Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

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

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• processes in 1, such as the Baylis–Hillman reaction [14], and the Rauhut–Currier reaction which gives dimers such as 2 as well as higher oligomers [10][15]. An oxa-Michael-initiated three-component intermolecular reaction of 1 with furfural and water has been reported to result in enone 3 (Figure 1) [16

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

• 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

• , it was observed that the MBH reaction of 6b with acrylonitrile A resulted in the formation of product 8bA which evidenced that 6b underwent Morita–Baylis–Hillman reaction at the electrophilic carbonyl center as well as Michael addition reaction at the nucleophilic nitrogen center (N-9). Similar

Azo-dimethylaminopyridine-functionalized Ni(II)-porphyrin as a photoswitchable nucleophilic catalyst

• Jannis Ludwig,
• Julian Helberg,
• Hendrik Zipse and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2119–2126, doi:10.3762/bjoc.16.179

• study is 4-(N,N-dimethylamino)pyridine derivative 1 (Figure 1). The parent 4-(N,N-dimethylamino)pyridine (DMAP, 2) is known as a nucleophilic catalyst in a number of reactions, for example the Baylis–Hillman reaction [27] and the Steglich esterification [28][29]. To achieve control of the catalytic

Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor

• Dalel El-Marrouki,
• Sabrina Touchet,
• Abderrahmen Abdelli,
• Hédi M’Rabet,
• Mohamed Lotfi Efrit and
• Philippe C. Gros

Beilstein J. Org. Chem. 2020, 16, 1722–1731, doi:10.3762/bjoc.16.144

• ). The nitrenones 3a–d were obtained in three steps from the appropriate commercially available cyclohexenones (Scheme 2). First, a Baylis–Hillman reaction between cyclohexanone and formaldehyde led to the formation of the corresponding Baylis–Hillman alcohols 1a/b in good yield [58], followed by a DMAP

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

Synthesis of 4-(2-fluorophenyl)-7-methoxycoumarin: experimental and computational evidence for intramolecular and intermolecular C–F···H–C bonds

• Vuyisa Mzozoyana,
• Fanie R. van Heerden and
• Craig Grimmer

Beilstein J. Org. Chem. 2020, 16, 190–199, doi:10.3762/bjoc.16.22

• , numerous methods for the synthesis of these compounds have been developed, examples are the Pechmann condensation [10][11], Stille coupling reaction [12], Knoevenagel condensation [13], Heck coupling reaction [14], Kostanecki reaction, Baylis–Hillman reaction [15], Michael reaction [16], Suzuki–Miyaura

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

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

• 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

• of these processes (Scheme 11 and Scheme 12) can be explained by the favored transition states proposed in Scheme 12 based on the fact that the proton transfer constitutes the rate-determining step in the aza-Morita–Baylis–Hillman reaction [58][59][60]. Indeed, in these favored transition states, the

• first asymmetric organocatalytic synthesis of chiral 3-amino-2-oxindoles based on enantioselective aza-Morita–Baylis–Hillman reaction of N-Boc-isatin imines 3 with activated nitroolefins 39 [62]. The best results were achieved by using cinchona alkaloid-derived thiourea catalyst 40 in toluene at −10 °C

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

• 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

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

• 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

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

• . – especially when it comes to the Morita–Baylis–Hillman reaction, although they are in no way limited to these, and one can only expect the prevalence of these remarkable bifunctional catalysts within the literature to increase over the coming years. The structural diversity of the cinchona alkaloids, along

Application of 7-azaisatins in enantioselective Morita–Baylis–Hillman reaction

• Qing He,
• Gu Zhan,
• Wei Du and
• Ying-Chun Chen

Beilstein J. Org. Chem. 2016, 12, 309–313, doi:10.3762/bjoc.12.33

• high yield by using N-methylisatin (4) as the substrate (Scheme 1). Conclusion In summary, we have developed an efficient and enantioselective Morita–Baylis–Hillman reaction between 7-azaisatins and maleimides and other activated alkenes in the presence of the bifunctional catalyst β-ICD. 7-Azaisatins

