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

• oxidation states (Cu(0), Cu(I), Cu(II), and Cu(III)). Copper has been known for a long time to act as a catalyst for cross-coupling reactions (Ullmann–Goldberg reaction), cyanation of aryl halides (Rosenmund–von Braun reaction), Hurtley reaction and intermolecular oxidative cyclization of haloalkynes [41

• Cu2O as a byproduct which was marked by the change of color from initial green to red. The theoretical study was carried out to check the feasibility of the reaction by calculating Gibbs free energy difference for each step (Scheme 42). The capability of copper to catalyze the cyanation reaction was

• . Substituted aryl ketones, heteroaryl methyl ketones, and α,β-unsaturated methyl ketones were also well tolerated by the reaction (Scheme 44). The reaction was also successful in a two-step procedure in which the product of 2-AP and ketone can also be subjected to cyanation with benzyl cyanide thereby proving

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• of a chiral auxiliary with lithium dibutylcuprate. Next, titanium tetrachloride-catalyzed cyanation secured another carboxy group and after a few transformations an oxazolidinone (4S,5R)-39 was obtained as a major (7:1) product readily purified chromatographically. To complete the synthesis of (2S,3R

• or tributyltin cyanides and the stereochemical outcome of these reactions strongly depends on the protecting group. Diastereoisomeric excesses of 60–80% were observed in the cyanation of tert-butyldimethylsilyl ether 107a and 108a was the major product, while for the acetate 107b the selectivity was

• this imide with a reagent obtained from (R)-binaphthol [(R)-BINAL-H] followed by acetylation furnished the triacetate (3R,4S)-111 as a single diastereoisomer after chromatographic purification (Scheme 27). However, its cyanation as described earlier gave a 38:62 mixture of diacetates (3R,4R,5S)-112 and

Reactions of 3-(p-substituted-phenyl)-5-chloromethyl-1,2,4-oxadiazoles with KCN leading to acetonitriles and alkanes via a non-reductive decyanation pathway

• Akın Sağırlı and
• Yaşar Dürüst

Beilstein J. Org. Chem. 2018, 14, 3011–3017, doi:10.3762/bjoc.14.280

• structures, cyanation attempts of 5-(chloromethyl)-3-phenyl-1,2,4-oxadiazoles 1 with excess KCN at room temperature in CH3CN have been investigated leading to trisubstituted acetonitrile 3 instead of anticipated product 2. This result is in accord with a previous report where only one example (3a) has been

• . Cyanation through 5-chloromethyl-3-(p-substituted-phenyl)-1,2,4-oxadiazole. Expanded HSQC spectrum of 4a and 3a. X-ray ORTEP plots of 3a and 4e. Plausible mechanism for the formation of 3. Plausible mechanism for the formation of 4 via decyanation of 3. Optimisation of reaction conditions. Formation of 3

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• of substrates make this an ideal method for introducing nucleophilic ligands onto aromatic rings. Another publication from the Nicewicz group demonstrates the C–H direct cyanation of a variety of aromatic and heteroaromatic substrates. TMSCN is employed as the cyanide source, acridinium salts as the

Cobalt-catalyzed C–H cyanations: Insights into the reaction mechanism and the role of London dispersion

• Eric Detmar,
• Valentin Müller,
• Daniel Zell,
• Lutz Ackermann and
• Martin Breugst

Beilstein J. Org. Chem. 2018, 14, 1537–1545, doi:10.3762/bjoc.14.130

• Abstract Carboxylate-assisted cobalt(III)-catalyzed C–H cyanations are highly efficient processes for the synthesis of (hetero)aromatic nitriles. We have now analyzed the cyanation of differently substituted 2-phenylpyridines in detail computationally by density functional theory and also experimentally

• . Based on our investigations, we propose a plausible reaction mechanism for this transformation that is in line with the experimental observations. Additional calculations, including NCIPLOT, dispersion interaction densities, and local energy decomposition analysis, for the model cyanation of 2

• cyanation of arenes (Scheme 2) [30][31][32][33][34]. Dispersion effects can be envisioned to be highly important in this system, as the relatively C–H-rich ligand Cp* can interact with both substrates within the cobalt complexes. In 2015, Li and Ackermann have proposed the catalytic cycle (C–H cobaltation

Preparation, structure, and reactivity of bicyclic benziodazole: a new hypervalent iodine heterocycle

• Akira Yoshimura,
• Michael T. Shea,
• Cody L. Makitalo,
• Melissa E. Jarvi,
• Gregory T. Rohde,
• Akio Saito,
• Mekhman S. Yusubov and
• Viktor V. Zhdankin

Beilstein J. Org. Chem. 2018, 14, 1016–1020, doi:10.3762/bjoc.14.87

• efficient electrophilic atom-transfer reagents useful for conversion of various organic substrates to the corresponding products of azidation [7][8][9][10][11], amination [12][13], cyanation [14][15][16][17], alkynylation [18][19][20], or chlorination [21][22]. Recently, Zhang and co-workers reported the

