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

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• morpholine first required the reaction with iodotrimethylsilane and furnished diamino alcohol 82 which after N-debenzylation and acylation gave (1R,2R)-81. In a similar way other GCS inhibitors, e.g., ᴅ-threo-P4 (1R,2R)-83a and ᴅ-threo-4'-hydroxy-P4 (1R,2R)-83b (Scheme 20) were obtained and examined as

Different reactivity of phosphorylallenes under the action of Brønsted or Lewis acids: a crucial role of involvement of the P=O group in intra- or intermolecular interactions at the formation of cationic intermediates

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1491–1504, doi:10.3762/bjoc.15.151

• able to measure its 1H NMR spectrum in D2O at elevated temperature (80 °C, see Supporting Information File 1). Taking into account the stability of the P–N bond against hydrolysis, we conducted reactions of the cations A, B, and F–H with morpholine (Scheme 3). Amides 6a,b were isolated as products of

• these reactions in excellent yields. The plausible reaction mechanism includes at the first stage nucleophilic attack of morpholine onto the phosphorus cationic center that gives cation I, which is transformed into species J. Hydrolysis of the latter leads to cation K and then finally to amides 6a,b. We

• ) gave cations A and B, respectively. The interaction of these species with morpholine followed by hydrolysis furnished the target amides 6a,b in total yields of 60–90% (see procedures in Supporting Information File 1). It should be noted that allene 1d bearing no alkyl groups and monoalkylated allene 1c

Remarkable effect of alkynyl substituents on the fluorescence properties of a BN-phenanthrene

• Alberto Abengózar,
• David Sucunza,
• Patricia García-García and
• Juan J. Vaquero

Beilstein J. Org. Chem. 2019, 15, 1257–1261, doi:10.3762/bjoc.15.122

• , whose emission maxima are slightly red-shifted (395 and 392 nm vs 356 nm for unsubstituted 1a). In contrast, 7-alkynyl-substituted BN-phenanthrenes 1e and 1f show emission maxima analogous to that of the parent BN-phenanthrene 1a. With regard to the fluorescence quantum yield, phenyl and morpholine

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• most of the cases, the Z-isomer as the sole or main product, while tert-butyl derivatives gave the E-isomer selectively. On the secondary amine side, morpholine, piperidine, pyrrolidine and dibutylamine all rendered the reaction efficiently. A plausible explanation for the mechanism of this

Diaminoterephthalate–α-lipoic acid conjugates with fluorinated residues

• Leon Buschbeck,
• Aleksandra Markovic,
• Gunther Wittstock and
• Jens Christoffers

Beilstein J. Org. Chem. 2019, 15, 981–991, doi:10.3762/bjoc.15.96

• trifluoromethylated benzaldehyde was accomplished as described for compound 2 and furnished product 6 in 91% yield. The Alloc-protecting group was then cleaved (95% yield of product 8) in a palladium-catalyzed allylic substitution reaction with morpholine as a scavenger of the allylic cation [45][46]. Finally, the

• -(trifluoromethyl)benzylamino]terephthalate (8): Under exclusion of air and moisture, morpholine (1.17 mmol, 102 mg, 5.0 equiv) was added to a solution of carbamate 6 (0.234 mmol, 129 mg, 1.0 equiv) in abs. CH2Cl2 (3 mL). The mixture was degassed (three cycles of freeze, pump and thaw). Then Pd(PPh3)4 (12 µmol, 14

Hoveyda–Grubbs catalysts with an N→Ru coordinate bond in a six-membered ring. Synthesis of stable, industrially scalable, highly efficient ruthenium metathesis catalysts and 2-vinylbenzylamine ligands as their precursors

• Kirill B. Polyanskii,
• Kseniia A. Alekseeva,
• Pavel V. Raspertov,
• Pavel A. Kumandin,
• Eugeniya V. Nikitina,
• Atash V. Gurbanov and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2019, 15, 769–779, doi:10.3762/bjoc.15.73

• concluded that dichloromethane is the best solvent for this reaction. At 40 °C, concentrations from 1.0 to 0.1 mol % of the morpholine-based complex 11d showed the best catalytic activity by providing styrene in 91–97% yields (entries 12 and 13 of Table 3). The somewhat less sterically loaded N,N-diethyl

An efficient and concise access to 2-amino-4H-benzothiopyran-4-one derivatives

• Peng Li,
• Yongqi Wu,
• Tingting Zhang,
• Chen Ma,
• Ziyun Lin,
• Gang Li and
• Haihong Huang

Beilstein J. Org. Chem. 2019, 15, 703–709, doi:10.3762/bjoc.15.65

• strong nucleophilicity of piperazine and morpholine, the substrates with electron-donating/withdrawing and halogen groups smoothly delivered the N-substituted 2-aminobenzothiopyranones 4j–o and 4t,u in good to excellent yields. Specifically, the substrates containing a strong electron-withdrawing group

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

• presence of triethylamine under mild conditions (CH2Cl2, −78 °C) [55] and the in situ-generated cyanate 27 underwent a sigmatropic rearrangement into the corresponding isocyanate 28. The formation of this reactive isocyanate intermediate was ascertained by the addition of morpholine which enabled the

A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive N-chloramines

• Katherine E. Jolley,
• Michael R. Chapman and
• A. John Blacker

Beilstein J. Org. Chem. 2018, 14, 2220–2228, doi:10.3762/bjoc.14.196

• equivalents of aldehyde 17 led to 30% product formation (Table 3, entry 6). Notably, other oxidants such as H2O2 and NaOCl failed to produce any amide product. Likewise, attempts to couple morpholine in place of its N-chloro derivative reached only 19% conversion. Following the investigation of the batch

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