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

• could be isolated (Scheme 34). Another class of heterocycles, α-silylated N-alkylated indoles 201–205 recently reported by Xu and co-workers, were formed using a nonracemic Cu–NHC catalyst through the enantioselective addition of the PhMe2Si group to α,β-unsaturated carbonyl indoles 200 (Scheme 35). The

• B2pin2 in moderate to excellent yields [127]. 2.3 β-Borylation of α,β-unsaturated compounds The use of an inexpensive transition metal like copper as catalyst is attractive for β-borylations of α,β-unsaturated carbonyl compounds, that can then be further functionalized. In 2000, an initial report

• difficulties typically associated with conversions of pinacol esters to trifluoroborates. An asymmetric 1,4-borylation of α,β-unsaturated carbonyl derivatives, e.g., 428 and 429, was reported using a combination of Cu(MeCN)2PF6/L47 with either bisboronic acid (BBA, 430) or tetrakis(dimethylamino)diboron (431

Copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters with chiral phenol–carbene ligands

• Shohei Mimura,
• Sho Mizushima,
• Yohei Shimizu and
• Masaya Sawamura

Beilstein J. Org. Chem. 2020, 16, 537–543, doi:10.3762/bjoc.16.50

• work of Stryker and co-workers on triphenylphosphine-stabilized copper hydride complexes [1][2], copper hydrides have been widely used for conjugate reductions of α,β-unsaturated carbonyl compounds [3]. Especially a chiral copper catalyst combined with a stoichiometric amount of a silane reagent, which

• generated copper hydride in situ, has successfully been utilized for enantioselective reactions with β,β-disubstituted α,β-unsaturated carbonyl compounds [4][5][6][7][8][9][10][11]. The pioneering work of Buchwald and co-workers on the enantioselective conjugate reduction of α,β-unsaturated esters using a

• chiral p-tol-BINAP/copper catalyst established the excellent utility of chiral bisphosphine ligands for this type of reaction [4]. Surprisingly, however, chiral ligands based on N-heterocyclic carbenes (NHCs) [12] have not been applied to the conjugate reduction of α,β-unsaturated carbonyl compounds

Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions

• Clément Ghiazza and
• Anis Tlili

Beilstein J. Org. Chem. 2020, 16, 305–316, doi:10.3762/bjoc.16.30

• in the reaction, resulting from an oxidative addition of the trifluoromethylselenolated copper(I) complex to the α-brominated unsaturated carbonyl compound. Afterwards, a reductive elimination would take place to afford the α-trifluoromethylselenylated α,β-unsaturated carbonyl compound and copper(I

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

• method for the enantioselective synthesis of 4,5,5-trisubstituted γ-butyrolactones 193 using an electroreductive coupling of diaryl ketones 191 with α,β-unsaturated carbonyl compounds 190 bearing chiral auxiliaries derived from imidazolidin-2-one and oxazolidine-2-ones (Scheme 60). Compound 191 underwent

In water multicomponent synthesis of low-molecular-mass 4,7-dihydrotetrazolo[1,5-a]pyrimidines

• Irina G. Tkachenko,
• Sergey A. Komykhov,
• Vladimir I. Musatov,
• Svitlana V. Shishkina,
• Viktoriya V. Dyakonenko,
• Vladimir N. Shvets,
• Mikhail V. Diachkov,
• Valentyn A. Chebanov and
• Sergey M. Desenko

Beilstein J. Org. Chem. 2019, 15, 2390–2397, doi:10.3762/bjoc.15.231

• starting material and subsequent dihydropyrimidine ring formation. The first approach [6][7] represents a two-component cyclocondensation of 5-aminotetrazole (1) as binucleophilic component and bielectrophilic α,β-unsaturated carbonyl compounds 2 (Scheme 1, reaction 1). The second method [8][9][10][11][12