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• (5H)-one derivatives 204 by refluxing in 1 N sodium hydroxide. Pyrazolo[3,4-d]pyrimidinone 204 were further chlorinated by phosphorus oxychloride and subsequently converted to carboxylic esters 207 via cyanation followed by hydrolysis and esterification. Kaplan et al. [20] explored the synthesis of

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• investigated the phase-transfer catalysed α-cyanation of ketoesters 1 using hypervalent iodine-based cyanide transfer reagents [97]. Hereby we observed the in situ oxidation of the PTC counter anions (Br− or I−) and subsequent α-halogenation of 1. We tried to employ and optimise this procedure, but without any

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• is proposed (Scheme 29) [135][136]. Such a pathway could also apply for the reductive decyanation of diphenylacetonitriles induced by organolithiums or Grignard reagents [137][138]. This reaction, applied to nitriles substituted with suitable leaving groups appears as a cyanation method of

Poly(ethylene glycol)s as grinding additives in the mechanochemical preparation of highly functionalized 3,5-disubstituted hydantoins

• Andrea Mascitti,
• Massimiliano Lupacchini,
• Ruben Guerra,
• Ilya Taydakov,
• Lucia Tonucci,
• Nicola d’Alessandro,
• Frederic Lamaty,
• Jean Martinez and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 19–25, doi:10.3762/bjoc.13.3

• other alternative energy inputs is still scarce. Only three examples highlight their peculiar role for metal-catalysed processes in a ball mill (Mirozoki–Heck reaction) [6], by ultrasound (copper-catalysed cyanation reaction) [7], and for co-crystal formation in the polymer-assisted grinding process

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

• Michal Medvecký,
• Igor Linder,
• Luise Schefzig,
• Hans-Ulrich Reissig and
• Reinhold Zimmer

Beilstein J. Org. Chem. 2016, 12, 2898–2905, doi:10.3762/bjoc.12.289

• -forming reactions such as Sonogashira, Heck, or Suzuki coupling reactions as well as a cyanation reaction. These cross-coupling reactions led to a series of 5-alkynyl-, 5-alkenyl-, 5-aryl- and 5-cyano-substituted 1,2-oxazine derivatives being of considerable interest for further synthetic elaborations

• -24 employing phenylboronic acid 23 under the same reaction conditions in excellent yield. In the last example of palladium-catalyzed reactions, we set out to prove a 5-iodo-1,2-oxazine 4 as substrate in a cyanation reaction that would lead to a 5-cyano-substituted derivative. The installation of a

Economical and scalable synthesis of 6-amino-2-cyanobenzothiazole

• Jacob R. Hauser,
• Hester A. Beard,
• Mary E. Bayana,
• Katherine E. Jolley,
• Stuart L. Warriner and
• Robin S. Bon

Beilstein J. Org. Chem. 2016, 12, 2019–2025, doi:10.3762/bjoc.12.189

• ), which has an amine handle for straight-forward derivatisation. Here we present an economical and scalable synthesis of ACBT based on a cyanation catalysed by 1,4-diazabicyclo[2.2.2]octane (DABCO), and discuss its advantages for scale-up over previously reported routes. Keywords: ACBT; cyanation; 2

• commercial suppliers, but expensive. Thus, the development of an economical and scalable synthesis of ACBT would enable studies that require larger amounts of this building block. The traditional synthesis of ACBT 8 involves the cyanation of 6-amino-2-chlorobenzothiazole (7) with an excess of potassium

• , organocatalytic cyanation. In addition, the use of filtrations and crystallisations for purification, in combination with control of reaction rate and heat output in the cyanation step, makes this procedure readily scalable. Results and Discussion In order to install the cyano group of ACBT 8 under mild

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• catalytic cyanation–enantioselective protonation of α-substituted α,β-unsaturated N-acylpyrroles 151 using a chiral polynuclear Gd complex (Scheme 35) [63]. Using a gadolinium catalyst derived from tridentate ligand 152, conjugate addition of cyanide followed by enantioselective protonation occurred with

• cyanation–enantioselective protonation of N-acylpyrroles. Tanaka’s hydroacylation of acrylamides with aliphatic aldehydes. Ellman’s enantioselective addition of α-substituted Meldrum’s acids to terminally unsubstituted nitroalkenes. Ellman’s enantioselective addition of thioacids to α,β,β-trisubstituted

Copper-catalyzed aerobic radical C–C bond cleavage of N–H ketimines

• Ya Lin Tnay,
• Gim Yean Ang and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2015, 11, 1933–1943, doi:10.3762/bjoc.11.209

• the construction of oxaspirocyclohexadienones as well as in the electrophilic cyanation of Grignard reagents with pivalonitrile as a CN source. Keywords: C–C bond cleavage; copper; ketimines; molecular oxygen; radical; Introduction Alkylideneaminyl radicals (iminyl radicals) have been utilized for

• applications of the copper-catalyzed aerobic C–C bond fission of iminyl radical species for the synthesis of oxaspirocyclohexadienones as well as the electrophilic cyanation of Grignard reagents using the readily available pivalonitrile as a CN source. Results and Discussion We further explored the reactivity

