Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• powerful tool for performing organic reactions [1] and polymerizations [2]. In this context phosphines have proven to be potent Lewis-base catalysts [3][4] for a variety of reactions [5], including but not limited to Rauhut–Currier [6], Morita–Baylis–Hillman [7], and Michael reactions [8][9][10]. In all

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• the synthesis of spirooxindole derivatives continues to be a highly active subject in organic synthesis [31][32][33][34][35]. In recent years, the readily available isatin-derived Morita–Baylis–Hillman (MBH) carbonates have become one of the most powerful reagents for the construction of diverse

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• Morita–Baylis–Hillman carbonates from isatins by using a Lewis base catalytic system (Scheme 52) [84]. Screening several organocatalysts showed that the 1,3-oxo-ethynylation of starting materials with silylethynyl-1,2-benziodoxol-3(1H)-ones 123 was obtained by using catalyst N, while 1,3

• conjugate Lewis base Brønsted acid catalyst. Sulfenylation of deconjugated butyrolactams. Intramolecular sulfenofunctionalization of alkenes with phenols. Organocatalytic 1,3-difunctionalizations of Morita–Baylis–Hillman carbonates. Organocatalytic sulfenylation of β‑naphthols. Acid-promoted

Metal catalyst-free N-allylation/alkylation of imidazole and benzimidazole with Morita–Baylis–Hillman (MBH) alcohols and acetates

• Olfa Mhasni,
• Jalloul Bouajila and
• Farhat Rezgui

Beilstein J. Org. Chem. 2023, 19, 1251–1258, doi:10.3762/bjoc.19.93

• performed using DABCO as an additive, leading to the corresponding 1,4-adducts in 70–84% yields. Keywords: allylic substitution; aza-Michael addition; imidazole; Morita–Baylis–Hillman; Introduction Morita–Baylis–Hillman (MBH) adducts are multifunctionalized compounds having both a hydroxy moiety and a

Selective construction of dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] via three-component reaction

• Ziying Xiao,
• Fengshun Xu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1234–1242, doi:10.3762/bjoc.19.91

• [12][13][14][15]. On the other hand, Morita–Baylis–Hillman (MBH) carbonates of isatins, which could be easily prepared by the MBH reactions of isatins with acrylonitrile or alkyl acrylates also became valuable synthons [16][17][18][19][20][21][22][23][24][25]. The active 3-methyleneoxindoles could act

Morita–Baylis–Hillman reaction of 3-formyl-9H-pyrido[3,4-b]indoles and fluorescence studies of the products

• Nisha Devi and
• Virender Singh

Beilstein J. Org. Chem. 2022, 18, 926–934, doi:10.3762/bjoc.18.92

• medicinal importance is the reason that the synthesis of β-carboline-containing derivatives has been an exciting area for researchers [34][35][36][37][38][39][40]. The Morita–Baylis–Hillman (MBH) reaction is an astonishing C–C bond forming reaction between a carbonyl electrophile and an activated alkene

• group has also investigated the scope of 1-formyl-β-carbolines for generating unique molecular hybrids by application of the Morita–Baylis–Hillman reaction [48][49][50]. It was also revealed from a detailed literature survey that only limited reports have been documented toward exploration of 3-formyl

• methodology is decorated with several advantages like scalability and selectivity. Additionally, no column chromatographic purification was required at any stage and each step was high yielding. After the synthesis of starting materials, the Morita–Baylis–Hillman reaction was explored for C-3

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• (sp3)–H allylic alkylation of 2-alkylpyridines with Morita–Baylis–Hillman (MBH) carbonates is described. A plausible mechanism of the reaction might involve a tandem SN2’ type nucleophilic substitution followed by an aza-Cope rearrangement. Various alkyl substituents on 2-alkylpyridines were tolerated

• ; Morita–Baylis–Hillman carbonates; Introduction Pyridines are among the most important heterocyclic structural moieties in many biologically active natural products, pharmaceuticals, and agrochemicals [1][2][3]. Therefore, the development of efficient strategies for functionalized pyridine derivatives

• acetamides and acetates catalyzed synergistically by a metal acyclic iridium complex and a chiral Cu(I) complex [19]. Besides transition-metal-catalyzed allylic substitution reactions, Lewis-base-catalyzed allylic functionalizations using Morita−Baylis−Hillman (MBH) adducts as electrophilic allylic