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• acids. In 2014, a Cu(I/II)-catalyzed α-trifluoromethylation of α,β-unsaturated carbonyl compounds were unfolded by the Bi group (Scheme 77) [140]. The reaction was applied to a broad range of carbonyl compounds, including enones, α,β-unsaturated esters, thioesters, and amides. Notably, the authors

Isolation of fungi using the diffusion chamber device FIND technology

• Benjamin Libor,
• Henrik Harms,
• Stefan Kehraus,
• Ekaterina Egereva,
• Max Crüsemann and
• Gabriele M. König

Beilstein J. Org. Chem. 2019, 15, 2191–2203, doi:10.3762/bjoc.15.216

• IR spectrum displayed an absorption band at 1670 cm−1 indicating the presence of an α,β-unsaturated carbonyl moiety [19]. The 1H NMR spectrum (Table S4, Supporting Information File 1) exhibited characteristic singlets for three methyl groups, as well as two olefinic protons, together with the MS data

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• obtained β-ketoenamides are alkenes with a remarkable assembly of functional groups: they are enamides, enol ethers and α,β-unsaturated carbonyl compounds at the same time. In addition, their methyl ketone subunit is required for some of the subsequent transformations, e.g., the synthesis of pyridin-4-ols

Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• . Compounds 11 and 12 were separated during the isolation process and initially constructed to enable target identification. Compounds 11 and 12 might act as Michael acceptor (α,β-unsaturated carbonyl) and attach irreversibly and covalently to a potential target [23]. After purification and characterization

• -methylvaleric moiety (1–7) were active against S. aureus. Substitution of the side chain in the α-keto amide significantly affects the bioactivity, as seen for compounds 8, 9 and 10. Furthermore, attempts to identify a possible target by the incorporation of an α,β-unsaturated carbonyl moiety, as it should bind

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• carboxylation of mesityl triflate (5) at 40 °C proceeded successfully, affording 6 in 77% yield (Scheme 6) Carboxylation of α,β-unsaturated nitriles and esters α,β-Unsaturated carbonyl compounds are good substrates for conjugate additions that use a catalytic amount of a metal complex and a stoichiometric

Addition of dithi(ol)anylium tetrafluoroborates to α,β-unsaturated ketones

• Yu-Chieh Huang,
• An Nguyen,
• Simone Gräßle,
• Sylvia Vanderheiden,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2018, 14, 515–522, doi:10.3762/bjoc.14.37

• examples for additions of activated (EWG-substituted) ketene 1,3-dithioacetals to α,β-unsaturated carbonyl compounds are literature known [31][32] but concepts for a versatile (metal-free) application of this reaction to starting materials lacking the EWG in α-position are still missing. Results and

• HBF4. The scope of the dithi(ol)anylium TFB addition to α,β-unsaturated carbonyl compounds In order to determine the scope of the herein presented reaction, we used compound 1c for further conversions indicating the possible challenges and aims of forthcoming projects (Scheme 5). With two selected

Gram-scale preparation of negative-type liquid crystals with a CF₂CF₂-carbocycle unit via an improved short-step synthetic protocol

• Tatsuya Kumon,
• Shohei Hashishita,
• Takumi Kida,
• Shigeyuki Yamada,
• Takashi Ishihara and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 148–154, doi:10.3762/bjoc.14.10

• the other hand, the β-carbon at the α,β-unsaturated carbonyl moiety of Int-I may be susceptible to attack by the vinylic Grignard reagent, as shown by the purple arrow in Scheme 3, because of the high electrophilicity and lack of steric hindrance. As a consequence, Int-I also undergoes conjugate

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• -fluoro-2-phosphonoacetate (1) was converted into the α-fluoro-α,β-unsaturated carbonyl 3 using the HWE olefination. The (Z)-isomer was obtained with complete selectivity. Then, reduction of the ester into the corresponding alcohol followed by a Mitsunobu reaction allowed the insertion of the NH

Rh(II)-mediated domino [4 + 1]-annulation of α-cyanothioacetamides using diazoesters: A new entry for the synthesis of multisubstituted thiophenes

