Asymmetric Michael addition reactions catalyzed by calix[4]thiourea cyclohexanediamine derivatives

• Zheng-Yi Li,
• Hong-Xiao Tong,
• Yuan Chen,
• Hong-Kui Su,
• Tangxin Xiao,
• Xiao-Qiang Sun and
• Leyong Wang

Beilstein J. Org. Chem. 2018, 14, 1901–1907, doi:10.3762/bjoc.14.164

• clearly showed that the upper rim-functionalized hydrophobic calixarene scaffold played an important role in cooperation with the catalytic center to the good reactivities and enantioselectivities. Keywords: asymmetric Michael addition reaction; calix[4]arene; cyclohexanediamine; thiourea; Introduction

• convenience and good stereoselectivity [5][6]. Accordingly, different versions of this reaction have been extensively studied. Notably, the Michael addition reaction of 1,3-dicarbonyl compounds to conjugated nitroalkenes is very important for the synthesis of chiral nitro carbonyl compounds, such as bioactive

• the new chiral amino-substituted thioureas [33][39]. For this, the Michael addition reaction of acetylacetone (8) to β-nitrostyrene (7a) was chosen as the model reaction to evaluate the efficiency of compounds 1–4 as chiral organocatalysts (Table 1, entries 1–4). From Table 1, it can be seen that the

Water-soluble SNS cationic palladium(II) complexes and their Suzuki–Miyaura cross-coupling reactions in aqueous medium

• Alphonse Fiebor,
• Richard Tia,
• Banothile C. E. Makhubela and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1859–1870, doi:10.3762/bjoc.14.160

• bond distances (Å) and bond angles (°); S(1)–Pd(1)–Cl(1) 93.27(4), S(2)–Pd(1)–Cl(1) 93.34(4), N(1)–Pd(1)–S(1) 86.70(9), N(1)–Pd(1)–S(2) 86.71(9), C(6)–S(1)–C(9) 100.2(2), C(7)–S(2)–C(13) 102.72(2), S(1)–C(6) 1.808(4), S(2)–C(7) 1.816(4), Pd(1)–Cl(1) 2.3044(10). Energy profile for the oxidative addition

• reaction involving 4-bromoanisole and Pd(II) catalyst precursor 17d. The change in energy for 17d was calculated by computing it in kcal/mol as a cation at 298.15 K and 1 atm. Reusability of pincer complex 17d as a catalyst for the Suzuki–Miyaura cross coupling reaction. Synthesis of pincer ligands 19a–d

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• asymmetric Michael addition reaction of thiophenol could be catalyzed by inherently chiral calixarenes bearing amino alcohol/phenol structure [47][48]. In order to see the effect of the diarylmethanol moiety, Shirakawa and Shimizu used 43 (Figure 6) as organocatalyst in the Michael addition reaction between

• -cyclohepten-1-one and chalcone were also tested as substrates for the Michael addition reaction and the corresponding adducts were obtained in good yield with moderate enantioselectivity (13–23% ee). Calixarene-derived thiourea seemed to be an interesting backbone for design of new organocatalysts for

• the presence of calix[4]arene ligands 36–39. Asymmetric hydrogenation of 41a and 41b catalyzed by in situ-generated catalysts comprised of [Rh(COD)2BF4] and calix[4]arene-based chiral diphosphite ligands [(S,S)-40]. Asymmetric Michael addition reaction of 44 with 45 catalyzed by 43. Asymmetric Michael

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

Hypervalent iodine-guided electrophilic substitution: para-selective substitution across aryl iodonium compounds with benzyl groups

• Cyrus Mowdawalla,
• Faiz Ahmed,
• Tian Li,
• Kiet Pham,
• Loma Dave,
• Grace Kim and
• I. F. Dempsey Hyatt

