Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• (Scheme 30). The reaction showed good compatibility with various functional groups. The proposed mechanism (Scheme 30b) involves the silver-catalyzed decarboxylation of heteroaryl acid 156 followed by transmetalation providing palladium intermediate 160. Further, C–H activation of pyridine N-oxide 9

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• the enol carboxylate and subsequent 1,2 radical rearrangement and decarboxylation. Moderate to good yields of dibenzo[b,f]oxepine carboxylates 25 were achieved (63–85%). Stopka et al. [46] reported on tandem C–H functionalisation and ring expansion as an alternative to the Wagner–Meerwin rearrangement

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• formation of the fused cyclobutane acid 162 as the desired precursor for the cyclooctane formation. The ring expansion was achieved in the presence of an iridium catalyst and under blue LED irradiation, via the trapping by TEMPO or O2 of the cyclobutyl radical resulting from decarboxylation, which allowed a

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• –Giese coupling, followed by reductive cleavage of the lactone moiety with LiI. Enzymatic hydroxylation by the BM3 MERO1 variant worked equally well to provide the 3-hydroxylated product 46. Photochemical radical decarboxylation of the formed mercaptopyridine derivative and radical capture by iodoform

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• . Subsequent decarboxylation of thiazolooxazol-1-one I affords non-stabilized azomethine ylide (AY) for 1,3-dipolar cycloaddition with olefinic oxindole 4a to give spirooxindolepyrrolothiazoles 5 and 7. The endo-TS is more favorable than exo-TS for the 1,3-dipolar cycloaddition to afford the major and minor

Isolation and biosynthesis of daturamycins from Streptomyces sp. KIB-H1544

• Yin Chen,
• Jinqiu Ren,
• Ruimin Yang,
• Jie Li,
• Sheng-Xiong Huang and
• Yijun Yan

Beilstein J. Org. Chem. 2022, 18, 1009–1016, doi:10.3762/bjoc.18.101

• ) probably undergoes rearrangement, decarboxylation, methylation reaction, and further modification to generate compounds 1 and 2. Conclusion S. sp. KIB-H1544 was isolated from the rhizosphere soil of Datura stramonium L. Two novel diarylcyclopentenones daturamycins A and B and one new p-terphenyl

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• dihalogenations. As known, the decarboxylation (or desulfonation) was observed in the case of salicylic acids and anthranilic acids (or sulfanilic acids) leading to 2,4,6-trihalogenated products when 3 equiv of NXS was used. Simple instrumentation, metal-free approach, cost-effectiveness, atom economy, short

• aniline (entry 5, Table 2) afforded the 2,4,6-tribromo derivatives in the presence of NBS in excellent yields just by grinding for 5 min. Similarly, 3 equiv of NIS ensured the formation of 2,4,6-triiodo derivatives in over 90% yields (entries 8 and 11, Table 2). As known, easy decarboxylation (or

• halogenation without much substituent effect and by just controlling the stoichiometry of NXS a series of mono-, di-, and trihalogenated phenols and anilines were obtained in a chemoselective manner in good to excellent yields within 2–15 min of grinding. Spontaneous decarboxylation (or desulfonation) was

Morita–Baylis–Hillman reaction of 3-formyl-9H-pyrido[3,4-b]indoles and fluorescence studies of the products

• Nisha Devi and
• Virender Singh

Beilstein J. Org. Chem. 2022, 18, 926–934, doi:10.3762/bjoc.18.92

• ʟ-tryptophan (1) was much faster than with the tryptophan ester, taking only 45 minutes to complete. Interestingly, KMnO4 oxidation was selective, with no decarboxylation seen. Within 15 minutes, further treatment of 3a–e with methyl iodide in the presence of K2CO3 provided the corresponding methyl

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• a Z/E ratio of 95:5. Additionally, the authors developed an alternative synthesis of civetone (69) by metathesis of ethyl 9-decenoate and subsequent Dieckmann cyclization in flow, followed by a saponification and decarboxylation process in batch providing (Z)-civetone in 48% yield over three steps

