Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• were prepared by the reaction of 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietane (1) with the corresponding substrates, resulting in the selective alkylation of one of the nitrogen atoms of the imidazole ring. The reaction proceeds under mild conditions in a polar solvent, giving the alkylated

• products in 47–78% yield. While for purine and 4- and 5-azabenzimidazole, the reaction led to a mixture of two isomers, the reaction of adenine and the corresponding 2-fluoro derivative was regioselective, resulting in the formation of only one isomer in each case. The alkylation of theophylline led to the

• °C, 1 d), leading (unexpectedly) to the formation of only one isomer (5a and 6a, respectively) in each case (Scheme 4). Another surprising feature of these reactions was the selective alkylation of the nitrogen atoms of the imidazole ring rather than the amino group. This is in sharp contrast to the

Selective recognition of ATP by multivalent nano-assemblies of bisimidazolium amphiphiles through “turn-on” fluorescence response

• Rakesh Biswas,
• Surya Ghosh,
• Shubhra Kanti Bhaumik and
• Supratim Banerjee

Beilstein J. Org. Chem. 2020, 16, 2728–2738, doi:10.3762/bjoc.16.223

• -imidazol-1-yl)methane (5) was synthesized from imidazole (4) and CH2Br2 following a literature procedure [62][63] with slight modifications. Then, BImNs (N = 4, 10, 12, 14) were synthesized from 5 by mono-alkylation using the corresponding n-alkyl halides in DMF. Finally, PBImNs (N = 4, 10, 12, 14) were

Synthesis and characterization of S,N-heterotetracenes

• Astrid Vogt,
• Florian Henne,
• Christoph Wetzel,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2020, 16, 2636–2644, doi:10.3762/bjoc.16.214

• quantitative yield [47]. Single crystals of intermediate thienopyrrole 25 were obtained by slow evaporation of a chloroform solution and an X-ray structure analysis was performed. Structural details and packing motifs of the molecule are described in Supporting Information File 1. Alkylation to N-propyl

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• with photoredox catalysis was reported by Nicewicz and MacMillan [1] for the alpha alkylation of aldehydes 1 with various alkyl bromides bearing an electron-withdrawing substituent 2, which while seemingly trivial, was not possible with enamine catalysis alone (Scheme 1). The proposed mechanism

• ketyl radical anion 166•−. The latter intermediate 166•− can then abstract an iodine atom from another molecule of 163 to propagate the chain reaction and generate alkyl iodide 167, which collapses to give the desired enantioenriched alkylation products 168 in moderate yields and excellent

Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots

• Elizabeth A. Margolis,
• Rebecca J. Keyes,
• Stephen D. Lockey IV and
• Edward E. Fenlon

Beilstein J. Org. Chem. 2020, 16, 2314–2321, doi:10.3762/bjoc.16.192

• ), whereas host 1 and guest 3 would lead to a 75 backbone-atom trefoil (and unknotted macrocycle). Results and Discussion The synthesis of bis-macrocyclic host 1 began by breaking the symmetry of naphthalene-1,5-diol (4) by alkylation of one of the alcohols with 2-azidoethyl mesylate to yield azide 5 in 27

• % yield (Scheme 1). Alkylation of 5 with 1,2-dibromoethane provided key intermediate azido-bromide 6 in 60% yield. This two-step route to 6 is efficient, but the 16% overall yield was lower than desired. An alternate route began by converting diol 4 to bis(2-hydroxyethoxy)naphthalene 7 in 92% yield by

• ascorbic acid to provide a 42% yield of triazole 11. Alkylation of diethyl 2,5-dihydroxyterephthalate (12) with 11 under standard conditions provided low yields (12–18%) of the core diester 13, which contains all the atoms of host 1. The yields for this route were disappointingly low, so it was hoped that

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• achieve this goal, they commenced with the two-fold Friedel–Crafts alkylation reaction of sumanene (2) with 2,5-dichloro-2,5-dimethylhexane (50) involving AlCl3 to generate compound 51 which on subsequent oxidation provided triketosumanene 52 (Scheme 11). Finally, compound 52 was reacted with ethylene