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

• .17.140 Abstract The chiral (salen)Cr(III)/BF3·OEt2 catalytic combination was found to be an effective catalyst for intramolecular Friedel–Crafts cyclization of electron-deficient Morita–Baylis–Hillman adducts. In presence of mild reaction conditions the chiral (salen)Cr(III)/BF3·OEt2 complex affords 2

• -substituted-1H-indenes from unique substrates of Morita–Baylis–Hillman adducts via an easy operating practical procedure. Keywords: boron trifluoride etherate; chiral (salen)chromium(III); intramolecular Friedel–Crafts cyclization; Morita–Baylis–Hillman adducts; substituted-1H-indenes; Introduction

• -deficient arenes [4][5][6][7]. Operating FC reactions in versatile synthons such as Morita–Baylis–Hillman (MBH) adducts is a challenging process. Inter/intramolecular Friedel–Crafts reactions of Morita–Baylis–Hillman adducts leads to a variety of products such as quinolinones [8], cycloheptene-6

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

• gram-scale experiment, affording the desired product 21a with excellent yield and ee (Scheme 6b). Ren et al. reported an enantioselective reaction of cyclopent-2-enone-derived Morita–Baylis–Hillman (MBH) alcohols 24 with 4-hydroxycoumarins 1 catalyzed by a chiral primary amine derived from

• described an allylic alkylation reaction between 3-cyano-4-methylcoumarins 39 and Morita–Baylis–Hillman (MBH) carbonates 40 [45]. In this case, the catalyst (DHQ)2PYR 42 activates the MBH substrate and generates the dienolate in the vinylogous coumarin moiety, acting as a base. After the nucleophilic

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• cyclic peptide motif (Scheme 11). Dipeptide substrate 26f decorated with a Morita–Baylis–Hillman carbonate underwent the intramolecular C–H allylation process to yield cyclic peptide 28f under dilute reaction conditions. This macrocyclization strategy introduces an exocyclic olefin motif onto the cyclic

• peptide, which can be further utilized as a Michael acceptor for a variety of nucleophiles. Based on their manganese-catalyzed allylation using Morita–Baylis–Hillman carbonates, the Ackermann group established an applicable late-stage C–H glycosylation of peptides (Scheme 12) [95]. Thus, allylative

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

• Susanne M. Fischer,
• Simon Renner,
• A. Daniel Boese and
• Christian Slugovc

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

• chemistry; organocatalysis; phosphine; solvent-free synthesis; Introduction Phosphines are potent nucleophiles that are used as catalysts in many reactions, like Rauhut–Currier, Morita–Baylis–Hillman or Michael reactions [1][2][3]. The first step of these reactions is a conjugate addition of the phosphine

• -donating groups (e.g., -CH3, -OMe, -NMe2) at the aryl moieties. In this way, the electron density on the phosphorous and thus the nucleophilicity is increased. This strategy has for example been exploited in the reaction of ethyl acrylate with 4-nitrobenzaldehyde [16], in aza-Morita–Baylis–Hillman

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

• employing the gem-disubstituted substrate 42 to obtain 43 in excellent yield and with a slightly better reaction time (1.5 days). Under improved conditions using stoichiometric amounts of vanadium hydride, the unprotected Morita–Baylis–Hillman alcohol 44 was subjected to cyclization to furnish 45 in good

Azidophosphonium salt-directed chemoselective synthesis of (E)/(Z)-cinnamyl-1H-triazoles and regiospecific access to bromomethylcoumarins from Morita–Baylis–Hillman adducts

• Soundararajan Karthikeyan,
• Radha Krishnan Shobana,
• Kamarajapurathu Raju Subimol,
• J. Helen Ratna Monica and
• Ayyanoth Karthik Krishna Kumar

Beilstein J. Org. Chem. 2020, 16, 1579–1587, doi:10.3762/bjoc.16.130

• , Madurai, Tamil Nadu, India 10.3762/bjoc.16.130 Abstract The direct transformation of Morita–Baylis–Hillman (MBH) adducts into molecules of interest is a crucial process wherein allylic hydroxy-protected or halogenated MBH adducts are commonly preferred. Herein, we report an azidophosphonium salt (AzPS