Beilstein J. Org. Chem. 2018, 14, 1039–1045, doi:10.3762/bjoc.14.91

• solubility of trifluoroborates in the solvents used. The displacement of silyl and boron groups with hypervalent iodine seems to suggest that a transmetallation event from Si/B to I is occurring rather than an addition reaction to the unsaturation of the benzyl group followed by elimination of the metalloid

Gram-scale preparation of negative-type liquid crystals with a CF₂CF₂-carbocycle unit via an improved short-step synthetic protocol

• Tatsuya Kumon,
• Shohei Hashishita,
• Takumi Kida,
• Shigeyuki Yamada,
• Takashi Ishihara and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 148–154, doi:10.3762/bjoc.14.10

• addition reaction, a Michael addition reaction, giving rise to the corresponding magnesium enolate Int-L. The subsequent hydrolysis of Int-L then leads to the γ-hydroxyketone 8a', which easily tautomerizes into the more stable 5-membered hemiacetal 8a. From the above insight into the reaction mechanism, if

• the 1,2-addition reaction of Int-I proceeds in preference to the conjugate addition reaction, the desired octa-1,7-diene 5a should be produced in higher yield. However, no significant improvement was observed after various attempts such as employing a more nucleophilic lithium reagent instead of the

From dipivaloylketene to tetraoxaadamantanes

• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2018, 14, 1–10, doi:10.3762/bjoc.14.1

• dimerization of dipivaloylketene (2), itself obtained in high yield by FVP of furan-2,3-dione 6 (Scheme 3). Ketene 3 reacts with a variety of nucleophiles in an addition reaction to the ketene function, thereby transforming the ketene to enol derivatives 14 or 9 of 1,3-dioxin-4-ones. Subsequently, these enols

Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

• Irwan Iskandar Roslan,
• Kian-Hong Ng,
• Gaik-Khuan Chuah and
• Stephan Jaenicke

Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270

• bonds and its subsequent cleavage by the triflate forms B [99]. The InIII metal center also coordinates to the keto carbon of methyl acetoacetate (2a) and thus brings both substrates in close proximity to one another [100][101]. An addition reaction ensues the formation of C which is followed by proton

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• addition reaction only in reactions with methyl iodide and benzyl iodide [9]. A similar alkylation of isopropenyldiphenylphosphine with methyl iodide in ether solution under a nitrogen atmosphere leading to isopropenylmethyldiphenylphosphonium iodide (3) in a yield of 97% was described by Schweizer and

Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones

• Sergii V. Melnykov,
• Andrii S. Pataman,
• Yurii V. Dmytriv,
• Svitlana V. Shishkina,
• Mykhailo V. Vovk and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259

• -methoxyethyl substituents which demonstrated low reactivity in the addition reaction with ester analogue 1a. It can thus be inferred that the substituents R1 and R2 have almost no impact on the outcome of the decarboxylative addition provided a highly reactive nucleophilic component such as malonic acid

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• Ellman’s chiral sulfinamide to provide a sulfinylimine [29][30][31][32][33][34], which was reacted with (trimethylsilyl)ethynyllithium [1][14][45][46][47][48]. The terminal TMS group was cleaved off after the addition reaction [49][50] (Table 1). Several conditions for the condensation of aldehydes with

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• exclusively [69]. In the case of the isomeric 2,3- and 3,4-diaminopyridines, the initial addition reaction occurred via the attack of the more nucleophilic NH2 group at the 3-position [69]. Less nucleophilic 1,2-diamines, such as 5,6-diaminouracil and -thiouracil or 1,2-diaminobenzimidazole, react with E-1 in

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• Na2CO3. The efficiency of the addition reaction depends on both electron enrichment of the aromatic ring and the electron-withdrawing character of the substituent in nitrosoalkene NSA14. 1,3-Dimethoxybenzene gave the corresponding substitution products in highest yield, while anisole proved to be

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• K2CO3 (Scheme 3). Michael adducts were isolated with good to excellent yield (76–99%) in a high-speed vibration mill (HSVM) within 10–60 min [51]. Bolm and co-workers reported an organocatalytic asymmetric version of Michael addition reaction under planetary-milling (PM) conditions. Differently