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• [192], reliable and commercially available [193]. Selectfluor® is synthesized on a multiton p.a. scale in a simple and efficient method (Scheme 3) [193]. The precursor 24 is prepared by alkylation of DABCO (1,4-diazabicyclo[2.2.2]octane) with DCM. A counterion exchange with NaBF4 causes NaCl

Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate

• Mysore Bhyrappa Harisha,
• Pandi Dhanalakshmi,
• Rajendran Suresh,
• Raju Ranjith Kumar and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2020, 16, 2108–2118, doi:10.3762/bjoc.16.178

• just at the start of the reaction and b is the photograph after the completion of the reaction. Further, the utility of the thiol group in 3 for the generation of a library of compounds was demonstrated by the simple acetylation and alkylation (Scheme 4 and Scheme 5). The acetylation of the thiol group

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

• presence of Pd/C. However, phosphonate 7 was unstable: already during its isolation, it was partially transformed into compounds 8 and 9. It can be assumed that N-alkylation by the phosphoryl group occurs [47][48][49]. To avoid this undesirable process, the product 7 was formylated before its isolation

Synthesis of 3(2)-phosphonylated thiazolo[3,2-a]oxopyrimidines

• Ksenia I. Kaskevich,
• Anastasia A. Babushkina,
• Vladislav V. Gurzhiy,
• Dmitrij M. Egorov,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2020, 16, 1947–1954, doi:10.3762/bjoc.16.161

• most accessible approach to the synthesis of 5H-thiazolo[3,2-a]pyrimidine-5(7)-ones is the reaction of 2-thiouracil derivatives with α-halo ketones and α-halo acids, involving successive alkylation and condensation steps (Scheme 3) [17][18][19][20][21]. A convenient one-step synthesis of

Synergy between supported ionic liquid-like phases and immobilized palladium N-heterocyclic carbene–phosphine complexes for the Negishi reaction under flow conditions

• Edgar Peris,
• Raúl Porcar,
• María Macia,
• Jesús Alcázar,
• Eduardo García-Verdugo and
• Santiago V. Luis

Beilstein J. Org. Chem. 2020, 16, 1924–1935, doi:10.3762/bjoc.16.159

• mmol Cl/g,) was used as the starting material for the immobilization of N-arylimidazoles 2a and 2b, following the traditional alkylation protocol [18][19]. The preparation of these modified polymers was monitored by FT–ATR–IR, FT-Raman using a micro-spectroscopy accessory and the NBP test [20][21]. The

Design, synthesis and application of carbazole macrocycles in anion sensors

• Alo Rüütel,
• Ville Yrjänä,
• Sandip A. Kadam,
• Indrek Saar,
• Mihkel Ilisson,
• Astrid Darnell,
• Kristjan Haav,
• Tõiv Haljasorg,
• Lauri Toom,
• Johan Bobacka and
• Ivo Leito

Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157

• functional groups in the 3,6-positions of the carbazole. High lipophilicity is achievable by using alkylation and leads to the possibility of using the receptor dissolved in the lipophilic polymeric sensor membrane, without the need for chemical linking. Cyclization of the receptor is possible via the

• water (and possibly also in DMSO). Synthesis The general synthesis route is presented in Scheme 1. It was to some extent similar to the one that has previously been published by Sanchez et al. and Liu et al. [6][29] (see below). The synthetic route relied on the initial alkylation of the 3 and 6

• lead to acceptable results. Therefore, we decided to modify the reaction scheme. After alkylation, compound 2 was instead brominated, followed by amination of 4 leading to the desired diamino product 5a. Amine protection and subsequent coupling procedures, leading to 8, were the same as described in

Stereoselective Biginelli-like reaction catalyzed by a chiral phosphoric acid bearing two hydroxy groups

