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

• nitrile 63 could be obtained by the reaction of phenylacetonitrile (61) with 1,2-dibromo-1,1-difluoroethane (62) using sodium amide as the base (Scheme 27) [69]. However, the yield of this reaction was only 10%. The gem-difluorocyclopropanes 65 were synthesized from the reaction of gem-difluoroolefins 64

• nitrile hydratase–amidase-containing biocatalytic system and showed a high chemo-, regio-, and enantioselectivity in the hydrolysis of nitriles and dinitriles. The biocatalytic transformations of nitrile 81 (Scheme 33) supplied an effective route to optically active 2,2-difluorosubstituted 3

• by the two attached fluorine atoms. The nucleophilic attack of the nitrile, followed by cyclization and aromatization could then give the pyrrole derivatives 142. Later, Xiao et al. performed another ring-opening reaction of gem-difluorocyclopropyl ketones 143, this time mediated by BX3 (X = F, Cl

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

• underwent successive intramolecular Michael addition and hydrolytic nitrile reduction to give 79 in 46% yield in two steps. Extensive studies of the nitrile reduction eventually identified that Et3Al and DIBAL-H could effectively reduce the nitrile group to the corresponding aldehyde and treatment with

Naphthalonitriles featuring efficient emission in solution and in the solid state

• Sidharth Thulaseedharan Nair Sailaja,
• Iván Maisuls,
• Jutta Kösters,
• Alexander Hepp,
• Andreas Faust,
• Jens Voskuhl and
• Cristian A. Strassert

Beilstein J. Org. Chem. 2020, 16, 2960–2970, doi:10.3762/bjoc.16.246

• considerations: (1) the p-phenyl substituents act as electron-donor units and as AIE activators; (2) the nitrile groups provide a significant π-acceptor strength, and also promote hydrogen bonding in the aggregates [39][40][41][42]. By varying the substituents at the phenyl groups ranging from mild π-donors

• some intermolecular CH…π interactions between the C–H units of the residual tolyl group and the central ring of the naphthalonitrile bearing two nitrile groups with a CH/π-ring distance of 2.780 Å (Figure 2A). Even though the naphthalonitrile planes of two adjacent head-to-tail-arranged molecules are

• together by C–H…N intermolecular hydrogen bonds with distances of 3.006 Å for C–H(2e)/N(6) and 3.083 Å for C–H(2d)/N(6) while involving hydrogen atoms of the tolyl moieties and the nitrogen atoms of nitrile groups. Then, these dimeric substructures are linked by C–H…N intermolecular interactions to

Ultrasound-assisted Strecker synthesis of novel 2-(hetero)aryl-2-(arylamino)acetonitrile derivatives

• Emese Gal,
• Luiza Gaina,
• Hermina Petkes,
• Alexandra Pop,
• Castelia Cristea,
• Gabriel Barta,
• Dan Cristian Vodnar and
• Luminiţa Silaghi-Dumitrescu

Beilstein J. Org. Chem. 2020, 16, 2929–2936, doi:10.3762/bjoc.16.242

• -nitrile pharmacophoric units. In this work we report the experimental procedure for the ultrasound-assisted addition of the TMSCN nucleophile to heterocyclic aldimines. The substrates tested were mostly represented by a series of phenothiazinyl aldimines, but the scope of the new synthetic procedure was

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

• shown that the spin switching efficiency is strongly dependent on the solvent and on the substituent at the 4-position of the pyridine unit. We now introduced thiol, disulfide, thioethers, nitrile and carboxylic acid groups and investigated their spin switching efficiency. Keywords: azopyridines; Ni(II

Thermodynamic and electrochemical study of tailor-made crown ethers for redox-switchable (pseudo)rotaxanes

• Henrik Hupatz,
• Marius Gaedke,
• Hendrik V. Schröder,
• Julia Beerhues,
• Arto Valkonen,
• Fabian Klautzsch,
• Sebastian Müller,
• Felix Witte,
• Kari Rissanen,
• Biprajit Sarkar and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2020, 16, 2576–2588, doi:10.3762/bjoc.16.209

• the optoelectronic properties of the NDI unit. The binding properties suggest that the combination of the A1·BArF24 axle and NDIC8 is optimal for the synthesis of an NDI-containing [2]rotaxane. We applied Takata’s catalyst-free stoppering approach [58] using the nitrile oxide St for the preparation of

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

• enolisable ketone 293 is used, enolate complex 294 can be formed in the presence of base (Scheme 49a) [116]. The complex in this example is then proposed to proceed via an oxidative quenching cycle with bromo nitrile 295 to form α-cyano radicals 295• that then add to another molecule of 294

Recent synthesis of thietanes

• Jiaxi Xu

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

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• corresponding to the free iminoxyl radical, which indicates the reversibility of dimerization [53]. During the oxidation of pivalic aldoxime 1e by Ag2O, the formation of nitrile oxide 6e was observed, which then slowly dimerized to the corresponding furoxan 7e. The kinetics of the decomposition of dialkyl

