Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• tetraamino-bisthiourea chiral macrocycles were synthesized [30]. When applied in catalyzing the decarboxylative addition of phenyl β-ketoacids to cyclic imines bearing sulfamate heading group, an interesting substrate-induced assembly catalysis mode was uncovered [30]. To expand more applications, herein we

• cavity could resemble the circumstance of the catalytic triad of Polyketide synthases (PKSs) [40][41][42] (Figure 1). On the other hand, the organocatalytic asymmetric decarboxylative addition reactions of MAHTs to imines provide an efficient means for accessing valuable chiral β-amino esters [43][44][45

• established the optimal reaction conditions, the substrate scope was explored. Reactions of various isatin imines 6a–w with MAHT 7a were firstly investigated (Scheme 2). Different N-substituents on isatins caused a significant effect. For non-substituted (6b) or other substrates with larger substituents (6c–g

Synthesis of piperidine and pyrrolidine derivatives by electroreductive cyclization of imine with terminal dihaloalkanes in a flow microreactor

• Yuki Naito,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2022, 18, 350–359, doi:10.3762/bjoc.18.39

• only one report on the electroreductive synthesis of piperidine derivatives: namely Degrand and co-workers demonstrated electroreductive cyclization using imines and terminal dihaloalkanes to provide piperidine derivatives (Scheme 2) [27]. In this reaction, a stable radical anion is produced from the

• time, extremely fast molecular diffusion, and expelling the reaction product to avoid over-oxidation or over-reduction. We have previously reported the electrochemical carboxylation of several imines in a flow microreactor to afford the corresponding α-amino acids in good to moderate yields [33][34][35

• ]. The key features of this method are the effective cathodic reduction of imines and their rapid use for the subsequent reactions in a microflow system. Successful preliminary results prompted us to perform the electroreductive cyclization of an imine with terminal dihaloalkanes to afford heterocyclic

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

• Marco Manenti,
• Leonardo Lo Presti,
• Giorgio Molteni and
• Alessandra Silvani

Beilstein J. Org. Chem. 2022, 18, 303–308, doi:10.3762/bjoc.18.34

• products we disclosed the efficient homocoupling of oxindole-based N-tert-butanesulfinyl imines, with the generation of chiral, quaternary 1,2-diamines in a mild and completely stereoselective way. The obtained 3,3′-bisoxindole derivatives were fully characterized by NMR and single-crystal X-ray

• the bis(cyclotryptamine) family [24][25][26][27]. In light of these considerations and as, to our knowledge, no borylcopper-mediated homocoupling of N-tert-butanesulfinyl imines have been documented before, we consider useful to share our findings and to accurately describe the obtained products

• products, besides relying on performed control experiments, we also refer to the underdeveloped umpolung reactions of imines, considering, in particular, the copper-catalyzed process reported quite recently by Zhang, Hou and co-workers [29]. In our case, we presume the possible reaction mechanism shown in

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• cyclopropenimines exemplify Brønsted base organocatalysts that are useful for diverse reactions not easily accessible by other means. Here, Lambert and co-workers employed this type of catalyst in the formation of pyroglutamates via enantioselective Michael addition of amino ester imines [22]. Phase-transfer

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

• . These data indicated that 47b targets p38 kinase and NF-κB and may serve as an anti-inflammatory agent (Scheme 13). In 2020, Almeida and co-workers [92] synthesized naphthoquinone imines from β-NQSNa (18) with modifications in β-carbonyls. These compounds were obtained in a sequence of reactions

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• imines, Schiff bases have the general organic function -C=N- [2], and are known to have a wide range of biological activities, including antioxidant [3], antitubercular [4], antibacterial [5], antimicrobial [6], and antifungal properties [7], in addition to their role as chemosensors [8] (Figure 1

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• well as by Sm(OTf)3-catalyzed stereoselective [3 + 2] cycloaddition of bis-silyldienediolate and imines, in turn synthesized from anthranylamides and benzaldehydes [32]. A promising approach to the synthesis of 2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-one derivatives substituted at the pyrrolidine

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

• reactants, resulting in enantioenriched 3,3'-bisindole derivatives with multiple chirality. In the presence of the chiral phosphoric acid catalyst CPA 9, various groups of 2-substituted 3,3'-bisindoles and isatin-derived imines were tolerated and gave good to high yields (up to 80%) and moderate to

