yields. Nucleophilic addition to 5- and 6-membered cyclic tosyloxyenones. Synthesis, functionalization and applications of triazoles. The reaction was performed using 0.2 mmol N-tosyl-1,2,3-triazole 1 and 0.2 mmol of cyclohexyl-1,3-dione 2. Yields are determined after silica gel column

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• give methanofullerenes Scientists are currently focusing on methods for the functionalization of the fullerene core that provide a high selectivity and yield. The electron-deficient polyene C60 readily undergoes radical addition, nucleophilic addition, and cycloaddition processes. Therein, the decrease

• methylene function in halo-substituted substrates and with facilitation of bases, methanofullerenes with various structures are formed rather smoothly. It is believed that nucleophilic addition of an α-halocarbanion to C60 occurs initially, followed by intramolecular substitution of the halogen atom by an

• because the variability of the substituents in the cyclopropane moiety is very high. Cyclopropanation of C60 with diazo compounds At the end of 1991, Suzuki [80] reported the first fullerene-containing derivative obtained by nucleophilic addition of diphenyldiazomethane to C60. The reaction of C60 with

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

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

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• prone to a nucleophilic addition than the free thioimidate group) they also make the α-thioiminium/thioimidate group more reactive. These two effects are antagonistic and therefore a thorough study of the R4 substituent influence is necessary. On the other hand, mono- as well as disubstitution of the

• fulfilled – i.e., the substantial acidity of a hydrogen at C3 and a more stable α-thioiminium group necessary for the internal nucleophilic addition giving the thiirane intermediate (route b). It is well known that the acidity of carbon acids in acetonitrile is much lower than in polar aprotic solvents

Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes

• Olga Bakhanovich,
• Viktor Khutorianskyi,
• Vladimir Motornov and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44

• of the rhodium-catalyzed transannulation to pyrroles has recently been investigated computationally with N-sulfonyltriazoles [31]. It seems that the formed rhodium carbenoid B reacts with the alkyne in a concerted process and even in the presence of Ag+ salts, a nucleophilic addition of silver

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• ] and Huang [20][21]. Adolfsson expanded this by the use of molybdenum-based catalysts [22]. The reductive approach allows the issues associated with nucleophilic addition to amide carbonyl groups to be overcome and as such is finding its place in a growing number of synthetic applications [10]. The

• the light of Woerpel’s model, which characterizes the direction of nucleophilic addition to oxocarbenium ions [41][42][43]. According to this concept, the conformational stability of the compound in question is the key property to consider when predicting the reaction’s stereoselectivity. When the

Synthesis of tetrafluorinated piperidines from nitrones via a visible-light-promoted annelation reaction

• Vyacheslav I. Supranovich,
• Igor A. Dmitriev and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2020, 16, 3104–3108, doi:10.3762/bjoc.16.260

• propensity of the corresponding nitrones towards nucleophilic addition of ascorbate. The nitrones derived from α-unbranched aliphatic aldehydes also provided the expected piperidines (products 3m–q) in reasonable yields. In case of 3n there was some unidentified side product formed under the standard

An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• malononitrile under catalyst-free conditions have been reported [29]. Wang et al. reported the functionalization of benzylic C–H bonds of 2-methylazaarenes by nucleophilic addition to aromatic aldehydes catalyzed by acetic acid using harmful chlorinated solvent, and this reaction suffers from longer reaction

• mmol of 1a will inter react to another 1 mmol of 1a) and this inter reaction influences the nitrogen atom present in the compound to act as a Brønsted base. This resulting Brønsted base accepts benzylic C–H protons to furnish the respective enamine A, which facilitates the further nucleophilic addition

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• between carboxylic acid/alcohol 76 and enal 77 (Scheme 10a) [46]. Analogously to the mechanism outlined in Scheme 9, it was proposed that formation of excited state iminium ion 66* is used to oxidise 76 to give radical cation 76•+ and alkyl radical 66•. Nucleophilic addition from the carboxylic acid or

• al. [94] it is suggested that this reaction uses 1O2 for the oxidation, and proceeds through transition state 219‡ for the hydrogen-bonded catalysed nucleophilic addition step. Jiang et al. recently applied a similar dual catalytic system to the dehalogenative protonation of α,α-chlorofluoro ketones

