Emission solvatochromic, solid-state and aggregation-induced emissive α-pyrones and emission-tuneable 1H-pyridines by Michael addition–cyclocondensation sequences

• Natascha Breuer,
• Irina Gruber,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 2684–2703, doi:10.3762/bjoc.15.262

• Strukturchemie, Universitätsstraße 1, D-40225 Düsseldorf, Germany 10.3762/bjoc.15.262 Abstract Starting from substituted alkynones, α-pyrones and/or 1H-pyridines were generated in a Michael addition–cyclocondensation with ethyl cyanoacetate. The peculiar product formation depends on the reaction conditions as

• alkynylation–Michael addition–cyclocondensation (AMAC) multicomponent syntheses of α-pyrones [23]. While most α-pyrones neither fluoresce in solution nor in the solid state specific substitution patterns have been identified for fluorophore design for this heterocyclic family. Tominaga and co-workers

• effects of base and temperature on Michael addition–cyclocondensation sequences in the formation of α-pyrones and/or 1H-pyridines starting from diversely substituted alkynones and cyanoethylacetate. This bifurcating domino process furnishes small chromophore libraries which were characterized by

1,5-Phosphonium betaines from N-triflylpropiolamides, triphenylphosphane, and active methylene compounds

• Vito A. Fiore,
• Chiara Freisler and
• Gerhard Maas

Beilstein J. Org. Chem. 2019, 15, 2603–2611, doi:10.3762/bjoc.15.253

• their isolation and structural characterization are still less common. A very convenient access to such betaines is provided by the nucleophilic addition of tertiary phosphanes to electron-deficient alkenes, alkynes and allenes (phospha-Michael addition), which generates the betaines as reactive

• -catalyzed reactions of acetylenic ketones and esters with pinacolborane have been discussed [7][8]. The Michael addition of PPh3 at acetylenic carbonyl compounds generates phosphonium/vinyl anion intermediates which have been trapped with CH-, NH-, OH- and SH-acids [5]. In this manner, the 1:1:1 reaction of

• (Scheme 2). They turned out to be excellent substrates for transamidation reactions (reaction 1) [18], whereas tertiary phosphanes Ph2P–X (X = SiMe3, Cl) underwent Michael addition leading to silylphosphanylation (reaction 2) or hydrophosphorylation (reaction 3) of the C–C-triple bond, respectively [19

Synthetic terpenoids in the world of fragrances: Iso E Super^® is the showcase

• Alexey Stepanyuk and
• Andreas Kirschning

Beilstein J. Org. Chem. 2019, 15, 2590–2602, doi:10.3762/bjoc.15.252

• ]. Oxidation, iodocarboxylation and elimination yielded the lactone 43. A series of functional group manipulations provided enone 44, which underwent a cuprate-mediated Michael addition and liberation of the aldehyde 46 upon ozonolysis. After intramolecular aldol condensation the resulting enone 47 was

Targeted photoswitchable imaging of intracellular glutathione by a photochromic glycosheet sensor

• Xianzhi Chai,
• Hai-Hao Han,
• Yi Zang,
• Jia Li,
• Xiao-Peng He,
• Junji Zhang and
• He Tian

Beilstein J. Org. Chem. 2019, 15, 2380–2389, doi:10.3762/bjoc.15.230

• high intracellular concentration of GSH is another feature for HepG2 cells. Therefore, amounts of work on HepG2 cell imaging have targeted GSH as the characteristic biomarker [40][41]. Strategies like reduction of disulfide [42][43][44] and Michael addition [45][46][47] have been utilized to design

Synthesis of 1-azaspiro[4.4]nonan-1-oxyls via intramolecular 1,3-dipolar cycloaddition

• Yulia V. Khoroshunova,
• Denis A. Morozov,
• Andrey I. Taratayko,
• Polina D. Gladkikh,
• Yuri I. Glazachev and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2019, 15, 2036–2042, doi:10.3762/bjoc.15.200

• and 3-nitropentane (Scheme 1). In brief, the reaction of nitrocyclohexane and acrolein in a CH3ONa/CH3OH solution afforded the corresponding nitroaldehyde 3b with a 70% yield. Of note, the Michael addition of 3-nitropentane to acrolein was accompanied by remarkable tarring and gave a much lower yield

Fluorinated azobenzenes as supramolecular halogen-bonding building blocks

• Esther Nieland,
• Oliver Weingart and
• Bernd M. Schmidt

Beilstein J. Org. Chem. 2019, 15, 2013–2019, doi:10.3762/bjoc.15.197

• ][22][23][24]. Huber and co-workers demonstrated the activation of a carbonyl group by halogen bonding, and successfully applied this concept to catalysts for Michael addition reactions [25] and also employed neutral [26], and hypervalent iodolium derivatives as activators in a halide abstraction

