Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

•  13). However, when conducting the reaction in a ratio of 1:10 at room temperature during 24 h, we observed the formation of N1,N2-dibenzyloxalamide (9) as a major product (NMR yield of about 90%) (Scheme 14). Our attempts to employ other alkylamines (diethylamine, morpholine, and cyclohexylamine) to

• room temperature for 24 h), a mixture of unidentified substances was formed. Interestingly, in the reaction of APBTT 1a with morpholine, we succeeded to isolate the product 10a (Scheme 15) [56]. Product 10a was formed in a result of a nucleophilic attack of morpholine on the C1 position of APBTT 1a

• closed microreaction V-vial. Reaction of APBTT 1a with an excess of benzylamine. Reaction of APBTT 1a with morpholine. Reaction of APBTT 1a with aniline (11a). Derivatization of PBTA 12aa. Reaction of APBTTs 1a–h and arylamines 11a–d. Isolated yields are given; reaction scale: a mixture of 1 (0.45 mmol

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• affect the diastereomeric ratio, resulting in even opposite selectivity. Roush and co-workers have presented a simple stereoselective reductive aldol procedure for the synthesis of tetrasubstituted enolates 210 from substituted morpholine acrylamides 209 (Scheme 54) [99]. Subsequent trapping of the boron

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• procedures [77][78][79][80]. Thereafter, the pyrazole-3-carbaldehyde 1, morpholine (C) and elemental sulfur were selected as the model substrates towards the preparation of pyrazole-linked thioamide derivatives. To begin with, an experiment was executed with model reactants in the presence of catalytic

• 5D in low yield (34%). During the preparation of pyrazole C-4-conjugated thioamides 5A–E and 6–8C, it was also noticed that when the reaction was exercised with morpholine (C), the reaction was accomplished in lesser time (36 min to 1 h) as compared to other secondary amines. To further validate the

• -carbaldehyde 1, morpholine (C) and elemental sulfur under the standard reaction conditions as depicted in Scheme 5. It was noticed that this one-pot operation was completed within 2.5 hours and smoothly furnished the desired product, (5-(4-fluorophenyl)-1-phenyl-1H-pyrazol-3-yl)(morpholino)methanethione (1C

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• (results not shown in scheme). Conversely, in reactions with electron-rich olefins, better yields are observed for the inverse electron demand Diels–Alder reaction (Scheme 9c). For example, the enamine 46, derived from cyclohexanone and morpholine, was readily annulated by 45 to afford the decalin ring

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• inducing the reaction. Under the same conditions, FPD 1k containing a morpholine fragment (Scheme 4) was involved in the reaction with 2a which gave the expected product 3ka in a fairly good yield of 56% and dr 99:1. The characteristic signals in the NMR spectra of the products 3aa and 3ka appeared to be

• . Benzoxazine, quinoxaline, and morpholine FPDs were successfully involved into the reaction, with the modification of diazo compounds decreasing the reaction yield. The reaction time of the cycloaddition was found to be independent on substituents in the aroyl moiety of FPDs 1. The described reaction is the

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• Petasis boron-Mannich (PBM) reaction of glyoxalic acid (30a) or salicylic aldehyde (30b), with morpholine (29) and p-methoxyphenylboronic acid (31) furnished α-aminocarboxylic acid 32a and phenol 32b in excellent yield (98% and 93%), again much higher than the yields found for the batch protocol (77% and

Synthesis of novel [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines and investigation of their fungistatic activity

• Anna V. Korotina,
• Svetlana G. Tolshchina,
• Rashida I. Ishmetova,
• Natalya P. Evstigneeva,
• Natalya A. Gerasimova,
• Natalya V. Zilberberg,
• Nikolay V. Kungurov,
• Gennady L. Rusinov,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2022, 18, 243–250, doi:10.3762/bjoc.18.29

• analysis of antifungal activity, the previously described [37] 3-methyl- and 3-phenyltriazolo[4,3-b][1,2,4,5]tetrazines 10a,b were used as structural analogues of compounds 3a,b. Furthermore, in the reactions of compound 10a with methanol, heptylamine and morpholine, new derivatives 11a–c have been

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• only generated with 7-aryl-Trp staple. C) On-resin modification of amines (n = 1: Dab, n = 2: Orn, n = 3: Lys) in i + 4 position to obtain organoboron side chains with increased linker flexibility. Reaction conditions: (a) Pd(PPh3)4, morpholine in DCM, 2 × 20 min; (b) carboxylic acid, HATU, DIEA in DMF