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• ) [64][65][66][67]. The Fe(II) is coordinated by the conserved 2-His-1-Asp residues and a 2OG in the active site. The binding of a substrate in the active site, where it is close to the Fe(II) center, provides a coordination site for O2. Subsequently, the oxidative decarboxylation of 2OG generates a

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• 87%). Pericyclic reactions such as the Diels–Alder and hetero-Diels–Alder cycloadditions, the Alder-En reaction, as well as the decarboxylation of α-alkylated malonic acids, are also suitable for flow protocols in combination with inductive heating (Scheme 10, case A) [53]. The yields but especially

• decarboxylation of the malonic acid derivative 42 to give pent-4-enecarboxylic acid (43). In many cases, the flow protocol provided improved yields compared to the corresponding batch syntheses. Palladium-catalyzed cross-coupling reactions require higher temperatures and thus can be realized in an inductively

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• )] (k298 = 32.2 kHz) move across the deck 82 and prevent binding of the protonated DABCO at the ZnPor binding sites. Use of the fuel acid 112 or 113 instead of applying the TFA/DBU acid/base combination leads initially to protonation of DABCO but due to the decarboxylation of 114 the resulting strong base

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• for the addition product was due to the competitive decarboxylation of the sole MAHT substrate in the presence of a higher loading of the macrocycle containing tertiary amine basic sites. Decreasing the amount of MAHT substrate from 1.5 equiv to 1.0 equiv or increasing to 2.0 equiv did not give better

• outcome (Table 3, entries 4 and 5). Performing the reaction at 0 °C led to a very slow conversion, while at 40 °C the reaction became much faster but gave a diminished yield due to the competitive decarboxylation side reaction (Table 3, entries 6 and 7). In both cases, the enantioselectivity did not turn

• by one or both of the two thiourea sites through hydrogen bonding to accept the enolate attack. The chiral environment provided by the (S,S)-cyclohexanediamine part governed the face-selective attack and led to the R-configurated product. In the last step, the decarboxylation leads to the enolate of

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• useful alkylation approach is the Kochi–Anderson method [76] (or also known as Jacobsen–Torssell method [77][78]), via oxidative decarboxylation, where the quinone reacts with a carboxylic acid in the presence of silver(I) nitrate and ammonium or potassium peroxydisulfate. Nucleophilic free radicals are

• generated from the carboxylic acid through decarboxylation mediated by [Ag+]-peroxydisulfate, followed by their coupling with the quinone, providing the respective alkylated product. One of the first practical applications of this methodology to produce menadione (10) was described by Ashnagar and co

• ][139][140][141]. In 2001, Salmon-Chemin and co-workers described the preparation of alkylated compounds 89 and 90 via oxidative decarboxylation of diacids and N-Boc-protected amino acids β-alanine, γ-aminobutyric acid, 5-aminovaleric acid, and 6-aminocaproic acid [131]. The compounds were obtained in

Synthesis of 5-unsubstituted dihydropyrimidinone-4-carboxylates from deep eutectic mixtures

• Sangram Gore,
• Sundarababu Baskaran and
• Burkhard König

Beilstein J. Org. Chem. 2022, 18, 331–336, doi:10.3762/bjoc.18.37

• ester group at C5 and an alkyl group at C6 position. A group of researchers from Merck reported the synthesis of 5-unsubstituted DHPMs via a Biginelli reaction followed by saponification of the ester and subsequent decarboxylation [22]. Later, Bussolari and McDonnell demonstrated the synthesis of 5

Trichloroacetic acid fueled practical amine purifications

• Aleena Thomas,
• Baptiste Gasch,
• Enzo Olivieri and
• Adrien Quintard

Beilstein J. Org. Chem. 2022, 18, 225–231, doi:10.3762/bjoc.18.26

• their protonated salt formation, enabling the separation with the impurities. From these amine salts, simple decarboxylation of TCA liberates volatile CO2 and chloroform affording directly the pure amines. Through this approach, a broad range of diversely substituted amines could be isolated with

