Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• external nucleophile, the successive proton loss leads to the formation of the 2,6-disubstituted dihydropyran. The regioselectivity of the Prins reaction is explained through the intermediates formed during the course of the reaction (Scheme 4). The Z-homoallylic alcohol reacts with an activated aldehyde

• synthesis of THPs. Developments towards the Prins cyclization. General stereochemical outcome of the Prins cyclization. Regioselectivity in the Prins cyclization. Mechanism of the oxonia-Cope reaction in the Prins cyclization. Cyclization of electron-deficient enantioenriched alcohol 27. Partial

Manganese/bipyridine-catalyzed non-directed C(sp³)–H bromination using NBS and TMSN₃

• Kumar Sneh,
• Takeru Torigoe and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2021, 17, 885–890, doi:10.3762/bjoc.17.74

• ]. The regioselectivity is controlled by the formation of a six-membered cyclic intermediate. Directing-group-assisted C(sp3)−H halogenation reactions are efficient for promoting regioselective C(sp3)−H halogenations (Scheme 1c) [24][25][26][27][28]. In these reactions, the C(sp3)–H bond at the β

• (sp3)–H bromination reaction proceeded selectively at the benzylic position and their corresponding brominated products (2k, 2l and 2m) were obtained in 61, 57 and 55% yield, respectively. We next investigated the regioselectivity of the reaction using substrates with two possible reaction sites. The

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• as reduction in waste generation, step-economy, minimum use of solvents, along with atom and bond-forming economy. In addition, MCRs are eco-friendly with simple purification procedures, faster reactions favoring chemo- and regioselectivity in some cases [5][6][7]. The multicomponent strategy has

• the high nucleophilicity of the amino group in the substrate 23 to control the regioselectivity of the reaction (Scheme 9). 3 Indoles Indoles have a bicyclic structure consisting of a six-membered benzene ring fused with a five-membered nitrogen-containing pyrrole ring. Figure 3 depicts some of the

• potential rearrangement explained the regioselectivity during ring closure as depicted in Scheme 44. Theoretically, two regioisomeric pairs of adenine (115, A) and isoadenine are possible (C, D) (Scheme 44). However, using the multicomponent approach one product, 4-amino-7-arylimidazo[1,2-a][1,3,5]triazines

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• limitations that we had encountered in terms of yield and regioselectivity were presumably specific to the ambident nucleophile 6. We considered that a different ambident nucleophile, a phenol, might also give unusual selectivity for production of a bis(aryloxy)fluoromethane over a Reimer–Tiemann formylation

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

• depends on the association of eosin Y and oxidant 4 to a donor–acceptor EY–4 ground-system complex (high reactivity). Due to the ability of aryl groups to stabilize the formed alkenyl radical, this protocol could control regioselectivity efficiently with unsymmetrical alkynes. In addition, EPR

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• compounds and N-tosyl triazole in moderate to high yields. Our synthesis takes place with complete regioselectivity as confirmed by crystallographic analysis which is rationalized by a suitable mechanistic proposal. This method provides an efficient, versatile and straightforward strategy towards the

• -arylation [32], NIS-mediated N2-arylation [33], etc. Although these are significant advances towards metal-free functionalization of triazoles, many of them suffer from poor regioselectivity. Therefore, a new method for N1-selective alkylation of the triazole moiety under simple, mild and metal-free

Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes

• Olga Bakhanovich,
• Viktor Khutorianskyi,
• Vladimir Motornov and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44

• phenylacetylene leads to a mixture of 3,4-diphenylpyrrole 2a and 2,4-diphenylpyrrole 2a’. However, repeating the experiment without the silver catalyst afforded the same results showing that the silver catalyst was not necessary in our case and that the product regioselectivity was not dependent on the silver

Deoxygenative C2-heteroarylation of quinoline N-oxides: facile access to α-triazolylquinolines

• Geetanjali S. Sontakke,
• Rahul K. Shukla and
• Chandra M. R. Volla

Beilstein J. Org. Chem. 2021, 17, 485–493, doi:10.3762/bjoc.17.42

• isoquinolines was achieved from readily available N-oxides and N-sulfonyl-1,2,3-triazoles. A variety of α-triazolylquinoline derivatives were synthesized with good regioselectivity and in excellent yields under mild reaction conditions. Further, a gram-scale and one-pot synthesis illustrated the efficacy and

• secondary amines as the nucleophiles [49]. In their protocol, the regioselectivity is controlled by PyBroP catalyst, which acts as the N-oxide activator. Manley and Bilodeau reported the amidation of heterocyclic N-oxides at the C2-position using oxalyl chloride for activating the N-oxides [50]. In addition