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• ferrocene carboxylic amide 1a with morpholine (2a) using 8-amonoquinoline as directing group [51][52][53][54][55][56]. The ortho-aminated ferrocenylamide 3a was isolated in 11% yield in the presence of CuI, N-methylmorpholine N-oxide (NMO) and K2CO3 in DMF (Table 1, entry 1). When the reaction was conducted

• ][58]. We then explored the scope of multifarious amines. As displayed in Scheme 3, a range of cyclic amines, such as morpholine 4a,b, piperazine 4c, piperidine 4d–j and thiomorpholine 4l,m, reacted smoothly to give the amination products in 23% to 85% yields. A variety of synthetically useful

• preparation of ferrocene–drug conjugates effectively. Mechanistic studies indicated that the C–H activation step was the rate-determining step. 3d-Transition-metal-catalyzed C–H functionalization to access functionalized ferrocenes. Scope of ferrocenes with morpholine. Scope of various amines with 1a

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• ) [101]. Later it was shown that alkynyl diol 150 when treated with 20 mol % Hg(OTf)2 followed by Et3SiH afforded bispyranoyl ketone 151, but when Hg(OTf)2 was increased (1 equiv) then fused pyran-oxocane derivative 152 was isolated [102]. Six-membered morpholine derivatives were also synthesized by

• catalytic Hg(II)-salt-induced cyclization. Yamamoto and co-workers published the intermolecular cyclization of alkynyl-carboxylic acid 153 to produce 6-membered morpholine type ring compound 154 and compound 155 [103]. The stereochemistry of the chiral amino acid was not conserved in the cyclized product

• acids and alcohol to furan, pyran, and spirocyclic derivatives. Hg(II)-salt-mediated cyclization of 1,4-dihydroxy-5-alkyne derivatives. Six-membered morpholine derivative formation by catalytic Hg(II)-salt-induced cyclization. Hg(OTf)2-catalyzed hydroxylative carbocyclization of 1,6-enyne. a) Hg(OTf)2

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• . Moreover, TMS-substituted alkyne was suitable for this Huisgen reaction to achieve the desired triazole product. Next, some triazene scaffolds, such as dimethylamino-, pyrrolidine-, piperidine-, morpholine-, and piperazine-derived triazenes were screened. Aryl azides containing Br, I, Me, and MeO as well

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• was related to enhancement of selective absorption, considering the use of a visible-light source. In 2019, Glorius and colleagues [11] proposed a method of employing an EDA complex formed by indole derivative 98 and the Katritzky salt 99 as well as morpholine as organic base to obtain alkylated

• indole derivatives 100 under blue-light irradiation (Scheme 35). Given the UV–vis spectra of the reaction mixture and its components, there was no evidence of the formation of a ternary EDA complex between Katritzky salt 99, 98, and morpholine. Moreover, the TDDFT calculation showed that electron

• 104. Subsequently, alkyl radical 104 is captured by indole 98, giving benzyl radical 105. The alkylated indole derivative 100 and morpholine salts are provided via proton-coupled electron transfer (PCET) with EDA complex 102 formed by morpholine and 99 (Scheme 36). As a rare example of EDA

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• selectively alkylated on the nitrogen atom [30][36]. For our purposes, the simple alkyl halides (MeI, iPrI), and 2-chloro-N,N-dimethylethylamine hydrochloride and 4-(2-chloroethyl)morpholine hydrochloride, were chosen as the alkylating agents. Thus, the desired N-methyl and N-isopropyl lactams 3a,b (3a R1

• Information File 1). In the next step, the bromolactams 3 were subjected to a thermal palladium cross-coupling reaction with various amines and polyamines. To optimize the reaction conditions, we investigated the reaction of 4-bromo-2-methylphthalazin-1(2H)-one (3a) with morpholine as the model substrates

• cross-coupling reaction. To confirm this idea, we carried out an experiment in which to the in situ-generated (BINAP)Pd complex (Pd2(dba)3/rac-BINAP or (R)-BINAP; 15:15 mol %) morpholine was added prior to the addition of lactam 3a. As a result, we obtained the target 4-(morpholin-4-yl) derivative 5a in

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• morpholine amide 7. The synthesis started by selective SNAr reaction with 4 and tert-butyl ((cis)-4-aminocyclohexyl)carbamate affording the intermediate nicotinic acid 5 in 70% yield without the need for chromatography. Subsequent amide coupling using TBTU afforded 2-chloro precursor 6 in excellent yield