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• ]pyrrolidin-1-yl group [64]. The synthesis of the corresponding pyrrolidine (3S,3'R)-68 began from the aziridine (E)-acrylate (2R,1'S)-69a (Scheme 18) readily prepared from the aldehyde (2S,1'S)-6 [31]. Michael addition of nitromethane to the acrylate (2R,1'S)-69a gave an inseparable mixture (70:30) of

• -Boc-3,4-diaminopentanoic acid ((3R,4S)-155) was synthesized from the Z-acrylate (2R,1'R)-156a prepared in a highly (88:12) stereoselective olefination of the aziridine aldehyde (2S,1'R)-6 (Scheme 40) [60]. Michael addition of (S)-1-phenylethylamine to 156a gave almost pure (>99:1) β-amino ester 157

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• -benzenedicarboxylate), Puthiaraj and co-workers have unprecedently discovered the catalytic activity of this metal-organic framework (MOF) for the synthesis of imidazo[1,2-a]pyridines [100]. The three-component, one-pot reaction between 1, 3 and nitromethane (10, Scheme 5) involved an intermolecular aza-Michael

• addition with a subsequent intramolecular cyclization catalyzed by Cu(BDC)MOF. Further, the LC–MS study of the reaction mixture has shown the imine formation to be the major pathway rather than β-nitrostyrene. The reaction involved a two-step reaction mechanism in which aza-Michael adduct 13 was formed in

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• covalent inhibitor of 4-amino-4-deoxychorismate (ADC) synthase, which is the enzyme that catalyzes the conversion of chorismate and glutamine into ADC and glutamate, the first step in the biosynthesis of p-aminobenzoic acid (PABA) in bacteria [6]. Specifically, AbC binds via a Michael addition between a

• , which suggests a suitable level of structural truncation of compound 2. Further docking studies, using covalent docking, also showed that both atrop-O-benzyl-desmethyl-abyssomicin C and 2 can bind to the active site cysteine via a Michael addition to the α,β-unsaturated ketone, still maintaining the

One-pot activation–alkynylation–cyclization synthesis of 1,5-diacyl-5-hydroxypyrazolines in a consecutive three-component fashion

• Christina Görgen,
• Katharina Boden,
• Guido J. Reiss,
• Walter Frank and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 1360–1370, doi:10.3762/bjoc.15.136

• diphenylbut-3-yne-1,2-dione (3a) increased from 63 to 76%. The terminal cyclization step, consisting of a Michael addition of benzoyl hydrazide (4b) to diphenylbut-3-yne-1,2-dione (3a) followed by a cyclizing addition of the central hydrazide nitrogen atom to the carbonyl group, was monitored by GC–MS and

• consecutive three-component process clearly is superior. With four bond-forming steps (activation, alkynylation, Michael addition, and cyclization) the average yield per bond-forming step accounts to 94%. With the optimized conditions of the consecutive three-component synthesis in hand (hetero)arylglyoxylic

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

• Alexander N. Reznikov,
• Anastasiya E. Sibiryakova,
• Marat R. Baimuratov,
• Eugene V. Golovin,
• Victor B. Rybakov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2019, 15, 1289–1297, doi:10.3762/bjoc.15.127

• University, Leninskie Gory, 1, 119991, Mosсow, Russian Federation 10.3762/bjoc.15.127 Abstract Functionally substituted sulfones with stereogenic centers are valuable reagents in organic synthesis and key motifs in some bioactive compounds. The asymmetric Michael addition of β-ketosulfones to conjugated

• ; Michael addition; nickel complexes; nitroalkenes; Introduction Sulfones are widely used in organic synthesis, particularly, in various reactions of C–C and C=C-bond formation [1][2][3][4]. The use of sulfones in Julia–Kocienski [1] and Ramberg–Bäcklund reactions [2] made this class of compounds

• acids are attached to 1,2-disubstituted α,β-unsaturated sulfones in the presence of the Rh/(S,S)-chiraphos catalytic system. Modern methods for the synthesis of functionalized sulfones, with stereocenters in the side chain, by Michael addition are based, mainly, on the use of vinyl sulfones as Michael

Ugi reaction-derived prolyl peptide catalysts grafted on the renewable polymer polyfurfuryl alcohol for applications in heterogeneous enamine catalysis

• Alexander F. de la Torre,
• Gabriel S. Scatena,
• Oscar Valdés,
• Daniel G. Rivera and
• Márcio W. Paixão

Beilstein J. Org. Chem. 2019, 15, 1210–1216, doi:10.3762/bjoc.15.118

• asymmetric Michael addition of n-butanal to β-nitrostyrene that was used as a model reaction. This work supports the potential of multicomponent reactions towards the assembly of catalysts and their simultaneous functionalization for immobilization. Keywords: flow chemistry; heterogeneous catalysis