• proposal. Next, we turned our attention to apply the present copper-catalyzed aerobic C–C bond fission process in the electrophilic cyanation of Grignard reagents. As carbonitriles are omnipresent components in various natural products, dyes and potent pharmaceutical drugs [60][61][62], new and versatile

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• diastereoselectivities. Starting in 2005, Shibasaki and co-workers reported both the gadolinium and strontium-catalyzed asymmetric 1,4-cyanation of α,β-unsaturated N-acylpyrroles [205][206][207]. N-Acylpyrroles have proven to be useful alternatives to Weinreb amides, because they share many of the same advantages but N

• -acylpyrroles are more reactive at the carbonyl unit and the tetrahedral intermediate is more stable than the Weinreb amides [208]. Based on their previous work on the Strecker reaction [209][210][211], Shibasaki and co-workers used a gadolinium-based catalyst for the 1,4-cyanation (Scheme 25). Overall, this

• reaction proceeded in good to excellent yields and high enantioselectivies, with Michael acceptors having aryl or alkyl groups on the β-carbon. In 2014, Wang and co-workers reported a Lewis acid-catalyzed asymmetric 1,4-cyanation of α,β-unsaturated amides and ketones [212]. Though much work has been done

One-pot synthesis of cyanohydrin derivatives from alkyl bromides via incorporation of two one-carbon components by consecutive radical/ionic reactions

• Shuhei Sumino,
• Akira Fusano,
• Hiroyuki Okai,
• Takahide Fukuyama and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2014, 10, 150–154, doi:10.3762/bjoc.10.12

• , AIBN, and Et3N, which gave moderate to good yields of cyanohydrin derivatives 3. This protocol represents a one-pot method [32][33] based on radical carbonylation and ionic cyanation. Experimental Typical procedure for radical/ionic three-component coupling reaction leading to cyanohydrin derivatives 1

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• dark after 4 h irradiation. This observation supports the formation of hydroperoxide intermediate 21. Tan and coworkers employed a cocatalyst system composed of the organic dye Rose Bengal and graphite oxide (GO) for α-cyanation of N-aryltetrahydroisoquinolines (Scheme 7) [70]. The use of GO as

• carbocatalyst, pioneered by the Bielawski group, has been shown to facilitate a variety of reactions including oxidation, reduction, dehydration, and C–C bond formation [71][72][73][74]. GO was found to improve the yields of the α-cyanation reaction, and this was the first example of using GO to promote visible

• were realized with slower formation of the iminium ions. This was achieved by use of [Ru(bpy)3](PF6)2 in conjunction with a weak light source (5 W fluorescence bulb). The Che group synthesized a photoactive gold(III) complex that was shown to catalyze α-cyanation of N-aryltetrahydroisoquinolines [75

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

Total synthesis of (±)-coerulescine and (±)-horsfiline

• Mukund G. Kulkarni,
• Attrimuni P. Dhondge,
• Sanjay W. Chavhan,
• Ajit S. Borhade,
• Yunnus B. Shaikh,
• Deekshaputra R. Birhade,
• Mayur P. Desai and
• Nagorao R. Dhatrak

Beilstein J. Org. Chem. 2010, 6, 876–879, doi:10.3762/bjoc.6.103

• radical cyclizations [20][21][22][23][24], electrophilic cyclization [25], asymmetric nitroolefination reaction [26], palladium asymmetric allylic alkylation [27], palladium-catalyzed domino Heck–cyanation [28], Pd-catalyzed intramolecular cyanoamidation [29][30], NHC-mediated O- to C-carboxyl transfer

Synthesis of novel photochromic pyrans via palladium- mediated reactions

• Christoph Böttcher,
• Gehad Zeyat,
• Saleh A. Ahmed,
• Elisabeth Irran,
• Thorben Cordes,
• Cord Elsner,
• Wolfgang Zinth and
• Karola Rueck-Braun

Beilstein J. Org. Chem. 2009, 5, No. 25, doi:10.3762/bjoc.5.25

• cyanation, carbonylation and Sonogashira cross-coupling starting from bromo-substituted naphthopyran 1 and benzopyrans 2a/b. A novel photoswitchable benzopyran-based ω-amino acid 6 for Fmoc-based solid-phase peptide synthesis is presented. The photochromic behaviour of the 3-cyano-substituted benzopyran 5a

• rearrangement reactions [25]. Since nitriles are important intermediates in the synthesis of carboxylic acids and derivatives, and for the introduction of aminomethyl substituents, we started our studies with palladium-catalyzed cyanation reactions. The studies were then extended towards a Heck carbonylation in

• for the fine chemical industry, a variety of methods have been developed recently for the efficient cyanation of aryl halides under mild conditions. By applying electron-rich phosphanes and either Zn(CN)2 or K4[Fe(CN)6], the transformation of chlorides to nitriles was successfully achieved under

Asymmetric reactions in continuous flow

• Xiao Yin Mak,
• Paola Laurino and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2009, 5, No. 19, doi:10.3762/bjoc.5.19

• been reported, and these have been performed in microfluidic flow systems [10][11] consisting usually of micro-scale channels. The use of microreactors has been found to be especially useful for catalyst/ligand screening, as only low loading of reagents is required. The enantioselective silyl-cyanation