• ruthenium catalyst. This possible reaction pathway was confirmed by a control experiment in which the hydroxyiminomethylisoxazoline was transformed to a nitrile in the presence of [RuCl2(p-cymene)]2. Aromatic oximes with various substituents, as well as heteroaromatic oximes, give cyano-substituted

• oximes (products 147e,f) were successfully used. Oxidative cyclization of unsaturated oximes with the formation of isoxazolines or cyclic nitrones and the introduction of a nitrile group was achieved using the CuCN/N,N,N′,N′′,N′′-pentamethyldiethyltriamine (PMDETA)/TBHP system (Scheme 50) [139]. Other

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

• nitrile 48a with 30% HCl aq/acetic acid, gave the 4-fluorophenylalanine·HCl 49a in a good overall yield (67%) [47] (Scheme 11). 1.4. Hydrolysis of Erlenmeyer’s azalactone A multistep Erlenmeyer azalactone synthesis was reported as an important method for the synthesis of fluorinated α-amino acids 53a–h

• (126). Then, reaction of 127 (1.0 mmol) with 1.5/1.0 equiv of diethylaluminum cyanide (Et2AlCN)/iPrOH at −78 °C in THF gave nitrile 128. Deprotection of the latter, followed by hydrolysis of the nitrile group afforded syn-(2S,3S)-(+)-3-fluorophenylalanine (129) [65] (Scheme 28) . 2.3. Multistep

• ] (Scheme 41). An alternative approach to the difluorinated compound 168a was achieved by the condensation of 164a with (S)-1-phenylethylamine (169), to give the imine 170. Heating of imine 170 with TMSCN in the presence of zinc iodide [82] generated the nitrile 171 as a 1:1 mixture of diastereoisomers

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

• using 4 mol % of tetra-n-butylammonium fluoride (TBAF) as an activator of TMSCN (conditions B). Following this second protocol, the primary α-aminonitriles were rapidly prepared in relevant yields (up to 87%) and converted to the corresponding α-amino acids by hydrolysis of the nitrile (Scheme 57

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

• attached to the triflate bearing carbon. In this way, different classes of substrates bearing either a nitrile (17) or ethyl ester (21) easily underwent conversion to the corresponding silylated products 18–20 in moderate to good yields (Scheme 5). This method was extended to the use of enantiomerically

Synthesis of organic liquid crystals containing selectively fluorinated cyclopropanes

• Zeguo Fang,
• Nawaf Al-Maharik,
• Peer Kirsch,
• Matthias Bremer,
• Alexandra M. Z. Slawin and
• David O’Hagan

Beilstein J. Org. Chem. 2020, 16, 674–680, doi:10.3762/bjoc.16.65

• relative to other polar substituents such as nitrile and ester groups, and this reduces intermolecular interactions leading to lower viscosities and thus increased life time reliability [4][5]. A significant effort has been devoted to the development of liquid crystals with either positive or negative

Cascade trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles

• Ming-Xi Bi,
• Shuai Liu,
• Yangen Huang,
• Xiu-Hua Xu and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2020, 16, 657–662, doi:10.3762/bjoc.16.62

• effect of the substitution on the indole ring. Both electron-donating and withdrawing groups at different positions of the indole ring produced the bis(trifluoromethylthiolated) products 2a–o in moderate to good yields. A wide range of functionalities such as alkyl, alkoxy, nitro, nitrile, ester

• were subjected to the standard conditions, the cascade trifluoromethylthiolation and cyclization occurred to yield trifluoromethylthiolated pyrrolo[1,2-a]indol-3-ones (4a–d) in moderate yields (Scheme 3). The functionalities including alkyl, aryl, nitrile, and acyl were also well tolerated in this

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• the quinazoline ring (Scheme 17) and the phosphine was introduced via metal-catalyzed phosphorylation. The ligands were synthesized in eight steps with relatively good yield. The reaction between substituted nitrile derivatives 87 and anthranilic acid (88) catalyzed by sodium methoxide formed

The use of isoxazoline and isoxazole scaffolding in the design of novel thiourea and amide liquid-crystalline compounds

• Itamar L. Gonçalves,
• Rafaela R. da Rosa,
• Vera L. Eifler-Lima and
• Aloir A. Merlo

Beilstein J. Org. Chem. 2020, 16, 175–184, doi:10.3762/bjoc.16.20

• , 8, 9, 12 and 13 were then prepared by [3 + 2]-1,3-dipolar cycloaddition of nitrile oxide (ArCNO) formed in situ from oximes and a number of alkenes as dipolarophiles, to yield the precursors of the cycloadducts isoxazolines 2, 7 and 11 regioselectively. The cycloadducts were subjected to SnCl2

Efficient method for propargylation of aldehydes promoted by allenylboron compounds under microwave irradiation

• Jucleiton J. R. Freitas,
• Queila P. S. B. Freitas,
• Silvia R. C. P. Andrade,
• Juliano C. R. Freitas,
• Roberta A. Oliveira and
• Paulo H. Menezes

Beilstein J. Org. Chem. 2020, 16, 168–174, doi:10.3762/bjoc.16.19

• or nitrile group were used, the corresponding products 2q and 2r were obtained in good yields. The use of a heteroaromatic or an aliphatic aldehyde as substrates under the optimized conditions gave the corresponding homopropargylic alcohols 2s,t in moderate yields. The development of a solvent-free