A novel and robust heterogeneous Cu catalyst using modified lignosulfonate as support for the synthesis of nitrogen-containing heterocycles

• Bingbing Lai,
• Meng Ye,
• Ping Liu,
• Minghao Li,
• Rongxian Bai and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2888–2902, doi:10.3762/bjoc.16.238

• amines such as morpholine (9j) also showed high reactivity in this reaction and 10j was obtained in 81% yield. The substituent effect of 2-(phenylethynyl)acetophenone was studied subsequently, and the results showed that fluoro, chloro, aliphatic chain and cycloolefin-substituted 2-(phenylethynyl

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• fluorohydrin 10 suggested that the earlier dihydroxylation reaction had proceeded with 90% ee. The deoxyfluorination of 10 was then attempted using several reagents including DeoxoFluor, DeoxoFluor in combination with TMS-morpholine [29], and PyFluor [30]. The optimal yield of the threo-difluoroalkane 11 was

• obtained with DeoxoFluor at elevated temperature (Scheme 2). A side-product in this fluorination reaction was the tricyclic compound 12, which presumably formed through an electrophilic aromatic substitution reaction of the activated alcohol intermediate. The inclusion of TMS-morpholine [29] reduced the

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

• Alexander N. Reznikov,
• Dmitry S. Nikerov,
• Anastasiya E. Sibiryakova,
• Victor B. Rybakov,
• Evgeniy V. Golovin and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174

• octahydroindole [10], tetrahydroquinoline [11], tetrahydroisoquinoline [11][12], β-carboline [13], morpholine [14], and isoindoline [15] moieties have been developed. Obtained in an enantiomerically pure form, phosphonoproline and its analogues [16][17][18][19] were among the first compounds in this series

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• , mild oxidizing additives such as amine oxides, aminophosphines, phosphine oxides, and sulfoxides may be used as promoters to facilitate the dissociation step, by oxidatively removing one of the CO ligands in form of CO2 [40]. The most common oxidants are N-morpholine N-oxide (NMO), trimethylamine N

Efficient synthesis of piperazinyl amides of 18β-glycyrrhetinic acid

• Dong Cai,
• ZhiHua Zhang,
• Yufan Meng,
• KaiLi Zhu,
• LiYi Chen,
• ChangXiang Yu,
• ChangWei Yu,
• ZiYi Fu,
• DianShen Yang and
• YiXia Gong

Beilstein J. Org. Chem. 2020, 16, 798–808, doi:10.3762/bjoc.16.73

• biologically active substances. According to the first method, compound 12 reacted with morpholine in the presence of K2CO3/I2 to give compound 13, followed by successive amidation and N-Boc deprotection gave compound 17. It is noteworthy that the carboxyl group of compound 12 did not react with inorganic

• °C, 1 h; (b) morpholine, K2CO3/ I2, C2H5OH; (c)1-Boc-piperazine, CH3CN, NEt3, EDCl, HOBt, reflux, 24 h; (d) TFA, DCM, 0/25 °C; (e) chloroacetic anhydride, K2CO3, toluene, 130 °C, 1 h. Formation of piperazinyl amide 4: selected optimization reactions. Optimization of the reaction conditions for the

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• , and branched aliphatic substituents in the δ-position afforded preferably the 1,4-products. Importantly, when the morpholine moiety was used as N-substituent, the addition of diethylzinc to the enamide afforded the 1,6-addition product with 78% isolated yield and 91% ee. It is worth to underline that

• the morpholine group could easily allow further postfunctionalizations. Furthermore, thanks to the highly 1,6-enantioselective additions of methylmagnesium bromide (95% ee), this methodology was applied to the synthesis of the natural product penicillenol A by oxidative cleavage of the resulting 1,6

Synthesis and characterization of bis(4-amino-2-bromo-6-methoxy)azobenzene derivatives

• David Martínez-López,
• Amirhossein Babalhavaeji,
• Diego Sampedro and
• G. Andrew Woolley

Beilstein J. Org. Chem. 2019, 15, 3000–3008, doi:10.3762/bjoc.15.296

• cm × 8 mm). Then, morpholine (84 mg, 0.96 mmol), tris(dibenzylideneacetone)dipalladium(0) (29.3 mg, 0.032 mmol), RuPhos (29.8 mg, 0.064 mmol), and cesium carbonate (302.4 mg, 0.96 mmol) were added. The mixture was heated at 100 ºC in the pressure tube for 24 hours. The reaction progress was monitored