• Xiaoyun Hu,
• Jianxin Guo,
• Cui Wang,
• Rui Zhang and
• Victor Borovkov

Beilstein J. Org. Chem. 2020, 16, 1875–1880, doi:10.3762/bjoc.16.155

• butanetetraol 1 is a parent compound of TADDOLs, which conventionally are obtained from enantiopure tartaric acids. The hydroxy group composition of 1 ensures its diverse reactivity. In 2010, our group established a convenient access [18] to 1 via a direct alkylation of diethyl tartrates by using PhMgBr

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• alkylation of arenes. The ruthenium-catalyzed meta-selective C–H functionalization through arene σ-activation was already well established yet limited by harsh reaction conditions and elevated reaction temperatures. Both research groups hence hypothesized that the Ru-metallacyclic intermediate, generated via

• very efficient at room temperature while applying blue LED irradiation. Two slightly modified catalytic systems composed of a [Ru(p-cymene)Cl2]2 catalyst and either K2CO3 or KOAc bases promoted the direct meta-selective C(sp2)–H alkylation with secondary and tertiary alkyl halides, delivering the

Et₃N/DMSO-supported one-pot synthesis of highly fluorescent β-carboline-linked benzothiophenones via sulfur insertion and estimation of the photophysical properties

• Dharmender Singh,
• Vipin Kumar and
• Virender Singh

Beilstein J. Org. Chem. 2020, 16, 1740–1753, doi:10.3762/bjoc.16.146

• substituents at C1 (R4), compound 4eA with aromatic substituent exhibited better fluorescence due to extended conjugation. The effect of R2 substituent in these derivatives (4bA, 4dA, 4fA and 4gA) was also investigated and it was found that N-alkylation improved the photophysical properties along with higher

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

• sulfonamides 47, followed by the introduction of the fluoroallyl group via N-alkylation with previously described mesylate 38 provided fluorinated enynes 48 (Scheme 24). The enantioenriched starting materials 48 were then evaluated in the Co-mediated PKR to yield the bicyclic products 49 in moderate to good

Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner–Wadsworth–Emmons-based approach

• Rhys A. Lippa,
• John A. Murphy and
• Tim N. Barrett

Beilstein J. Org. Chem. 2020, 16, 1617–1626, doi:10.3762/bjoc.16.134

• taking place (Scheme 8) [24][25][26]. The autoxidation of phosphonates under THF/potassium tert-butoxide has been reported previously [27]. In order to circumvent racemisation of aldehyde 22 during the Horner–Wadsworth–Emmons olefination, alkylation of phosphoramidate 13 was explored using commercially

• phosphoramidate protecting group, which was superior to the more commonly applied Boc protecting group which was unstable to the lithiation. This synthetic route replaces traditional Wittig and tandem alkylation/reduction methodologies, which suffer from complications arising from troublesome byproducts and

• formation of dimer 28. Conditions: KOt-Bu, THF, 1 h, 68% yield. Alkylation of phosphoramidate 13 by iodide 29 to afford compound 30 and byproducts alcohol 31 and dimer 32. Use of bromide 33 or tosylate 34 afforded only compounds 31 and 32. Conditions: (i) s-BuLi (1.3 equiv), iodide 29, THF, −78 °C, 30 min

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions

• Gui-Feng Kang and
• Gang Zhang

Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120

• and orthoformates and provided a rapid entry to a variety of 4-aryl-6-(alkylthio)-3,4-dihydro-1,3,5-triazine-2(1H)-thiones (29 examples). The synthetic strategy relies on the dual role of thiourea in the cyclization with the aldehydes and the alkylation via an intermediate imidate formation. The

• are versatile building blocks in organic synthesis, capable of constructing acyl derivatives [29][30][31][32][33] and ether derivatives [34][35][36] through acylation and alkylation under the appropriate conditions. In view of what was explained above, and as a result of our interest in developing

• alkylation, and/or due to the instability of the imines formed. In order to further explore the substrate scope of this multicomponent reaction, next we wanted to use other orthoformates. Interestingly, under the similar reaction conditions triethyl orthoformate (3b), tripropyl orthoformate (3c), and