• solvents and conditions. As PFA-supported catalyst 3 proved more effective than 4, a comprehensive screening of solvents was carried out for the asymmetric Michael addition catalyzed by 3. This study showed that the yield can be increased up to 90% using isopropanol (Table 1, entry 9), while the

• material by β-nitrostyrene (50 times as residence time calculated) limits the formation of the Michael product and, consequently, lowers the chemical efficiency. Despite the good level of diastereocontrol in Michael addition (dr 95:5 syn/anti), a little drop in the enantioselectivity was observed (i.e., 74

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

• ) [21][22]. While these methods give access to highly substituted products, the requirement for a strong base could jeopardize their application in the context of synthesis of complex molecules. Furthermore, an electron-withdrawing group must be present on 18 to enable the Michael addition with thiol 14

Electrophilic oligodeoxynucleotide synthesis using dM-Dmoc for amino protection

• Shahien Shahsavari,
• Dhananjani N. A. M. Eriyagama,
• Bhaskar Halami,
• Vagarshak Begoyan,
• Marina Tanasova,
• Jinsen Chen and
• Shiyue Fang

Beilstein J. Org. Chem. 2019, 15, 1116–1128, doi:10.3762/bjoc.15.108

• electrophilic oligodeoxynucleotides (ODNs) was achieved using dimethyl-Dmoc (dM-Dmoc) as amino protecting group. Due to the high steric hindrance of the 2-(propan-2-ylidene)-1,3-dithiane side product from deprotection, the use of excess nucleophilic scavengers such as aniline to prevent Michael addition of the

• that contain electrophilic groups. However, at the current state of art one drawback of the technology is that large excess aniline has to be used as a scavenger to prevent the deprotection side product 1 from reacting with the deprotected ODNs via Michael addition. Aniline is a weak nucleophile, but

• aniline is needed to induce the β-elimination (see Scheme 1) and to prevent the side product 1 from reacting with the deprotected ODN via Michael addition [40]. Aniline is a weak base and only mildly nucleophilic. Electrophiles that are compatible with ODNs but reactive toward it are rare. However, using

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

• hour) generated annulated product 4a arising from C-allylation (C–C bond forming)/intramolecular O-Michael addition (O–C bond forming) sequence. The purification of the crude reaction was easier using the Pd(OAc)2 and dppb system (Table 1, entry 2), which was thus chosen to continue the optimization

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• the authors to propose that the first stage of the reaction would be the insertion of carbon monoxide into the Ar–I bond to produce aryl iodide 107, followed by the reaction with the nitrogen nucleophile to form amide intermediate 108. Finally, intramolecular Michael addition would furnish lactam unit

• involving a sequential enamine formation-Michael addition to produce intermediate 139, followed by intramolecular cyclization to 141 and aromatization through species 142 and 143 (Scheme 40). The cyclization step takes place in a regioselective manner, leading to five-membered heterocycle 141 rather than to

Efficient synthesis of pyrazolopyridines containing a chromane backbone through domino reaction

• Razieh Navari,
• Saeed Balalaie,
• Saber Mehrparvar,
• Fatemeh Darvish,
• Frank Rominger,
• Fatima Hamdan and
• Sattar Mirzaie

Beilstein J. Org. Chem. 2019, 15, 874–880, doi:10.3762/bjoc.15.85

• -one as a suitable Michael acceptor that can react with benzylamine or any primary amine to produce the intermediate A. There is a conjugated system in intermediate A that allows malononitrile to attack through Michael addition and produces the intermediate B (Scheme 2). Due to the presence of acidic

An efficient synthesis of the guaiane sesquiterpene (−)-isoguaiene by domino metathesis

• Yuzhou Wang,
• Ahmed F. Darweesh,
• Patrick Zimdars and
• Peter Metz

Beilstein J. Org. Chem. 2019, 15, 858–862, doi:10.3762/bjoc.15.83

• ; metathesis; Michael addition; organocatalysis; terpenes; Introduction The guaiane sesquiterpene (−)-isoguaiene (1) has been isolated from the liverworts Pellia epiphylla [1] and Dumortiera hirsuta [2] as well as from several Pimpinella species [3][4], while the (+)-enantiomer of 1 has been isolated from the

• feature a domino metathesis event and an organocatalytic Michael addition as the key steps. In closer analogy to our improved synthesis of clavukerin A (2) [8], a relay metathesis [9] of trienyne 3 was expected to lead to the hydroazulene 1 selectively. Trienyne 3 was envisioned to result from a