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

Morita–Baylis–Hillman reaction of acrylamide with isatin derivatives

• Radhey M. Singh,
• Kishor Chandra Bharadwaj and
• Dharmendra Kumar Tiwari

Beilstein J. Org. Chem. 2014, 10, 2975–2980, doi:10.3762/bjoc.10.315

• Abstract The Morita–Baylis–Hillman reaction of acrylamide, as an activated alkene, has seen little development due to its low reactivity. We have developed the reaction using isatin derivatives with acrylamide, DABCO as a promoter and phenol as an additive in acetonitrile. The corresponding aza version

• and in 91% yield in just 3 hours of reaction (Table 2, entry 1) was achieved. Encouraged by these results, the focus was shifted to the development of this aza-Morita–Baylis–Hillman reaction using isatin-derived ketimines [51][52][53]. This reaction could also lead to the construction of tertiary

• reaction time and in high yields (Scheme 2). The reaction scope was expandable to other activated alkene (acrylonitrile) and to other isatin derivatives with substituents on nitrogen (methyl, benzyl) and on the aryl ring (H, 5-chloro). Conclusion We have developed the Morita–Baylis–Hillman reaction of

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• defined geometry. Introducing a new motif, Shea et al. have synthesized achiral tridentate (thio)phosphorus triamides and assessed their catalytic activity relative to the established (m-(CF3)2-Ph)2thiourea [18]. In the Friedel–Crafts reaction of N-methylindole with β-nitrostyrene and the Baylis–Hillman

• reaction of methyl acrylate with benzaldehyde the substituted triamide catalysts show a comparable or an even superior activity relative to the thiourea analogue. Recently, Gale et al. demonstrated that the same phosphoric triamides effectively act as anion transporters by hydrogen bonding [19]. These

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• (−)-quinic acid (16) according to the route reported by Arthurs et al. [40] with minor modifications. After Baylis–Hillman reaction and subsequent silylation of the resulting free primary hydroxy group, substrate-controlled α-methylation of the lithium enolate proceeded with full stereocontrol [41][42

• and Baylis–Hillman reaction proceeded uneventfully to afford compound 62. Deprotection of the butane-2,3-diacetal under acidic conditions followed by selective silylation of the primary and the allylic hydroxy groups gave alcohol 63. The second quaternary center of the bicyclic C–D system 66 was

Total synthesis of (+)-grandiamide D, dasyclamide and gigantamide A from a Baylis–Hillman adduct: A unified biomimetic approach

• Andivelu Ilangovan and
• Shanmugasundar Saravanakumar

Beilstein J. Org. Chem. 2014, 10, 127–133, doi:10.3762/bjoc.10.9

• , (+)-grandiamide D, dasyclamide and gigantamide A, isolated from leaves of Aglaia gigantea, by making use of a common synthetic intermediate prepared by the Baylis–Hillman reaction. Asymmetric synthesis of the natural (+)-grandiamide D was accomplished from camphor sultam. Keywords: Baylis–Hillman reaction

• (14) [11]. In order to reduce the amount of acrylate and to increase the yield of compound (±)-16, the Baylis–Hillman reaction between the aldehyde 14 and ethyl acrylate (15) was tried using different catalysts such as DBU, quinuclidine [12] and n-Bu3P. DABCO was found to be a better catalyst and the

• (+)-grandiamide D (5). We assumed that the asymmetric Baylis–Hillman reaction [15] would be an ideal way to introduce chirality. Reaction between acryloyl sultam 19, and 2-((4-methoxybenzyl)oxy)acetaldehyde (14) in DMF [12], afforded cyclic product 20, which was then treated as such with TEA in ethanol to afford

A versatile and efficient approach for the synthesis of chiral 1,3-nitroamines and 1,3-diamines via conjugate addition to new (S,E)-γ-aminated nitroalkenes derived from L-α-amino acids

