Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• as amino-acid-like building blocks. Construction of 5-cycloaminyl-1,2-oxazole compounds was based on the reaction of β-enamino ketoester precursors with hydroxylamine hydrochloride in moderate yields. When using the starting chiral saturated N-heterocyclic carboxylic acids, the target adducts were

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• , carboxylic acids, tetrazoles, aldehydes, amidines, and amides [7][8][9][10][11]. This has been suitably transformed into structurally diverse and complex molecules. In 1927, Pongratz reported a method towards cyanation reactions [12]. From then, onwards, cyanation gained prime focus and achieved much

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• -nitroaryl compounds. Various 2-nitrobenzyl derivatives are used to photocage heteroatom functional groups, including alcohols, amines, carboxylic acids, and phosphates [11]. Typical photochemical pathways result in cleavage of a benzylic C–X bond following initial benzylic H-atom abstraction [11][13]. In

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• synthetic method that relies on a two-phase reaction system. Specifically, lactones are ring-opened and converted into dibromocarboxylic acids when treated with Br2 and a substoichiometric amount of PBr3. Subsequent treatment of these carboxylic acids with a base leads to the corresponding α-bromolactones

• conditions. Lactones were ring-opened with Br2 and a substoichiometric amount of PBr3, which led to the corresponding α-bromocarboxylic acids in good yields. These carboxylic acids subsequently underwent intramolecular cyclization in 1 h using a two-phase system (H2O/CHCl3) with R4N+OH− to afford α

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

• authors propose the intramolecular cyclization proceeds via the nucleophilic attack of a brominated or cationic benzylic position rather than a radical cyclization. In 2021, Tang and Zhang demonstrated a similar radical annulation of unsaturated carboxylic acids with disulfides for the synthesis of γ

• -lactones [146]. In 2020, Cai and co-workers reported a three-component intermolecular trifluoromethyl-esterification of activated alkenes 115 with NaOTf and aryl carboxylic acids 178 (Scheme 39) [147]. Notably, the use of NaOTf as a CF3 source, compared to pre-prepared trifluoromethylating agents like

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• substitution process. For example, compound 3b reacted with difluoroenolate to form the difluoroalkylated diarylmethane 5 in 83% yield via a Cu(OAc)2-catalyzed hydrodifluoroalkylation reaction [52]. Two other examples were the use of photoredox catalysis to generate acyl anions in situ from aromatic carboxylic

• acids via a triphenylphosphine-mediated deoxygenation process, followed by reaction with sulfonylated diarylmethane 3b to obtain diarylmethane ketone derivatives 6 and 7 [53]. To gain mechanistic insight into this C–S-bond cleavage sulfonylation reaction, some control experiments were conducted (Scheme

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• includes the reaction of readily available anthranilic amides or hydrazides with pent-4-yn-1-ols or -carboxylic acids promoted by PdCl4 [15], Au(І) [16][17][18] or Cu(ІІ) [19] salts. In another version, the target compounds were obtained by iodine-catalyzed reaction of the aforementioned anthranilic acid

Me₃Al-mediated domino nucleophilic addition/intramolecular cyclisation of 2-(2-oxo-2-phenylethyl)benzonitriles with amines; a convenient approach for the synthesis of substituted 1-aminoisoquinolines

• Krishna M. S. Adusumalli,
• Lakshmi N. S. Konidena,
• Hima B. Gandham,
• Krishnaiah Kumari,
• Krishna R. Valluru,
• Satya K. R. Nidasanametla,
• Venkateswara R. Battula and
• Hari K. Namballa

Beilstein J. Org. Chem. 2021, 17, 2765–2772, doi:10.3762/bjoc.17.186

• cycloaddition reactions and also serves as a precursor for the generation of important functional groups like amines, aldehydes, ketones and carboxylic acids. Even though the nitrile functional group is prevalent in the transformation into different functional groups, the synthetic approaches that incorporate