• success. Keywords: amines; decarboxylation; eco-compatible; out of equilibrium; purification; Introduction Isolation of pure amines from reaction mixtures or natural extracts is crucial in modern organic chemistry. However, the most widely applied methods for these purifications have remained unchanged

• cheap and simple acid enables a temporary protonation while time-controlled decarboxylation liberates volatile CO2 and chloroform as single waste (Scheme 2a). This strategy has been applied with success by the groups of Takata, Leigh, Kim and ours to time control different molecular switches ranging

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• alcohols 67 and aliphatic acids 173 (Scheme 37) [144]. Through a DCC-mediated dehydrogenative condensation with hydroperoxides, carboxylic acids could generate alkyl diacyl peroxides and peresters in situ. Decarboxylation followed by radical addition across the alkene 108 would generate a succeeding alkyl

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• provided the corresponding carboxylic acid, and further oxidative decarboxylation with lead tetraacetate and pyridine provided oxathiolane 20. Chu and co-workers [41][42] further established a more proficient system for the synthesis of (+)-BCH-189 (1a) from 1,6-thioanhydro-ᴅ-galactose (3d, Scheme 4

• . Reaction of 24 with pyridinium dichromate (PDC) in DMF solvent afforded the acid derivative 25. This derivative was converted to the key intermediate 20 by oxidative decarboxylation [33]. Han et al. [43] developed a method for the novel oxathiolane intermediate 2-(tert-butyldiphenylsilyloxy)methyl-5

• temperature, and oxidation with a mild oxidizing agent, PDC, provided 28. Using the reaction of lead tetraacetate with 28 via oxidative decarboxylation afforded oxathiolane acetate derivative 20a. The synthesis of a 1,3-oxathiolane precursor required for the preparation of 3TC (1) in four steps was reported

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• for the mode of action of this cascade arylation protocol (Figure 10) [73]. In the photocatalytic cycle, the SET event between the photoexcited iridium catalyst 10-II and the substrate oxalate 33 generates a tertiary carbon-centered radical 10-IV by decarboxylation and the reduced iridium(II

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• . Here the base assisted the condensation of 2-(fluorosulfonyl)difluoroacetic acid (115) with 1 followed by decarboxylation to give difluorocarbene and sulfinate 119, that combine to produce sulfanol 121, which in the presence of acid and reaction with another molecule of indole affords 105. In 2018

Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)

• Tania Xavier,
• Sylvie Condon,
• Christophe Pichon,
• Erwan Le Gall and
• Marc Presset

Beilstein J. Org. Chem. 2021, 17, 2085–2094, doi:10.3762/bjoc.17.135

• known as alkyl hydrogen malonates or hemimalonates, constitute an attractive class of pronucleophiles in the design of eco-compatible syntheses [1]. Indeed, they can serve as efficient precursors of ester enolates through decarboxylation [2][3], generally using a substoichiometric amount of a weak base

• step, the opening of the Meldrum's acid moiety with an alcohol 8. Indeed, this reaction was achieved under simple conditions and led to the desired products in useful yields, only limited by partial in situ decarboxylation. This strategy thus allowed the preparation of the isopropyl (4ch, 93%) and

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• introduces primary amines for 1,3-dipolar cycloaddition which is less explored due to the probability of competitive Strecker degradation over decarboxylation of azomethine ylides. The protocol reveals the efficiency of MW assisted reaction with reduced reaction time from 18 h to 12 min and enhanced the

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• a screen of bases, reactant ratios, reactor pressure, addition rates and temperature. A compound with the requisite molecular formula was produced as a minor product by the reaction of 6 (Scheme 3) with difluorocarbene generated at elevated temperature via decarboxylation of chlorodifluoroacetate