• aminating source. The reaction proceeds at room temperature in a short reaction time with excellent regioselectivity. The methodology was also found to be compatible with isoquinoline N-oxides and diversely functionalized N-sulfonyl-1,2,3-triazoles to establish a broad substrate scope for a variety of

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• -halopurines [41]. O-Alkylation of guanosine and inosine with Cu(I)-stabilized carbenes derived form α-diazocarbonyl compounds is also known [42]. Alkylation of 6-oxopurine derivatives under Mitsunobu conditions which usually proceeds with O-regioselectivity are mostly described for guanine derivatives [43][44

• regioselectivity of SNAr reactions was proved by 13C NMR comparison of the products 3a–i with similar compounds from literature [61]. Intriguingly, we were able to conserve the acetate protecting groups in product 3j, when the SNAr reaction was performed in the presence of DBU used as base. The artificial

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• nonfluorinated analogues (Eox (PhNMe2) = +0.71 V (SCE)), the radical cation 180 is formed under the reaction conditions, and deprotonation at the methylene unit near the CF3 group is highly favored because of the higher acidity, accounting for the observed high regioselectivity. In addition, the transient

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• regioselectivity of transesterifications of hydroxylated alkyl and/or aryl moieties are sparser [26][34][35][36]. The extent to which Lipozyme® TL IM catalyzes feruloyl transfer reactions involving substituted benzylic alcohols was thus investigated to establish its usefulness for the preparation of both various

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• selection of the reagents and catalysts. These have an influence on the mechanism and regioselectivity of the C–C bond cleavage. Although there are several different mechanisms for ring-opening reactions, in most cases there is a cleavage of the most weakened C–C bond due to the fluorine effect. This C–C

• in 105, which is associated with a difference in the regioselectivity of the C–C bond cleavage. The dissociation of the tosylate 104 to generate a cyclopropylmethyl carbocation A was accompanied by the cleavage of the proximal bond to form homoallylic products. The regioselectivity of the ring

• lengthening and weakening of the C2–C3 bond of the cyclopropane ring appeared to dictate the regioselectivity. Monofluoroalkenes 157 were formed from the reductive ring opening of gem-difluorocyclopropanes 156 with dimethylamine·borane and catalyzed by nickel(II) fluorido complexes (Scheme 67) [117]. 1

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• event. The SNAr–Arbuzov reaction of 2,6-bistriazolylpurines follows the general regioselectivity pattern of the C6-position being more reactive towards substitution, which was unambiguously proved by X-ray analysis of diethyl (9-heptyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)-9H-purin-6-yl)phosphonate

• chromatography. At the preparative level, the excess of P(OEt)3 was evaporated under vacuum (5 mbar) over 4–5 hours at 50 °C before further purification. The regioselectivity of the newly developed SNAr–Arbuzov reaction was unambiguously established by X-ray analysis of the product 4d, which was crystalized from

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• play the same role. Comparing the different pathways in Figure 5 and Figure 6, it emerged that the base-mediated process is clearly favored over the 1,2-H-shift. We were also aware of the regioselectivity issue that arose during the deprotonation due to the presence of two similar hydrogen atoms (Ha

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• isoindigo 100 was used as substrate, enantioselective [3 + 2] annulation with allene 101 in the presence of amino acid-derived bifunctional phosphine 102 produced adduct 103 in 90% yield with 92% ee and 4:1 regioisomeric ratio (rr). The authors suggested that the observed regioselectivity could be

Easy access to a carbohydrate-based template for stimuli-responsive surfactants

• Thomas Holmstrøm,
• Daniel Raydan and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2020, 16, 2788–2794, doi:10.3762/bjoc.16.229

• with high regioselectivity via the Černý epoxide [20]. Results and Discussion Synthesis The synthesis was initiated by a regioselective esterification of levoglucosan (1) with tosyl chloride in pyridine, first presented by Černý and co-workers, in order to afford the 1,6-anhydro-2,4-di-O-tosyl-β-ᴅ

Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation

• Alexander P. Molchanov,
• Mariia M. Efremova,
• Mariya A. Kryukova and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218

• reaction undergo cycloreversion under the reaction conditions. Keywords: azomethine imines; cycloaddition; diazabicyclohexanes; diaziridines; regioselectivity; Introduction Cyclic azomethine imines (AMIs) are very useful synthetic blocks for the preparation of diverse dinitrogenated heterocycles by 1,3