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• 12 in good yields (75–95%) with up to 99% ee. Several sulfonic acids and carboxylic acids were tested as co-catalysts and trifluoroacetic acid (TFA) was found to give the best results [28]. Here the role of the co-catalyst is to assist in the formation of the iminium intermediate (Table 2) [29]. It

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• ). In 2020, Zhang’s group [77] described the photoinduced copper-catalyzed decarboxylative alkynylation of redox-active esters with terminal alkynes. N-Hydroxy-tetrachlorophthalimide (TCNHPI, 36) derived from carboxylic acids was identified as the ideal radical precursor. Under irradiation, the CuI

• [100] groups reported that NHPI esters (67, 68) have been used as alkyl radical precursors in decarboxylative coupling reactions. These reactions feature a wide substrate scope. Primary, secondary, and tertiary alkyl carboxylic acids exhibit good yield, such as decarboxylative coupling reactions

Synthesis of new substituted 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids containing a tetracyclic tetrahydroisoquinoline core structure

• Agnieszka Grajewska,
• Maria Chrzanowska and
• Wiktoria Adamska

Beilstein J. Org. Chem. 2021, 17, 2511–2519, doi:10.3762/bjoc.17.168

• tetrahydroisoquinoline derivatives, 7,12-dihydro-6,12-methanodibenzo[c,f]-azocine-5-carboxylic acids by three component Petasis reaction with the use of aminoacetaldehyde acetals bearing substituted benzyl groups as the amine components followed by Pomeranz–Fritsch double cyclization reaction. By applying this method

• transformed into racemic tetrahydroisoquinoline-1-carboxylic acids [19], simple isoquinoline alkaloids [20], and (+)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid [21]. In this paper we report a straightforward synthesis of new strained tetracyclic tetrahydroisoquinoline derivatives

• , variously substituted 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids, via our modified method based on a combination of the Petasis reaction, in which we used aminoacetaldehyde acetals with substituted N-benzyl groups as the amine component and the Pomeranz–Fritsch double cyclization

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• , or mercuric trifluoroacetate as shown in Scheme 41 [97]. Alkyne carboxylic acids also undergo oxymercuration reactions to form furan- and pyran-like derivatives. When γ-alkyne carboxylic derivative 140 was refluxed with HgO the cyclization took place to give product 141 in almost quantitative yields

• -dihydroquinoline derivatives by Hg(OTf)2 and b) plausible mechanism of formation. Synthesis of Hg(II)-salt-catalyzed heteroaromatic derivatives. Hg(II)-salt-catalyzed synthesis of dihydropyranone derivatives. Hg(II)-salt-catalyzed cyclization of alkynoic acids. Hg(II)-salt-mediated cyclization of alkyne carboxylic

• acids and alcohol to furan, pyran, and spirocyclic derivatives. Hg(II)-salt-mediated cyclization of 1,4-dihydroxy-5-alkyne derivatives. Six-membered morpholine derivative formation by catalytic Hg(II)-salt-induced cyclization. Hg(OTf)2-catalyzed hydroxylative carbocyclization of 1,6-enyne. a) Hg(OTf)2

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

• radical and toluene as well as aldehyde; iv) product formation in a nickel catalytic cycle; and v) regeneration of nickel(II) species. Recently, the group of Huo developed a nickel-catalyzed enantioselective acylation of α-amino C(sp3)–H bonds with carboxylic acids under visible light irradiation (Scheme

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• anthracene derivatives 33. The strategy involved a palladium(II)-catalyzed tandem transformation with diphenyl carboxylic acids 31 and acrylates 32 (Scheme 7) [41]. This new methodology involved a carboxyl-directed C–H alkenylation, a carboxyl-directed secondary C–H activation, an intramolecular C–C-bond

• formation, and further decarboxylative aromatization. The authors used several diphenyl carboxylic acids bearing electron-donating and electron-withdrawing groups on the aromatic rings to produce the corresponding substituted anthracenes, such as compounds 33a–f, in good yields [41]. Recently, Kim and co

• employed palladium(II) acetate and visible light under O2 in the reactions between ethyl acrylate (192) and substituted diaryl carboxylic acids 193, to produce anthraquinones 194 in low to moderate yields (30–68%). In a direct comparison with the methodology proposed by Hong for the synthesis of

