Facile preparation and conversion of 4,4,4-trifluorobut-2-yn-1-ones to aromatic and heteroaromatic compounds

• Takashi Yamazaki,
• Yoh Nakajima,
• Minato Iida and
• Tomoko Kawasaki-Takasuka

Beilstein J. Org. Chem. 2021, 17, 132–138, doi:10.3762/bjoc.17.14

• Sandford group clarified the high potency of these compounds for the conjugate addition of N- as well as O-nucleophiles [21]. On the basis of such an idea, we tried two routes to gain access to 1) 4-substituted 6-(trifluoromethyl)salicylate derivatives (C-nucleophiles) and 2) 6-substituted 4

• -(trifluoromethyl)pyrimidines (N-nucleophiles), both in a concise fashion, with the full details, including the preparation of 2, being reported herein. Results and Discussion Investigations on the reaction conditions were carried out for the oxidation of propargylic alcohols 1, which were readily accessible by our

• structurally similar compounds [29] on the basis of 1) comparison of the chemical shift of the CF3 group and 2) the absence of a coupling between the vinylic and allylic protons. In order to explore other nucleophiles, we employed 1,3-diketones, such as 5-methylhexane-1,3-dione and 5,5-dimethylhexane-1,3-dione

Benzothiazolium salts as reagents for the deoxygenative perfluoroalkylthiolation of alcohols

• Armin Ariamajd,
• Nils J. Gerwien,
• Benjamin Schwabe,
• Stefan Dix and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2021, 17, 83–88, doi:10.3762/bjoc.17.8

• perfluoroalkylthiolate nucleophiles. Each of the other BT-SRF reagents (1.25 equiv) was reacted with alcohol 2a and NEt(iPr)2 (2 equiv) in MeCN at −40 °C and, after 2 h, the crude mixture was analysed by 1H and 19F NMR. As shown in Table 1, a significant decrease in the nucleophilic perfluoroalkylthiolation efficiency

Asymmetric Mannich reactions of (S)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimines with yne nucleophiles

• Ziyi Li,
• Li Wang,
• Yunqi Huang,
• Haibo Mei,
• Hiroyuki Konno,
• Hiroki Moriwaki,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2020, 16, 2671–2678, doi:10.3762/bjoc.16.217

• , Paseo Manuel Lardizábal 3, 20018 San Sebastián, Spain IKERBASQUE, Basque Foundation for Science, Alameda Urquijo 36-5, Plaza Bizkaia, 48011 Bilbao, Spain 10.3762/bjoc.16.217 Abstract In the present work, arylethynes were studied as new C-nucleophiles in the asymmetric Mannich addition reactions with (S

• yne nucleophiles have never been reported thus far. Accordingly, intrigued by this methodological deficiency, we decided to dedicate a special research project to this objective; herein, we report Mannich reactions between yne nucleophiles and aldimine 1 (Scheme 1c). The results reported in this work

• excellent level (>90% de) of stereocontrol reported for the Mannich additions of aldimine 1 with sp3 [42][55] and sp2 [56] nucleophiles, including lithiated aromatics [57] one would not anticipate such a dramatic drop in the selectivity in the reactions of sp nucleophiles. Accordingly, we considered the

Synthesis of 4-substituted azopyridine-functionalized Ni(II)-porphyrins as molecular spin switches

• Jannis Ludwig,
• Tobias Moje,
• Fynn Röhricht and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2589–2597, doi:10.3762/bjoc.16.210

• . Azopyridines 14, 16 and 18 were prepared by nucleophilic substitution with 2-methylpropane-2-thiol (13) and methyl 3-mercaptopropionate (15) as nucleophiles (Scheme 2). 3-(3-Bromophenylazo)-4-cyanopyridine (20) was directly obtained by conversion of 3-amino-4-cyanopyridine (19) and 3. Alkaline hydrolysis as

Clustering and curation of electropherograms: an efficient method for analyzing large cohorts of capillary electrophoresis glycomic profiles for bioprocessing operations

• Ian Walsh,
• Matthew S. F. Choo,
• Sim Lyn Chiin,
• Amelia Mak,
• Shi Jie Tay,
• Pauline M. Rudd,
• Yang Yuansheng,
• Andre Choo,
• Ho Ying Swan and
• Terry Nguyen-Khuong