• stereoselective Michael addition of aldehyde 4 to methyl vinyl ketone [7][8][10] followed by chemoselective elaboration of the two carbonyl functions. Finally, aldehyde 4 was traced back to the commercially available starting material (S)-citronellal (5). On the other hand, a more rarely used enediyne metathesis

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• proceeds through a domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction sequence. Keywords: 2-aminochromene; domino reaction; imidazo[1,2-a]pyridine; 2-iminochromene; Michael addition; multicomponent reaction; oxidation; pyridine amination; Introduction Domino reactions are well

• . Subsequent treatment of the reaction mixture with nucleophile, oxidant and a base leads to the Michael addition on C(4) of the chromene ring to produce 2-aminochromene B with incorporated nucleophilic moiety. Further cyclization and deprotonation furnishes anion C, which is easily oxidized to final product 5

• conclusion, we have developed a practical route towards substituted chromenoimidazopyridines through a sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction, employing cheap and abundant oxidants. The discovered process works in a broad substrate scope with

Nucleofugal behavior of a β-shielded α-cyanovinyl carbanion

• Rudolf Knorr and
• Barbara Schmidt

Beilstein J. Org. Chem. 2018, 14, 3018–3024, doi:10.3762/bjoc.14.281

• Rudolf Knorr Barbara Schmidt Department Chemie, Ludwig-Maximilians-Universität München, Butenandtstrasse 5–13 (Haus F), 81377 München, Germany 10.3762/bjoc.14.281 Abstract Sterically well-shielded against unsolicited Michael addition and polymerization reactions, α-metalated α-(1,1,3,3

Synthesis of indole–cycloalkyl[b]pyridine hybrids via a four-component six-step tandem process

• Muthumani Muthu,
• Rakkappan Vishnu Priya,
• Abdulrahman I. Almansour,
• Raju Suresh Kumar and
• Raju Ranjith Kumar

Beilstein J. Org. Chem. 2018, 14, 2907–2915, doi:10.3762/bjoc.14.269

• condensation–nucleophilic addition to carbonyl–Michael addition–N-cyclization–elimination–air oxidation sequence to afford structurally intriguing indole–cycloalkyl[b]pyridine-3-carbonitrile hybrid heterocycles in excellent yields. Keywords: cycloalkyl[b]pyridine-3-carbonitrile; cyclododecanone; 3-(1H-indol-3

• formation of (E)-3-(4-chlorophenyl)-2-(1H-indole-3-carbonyl)acrylonitrile (8). Simultaneously, the reaction of cyclododecanone (5a) with ammonium acetate affords the enamine 9. The Michael addition of 8 and the enamine 9 yields the intermediate 10. Then the amino group of 10 undergoes intramolecular

Microfluidic light-driven synthesis of tetracyclic molecular architectures

• Javier Mateos,
• Nicholas Meneghini,
• Marcella Bonchio,
• Nadia Marino,
• Tommaso Carofiglio,
• Xavier Companyó and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2018, 14, 2418–2424, doi:10.3762/bjoc.14.219

• Michael addition pathway (see Figure 1b) [6]. Prompted by the interest of developing novel light-driven microfluidic methods for the construction of biologically relevant molecular scaffolds, we investigated the reaction between MBP 1 and 3-unsubstituted coumarin (2a) and chromone (3a, Figure 1c). It was

• through a [4 + 2] cycloaddition manifold. b) Light-driven reaction between 2-MBP A and 3-substituted coumarin D for the synthesis of E through a Michael addition manifold. c) Light-driven reaction between 2-MBPs 1 and coumarin (2a) or chromone (3a) for the synthesis of privileged tetracyclic scaffolds 4

Synthesis and post-functionalization of alternate-linked-meta-para-[2ⁿ.1ⁿ]thiacyclophanes

• Wout De Leger,
• Koen Adriaensen,
• Koen Robeyns,
• Luc Van Meervelt,
• Joice Thomas,
• Björn Meijers,
• Mario Smet and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2190–2197, doi:10.3762/bjoc.14.192

• deprotonation of the OH group and subsequent chloride loss of 4 an o-quinoid structure 9 is formed in situ, that quickly reacts with the deprotonated thiol 10 via Michael addition (Scheme 3, route A) [28][29][30]. However, as aromatic thiols at the benzylic position are good leaving groups, conversely β

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

Assessing the possibilities of designing a unified multistep continuous flow synthesis platform

• Mrityunjay K. Sharma,
• Roopashri B. Acharya,
• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2018, 14, 1917–1936, doi:10.3762/bjoc.14.166

• reaction stream containing Michael addition product is mixed with hydrogen gas (from H2 cylinder) in mixer M7. The resulting two-phase mixture can be passed to reactor R7 packed with Pd/DMPSi-C catalyst and maintained at 100 °C. The reaction stream can then be passed in intermediate tank T7 where unreacted