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• hydroquinolinone, chromene, piperidine, peptide, lipid, and glycoside moieties (Scheme 2). Bojanowski and co-workers developed a methodology to synthetize 3,4-dihydrocoumarins 10 through a decarboxylative and dearomatizative cascade reaction [33]. This reaction was carried out using coumarin-3-carboxylic acids 8

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

• usually mediated by V(V) and V(IV)-oxo-peroxo complexes, which are produced in situ from vanadium-oxo and dioxo precatalysts in the presence of oxidants, such as H2O2, O2, and tert-butyl hydroperoxide (TBHP) [76][77][78][79][80][81][82]. Inorganic acids and chelating and non-chelating carboxylic acids

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• ′-carboxylic acids 65a–c which in turn were prepared through the (2,2,6,6-tetramethylpiperidin-1-oxyl) (TEMPO) and 1,1-bis(acetoxy)iodobenzene (BAIB)-assisted oxidation of the 5′-hydroxymethylene group in adenosine/uridine by following the methodology developed by Epp and Widlanski [53]. The nucleoside-5

• ′-carboxylic acids 65a–c were reacted with 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) as coupling reagent followed by reaction with phthalazin-1-ylhydrazin hydrochloride in DMF in the presence of diisopropylethylamine (DIPEA) as base to afford the double-headed

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

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds

• Guanglong Pan,
• Qian Yang,
• Wentao Wang,
• Yurong Tang and
• Yunfei Cai

Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89

• CN-K-based heterogeneous protocol for the cyanomethylarylation of N-arylallylamines with acetonitrile. Pleasingly, after the systematic evaluation of various NHPI esters, which are easily prepared from readily available carboxylic acids, the yield of the product 3a could be increased to 75% when

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• library of carboxylic acids 72 in the presence of coupling reagents (Scheme 11) [27]. Alternatively, the 1,3-protected glycerol 73 was first converted into various 2,3-protected glycerols 74, which were further transformed to methyl 2-alkoxy-3-hydroxypropanoates 75. Following a similar strategy as above

Unexpected rearrangements and a novel synthesis of 1,1-dichloro-1-alkenones from 1,1,1-trifluoroalkanones with aluminium trichloride

• Beatrice Lansbergen,
• Catherine S. Meister and
• Michael C. McLeod

Beilstein J. Org. Chem. 2021, 17, 404–409, doi:10.3762/bjoc.17.36

• mass spectrometry and so it was converted to carboxylic acids 14 and 15 by the treatment with silica gel and NaOH, respectively, in order to confirm its identity. A possible mechanism for the formation of 13 from 5n could involve the formation of a terminal carbocation from trichloroalkanone 8n

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• . Results and Discussion Flow investigations commenced with the development of a continuous Curtius rearrangement process based on previous reports [22][23][24]. Specifically, we targeted utilization of a range of commercially available carboxylic acids 1 (1.0 equiv) in combination with DPPA (2, 0.9 equiv

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• introduction before being biotransformed to new trifluoromethyl-containing metabolites (Figure 15). 19F NMR was also employed to determine the degree of biotransformation of drug-like fluorophenylpyridine carboxylic acids in the same fungus [107]. However, aside from these few examples, the technique is not

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

• hydrogenolysis of benzyl ethers (H2, Pd) [72], DIBAL-H reduction of esters to form alcohols [73], oxidative cleavage of vinyl groups to form carboxylic acids (KMnO4) [74], and the conversion of the acids into amines using the Curtius rearrangement (SOCl2, followed by Me3SiN3, thermolysis, and acid hydrolysis of

• O–H and N–H bonds of water, alcohols, carboxylic acids, and amines to form the observed products 121. 1,1-Difluoro-2-siloxy-2-vinylcyclopropane (122) was subjected to a fluoride-catalyzed ring opening to afford 1-fluorovinyl vinyl ketones such as 123. These compounds underwent a Lewis acid-catalyzed