Beilstein J. Org. Chem. 2020, 16, 2087–2099, doi:10.3762/bjoc.16.176

• using UPLC-MS The supernatant was purified using Protein A HP SpinTrap (GE Healthcare). The purified glycoprotein obtained was buffer exchanged into water using a 10 kDa molecular weight cut-off filter (Merck Millipore) to eliminate any salts and nucleophiles that could interfere with the subsequent

Efficient [(NHC)Au(NTf₂)]-catalyzed hydrohydrazidation of terminal and internal alkynes

• Maximillian Heidrich and
• Herbert Plenio

Beilstein J. Org. Chem. 2020, 16, 2080–2086, doi:10.3762/bjoc.16.175

• ; Introduction Cationic gold complexes with weakly coordinating counterions (which are often considered to be solvent-separated ions) [1][2][3], render powerful catalysts for the transformation of organic substrates [4][5][6], specifically the reactions of alkynes with a variety of heteroatom nucleophiles

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

• variety of nucleophiles to afford products containing a C(CF3)NR2 moiety. In particular C(CF3)NHR and C(CF3)NH2 groups are of interest as pharmacophores in the design of bioactive compounds [10][11][12][13]. Simple α-(trifluoromethyl)iminium salts (RCH(CF3)=N+Me2 X−, R= H, CF3) with weakly nucleophilic or

• non-nucleophilic anions can be isolated [14][15], but in organic synthesis, they are most often generated in situ from suitable precursors and are directly exposed to diverse nucleophiles. Such transformations have been achieved using CH2(CF3)NR2 as the iminium ion precursors [15

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

• -acyliminium intermediate is provided to explain the addition product distribution. Results and Discussion We began our study by using the iridium catalyst Ir[(ppy)2(dtbbpy)]PF6 (17) and the reaction conditions used in the addition of amine nucleophiles to enamides [48][50]. By exploiting these reaction

• = 2.0 Hz, 1H) ppm, respectively. Crucially, it is apparent that using the photoredox conditions described in Scheme 3, the aniline nucleophile adds primarily at the α-position of the allenamide 15; this is in contrast to the archetypal electrophilic activation modes where comparable nucleophiles add to

• explored oxygen nucleophiles in their photoredox-catalyzed addition to enamides [48]. Consequently, the use of excess methanol provided the addition product 38, resulting from α-addition, in a modest isolated yield. The stability of product 38 was marginal, but an improved stability of the N,O’-allyl

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

• nucleophiles [37][38][39]. The assignment of the reaction product to the 5-oxo isomer was made based on 13C NMR spectral analysis: the carbon atoms of the CH=СR fragment (R=CH3, Ph) are represented by a strong signal at δC 101–105 ppm (СН=) and a weak signal at δC 157–158 ppm (=CR). These data coincide with

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• through an olefination reaction with benzothiazoyl sulfones (Scheme 1) [22]. With these fluoroalkylidene-oxetanes in hands, we studied the selectivity of ring-opening reactions with heteroatom nucleophiles in order to access tetrasubstituted fluoroalkenes. A control of the geometry of these reactions

• would allow ready access to novel fluorinated ACN precursors. At the outset the opening of the oxetane ring of 1 by a range of nucleophiles was trialed under acidic conditions. Inspired by Yadav et al. [23], methanol (20 equiv) was used as nucleophile in the presence of camphorsulfonic acid (CSA, 1

• mercaptobenzothiazole (Table 1). However, the reaction was not selective and afforded a mixture of E/Z alkenes 1c. The functionalization of alkene E-1d via displacement of the bromine atom (Scheme 8), with nucleophiles such as CsF and NaN3 was then studied. When the reaction was performed in DMF products E-23 and Z-24

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

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

• results may suggest that fluoroalkyl groups behave as bulky substituents rather than as electron-withdrawing ones, perhaps due to the purely inductive nature of the latter [71]. In the same work, the authors described the conjugated addition of several nucleophiles to model substrate 59d (Scheme 33). In