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• more nucleophilic in the addition reaction to isocyanates (Scheme 15a). The ability to selectively convert o-pda into non-symmetrical mono-thioureas provided an opportunity to synthesize hybrid urea–thiourea derivatives 37a–d in a one-pot, two-step mechanochemical solvent-free process. After ball

• hydantoins. The in situ basic conditions, necessary for the deprotonation of the amino acid methyl ester hydrochloride salts in order to make the amino group nucleophilic, were generated by the hydrolysis of KOCN. Following the addition reaction with KOCN starting from hydrochloride salts of L-phenylalanine

Transition-metal-free one-pot synthesis of alkynyl selenides from terminal alkynes under aerobic and sustainable conditions

• Adrián A. Heredia and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2017, 13, 910–918, doi:10.3762/bjoc.13.92

• , respectively). This result shows that under the conditions used, the Ph2Se2 addition reaction to the triple bond competes with Se-alkynylation. This side reaction is less efficient when the concentration decreases, favoring the reaction of interest when the amount of solvent increases. Subsequently, a set of

• ). However, with 6-bromohex-1-ene the yield of compound 5d dropped to 41% (Table 3, entry 5) and 2-methyltetrahydro-2H-selenopyran was detected by GC–MS. This indicates a possible competitive intramolecular addition reaction between the selenium atom-centered radical and the alkenyl moiety. The reaction with

The synthesis of α-aryl-α-aminophosphonates and α-aryl-α-aminophosphine oxides by the microwave-assisted Pudovik reaction

• Erika Bálint,
• Ádám Tajti,
• Anna Ádám,
• István Csontos,
• Konstantin Karaghiosoff,
• Mátyás Czugler,
• Péter Ábrányi-Balogh and
• György Keglevich

Beilstein J. Org. Chem. 2017, 13, 76–86, doi:10.3762/bjoc.13.10

• compounds. Study on the addition of diethyl phosphite to N-benzylidene(butyl)amine by in situ FTIR spectroscopy Then, we wished to follow the addition reaction of DEP to N-benzylidene(butyl)amine (1a) at 80 °C in acetonitrile (Scheme 2) by in situ Fourier transform IR spectroscopy. Initially the IR spectra

• scale. This calculation (MCR-ALS, multivariate curve resolution – alternating least squares) gives the concentration profiles of the components and also the spectra of pure components. From Figure 3, it can be seen that the addition reaction was complete after 3.5 h. Finally, the characteristic IR

• components in the addition reaction at 80 °C in acetonitrile. Atomic numbering with anisotropic displacements plot of 5b at −100 °C. Atomic numbering with anisotropic displacements plot of 5d at −100 °C. The energy diagram for the reaction with dimethyl phosphite. The energy diagram for the reaction with

p-Nitrophenyl carbonate promoted ring-opening reactions of DBU and DBN affording lactam carbamates

• Madhuri Vangala and
• Ganesh P Shinde

Beilstein J. Org. Chem. 2016, 12, 2086–2092, doi:10.3762/bjoc.12.197

• products [12]. Subsequently, Ma and Dolphin isolated chlorin-e6 lactams from the reaction of methyl pheophorbide with DBU and DBN promoted by trialkyl triflates [13]. Additionally, the conjugate addition reaction of DBU to diarylpyrone [14] and Baylis–Hillman acetates [15] also gave caprolactam products. A

Enantioselective addition of diphenyl phosphonate to ketimines derived from isatins catalyzed by binaphthyl-modified organocatalysts

• Hee Seung Jang,
• Yubin Kim and
• Dae Young Kim

Beilstein J. Org. Chem. 2016, 12, 1551–1556, doi:10.3762/bjoc.12.149

• of organocatalysts [38][39][40][41][42][43][44][45], we have reported the catalytic asymmetric decarboxylative aldol addition reaction of isatins with benzoylacetic acids catalyzed by chiral binaphthyl-based squaramide [46]. Here we wish to report the enantioselective addition reaction of diphenyl