• Jury J. Medvedev,
• Ilya V. Efimov,
• Yuri M. Shafran,
• Vitaliy V. Suslonov,
• Vasiliy A. Bakulev and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2017, 13, 2569–2576, doi:10.3762/bjoc.13.253

• domino reactions of diazo compounds with intermediate formation of ylides [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. Thus, it was for example shown that ammonium or oxonium ylides generated in the course of intermolecular processes can be easily trapped by ketones, imines, α,β-unsaturated

• carbonyl compounds, activated multiple bonds, or other nucleophiles to furnish heterocyclic cores [22][23][24][25][26][27][28][29][30][31][32]. Similar intramolecular transformations of intermediate ylides with several nucleophilic reaction centers in the initial substrate, are also possible. The known

A novel synthetic approach to hydroimidazo[1,5-b]pyridazines by the recyclization of itaconimides and HPLC–HRMS monitoring of the reaction pathway

• Dmitry Yu. Vandyshev,
• Khidmet S. Shikhaliev,
• Andrey Yu. Potapov,
• Michael Yu. Krysin,
• Fedor I. Zubkov and
• Lyudmila V. Sapronova

Beilstein J. Org. Chem. 2017, 13, 2561–2568, doi:10.3762/bjoc.13.252

• itaconimides, four primary adducts 5–8 could result (Scheme 5) based on the well-known fact that the heterocyclization reactions of α,β-unsaturated carbonyl compounds with dinucleophilic reagents typically begin with addition like Michael’s reaction, including heterocyclic dinucleophiles [39][40][41][42

• equivalent of C1-electrophile: R2COOH/T3P® [15], BrCN (R2 = NH2) [16], ArNCS/DCC (R2 = NHAr) [20]. Heterocyclization of 1-aminoimidazoles with 1,3-dicarbonyl or α,β-unsaturated carbonyl compounds (route B). Conditions: i) R1 = NH2, NHAlk, R2 = Ph, R3,4 = Alk, Ar, solvent-free [24], AcOH [25][26], R3 = Ph, R4

Regiodivergent condensation of 5-alkoxycarbonyl-1H-pyrrol-2,3-diones with cyclic ketazinones en route to spirocyclic scaffolds

• Alexey Yu. Dubovtsev,
• Maksim V. Dmitriev,
• Аndrey N. Maslivets and
• Michael Rubin

Beilstein J. Org. Chem. 2017, 13, 2179–2185, doi:10.3762/bjoc.13.218

• cyclocondensation of six-membered cyclic enamines 1 (vinylogous secondary amides) with 5-methoxycarbonyl-1H-pyrrolediones 2 [39][40][41]. This transformation involved the Michael addition of an enamine to the α,β-unsaturated carbonyl fragment of a pyrroledione and subsequent 5-exo-trig intramolecular nucleophilic

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• (Scheme 23). α,β-Unsaturated carbonyl compounds could also undergo a trans-bromination reaction efficiently within 40 min. Following to Wang’s report, Stolle and co-workers also reported a similar method of aryl bromination and chlorination using NaBr and NaCl, respectively, in the presence of oxidizing

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

• -oxygenation reactions above, also the introduction of a nitrogen-based functionality alpha to a carbonyl group can be achieved by several complementary strategies. One powerful option is to carry out Michael addition-initiated aziridination reactions of α,β-unsaturated carbonyl acceptors [18][138][139][140

Development of a method for the synthesis of 2,4,5-trisubstituted oxazoles composed of carboxylic acid, amino acid, and boronic acid

• Kohei Yamada,
• Naoto Kamimura and
• Munetaka Kunishima

Beilstein J. Org. Chem. 2017, 13, 1478–1485, doi:10.3762/bjoc.13.146

• materials, such as α-haloketones and primary amides [8], alkynes and nitriles [9], amines and α,β-unsaturated carbonyl compounds [10], etc. [11] have been reported. However, these reactions are often conducted under harsh reaction conditions and multistep syntheses of the starting materials are needed. ii

