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

• which a substrate passes through the microreactor without interacting. In some cases, this residence time is measured by the time a dye needs to pass through the reactor. In this work, it was calculated by dividing V0 by the used flow rate (Φ) of 2.5 µL/min. The study of the Michael reaction under

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• /aza-Michael reaction of 3,6-dihydro-1,2-dioxines followed by diastereoselective reduction [25]. Most of these methods employ starting materials or catalysts, which are not commercially available, and also require operationally demanding reaction conditions. Hence a need to develop a simple, efficient

DABCO- and DBU-promoted one-pot reaction of N-sulfonyl ketimines with Morita–Baylis–Hillman carbonates: a sequential approach to (2-hydroxyaryl)nicotinate derivatives

• Soumitra Guin,
• Raman Gupta,
• Debashis Majee and
• Sampak Samanta

Beilstein J. Org. Chem. 2018, 14, 2771–2778, doi:10.3762/bjoc.14.254

• -Michael reaction between MBH carbonates derived from an acrylate/acrylonitrile and N-sulfonyl ketimines as C,N-binucleophiles catalyzed by DABCO, followed by elimination of SO2 under the influence of base and subsequent aromatization in an open atmosphere. Keywords: MBH carbonates; metal-free; N-sulfonyl

• ' fashion to make a very reactive allyl ammonium intermediate 6. The latter further involves in the SN2' reaction with in situ generated carbanion intermediate 1a' forming SN2-adduct 3a. It undergoes an intramolecular aza-Michael reaction in the presence of DABCO, leading to tricyclic product 4a. For the

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

• Gisela V. Saborit,
• Carlos Cativiela,
• Ana I. Jiménez,
• Josep Bonjoch and
• Ben Bradshaw

Beilstein J. Org. Chem. 2018, 14, 2597–2601, doi:10.3762/bjoc.14.237

• takes place from polyfunctionalized cyclohexanones or related compounds through a Michael reaction [7], successive inter- and intramolecular radical processes [8], intramolecular carbene addition/cyclization [9][10], aldol cyclizations either under Lewis acid catalysis [11] or from diazoketones in the

• , following our previously developed procedure, to give decahydroquinoline 1 [23]. The removal of the tert-butyl ester group with TFA, followed by treatment with LiOH in refluxing THF promoted a retro-aza-Michael reaction yielding the ring-opened product 3 [33]. The latter was trapped in situ with benzyl

• bromide to furnish cyclohexenone 4 in 86% overall yield over the two steps from 1. Additionally, the overall transformation from the starting material 2 was also performed in a one-pot sequence involving six reactions, namely, an intermolecular Michael reaction, aldol cyclization, intramolecular aza

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

• During the past decades, asymmetric organocatalysis has played an important role as a tool for the syntheses of chiral molecules under mild conditions [1][2][3][4]. Among these reactions, the asymmetric Michael reaction is a powerful strategy to construct versatile intermediates due to its synthetic

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

• ]annulenes as a novel series of potent and specific αv integrin antagonists starting from 4,5-benzotropone (11) (Figure 4 and Scheme 13) [73]. TBS-enol ether intermediate 68 was first formed by the Mukaiyama–Michael reaction of O-silyl ketene acetal to 4,5-benzotropone (11) at low temperature in the presence

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• intramolecular aza-Michael reaction by means of both a chiral auxiliary and a catalyst for stereocontrol is reported for the synthesis of optically active isoindolinones. A selected cinchoninium salt was used as phase-transfer catalyst in combination with a chiral nucleophile, a Michael acceptor and a base to

• provide 3-substituted isoindolinones in good yields and diastereomeric excesses. This methodology was applied to the asymmetric synthesis of a new pazinaclone analogue which is of interest in the field of benzodiazepine-receptor agonists. Keywords: asymmetric organocatalysis; Aza-Michael reaction; phase

• carbon stereocenter alpha to the nitrogen [10][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]. Though various metal or organic catalysts were used to promote the aza-Michael reaction in different syntheses for the creation of nitrogen–carbon bonds, phase-transfer catalysts were less studied

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• produce compound 98 [213] (Figure 28A). A second example corresponds to the nucleophilic addition of N-heterocyclic phosphine 99 to a nitroalkene (phospho-Michael reaction) as shown in Figure 28B. The thiourea unit in 99 plays a crucial role by assuming intramolecular interaction with the nitro function

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

• bases like NaOH, KOH, NaOEt etc. have been used as catalyst for the Michael addition of 1,3-dicarbonyl compounds to α,β-unsaturated ketones. In 2004, Wang and co-workers first reported a mechanochemical Michael reaction of 1,3-dicarbonyl compounds with chalcones and azachalcones using the mild base

• -(S)-proline derived catalyst [49]. b) Report using α,α-dipeptide-based catalyst [50]. Mechanochemical Michael reaction [51]. Mechanochemical organocatalytic asymmetric Michael reaction [52]. Mechanochemical Morita–Baylis–Hillman (MBH) reaction [53]. Mechanochemical Wittig reactions [55