• powerful synthetic tools. Keywords: halomethylcoumarin; Morita–Baylis–Hillman adducts; organocatalyst; phosphonium salt; triazolation; Introduction The presence of versatile functional groups in close proximity classifies Morita–Baylis–Hillman adducts as privileged key scaffolds for synthetic organic

• ]. Among the known synthetic transformations using functionalized MBH adducts, cycloaddition reactions are challenging and attractive for synthetic organic chemists. In this context, acetate-functionalized Morita–Baylis–Hillman adducts have been extensively utilized over other precursors. For example

Synthesis of novel sulfide-based cyclic peptidomimetic analogues to solonamides

• José Brango-Vanegas,
• Luan A. Martinho,
• Lucinda J. Bessa,
• Andreanne G. Vasconcelos,
• Alexandra Plácido,
• Alex L. Pereira,
• José R. S. A. Leite and
• Angelo H. L. Machado

Beilstein J. Org. Chem. 2019, 15, 2544–2551, doi:10.3762/bjoc.15.247

• have been synthesized via solid-phase peptide synthesis and SN2’ reaction on a Morita–Baylis–Hillman (MBH) residue introduced at the N-terminal of a tetrapeptide. This last step takes advantage of the electrophilic feature of the MBH residue and represents a new cyclization strategy occurring. The

• cysteine sulfhydryl side chain to electrophilic Cβ of an O-acetylated Morita–Baylis–Hillman (MBH) adduct residue (Scheme 1). Despite reports describing the use of amino acid residues with nucleophilic side chains to prompt the macrocyclization of peptides and their mimetics, to the best of our knowledge

New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions

• Iveta Chena Tichá,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2019, 15, 830–839, doi:10.3762/bjoc.15.80

• enantioselective reactions (mainly because of the nucleophilic center on the chiral quinuclidine skeleton) [20]. More importantly, they are a privileged class of chiral catalysts, which are well known for their use in Michael additions [21], Morita–Baylis–Hillman reactions [22], and aldol reactions [23], among

• demanding cinchona groups. Additionally, some of these new CD derivatives showed promising results of up to 75% ee in the AAA reactions of Morita–Baylis–Hillman (MBH) carbamates and significant differences depending on the attached cinchona alkaloid (cinchonine, cinchonidine, quinine, quinidine) as well as

• the decarboxylative asymmetric allylic amination of a Morita–Baylis–Hillman carbamate (10 mol % of catalyst, up to 75% ee, up to 76% isolated yield). We believe that these new CD derivatives comprising cinchona alkaloids will be suitable catalysts of other asymmetric reactions using them under green

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• substitution at C3 [63]. As illustrated with the preparation of alcohol 60, the strategy relies on a sila-Morita–Baylis–Hillman reaction between cyclopropenylsilane 59 and 3-phenylpropanal catalyzed by electron-rich tris(2,4,6-trimethoxyphenyl)phosphine (TTMPP) [63]. After desilylation, cyclopropenylcarbinol

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

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• additions to isatin imines have been developed, including Mannich reactions, aza-Morita–Baylis–Hillman reactions, Friedel–Crafts reactions, aza-Henry reactions, additions of heteronucleophiles, Strecker reactions, among others. The goal of this review is to update the catalytic asymmetric synthesis of

• lowest yield (31%). The authors have proposed that the true catalyst of the reaction was a chiral tin iodide methoxide 34 in situ generated from chiral tin bromide 30, two equivalents of NaI and NaOMe (Scheme 10). Enantioselective aza-Morita–Baylis–Hillman reactions The Morita–Baylis–Hillman reaction is

• -methylene-β-hydroxycarbonyl compounds [50][51][52][53][54][55][56]. The aza-variant of this process consists in using an activated imine instead of an aldehyde, thus affording α-methylene-β-aminocarbonyl derivatives. In 2015, Takizawa et al. developed enantioselective aza-Morita–Baylis–Hillman reactions of

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

• –Hillman reaction The Morita–Baylis–Hillman reaction (MBH) employs olefins, tertiary amine catalysts and electrophile aldehydes to produce multifunctional products. Mack et al., found a significant enhancement in the rate of a Morita–Baylis–Hillman (MBH) reaction under ball milling conditions (Scheme 5

