Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• N,S-acetals; β-keto amide; β-keto thioester; dodecylbenzenesulfonic acid; hydrolysis; Introduction In the past decades, the application of easily available and stable α-oxo ketene N,S-acetals as significant synthons has received more and more attention in organic synthesis due to their unique

• form adduct I', which is then transformed into intermediate II' by elimination of ethanethiolate. Subsequently, β-keto amide 3a is obtained when II' releases H+. Conclusion In summary, we have successfully developed an environmentally friendly method for the selective aqueous synthesis of β-keto

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

• Yordanka Mollova-Sapundzhieva,
• Plamen Angelov,
• Danail Georgiev and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• intermediate β-enamino amides 2 are easily available by condensation of the corresponding β-keto amide 1 and an amine (Scheme 1, conditions i). As the amine here plays only an auxiliary role, for the purpose of this research we opted for inexpensive ethylamine. Compounds 2 were obtained by simply stirring a

• dichloromethane solution of the corresponding keto amide 1 with a slight excess of 70% aqueous ethylamine over Na2SO4 and were used directly in the next step, without purification. These compounds are highly reactive at their α-position towards acylating reagents and this provides an opportunity to prepare the

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• partners. The scope of the protocol was further expanded to a radical cyclization/aminocarbonylation cascade reaction yielding the bis-carbonylated α-keto amide 26h in 31% yield. 2.1.2 C(sp3)–X activation: The generation of alkyl radicals using alkyl halides as precursors proves very challenging due their

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

• protocol proceeds in an undivided cell equipped with graphite plate electrodes under constant current conditions. Various active methylene ketones, including β-keto ester, β-keto amide, β-keto nitrile, β-keto sulfone and 1,3-diketones, can be converted to the corresponding 2-aminothiazoles. Mechanistically

• performed in an undivided cell with NH4I as the mediator and cheap graphite plate as the working electrode. Various active methylene ketones, including β-keto ester, β-keto amide, β-keto nitrile, β-keto sulfone and 1,3-diones proved to be compatible with the protocol. Since external oxidants and

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

• -phenylethylamine derivative 2 with an α-keto amide moiety, which could be identified upon heterologous expression of the appropriate gene cluster in E. coli [15]. Moreover, elongated nematophin derivatives, namely nevaltophins from Xenorhabdus PB62.4, were described incorporating an additional valine. As 1 and

• described as a potent inhibitor of various proteases, in particular trypsin and thrombin [17][18][19]. Hereby, the α-keto amide covalently binds to the serine oxygen in the active site under formation of a stable tetrahedral hemiketal. Furthermore, substitution of the indole hydrogen by alkyl, aryl or

• -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

Synthesis of functionalised β-keto amides by aminoacylation/domino fragmentation of β-enamino amides

• Pavel Yanev and
• Plamen Angelov

Beilstein J. Org. Chem. 2018, 14, 2602–2606, doi:10.3762/bjoc.14.238

• lowered the yields of compounds 5. Only the phthaloyl-protected derivative 3k gave the corresponding keto amide 5k in both, high yield and good er (95:5) when the Boc-deprotection was performed in 1:9 TFA/CH2Cl2 for 30 min. Domino fragmentation of ω-aminoacyl intermediates 4 to N-protected ω-amino-β

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• Michael addition of the enol of the α-keto-amide 78 to nitroalkene 79, subsequent Michael addition of nitronates to the second equivalent of nitroalkene 79 and finally a Henry-type reaction between nitronate and the highly electrophilic carbonyl of the α-keto-amide, resulting in the final product 76. In

Investigation on the reactivity of α-azidochalcones with carboxylic acids: Formation of α-amido-1,3-diketones and highly substituted 2-(trifluoromethyl)oxazoles

• Kandasamy Rajaguru,
• Arumugam Mariappan,
• Rajendran Suresh,
• Periasamy Manivannan and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2015, 11, 2021–2028, doi:10.3762/bjoc.11.219

• . The N-(2-keto)amide skeleton is of particular interest, as it serves as a synthetic precursor for various small heterocyclic compounds such as imidazoles, oxazoles and thiazoles [7][8][9]. Azirine, the smallest nitrogen-containing unsaturated three-membered heterocyclic system, is well known as a