• phosphonate to ketimines derived from isatins catalyzed by binaphthyl-modified bifunctional organocatalysts (Figure 1). Results and Discussion To determine suitable reaction conditions for the organocatalytic enantioselective addition reaction of diphenyl phosphonate to ketimines derived from isatins, we

• at room temperature (Table 1, entries 1–6). Catalyst III, which is a binaphthyl-modified squaramide bifunctional organocatalyst, was the best catalyst for this enantioselective addition reaction (90% ee, Table 1, entry 3). In order to improve the selectivity, different solvents were tested in the

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• one-pot reaction of 2-bromobenzaldehydes 169, alkynes 170, amines 171, and diethyl phosphonate under multicatalytic conditions including palladium and copper salts (Scheme 37) [75]. This process presumably involves a sequential Sonogashira coupling/cyclization-nucleophilic addition reaction, which is

Towards the total synthesis of keramaphidin B

• Pavol Jakubec,
• Alistair J. M. Farley and
• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1096–1100, doi:10.3762/bjoc.12.104

• catalyst. We reasoned that a similar catalytic approach could be used to fix the absolute stereochemical configuration in the Michael addition reaction between δ-valerolactone pronucleophile 8 and nitro-olefin 9, although a degree of uncertainty as to the relative stereochemical outcome of the catalyst

• -valerolactone (10) with dimethyl carbonate, using LHMDS as the base, in 83% yield. The furanyl nitroolefin 11 was readily synthesised on multigram scale via a Henry condensation, according to literature procedures [20]. We were delighted to observe that the Michael addition reaction using our previously

• . Having played a key role in the Michael addition reaction and the nitro-Mannich lactamisation cascade, at this stage the nitro functionality had fully served its purpose. Accordingly, traceless reductive cleavage of the nitro group [22] using tributyltin hydride and AIBN was carried out to afford

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• acceptors in reactions promoted by bifunctional Brønsted bases. 1.2.1 Nitroalkenes as acceptors. Investigation of the base-catalyzed Michael addition reaction of 2-thio-1H-imidazol-4(5H)-ones 4 to nitroalkenes 5 [55] revealed that cinchona alkaloids such as quinine, (DHQ)2Pyr or even thiourea tertiary amine

• demonstrated to be either less reactive and/or less stereoselective in their addition reaction to nitrostyrene thus affording the corresponding Michael adducts with no diastereoselectivity and/or poor enantioselectivity (Scheme 3). Useful applications of the Michael adducts coming from the Michael addition of

• addition reaction of imidazolones to simple unsaturated esters and ketones revealed that whilst these reactions worked sluggish, they proceeded efficiently when α-silyloxyenones were used as Michael acceptors. In these cases and, under the conditions shown in Scheme 5, reaction of the 1,5

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• studies [123][124]. It should also be noted that a biomimetic domino guanidinylation–aza-Michael-addition reaction for the synthesis of the capreomycidine scaffold has been developed, which only furnished the target structures as stereoisomeric mixtures though [125]. The epicapreomycidine-derived

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• -pyran-6-carboxylate 3 using organocatalyst 4 [16]. Possible hydrogen-bonding for the reaction of (E)-methyl 2-oxo-4-phenylbut-3-enoate [16]. Asymmetric desymmetrization of 4,4-cyclohexadienones using the Michael addition reaction with malonates [17]. The enantioselective synthesis of α,α-disubstituted

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• vinylogous Michael addition reaction [48]. In this process, cyclic enones 52 are added to nitroalkenes 41 using dienamine catalysis (Scheme 13). Although no model is suggested with respect to how the 6’-OH is involved, it is clearly of importance as the analogous 6’-OMe derived cupreine catalyst gives