• Vera Lúcia Patrocinio Pereira,
• André Luiz da Silva Moura,
• Daniel Pais Pires Vieira,
• Leandro Lara de Carvalho,
• Eliz Regina Bueno Torres and
• Jeronimo da Silva Costa

Beilstein J. Org. Chem. 2013, 9, 832–837, doi:10.3762/bjoc.9.95

• alcohol; amino aldehyde; azide addition; Baylis–Hillman reaction; cyanide addition; Michael addition; Introduction Nitroalkenes constitute a class of organic compounds that present exceptional versatility in organic synthesis [1][2][3][4]. They are reactive in Michael reactions with a wide variety of

• partial HNO2 elimination from vicinal nitronitrile adducts. This behavior was not observed in other findings reported [78][81][82][83] and the corresponding vicinal nitronitriles were the sole products. It is important to note that 12a,b can in theory also be obtained by an aza-Baylis–Hillman reaction [15

Titanium-mediated reductive cross-coupling reactions of imines with terminal alkynes: An efficient route for the synthesis of stereodefined allylic amines

• Kebin Mao,
• Guoqin Fan,
• Yuanhong Liu,
• Shi Li,
• Xu You and
• Dan Liu

Beilstein J. Org. Chem. 2013, 9, 621–627, doi:10.3762/bjoc.9.69

• ], iodocyclocarbamates [19] and isoxazolines [20]. Although it has been reported that allylic amines can be synthesized by methods such as amination of allylic alcohols [21][22][23][24], direct allylic amination of simple alkenes [25][26][27], Morita–Baylis–Hillman reaction [28], alkenylation of imines [29][30][31][32

Reactions of salicylaldehyde and enolates or their equivalents: versatile synthetic routes to chromane derivatives

• Ishmael B. Masesane and
• Zelalem Yibralign Desta

Beilstein J. Org. Chem. 2012, 8, 2166–2175, doi:10.3762/bjoc.8.244

• of 28% (Scheme 18) [38]. Slightly better yields (33–40%) were achieved when 5-bromo-, 5-chloro- and 3,5-dichloro-substituted salicylaldehydes were employed in the reaction. Ravichandran utilized a classical 1,4-diazabicyclo[2.2.2]octane (DABCO)-catalyzed Baylis–Hillman reaction of salicylaldehyde (5

• isolated in this work. The mechanism of the DABCO-catalyzed reaction of salicylaldehyde and α,β-unsaturated compounds in the synthesis 3-substituted chromenes was proved to proceed through the Baylis–Hillman reaction by Kaye and co-workers [40][41] Their work involved the reaction of salicylaldehyde (5

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

• Chittaranjan Bhanja,
• Satyaban Jena,
• Sabita Nayak and
• Seetaram Mohapatra

Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191

• -Michael addition followed by aza-Baylis–Hillman reaction by means of an iminium-allenamine activation strategy. Later on, the same authors [49] in 2011 reported a similar tandem reaction (abnormal Baylis–Hillman) between 2-alkynals 5 and salicylaldehyde derivatives 1 catalyzed by proline derivatives

• by Xu and co-workers. Chiral secondary amine promoted oxa-Michael–aldol cascade reactions as reported by Wang and co-workers. Reaction of salicyl-N-tosylimine with aldehydes by domino oxa-Michael/aza-Baylis–Hillman reaction, as reported by Alemán and co-workers. Silyl prolinol ether-catalyzed oxa

Reactions of nitroxides XIII: Synthesis of the Morita–Baylis–Hillman adducts bearing a nitroxyl moiety using 4-acryloyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl as a starting compound, and DABCO and quinuclidine as catalysts

• Jerzy Zakrzewski

Beilstein J. Org. Chem. 2012, 8, 1515–1522, doi:10.3762/bjoc.8.171

• aldehydes. Keywords: 4-acryloyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl; DABCO; Morita–Baylis–Hillman reaction; nitroxides; quinuclidine; Introduction In the Morita–Baylis–Hillman (MBH) reaction, aldehydes react with a double bond activated by an electron-withdrawing group (EWG). The vinylic carbon