Synthesis of 3-alkenylindoles through regioselective C–H alkenylation of indoles by a ruthenium nanocatalyst

• Abhijit Paul,
• Debnath Chatterjee,
• Srirupa Banerjee and
• Somnath Yadav

Beilstein J. Org. Chem. 2020, 16, 140–148, doi:10.3762/bjoc.16.16

• tolerated several functional groups, including bromine and nitrile units, which provide ample scope for further manipulation of the products from the perspective of medicinal chemistry. The catalyst can be easily recovered and recycled in a colloidal solid form, enabling catalytic recycling and reusability

A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones

• Daniel P. Pienaar,
• Kamogelo R. Butsi,
• Amanda L. Rousseau and
• Dean Brady

Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287

• environmentally unfriendly transition-metal-based reactions. Acylations of in situ-generated nitrile anions with esters to produce β-ketonitriles were first reported long ago, for example by using sodium methoxide [2], sodium ethoxide [3] or sodium amide [4][5]. The reaction was found to proceed more efficiently

• when using sodium amide as the base [5], although the inherent risks of employing explosive sodium amide in synthesis are well known [6] and amidine side-product formation was observed at times through reaction of the nucleophilic amide base with nitrile. Furthermore, clearly two equivalents of base

• (and nitrile) were necessary to drive the reactions to completion as the acylated product is more acidic than the nitrile starting material. More recently, ester or Weinreb amide reactions with acetonitrile using lithium bases at low temperature [7], or similarly NaH at high temperatures [8], have been

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• involved the synthesis of precursor (+)-198 from phenylacetic acid and (−)-α-PEA via sequential amidation, reduction and Pictet–Spengler cyclization reactions. The key anodic oxidation in the presence of NaCN converted (+)-198 to α-amino nitrile (+)-199 with excellent diastereoselectivity. Upon further

Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

• Benedikt C. Melzer,
• Alois Plodek and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2304–2310, doi:10.3762/bjoc.15.222

• bromo substituent of the appropriate substrates 20a or 20b should converted into the respective organomagnesium product by bromine–magnesium exchange. In an expected subsequent Parham-type ring-closing reaction [33] the nucleophilic carbon at position 4 should trap the ester (or nitrile) group to lead

Regioselective Pd-catalyzed direct C1- and C2-arylations of lilolidine for the access to 5,6-dihydropyrrolo[3,2,1-ij]quinoline derivatives

• Hai-Yun Huang,
• Haoran Li,
• Thierry Roisnel,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2019, 15, 2069–2075, doi:10.3762/bjoc.15.204

• -arylated lilolidines were generally obtained in high regioselectivities and in good yields using aryl bromides as easily available aryl sources, acetates as inexpensive bases and PdCl(C3H5)(dppb) as air-stable catalyst. The reaction tolerated a wide variety of useful functional groups such as nitrile

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

• András György Németh,
• György Miklós Keserű and
• Péter Ábrányi-Balogh

Beilstein J. Org. Chem. 2019, 15, 1523–1533, doi:10.3762/bjoc.15.155

• -diimidazole or di-2-pyridyl thionocarbonate [57][58]. Decomposition of dithiocarbamate salts or thiocarbamates with various reagents offers a good alternative [59][60][61][62] as well, however, this approach first requires the synthesis of the appropriate precursor. Nitrile oxides react with thiourea to

• afford isothiocyanate and harmless urea [63][64][65], but one should note that the instability of the nitrile oxides leads to many byproducts, turning this approach less attractive. The synthesis of isothiocyanates starting from isonitriles involves sulfur-containing reagents such as thallium

• , we have turned our attention to different benzylic alcohols that could be utilized to further examine the functional group tolerance of the reaction. Notably, chlorine, bromine and iodine substituents were compatible with the transformation, providing 3m, 3n, 3r and 3s in 81–89% yield. The nitrile

Introduction of an isoxazoline unit to the β-position of porphyrin via regioselective 1,3-dipolar cycloaddition reaction

• Xiujun Liu,
• Xiang Ma and
• Yaqing Feng

Beilstein J. Org. Chem. 2019, 15, 1434–1440, doi:10.3762/bjoc.15.143

• Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China 10.3762/bjoc.15.143 Abstract Isoxazoline-linked porphyrins have been synthesized by a regioselective 1,3-dipolar cycloaddition reaction between vinylporphyrin 2 and nitrile oxides. The steric interaction directed the

• ; isoxazoline; macrocycles; nitrile oxide; porphyrin; Introduction In nature, porphyrin-type compounds play a prominent role in life [1]. It is well known that certain vital functions, like O2 transport, photosynthesis etc. depend on the action of porphyrin–metal complexes [2][3][4][5]. Inspired by the natural

• -generated nitrile oxide, which showed inferior selectivity and afforded regio-/stereoisomers [43]. NMR analysis assisted the identification of various isomeric isoxazoline-linked chlorin products. Here, we would like to report an artificial vinylporphyrin 2, which has been designed to control the