• I-15 leads to enamine I-16. In the presence of the CPA catalyst, an intramolecular Michael addition of the amino group to the enamine in I-16 leads to I-17. Subsequently, the imines I-15 and I-17 are converted to the intermediate I-18, which through elimination by cleavage of the C–C bond gives the

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• give imines, iminium salts, aldehydes and other, in some cases dimeric products [49]. Here, oxidation of the benzylic amino moiety should lead either to iminium ions (or N-acyl iminium ions) 4a as strong electrophiles or to stabilized radicals 4b which could undergo cyclization to give the fluorenone

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• , including enantioselective H-bonding-catalyzed additions to aliphatic N-Boc-imines with high stereoselectivity [22]. A broad range of β-aminonitroolefins were reduced to chiral β-aminonitroalkanes in high yields and excellent enantioselectivities using trichlorosilane as a reducing agent and an N

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• of prolinol silyl ether (cat. 120) and benzoic acid (A1) catalysts to bring about reaction between 3-formyl-substituted indoles or pyrroles 118 and diverse electrophiles, including carbonyls, imines and other Michael acceptors (Scheme 5) [69]. The reaction with secondary amines occurred via the

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• Scott Benz Andrew S. Murkin Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, New York 14260-3000, United States 10.3762/bjoc.17.172 Abstract In the presence of a suitable acid or base, α-hydroxyaldehydes, ketones, and imines can undergo isomerization that

• ; Introduction When treated with base, acid, heat, or light, many α-hydroxyaldehydes, ketones, or imines 1 undergo a 1,2-shift of one of the α-substituents to the adjacent unsaturated carbon, with a concomitant proton transfer to form compounds of type 2 (Figure 1) [1]. Differing from the related Wagner–Meerwein

• compounds; or (4) the use of imines (X = NR′′), which lead to more stable α-amino ketones. The α-ketol or α-iminol rearrangement is a synthetic organic tool used for ring expansions and contractions and other isomerizations that is also used in some biological pathways [2][3]. Works featuring these

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

• between N-heteroarenes 69 and redox-active esters 68. In 2018, Gong and co-workers [43] used benzyltrifluoroborates 71 as a benzylic radical source for the visible-light-induced alkylation of imines 70. In the catalytic system, chiral ligands initiated benzylic radical formation and governed the

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• pyridine derivatives have been developed through the intramolecular or intermolecular tandem addition annulation/functionalization of alkynes with some N-containing compounds, such as nitriles, oximes, and imines [15][16][17][18][19]. The pyrrole structural motif is also an invaluable five-membered N

Enantioselective PCCP Brønsted acid-catalyzed aminalization of aldehydes

• Martin Kamlar,
• Robert Reiberger,
• Martin Nigríni,
• Ivana Císařová and
• Jan Veselý

Beilstein J. Org. Chem. 2021, 17, 2433–2440, doi:10.3762/bjoc.17.160

• from preformed imines instead of aldehydes catalyzed by BINOL-phosphoric acid [17]. The corresponding aminals were prepared with a wide range of substitutions using aromatic, α,β-unsaturated, or aliphatic imines. Apart from chiral phosphoric acids, chiral quaternary ammonium salts were successfully

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

• -workers reported in 2004 an asymmetric Pictet–Spengler reaction of tryptamine-derived imines 4 in the presence of acetyl chloride and 2,6-lutidine, where the chiral thiourea catalyst 6 was employed to enable good yields and enantioselectivities (Scheme 2a) [32]. The initial motivation of their first

• participating directly as the nucleophile. First proposed anion-binding mechanism in the thiourea-catalyzed acetalization of benzaldehyde. a) Thiourea-catalyzed enantioselective acyl-Pictet–Spengler reaction of tryptamine-derived imines 4. b) Equilibrium between the ionic (SN1-type mechanism) and neutral form

Facile and innovative catalytic protocol for intramolecular Friedel–Crafts cyclization of Morita–Baylis–Hillman adducts: Synergistic combination of chiral (salen)chromium(III)/BF₃·OEt₂ catalysis

• Karthikeyan Soundararajan,
• Helen Ratna Monica Jeyarajan,
• Raju Subimol Kamarajapurathu and
• Karthik Krishna Kumar Ayyanoth

Beilstein J. Org. Chem. 2021, 17, 2186–2193, doi:10.3762/bjoc.17.140

• reaction at a yield of 61% and 72%, respectively. Encouraged by the outcome of this non-catalytic cycloaddition reaction, similar studies using 2-substituted-1H-indenes (6a–f) with azomethine imines are underway. Conclusion In summary we have developed an efficient synthetic protocol for intramolecular

Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)

• Tania Xavier,
• Sylvie Condon,
• Christophe Pichon,
• Erwan Le Gall and
• Marc Presset

Beilstein J. Org. Chem. 2021, 17, 2085–2094, doi:10.3762/bjoc.17.135

• widespread applications being aldol or Mannich-type addition reactions with carbonyl compounds and imines, respectively [4], and Galat olefination reactions of aldehydes [5][6][7]. Nevertheless, these developments have been mostly described with unsubstituted MAHOs, and the use of mono-substituted MAHOs

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• of α-substituted glutamates and pyroglutamates via a cyclopropenimine-catalyzed Michael addition of amino ester imines is described. Enantioselectivities of up to 94% have been achieved, and a variety of functional groups were found to be compatible. The impact of the catalyst structure and imine

• strategy for the enanantioselective conjugate addition of amino acid derivatives for this reaction remains an unmet goal. Our group previously described a chiral cyclopropenimine catalyst that displayed outstanding reactivity for addition reactions of glycine imines [40][41]. We hypothesized that this

• reactivity might be sufficient to overcome the reactivity limitations of pronucleophiles derived from other α-amino esters [42]. In this paper, we describe the use of cyclopropenimine catalysis for the enantioselective catalytic Michael reaction of α-substituted amino ester imines. Results and Discussion To

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

• reaction between 4-hydroxycoumarins 1 and aromatic imines 63 for the synthesis of α-benzylaminocoumarins 64 [54]. Among the cinchona alkaloid derivatives evaluated in this reaction, cupreine (65) was found to be the best option in terms of yields and enantioselectivities (Scheme 20). Both electron

• recently, the strategy via introducing secondary interactions for the design of the bifunctional catalysts achieved wide application in asymmetric reactions [74]. Wu et al. described a Mannich asymmetric addition of cyanocoumarins 39 to isatin imines 112 catalyzed by an amide-phosphonium salt 114. This

• -hydroxycoumarins (1) and aromatic imines 63 promoted by cupreine (65). Asymmetric addition of malonic acid half-thioesters 67 to coumarins 66 using the sulphonamide organocatalyst 69. Enantioselective 1,4-addition of azadienes 71 to 3-homoacyl coumarins 70. Michael addition/intramolecular cyclization of 3

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

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

• obtained exclusively as the trans diastereoisomer (Scheme 26B). Based on the previous work using the Fe(III)/silane system to promote hydrogen atom transfer to olefins, the Xu group explored the use of unsaturated imines 70 as radical acceptors in MHAT-driven radical conjugate additions with olefins [94

• good yields (Scheme 27A, 72a–j). However, better yields were observed with substrates with aromatic electron-donor substituents (72a and 72i). Other olefin-tethered functional groups were tolerated under the reaction conditions (Scheme 27A, 72k–n), and S-containing imines also delivered the alkylated

A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

• Greta Utecht-Jarzyńska,
• Karolina Nagła,
• Grzegorz Mlostoń,
• Heinz Heimgartner,
• Marcin Palusiak and
• Marcin Jasiński

Beilstein J. Org. Chem. 2021, 17, 1509–1517, doi:10.3762/bjoc.17.108

• -8057 Zurich, Switzerland Department of Physical Chemistry, Faculty of Chemistry, University of Lodz, Pomorska 163/165, 90236 Łódź, Poland 10.3762/bjoc.17.108 Abstract In-situ-generated N-aryl nitrile imines derived from trifluoroacetonitrile efficiently react with polycyclic 1,4-quinones, yielding

• naphthoquinone-derived products and low-intensity bands in the visible region (≈400 nm) for the anthraquinone series. Keywords: [3 + 2]-cycloadditions; fluorinated compounds; fused pyrazoles; N-heterocycles; nitrile imines; 1,4-quinones; Introduction The 1,4-quinone scaffold belongs to the most important

• exclusively [16]. Noteworthy, [3 + 2]-cycloadditions of nitrile imines to the C=O group of 1,4-quinones have not yet been reported. In a historical work by Rolf Huisgen et al., the first [3 + 2]-cycloadditions of some 1,4-quinones, e.g., 1,4-naphthoquinone (1a), with C,N-diphenyl nitrile imine (2) were

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

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

• -butanesulfinyl imines as reaction intermediates, including the synthesis of several natural products. The synthesis of nitrogen-containing heterocycles in which the nitrogen atom is not provided by the chiral imine will not be considered in this review. The sections are organized according to the size of the

• -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