• -(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

• within 30 min (Scheme 4). Excellent stereoselectivity was also achieved with a diastereomeric ratio of 98:2 and enantiomeric ratio up to 99:1. Simple flash column chromatographic purification methods, low catalyst loading, gram scale synthesis, etc. were advantageous for the reaction [52]. Morita–Baylis

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

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

• next screened as catalysts in Morita–Baylis–Hillman reaction, and their performance matched the previously published catalytic activity. An analogous click-type reaction between 4-nitrophenyl isothiocyanate and trans-1,2-diaminocyclohexane quantitatively afforded enantiomeric (1R,2R)-10 and (1S,2S)-10

Decarboxylative and dehydrative coupling of dienoic acids and pentadienyl alcohols to form 1,3,6,8-tetraenes

• Ghina’a I. Abu Deiab,
• Mohammed H. Al-Huniti,
• I. F. Dempsey Hyatt,
• Emma E. Nagy,
• Kristen E. Gettys,
• Sommayah S. Sayed,
• Christine M. Joliat,
• Paige E. Daniel,
• Rupa M. Vummalaneni,
• Andrew T. Morehead Jr,
• Andrew L. Sargent and
• Mitchell P. Croatt

Beilstein J. Org. Chem. 2017, 13, 384–392, doi:10.3762/bjoc.13.41

• . Pathway B involves a Morita–Baylis–Hillman type process. The role of water would be to hydrogen bond to the carboxylate to make the system more electrophilic (B). This would accelerate the addition of the phosphine to generate zwitterion C [58]. Preliminary modeling for this ion indicates that both the

First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

• Marwa Ayadi,
• Haitham Elleuch,
• Emmanuel Vrancken and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2906–2915, doi:10.3762/bjoc.12.290

• Montpellier Cedex 5, France 10.3762/bjoc.12.290 Abstract An efficient synthesis of a series of γ-ketoallylphosphonates through a direct conversion of both primary and secondary Morita–Baylis–Hillman (MBH) alcohols by trialkyl phosphites with or without DMAP, used as additive, and under solvent-free

• the corresponding phosphonates, with or without catalyst, was previously reported. Accordingly, Bodalski and co-workers [14] and then Swamy’s research group [15] described a direct route to allylphosphonates by treatment of Morita–Baylis–Hillman alcohols with chlorophosphites without any additive

• ]. Similarly, Das and co-workers [17] have directly converted acyclic Morita–Baylis–Hillman (MBH) alcohols into the corresponding allylphosphonates upon their treatment with trialkyl phosphite in the presence of FeCl3 (Scheme 1, reaction 2). On the other hand, treatment of MBH acetates with triethyl phosphite

Et₃B-mediated and palladium-catalyzed direct allylation of β-dicarbonyl compounds with Morita–Baylis–Hillman alcohols

• Ahlem Abidi,
• Yosra Oueslati and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2402–2409, doi:10.3762/bjoc.12.234

• -dicarbonyl compounds with both cyclic and acyclic Morita–Baylis–Hillman (MBH) alcohols, using Et3B as a Lewis acid promoter, is described herein. A wide range of the corresponding functionalized allylated derivatives have been obtained in good yields and with high selectivity. Keywords: allylic substitution

• ; Morita–Baylis–Hillman; palladium; triethylborane; Introduction In nucleophilic allylic substitutions, π-allylpalladium complexes are useful intermediates for the construction of carbon–carbon and carbon–heteroatom bonds in organic synthesis [1]. Usually, palladium species are used as catalysts in the

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• . found that β-isocupreidine (β-ICD, cat. 22) can efficiently catalyze the Morita–Baylis–Hillman (MBH) reaction of isatins with maleimides to generate the 3-substituted 3-hydroxyoxindoles in excellent yields (up to 96% yield) and with excellent enantioselectivity (up to >99% ee) under mild conditions

• bisthiourea (cat. 26)-catalyzed asymmetric Morita–Baylis–Hillman reaction of isatins with α,β-unsaturated γ-butyrolactam (Scheme 41) [58]. The reactions were performed in DCM at room temperature with catalytic amounts of DABCO (5 mol %). A variety of isatin derivatives were tested under this catalytic system