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

• Josef Jansa,
• Ramona Schmidt,
• Ashenafi Damtew Mamuye,
• Laura Castoldi,
• Alexander Roller,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2017, 13, 895–902, doi:10.3762/bjoc.13.90

• most common strategies employ reactions of 1,3-dicarbonyl compounds or α,β-unsaturated carbonyl compounds with substituted hydrazines [4][6][19]. To overcome the drawbacks of this method, namely insufficient regioselectivity [20], other accesses such as, for instance, regioselective metalations of N

Isoxazole derivatives as new nitric oxide elicitors in plants

• Anca Oancea,
• Emilian Georgescu,
• Florentina Georgescu,
• Alina Nicolescu,
• Elena Iulia Oprita,
• Catalina Tudora,
• Lucian Vladulescu,
• Marius-Constantin Vladulescu,
• Florin Oancea and
• Calin Deleanu

Beilstein J. Org. Chem. 2017, 13, 659–664, doi:10.3762/bjoc.13.65

• synthetic approaches towards the isoxazole core include the reactions of hydroxylamine with aryl-β-diketones [20], α,β-unsaturated carbonyl compounds [21], or α,β-unsaturated nitriles [22], and 1,3-dipolar cycloaddition reactions between alkenes or alkynes and nitrile oxides [23][24][25]. Nitrile oxides are

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• bond-donor activation of α,β-unsaturated carbonyl compounds in the [2 + 4] cycloaddition reaction of MVK and cyclopentadiene [88]. Halogen bond donor activation of imines in the [2 + 4] cycloaddition reaction of imine and Danishefsky’s diene [90]. Transfer hydrogenation catalyzed by a chiral halogen

Development of a continuous process for α-thio-β-chloroacrylamide synthesis with enhanced control of a cascade transformation

• Olga C. Dennehy,
• Valérie M. Y. Cacheux,
• Benjamin J. Deadman,
• Denis Lynch,
• Stuart G. Collins,
• Humphrey A. Moynihan and
• Anita R. Maguire

Beilstein J. Org. Chem. 2016, 12, 2511–2522, doi:10.3762/bjoc.12.246

• contain an α,β-unsaturated carbonyl motif in their structures. The value of exploring flow methodology, ultimately leading to an improved batch process, is keenly highlighted in this instance. The optimized batch process, developed through examining the use of continuous processing, can produce 20 g of

Rh-Catalyzed reductive Mannich-type reaction and its application towards the synthesis of (±)-ezetimibe

• Motoyuki Isoda,
• Kazuyuki Sato,
• Yurika Kunugi,
• Satsuki Tokonishi,
• Atsushi Tarui,
• Masaaki Omote,
• Hideki Minami and
• Akira Ando

Beilstein J. Org. Chem. 2016, 12, 1608–1615, doi:10.3762/bjoc.12.157

• Mannich-type reactions have been reported to give β-amino esters and/or β-lactams by using metal enolates [10][11][12][13][14][15][16][17]. In contrast, most of reductive Mannich-type reactions using imines and α,β-unsaturated carbonyl compounds gave β-amino esters, but there are only a few reports for a

• results using similar conditions did not give the corresponding products such as β-propiolactones. It is well known that the substituents on the α- or β-position of α,β-unsaturated carbonyl compounds affect the yields and stereoselectivities [37]. A rhodium–hydride complex derived from [RhCl(cod)]2 seems

Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals

• Haipan Zhu,
• Peile Du,
• Jianjun Li,
• Ziyang Liao,
• Guohua Liu,
• Hao Li and
• Wei Wang

Beilstein J. Org. Chem. 2016, 12, 1340–1347, doi:10.3762/bjoc.12.127

• ]. However, it is difficult to apply the catalytic system for the regio-controlled reaction with C=C bonds in α,β-unsaturated carbonyl compounds, particularly enals. The highly active aldehyde functionality reacts more favorably with the D–A cyclopropane resulting 1,3-dipoles, as elegantly demonstrated by