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

A chiral analog of the bicyclic guanidine TBD: synthesis, structure and Brønsted base catalysis

• Mariano Goldberg,
• Denis Sartakov,
• Jan W. Bats,
• Michael Bolte and
• Michael W. Göbel

Beilstein J. Org. Chem. 2016, 12, 1870–1876, doi:10.3762/bjoc.12.176

• ,S and R,R enantiomers of 25, the best numerical fit is obtained for kS,S/kR,R ≈ 6.5. When both steps, Diels–Alder and Michael reaction, are catalyzed by guanidine 10 in THF (see Table 1), at 45% conversion the R isomer of 28 and the R,R isomer of 25 are the dominant species. However, due to the

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

• -controlled Michael reaction remained present. Accordingly, we chose to probe reactivity and establish relative stereocontrol using a close model system comprising pronucleophile 8 and furanyl nitroolefin 11 (Scheme 1). The δ-valerolactone pronucleophile 8 was synthesised by the enolate acylation of δ

Supported bifunctional thioureas as recoverable and reusable catalysts for enantioselective nitro-Michael reactions

• José M. Andrés,
• Miriam Ceballos,
• Alicia Maestro,
• Isabel Sanz and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2016, 12, 628–635, doi:10.3762/bjoc.12.61

• organocatalysts in the stereoselective aza-Henry reaction [31]. Now we describe the results obtained in different stereoselective nitro-Michael additions promoted by these materials. Results and Discussion The ability of the supported catalysts (II–V) to promote the stereoselective nitro-Michael reaction was

• . General procedure for the nitro-Michael reaction using homogeneous catalysts (I and VI). The reactions were carried out as previously described [29]. To a mixture of nitrostyrene (0.3 mmol) and catalyst (0.015 mmol, 0.05 equiv), the 1,3-dicarbonyl compound (0.6 mmol, 2 equiv) was added and the reaction

• diastereomeric ratio was determined by 1H NMR spectroscopy of the purified product. General procedure for the nitro-Michael reaction using inmobilized catalysts (II, III, IV and V) [29]. To a mixture of β-nitrostyrene (0.3 mmol) and catalyst (0.015 mmol, 0.05 equiv), 1,3-dicarbonyl compound (0.6 mmol, 2 equiv

(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

• reaction providing oxazine derivatives 26, was reported by Ye and co-workers (Scheme 10) [21]. In this reaction, nucleophile 24 is coupled to arylenone 25 to give the desired product. Initially a Michael reaction is taking place, followed by cyclization. After screening of various acids, hydrobromic acid

• it near the enolate. In 2011, You and co-workers described the intramolecular desymmetrization of cyclohexadienones 69 catalyzed by thiourea 71, derived from cinchonine to give a bicyclic system 70 containing two chiral centers, utilizing an aza-Michael reaction (Scheme 24) [34]. The reaction

• constructed via a desymmetrization aza-Michael reaction. That key intermediate 72 was afforded in 91% yield and 97% ee. (Scheme 25). In 2012, Cobb and co-workers developed a novel asymmetric Michael–Michael reaction between nitrohex-4-enoates 73 and nitroolefins 74 to construct a cyclohexene moiety, bearing

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• intermolecular aza-benzoin reaction is followed by an intramolecular oxa-Michael reaction to form the observed product (Scheme 28). Enders reported a cascade reaction which is initiated by an NHC-catalysed aza-benzoin condensation between various aldehydes and nitrosobenzenes to generate the hydroxamic acids 47

Organocatalytic asymmetric Henry reaction of 1H-pyrrole-2,3-diones with bifunctional amine-thiourea catalysts bearing multiple hydrogen-bond donors

• Ming-Liang Zhang,
• Deng-Feng Yue,
• Zhen-Hua Wang,
• Yuan Luo,
• Xiao-Ying Xu,
• Xiao-Mei Zhang and
• Wei-Cheng Yuan

Beilstein J. Org. Chem. 2016, 12, 295–300, doi:10.3762/bjoc.12.31

• bifunctional multiple hydrogen-bond amine-thiourea-catalyzed Michael reaction of acetyl phosphonates with nitroolefins, giving a series of β-substituted nitro compounds with excellent stereoselectivity [34]. Therefore, as part of our research program aimed at establishing new methods for the construction of

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• enantioselective intramolecular oxa-Michael reaction of an α,β-unsaturated amide mediated by a newly developed benzothiadiazine catalyst. The Weinreb amide moiety and bromo substituent of the Michael adduct were utilized for the C–C bond formations to construct the scaffold. All four contiguous stereocenters of

• few asymmetric syntheses relying on the optical resolution of racemic intermediates [16][17][18][23]. Herein we report the first catalytic asymmetric synthesis of the key intermediate 2 through organocatalyzed-enantioselective intramolecular oxa-Michael reaction [24][25][26]. Results and Discussion

• condensation followed by diazo-transfer reaction. The chiral dihydrobenzofuran scaffold (5 or 6) could be synthesized by asymmetric intramolecular oxa-Michael reaction (AIOM) of α,β-unsaturated amides 7 or 8. Such reactions are generally considered to be challenging due to low nucleophilicity of the oxygen