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• for studying the possibility of an N-alkylation by alkyl bromide, formed during the silylation step. Finally, compound 13 was included to study the possibility of a chlorine for bromine exchange reaction. The phosphonocarboxylates 8 and 9 were used to explore whether the carboxyester group could be

• water and 1 equiv of TEA. Section 3: N-Alkylation As reported in the original paper [1], the McKenna reaction required up to 2 h at room temperature for simple phosphonates. However, depending on the structure of the phosphonate, longer reaction times are required, and the reaction is commonly carried

• the gas needed to be gently controlled to avoid BTMS removal from the reaction mixture. We encountered a different situation for compound 12. This substrate underwent N-alkylation under the McKenna reaction conditions only in the presence of Et3N, a commonly used additive for the protection of

Recent synthesis of thietanes

• Jiaxi Xu

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

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• reported a visible light-promoted photochemical reductive decarboxylation/alkylation of carboxylic acid analogs (Scheme 4) [45]. In this protocol, the carboxylic acids are converted into the corresponding RAE 4.1 by a condensation with N-hydroxyphthalimide. The organic dye eosin Y (OD13, E(PC/PC−) ≈ −1.1 V

• ), in the presence of the sacrificial electron donor DIPEA, can reduce these species under green light irradiation. The ensuing decarboxylation provides a C(sp3) radical, which undergoes a radical conjugate addition with a suitable Michael acceptor 4.2, providing the desired alkylation products 4.3. A

• protocol for the radical alkylation of imines using ammonium alkylbis(catecholato)silicates 5.4 as the C(sp3) radical precursors (Scheme 5b) [50]. 4CzIPN (OD6) was found again to be the best organic photocatalyst, triggering the oxidative fragmentation of the bis(catecholato)silicate. The so-formed alkyl

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• synthesized by alkylation of 26a,b with the chiral auxiliary 31, which was obtained by reaction of the cyclic dipeptide 30 with triethyloxonium tetrafluoroborate. The alkylation reaction of 26a,b was carried out with n-BuLi in THF at −78 °C to give 32a,b. Acid hydrolysis of the alkylated product 32a,b

• afforded the ethyl esters of tetrafluorophenylalanine 33a,b, which by alkaline hydrolysis afforded the tetrafluoro derivatives 29a and 29b, respectively [43] (Scheme 7). The syntheses of (R)-38a and (R)-38b were carried out by alkylation of the Schöllkopf reagent ((2S)-(+)-2,5-dihydro-3,6-dimethoxy-2

• -isopropylpyrazine, 34) with the corresponding fluorinated benzyl bromides 35a,b via intermediates 36a,b. The alkylation products were then hydrolyzed to generate the amino acid esters which were directly Boc protected to give the N-Boc-protected amino acid methyl esters 37a,b. Finally, ester hydrolysis afforded the

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• lead to versatile chiral building blocks, such as a β-alkyl-substituted aldehyde (66% yield, 94:6 er) or a β-bromo-γ-alkyl-substituted alcohol (71% yield, 93:7 er). The asymmetric allylic alkylation (AAA) is a very useful method that allows the enantioselective formation of C–C bonds, and copper

Aryl-substituted acridanes as hosts for TADF-based OLEDs

• Naveen Masimukku,
• Dalius Gudeika,
• Oleksandr Bezvikonnyi,
• Ihor Syvorotka,
• Rasa Keruckiene,
• Dmytro Volyniuk and
• Juozas V. Grazulevicius

Beilstein J. Org. Chem. 2020, 16, 989–1000, doi:10.3762/bjoc.16.88

• according to the reported procedure [28]. The subsequent alkylation of 1 using bromoethane afforded the N-ethylated dibromo compound 2 in 80% yield. The target compounds 3–6 were then obtained by Suzuki cross-coupling reactions between brominated acridan 2 and the respective phenylboronic acids in the