• this sense, while the addition of hard organometallic nucleophiles, such as lithium dialkylcuprates or Grignard reagents, failed, softer nucleophiles such as nitroalkanes cleanly added to the β-position, providing the Michael adduct 61. Unexpectedly, the conjugate addition reaction resulted in

Models of necessity

• Timothy Clark and
• Martin G. Hicks

Beilstein J. Org. Chem. 2020, 16, 1649–1661, doi:10.3762/bjoc.16.137

• interaction between halogens and nucleophiles as repulsive; whereas we now know that halogen-bonding attractions can be as strong as hydrogen bonds. There will be more such examples but it is important to identify the encompassing phenomenon, rather than defining a wealth of apparently unique interactions

NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

• Alyn T. Davies,
• Mark D. Greenhalgh,
• Alexandra M. Z. Slawin and
• Andrew D. Smith

Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129

• opening procedure, aryl and heteroaryl substitution of the trifluoromethylacetophenone, as well as variation of the α-aroyloxyaldehyde. Using α-aroyloxyaldehyde 4 and trifluoromethylacetophenone (5) as reactants, the variation of the nucleophile showed that a range of amine-based nucleophiles was readily

• with amine nucleophiles allowed access to β-trifluoromethyl-β-hydroxyamides in moderate to good yield as single diastereoisomers in excellent er following purification [61]. Organocatalytic enantioselective aldol approaches using trifluoroacetophenone derivatives. NHC-catalyzed approaches to β-lactones

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-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• spectroscopy. The spectra showed cross peaks between the protons from the cis-oriented alkyl-C-11b and H-1, which unequivocally proved the trans relative configuration of the substituents at C-1 and C-11b (Figure 4). 1-Alkyl-3,4-dihydroisoquinolines have been reported to react as C-nucleophiles or 1,3-C,N

• -ambident nucleophiles with electrophilic species [47][48][49][50]. Thus the formation of compounds 25–27 could be rationalized as including an initial nucleophilic attack of the enamine tautomer 19a of 3,4-dihydroisoquinoline 19 to the carbonyl carbon atoms of the anhydrides 5–7 followed by an anhydride

Recent synthesis of thietanes

• Jiaxi Xu

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

• in low to good yields by the reaction of 2-(1-haloalkyl)oxiranes 142 and 147 with ammonium monothiocarbamates 148 as the sulfur nucleophiles. First, a nucleophilic ring-opening of the oxiranes 142 and 147 by monothiocarbamates 148 gave rise to the S-(γ-halo-β-hydroxyalkyl)carbamates 149 with release

• -haloalkyl)thiiranes with various nucleophiles, nucleophilic ring expansion of thiiranes with sulfur ylides, and the electrophilic ring expansion of thiiranes with carbenes generated from sulfur ylides under the catalysis of transition-metal catalysts. 4.1.1 Synthesis via nucleophilic ring expansion of 2-(1

• -haloalkyl)thiiranes: A thiirane–thietane rearrangement took place upon the interaction of (1-haloaklyl)thiiranes 398 with hard and weak nucleophiles (:Nu−) in the presence of a base. It was an efficient method for the preparation of 3-substituted thietanes 400 from (1-haloalkyl)thiiranes 398 through an

Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides

• Mateo Berton,
• Kevin Sheehan,
• Andrea Adamo and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2020, 16, 1343–1356, doi:10.3762/bjoc.16.115

• columns of solid reagents and product receptacle. These components are deployed in a low-cost machine with a design amenable for the automated lab-scale generation of organomagnesium reagents on demand (Figure 1). Organomagnesium compounds are omnipresent reagents that serve as nucleophiles and bases

Ferrocenyl-substituted tetrahydrothiophenes via formal [3 + 2]-cycloaddition reactions of ferrocenyl thioketones with donor–acceptor cyclopropanes

• Grzegorz Mlostoń,
• Mateusz Kowalczyk,
• André U. Augustin,
• Peter G. Jones and
• Daniel B. Werz

Beilstein J. Org. Chem. 2020, 16, 1288–1295, doi:10.3762/bjoc.16.109

• )ethylene-1,2-dicarbonitrile (R = CF3) [8]. Both five-membered spirotetrahydrothiophenes 3 and seven-membered S,N-heterocycles (ketene imines) 4 were observed in the course of these reactions (Scheme 1). The latter products were trapped with suitable nucleophiles (R = CO2Me) or even isolated and identified