• intermediate 239•, which abstracts a hydrogen atom from TRIP-thiol to produce enantioenriched cyclic sulfonamides 239 in excellent yields and enantioselectivities (28 examples, up to 98:2 er). Chiral phosphates have also been used to catalyse the enantioselective nucleophilic addition of indoles 241 to imines

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• sensory material for selective recognition of cesium cations in water. In another event, Hirao’s group has prepared trioxosumanene 40 in the presence of RuCl3 and t-BuO2H which could be used as a key building block to generate diverse significant electroactive materials by virtue of nucleophilic addition

Azo-dimethylaminopyridine-functionalized Ni(II)-porphyrin as a photoswitchable nucleophilic catalyst

• Jannis Ludwig,
• Julian Helberg,
• Hendrik Zipse and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2119–2126, doi:10.3762/bjoc.16.179

• the Henry reaction, the nitroethane anion intermediate, coordinates to the Ni-porphyrin, which slows down nucleophilic addition to the nitrobenzaldehyde. Hence, the switchable catalyst 1 contains both, a catalytic center (nitrogen lone pair) and an inhibitor (Ni2+ ion). If the nitrogen lone pair

A complementary approach to conjugated N-acyliminium formation through photoredox-catalyzed intermolecular radical addition to allenamides and allencarbamates

• Olusesan K. Koleoso,
• Matthew Turner,
• Felix Plasser and
• Marc C. Kimber

Beilstein J. Org. Chem. 2020, 16, 1983–1990, doi:10.3762/bjoc.16.165

• radical adds to the central carbon of the allene giving a conjugated N-acyliminium that undergoes nucleophilic addition by arylamines and alcohols. Keywords: allenamide; allene; intermolecular; N-acyliminium; photoredox; Introduction Allenamides (Scheme 1, 1) and their congeners have attracted

• conjugated N-acyliminium 14. The iminium 14 could then undergo traditional nucleophilic addition giving the addition product. Given that the iridium complex Ir[(ppy)2(dtbbpy)]PF6 had been effective [47][48][50] in this radical/cationic pathway with enamides we would now like to report our preliminary

• nucleophilic addition at the α-position giving the observed N,N’-allylaminal product 43. Conversely, addition of a nucleophile at the γ-position of E-42 gives the observed Z-enamide 44; and addition at the γ-position of Z-42’ gives the same observed Z-enamide 44 after C–N bond rotation. Conclusion In

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• nucleophilic addition, the authors suggested the tentative mechanism depicted in Scheme 34. As shown, γ-fluoride loss from enolate I, formed after the conjugate Michael addition, would lead to the formation of difluoroenone II. This could in turn undergo a nucleophilic addition of water, followed by a retro

• PKR of chiral N-tethered 1,7-enyne bearing a vinyl fluoride [64]. Catalytic intramolecular PKR of chiral N-tethered 1,7-enynes [64]. Model fluorinated alkynes used by Riera and Fustero [70]. PKR with norbornadiene and fluorinated alkynes 58 [71]. Nucleophilic addition/detrifluoromethylation and retro

• Diels-Alder reactions [70]. Tentative mechanism for the nucleophilic addition/retro-aldol reaction sequence. Catalytic PKR with norbornadiene [70]. Scope of the PKR of trifluoromethylalkynes with norbornadiene [72]. DBU-mediated detrifluoromethylation [72]. A simple route to enone 67, a common

One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions

• Gui-Feng Kang and
• Gang Zhang

Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120

• nucleophilic addition of another molecule 2 takes place to furnish the tricomponent adduct 4, which undergoes elimination of ammonia to afford the corresponding ring-closed intermediate 7 [37]. The latter undergoes a proton-transfer process to form intermediate 10 [38]. Thereafter, the subsequent step involves

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• thiiranes was used for the synthesis of thietanes. Isocyanoalkanes 415 can be considered as nucleophiles. However, after the nucleophilic addition, they could become electrophiles. Thus, they can be applied in the nucleophilic ring expansion of thiiranes 416, in which the generated thiolates 417 as