Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• by two step hydrolysis gave the same product 223 in 28% yield. Phosphorus tribromide first reacted with more nucleophilic amide nitrogen atom to form dibromophosphanamine derivative 224 by loss of HBr. The more nucleophilic dibromophosphanamine derivative 224 further underwent a nucleophilic addition

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

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

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• this work. Firstly, the nucleophilic addition of tributylphosphine to the bis-chalcone gives the active zwitterionic species (A). Secondly, the Michael addition of the zwitterionic species (A) to isatylidene malononitrile at the C3-position of the oxindole scaffold results in adduct (B). Thirdly, the

• reaction, the nucleophilic addition of the zwitterion (A) to this compound takes place at the exocyclic position giving the adduct (E), which in turn proceeds with the intermediates (F) and (G) according to the above mentioned similar processes to give the spiro compound 5. The different addition direction

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• the nucleophilic addition and successive cyclization to happen. In addition, we further explored the scope of substrates with a trifluoromethyl group, a strong electron-withdrawing substituent, instead of methyl, an electron-donating group, in the 1,3-diketone starting materials (Table 2). The

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• )pyrroles [15]. The CsF-promoted nucleophilic addition of isocyanides to bromoacetylenes furnished the functionalized bromovinyl amides followed by Pd-catalyzed formation of 5-iminopyrrolone [16]. Sequential nucleophilic addition/intramolecular cyclization of amidine with bromoacetylenes led to imidazoles

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• thiourea moiety with the oxygen of the nitrosobenzene. The tertiary amine, present in the catalyst acts as a base in assisting the deprotonation of the highly acidic malonamate to generate the corresponding enolate. Subsequently, a face-selective nucleophilic addition of the enolate to nitroso selective

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• with reddish hues. The reaction with aniline forms the substitution product of the sulfonic group with a phenylamino group in a 90% yield. In his study, he proposed that the structure of the nucleophilic addition product was tautomer 19 (Scheme 1B). In search of a reagent that could form stable adducts

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• give amide 12 with a half-life (t1/2) of 6.4 h. The observation of N-formyl products can be rationalized with a bifurcating mechanism (Figure 5). Following photoactivation, H-atom abstraction and nucleophilic addition of water would produce the key intermediate B. Such hemi-aminal compounds would be

Me₃Al-mediated domino nucleophilic addition/intramolecular cyclisation of 2-(2-oxo-2-phenylethyl)benzonitriles with amines; a convenient approach for the synthesis of substituted 1-aminoisoquinolines

• Krishna M. S. Adusumalli,
• Lakshmi N. S. Konidena,
• Hima B. Gandham,
• Krishnaiah Kumari,
• Krishna R. Valluru,
• Satya K. R. Nidasanametla,
• Venkateswara R. Battula and
• Hari K. Namballa

Beilstein J. Org. Chem. 2021, 17, 2765–2772, doi:10.3762/bjoc.17.186

• achieved by treating 2-(2-oxo-2-phenylethyl)benzonitriles with amines in the presence of Me3Al. The reaction proceeds via a domino nucleophilic addition with subsequent intramolecular cyclisation. This method provides a wide variety of substituted 1-aminoisoquinolines with good functional group tolerance

• . Furthermore, the synthetic utility of this protocol was demonstrated in the successful synthesis of the antitumor agent CWJ-a-5 in gram scale. Keywords: 1-aminoisoquinolines; CWJ-a-5; intramolecular cyclisation; 2-(2-oxo-2-phenylethyl)benzonitriles; nucleophilic addition; Introduction Heterocyclic compounds

• suitably tailored benzonitriles 3 were cyclized in an intramolecular fashion by installing nuclophilic nitrogen onto the nitrile functionality would generate 1-aminoisoquinolines. Herein we describe our efforts on a Me3Al-mediated nucleophilic addition followed by an intramolecular cyclisation of 2-(2-oxo

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