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

• strong electrophiles and undergo nucleophilic additions with two-electron donors (Scheme 21a) [93][94]. In contrast, radical anions can act as very strong single-electron nucleophiles and are often subject to fragmentation to give a neutral free radical and a charged species (Scheme 21b) [77][95]. When a

• -opening driving force. N-Aryltetrahydroquinolines 34.1 have been intensively studied as a privileged scaffold for N-centred radical cation formations [138]. After iminium formation, formed by subsequent HAT on the amine radical cation, various nucleophiles can add, resulting in diverse functionalizations

The charge-assisted hydrogen-bonded organic framework (CAHOF) self-assembled from the conjugated acid of tetrakis(4-aminophenyl)methane and 2,6-naphthalenedisulfonate as a new class of recyclable Brønsted acid catalysts

• Svetlana A. Kuznetsova,
• Alexander S. Gak,
• Yulia V. Nelyubina,
• Vladimir A. Larionov,
• Han Li,
• Michael North,
• Vladimir P. Zhereb,
• Alexander F. Smol'yakov,
• Artem O. Dmitrienko,
• Michael G. Medvedev,
• Igor S. Gerasimov,
• Ashot S. Saghyan and
• Yuri N. Belokon

Beilstein J. Org. Chem. 2020, 16, 1124–1134, doi:10.3762/bjoc.16.99

• atoms to engage the ammonium groups of TAPM (see the crystal structure of the F-1a phase). This structure was thermodynamically stable and hinted at a possible activation of water or methanol as nucleophiles by the sulfate anions during the ring opening of epoxides. When the coordinated water was

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

• yields and no β-elimination products. The effective removal of the auxiliary using triflic anhydride with LiOH as nucleophile, gave product 177a in good yield. Alternative nucleophiles such as EtOH or methyl esters of amino acids, in the presence of catalytic amounts of CoCl2, afforded product 177b or

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

• of the organozinc reagents. To solve this problem, the intermediate of the N-acyl-4-methoxypyridinium salt must be formed in situ and added slowly to the solution of the Cu(OTf)2/L6 complex and dialkylzinc reagent at −78 °C. Several dialkylzinc reagents were found to be effective as nucleophiles in

• ]. Several alkylzirconocenes were examined, resulting in the respective products with 45–93% ee and 20–33% yield. The same group also described the copper-catalysed desymmetrisation of heterocyclic meso compounds via the AAA reaction, once again using alkylzirconocenes as nucleophiles (Scheme 10B). In this

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• biologically active compounds [104]. These compounds can be trapped with nucleophiles to produce the α-amino-substituted compounds, and be employed as substrates for a variety of chemical transformations such as Ugi- and Mannich-type reactions. In this regard, Seeberger and co-workers reported the primary

• ]. Che and co-workers showed that a variety of nucleophiles can be used for the α-functionalization of N-aryltetrahydroisoquinolines using a low Pd-TPFPP loading. This photocatalyst provided the α-aminonitriles in 71–85%, β-nitroamines in 72–83%, β-diester amines in 68–74%, and α-amino phosphonates in 63

• epoxidation agent of an electron-deficient olefin intermediate, which was formed by deaminative Mannich coupling between the imine and nucleophiles such as malononitrile and methyl cyanoacetate (Scheme 64) [109]. Overall, a variety of additional examples of porphyrin-photocatalyzed heteroatom oxidations are

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• ] described NHC–Cu (74)/base 1,2-additions at room temperature of silicon pro-nucleophiles onto aldehydes 81 leading to racemic silyl alcohols 82–87 (Scheme 17B). A detailed mechanistic study revealed that a Cu–Si species is involved, giving intermediate 77, which subsequently undergoes fast Brook

• racemic product 114 (Scheme 22, right) [56]. In 2010, Hoveyda [57] used CuCl along with an NHC ligand (L14) that enabled 1,4-additions of silicon nucleophiles to unsaturated ketones. The best results were obtained at low temperatures, giving both high chemical yields and products with high enantiomeric