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• -nitrobenzoyl)acetate to give a β-keto amide. The resulting amide was subjected to a Knorr cyclization in the presence of polyphosphoric acid to afford a quinolinone, which was further reduced to a quinoline in two steps. The Sandmeyer reaction permitted the replacement of the amide function with a carboxylic

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

An oxidative amidation and heterocyclization approach for the synthesis of β-carbolines and dihydroeudistomin Y

• Suresh Babu Meruva,
• Akula Raghunadh,
• Raghavendra Rao Kamaraju,
• U. K. Syam Kumar and
• P. K. Dubey

Beilstein J. Org. Chem. 2014, 10, 471–480, doi:10.3762/bjoc.10.45

• -eudistomin; eudistomin; keto amide; oxidative amidation; Introduction β-Carboline alkaloids [1] are widespread in plants, animals and some are formed naturally in the biological system. Rinehart et al. [2] reported the isolation of β-carboline alkaloids such as eudistomins [3] and several of its analogues

An efficient method for the construction of polysubstituted 4-pyridones via self-condensation of β-keto amides mediated by P₂O₅ and catalyzed by zinc bromide

• Liquan Tan,
• Peng Zhou,
• Cui Chen and
• Weibing Liu

Beilstein J. Org. Chem. 2013, 9, 2681–2687, doi:10.3762/bjoc.9.304

• -aryl β-keto amides as the substrates in this protocol, 4-pyridones are resulted, however, when using N-aliphatic-substituted β-keto amides as the partners of N-aryl β-keto amides under the same conditions, 2-pyridones are afforded. Keywords: β-keto amide; phosphorus pentoxide; 2-pyridones; 4-pyridones

• ; self-condensation; Introduction β-Keto amide and their derivatives are desired classes of intermediates for the synthesis of nitrogen- and oxygen-containing heterocyclic compounds since they possess six reactive sites in the same molecule (Scheme 1) [1][2][3][4][5][6][7]. A lot of reports can be found

Towards stereochemical control: A short formal enantioselective total synthesis of pumiliotoxins 251D and 237A

• Jie Zhang,
• Hong-Kui Zhang and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2013, 9, 2358–2366, doi:10.3762/bjoc.9.271

• mixture of lactams. Without separation, the mixture was treated with TBAF in dichloromethane to produce alcohols 18 and 20 (combined yield: 62% over 3 steps) in a ratio of 95:5 (determined by 1H NMR), along with the keto-amide 21 in 13% yield (Scheme 7). Separation of the mixture by column chromatography

Organic synthesis using (diacetoxyiodo)benzene (DIB): Unexpected and novel oxidation of 3-oxo-butanamides to 2,2-dihalo-N-phenylacetamides

• Wei-Bing Liu,
• Cui Chen,
• Qing Zhang and
• Zhi-Bo Zhu

Beilstein J. Org. Chem. 2012, 8, 344–348, doi:10.3762/bjoc.8.38

• , exemplified by the formation of 2a, is depicted in Scheme 6. Initially, the reaction involved generation of the known chlorinating agent (dichloroiodo)benzene (PhICl2) [39], followed by dichlorination of the β-keto amide of 3-oxo-N-phenylbutanamide (1a) to give intermediate 4. It is well known that Lewis

• carbonyl carbon atom affords intermediate 7. A subsequent carbon–carbon bond cleavage of the labile α,α-dichloro β-keto amide through a retro-Claisen condensation reaction [41] generates intermediate 8. Finally, the electrophilic attack of a proton on the carbon–carbon double bond resulted in the final

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• ). An attractive alternative synthesis of sunitinib introduces the amide side chain earlier by ring opening of 4-methyleneoxetan-2-one (43) with N,N-diethylethane-1,2-diamine (44) [10]. The resulting β-keto amide 45 is then converted to the analogous pyrrole by condensation with the previously mentioned

Novel tetracyclic structures from the synthesis of thiolactone-isatin hybrids

• Renate Hazel Hans,
• Hong Su and
• Kelly Chibale

Beilstein J. Org. Chem. 2010, 6, No. 78, doi:10.3762/bjoc.6.78

• , involves an in situ deprotonation at C-5 of the thiolactone ring system by the relatively basic potassium salt of 5. This is followed by the regioselective, intramolecular addition of the nucleophile to the ketonic carbonyl facilitated by (i) the strong electrophilicity of the α-keto amide group of the

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33