Organocatalytic and enantioselective Michael reaction between α-nitroesters and nitroalkenes. Syn/anti-selectivity control using catalysts with the same absolute backbone chirality

• Jose I. Martínez,
• Uxue Uria,
• Maria Muñiz,
• Efraím Reyes,
• Luisa Carrillo and
• Jose L. Vicario

Beilstein J. Org. Chem. 2015, 11, 2577–2583, doi:10.3762/bjoc.11.277

• Jose I. Martinez Uxue Uria Maria Muniz Efraim Reyes Luisa Carrillo Jose L. Vicario Department of Organic Chemistry II, University of the Basque Country (UPV/EHU), P.O. Box 644, 48080 Bilbao, Spain 10.3762/bjoc.11.277 Abstract The asymmetric and catalytic Michael reaction between α-nitroesters and

• extension of this behaviour to the Michael reaction between α-substituted nitroacetates and nitroalkenes. The Michael reaction is regarded as a fundamental tool for the formation of C–C bonds during the synthesis of complex molecules [33][34][35], in particular, being able to control both the simple and the

• , isolating the other possible diastereoisomer anti-3a in good yield, 88:12 dr and 90% ee. Once we had confirmed the good performance of the reaction in this intermolecular Michael reaction, we proceeded to evaluate the scope of this transformation in order to establish whether this method could be useful and

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• development of asymmetric variants of the Michael reaction. In early studies, chemists relied on chiral auxiliaries [5], heterocuprates [15][16], or natural product-based [17] ligands to induce high to modest stereoselectivity. In 1991, Alexandre Alexakis and co-workers reported the first asymmetric conjugate

• initial discovery [176][177], the Mukaiyama–Michael reaction has emerged as a reliable alternative to the use of metal enolates as nucleophiles in Michael reactions. Katsuki and co-workers reported the first application of this reaction to α,β-unsaturated amides [178]. Their reactions were promoted by

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• anodically generated 1,2-benzoquinone undergoes a Michael reaction with 62 under formation of adduct 63, which is further oxidized to give benzoquinone 64. Finally, anellation proceeds in a second Michael addition step under formation of heterocyclic compound 65. In the reported cases, both the generation of

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• enantioselectivity. In a relatively successful example, the chiral aminophosphine G9 catalyzed the asymmetric double-Michael reaction between o-tosylamidophenyl malonate and 3-butyn-2-one to give the indoline derivative in 69% yield and up to 10% ee (Scheme 53). 2.15 Annulation through tandem Michael addition/Wittig

Primary-tertiary diamine-catalyzed Michael addition of ketones to isatylidenemalononitrile derivatives

• Akshay Kumar and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2014, 10, 929–935, doi:10.3762/bjoc.10.91

• -component version of the reaction by a domino Knoevenagel–Michael sequence. The Michael adduct 4a was transformed into spirooxindole 6 by a reduction with sodium borohydride in a highly enantioselective manner. Keywords: 3,3'-disubstituted oxindoles; Michael reaction; organocatalysis; primary-tertiary

• diamine; spirooxindoles; Introduction The Michael reaction is one of the fundamental carbon–carbon bond forming reactions in organic synthesis, since a plethora of carbon nucleophiles and activated olefins could be expected to give versatile arrangements [1][2][3][4][5][6][7][8]. Among the various

• -tertiary diamine organocatalysts for Michael reaction via enamine activation has not been investigated so far [38]. With readily available and inexpensive natural amino acids as a chiral source, we developed very simple primary-tertiary diamine organocatalysts (Figure 2) for asymmetric aldol reactions [44

Phosphinate-containing heterocycles: A mini-review

• Olivier Berger and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2014, 10, 732–740, doi:10.3762/bjoc.10.67

• synthesis of chiral bicyclic phosphinates 23a–k by domino hydrophosphinylation/Michael/Michael reaction was realized by Fourgeaud et al. (Scheme 10) [25]. Several 1-oxa-3-aza-6-phosphabicyclo[3.3.0]octanes derivatives 23a–k were obtained in yields around 70% by reacting allenes 21 with imines 22 derived

• malonate anion. Tandem hydrophosphinylation/Michael/Michael reaction of allenyl-H-phosphinates. 5-Membered “cyclo-PALA” via intramolecular Mitsunobu reaction. 6-Membered “cyclo-PALA” via intramolecular Mitsunobu reaction. Intramolecular Kabachnik–Fields reaction. Tandem Kabachnik–Fields/alkylation reaction

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• tautomerizes, the authors proposed a plausible mechanism, in which tautomer 113 undergoes cyclization via an intramolecular Michael reaction to give intermediate 114. The next step involves cleavage of the dimethylamine group to afford the thiazole structures 115. In 2003, the same group also described a solid

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• based on a first Diels–Alder cycloaddition, as shown above. However, a recent report of Norsikian, Beau and co-workers described a novel sequence of tandem transformations which combined the Petasis reaction, intramolecular [4 + 2]-cycloaddition, cross metathesis and Michael reaction. This process gave