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

• moiety throughout (Scheme 3). Thus, the α,β-unsaturated ester 15 [25] was carried through a similar sequence to that previously described, i.e., dihydroxylation, cyclic sulfate formation, ring-opening with TBAF (although note the regioselectivity [31]), deoxyfluorination, and deprotection to deliver the

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• compounds, we selected some functionalized (to obtain valuable building blocks), cyclic (to obtain better insight into the stereochemistry), and usually symmetrical olefins (to eliminate regioselectivity issues). The first substrate, the cyclohexene diester (rac)-1, has a twofold rotational symmetry, that

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• -arylation process. As evidenced by LCMS analysis, the reaction with 6-methyl-4-(trifluoromethyl)pyrimidin-2(1H)-one provided a mixture of three cross-coupling products (not separated), with a total yield of no more than 18%, which suggests a poor regioselectivity. Conclusion We have optimized the reaction

Regioselective cobalt(II)-catalyzed [2 + 3] cycloaddition reaction of fluoroalkylated alkynes with 2-formylphenylboronic acids: easy access to 2-fluoroalkylated indenols

• Tatsuya Kumon,
• Miroku Shimada,
• Jianyan Wu,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2020, 16, 2193–2200, doi:10.3762/bjoc.16.184

• -formylphenylboronic acids under the influence of Co(acac)2·2H2O in two-component solvents of acetonitrile/2-propanol at reflux temperature for 18 h took place smoothly, affording the corresponding fluoroalkylated indenol derivatives in good yields. This reaction shows excellent regioselectivity, giving 2

• regioselectivity, leading to a mixture of 3-fluoroalkylated and 2-fluoroalkylated indenols, which was difficult to separate. Secondly, a trimer of fluoroalkylated alkynes was obtained as a side product since the cobalt(I) species produced by the cobalt(II)/Zn system worked as a suitable catalyst, leading to the

• resulted in the sluggish formation of the fluoroalkylated indenols or indanone (Table 1, entries 7–9). When 1,3-bis(diphenylphosphino)propane (dppp) was used as a phosphine ligand, the desired indenol 3aA was obtained in a moderate yield and with high regioselectivity of 98:2, together with a very small

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

• , and we are tentative to draw firm conclusions on the regioselectivity of the C(sp3)–H fluorination at this stage. After screening several PSCats that absorb light >400 nm, such as benzophenone, 9-fluorenone, xanthone, 9,10-phenanthrenequinone and benzil, the highest yield (82%) was achieved with

• was achieved with exclusive regioselectivity in peptides, with modest to moderate diastereomeric ratios of the fluorinated products (Scheme 29). With the optimum PSCat in hand, it was necessary to find a protecting group (PG) for the amine that would not undergo fluorination or oxidation when treated

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• of 1a and 2,3-dimethylbutadiene (DMBD), the regioselectivity of which is as expected for a highly asynchronous transition state with effective stabilization of the positive charge or a two-step ionic process (vide infra). The high electrophilic power of the 1-CF3-substituted propyn-1-iminium ion

A complementary approach to conjugated N-acyliminium formation through photoredox-catalyzed intermolecular radical addition to allenamides and allencarbamates

• Olusesan K. Koleoso,
• Matthew Turner,
• Felix Plasser and
• Marc C. Kimber

Beilstein J. Org. Chem. 2020, 16, 1983–1990, doi:10.3762/bjoc.16.165

• the regioselectivity of the addition being controlled by steric factors. Significantly, the formation of the key conjugated N-acyliminium intermediate using these photoredox conditions can be seen as complementary to the well-developed electrophilic activation modes of allenamides. We are currently

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

• (6)-substituted 2-thiouracils. The reaction of chloroethynylphosphonates with 6-substituted 2-thiouracils bearing electron-donor groups (CH3, Ph) proceeded with high regioselectivity involving the cyclization through the N3-nitrogen atom to form new 3-phosphonylated thiazolo[3,2-a]-5-oxopyrimidines

• with good yield. In the case of unsubstituted and 5-methyl-2-thiouracils, cyclization occurred predominantly through the N1 atom and partially via the N3-nitrogen atom to form a mixture of the corresponding thiazolo[3,2-a]-7- and 5-oxopyrimidines. A dramatic change in the reaction regioselectivity was

• . As the second reaction component, available 2-thiouracils were chosen as the most studied objects used for creating thiazolopyrimidine systems. The main objective of the study was to determine the regioselectivity of the reaction. Literature data mainly report the formation of 5-oxopyrimidines by