Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

Discrimination of β-cyclodextrin/hazelnut (Corylus avellana L.) oil/flavonoid glycoside and flavonolignan ternary complexes by Fourier-transform infrared spectroscopy coupled with principal component analysis

• Nicoleta G. Hădărugă,
• Gabriela Popescu,
• Dina Gligor (Pane),
• Cristina L. Mitroi,
• Sorin M. Stanciu and
• Daniel Ioan Hădărugă

Beilstein J. Org. Chem. 2023, 19, 380–398, doi:10.3762/bjoc.19.30

• was demonstrated by both thermal (TG–DTG and DSC) and chromatographic (GC–MS for the degradation compounds, i.e., aldehydes, formylated carboxylic acids, or dicarboxylic acids) methods [16]. Also, vegetable oils containing unsaturated FA moieties were stabilized by CD complexation. Common bean

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• H10Bpin with the borinic ester intermediate 44 showed no scrambling of the 10B label, suggesting a σ-bond metathesis mechanism for this transborylation reaction (Scheme 10). Thomas et al. reported the H-B-9-BBN-catalysed esterification of alkyl fluorides, using carboxylic acids and HBpin (Scheme 11) [75

• ]. Through a series of single-turnover experiments a reaction mechanism was proposed where H-B-9-BBN catalysed the dehydrocoupling of carboxylic acids 47 with HBpin through B‒O/B‒H transborylation, to give the acyloxy boronic ester 49. This underwent direct defluoronative carboxylation with the alkyl

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• is mediated by visible light irradiation. A wide range of substrates bearing different substituents and derived from ubiquitous carboxylic acids, including α-amino acids, were synthesized and examined under this very mild, efficient, and cost effective transition-metal-free synthetic method. These

• /cyclization cascades from acrylamides for the synthesis of oxindoles [39][40][41]. The radicals are typically generated from alkyl halides [42][43][44], carboxylic acids [45][46][47], simple alkanes [48], alkylboronic acids [49], isocyanides [50], or other [51][52][53]. In this context, the group of Fu

• reported a Ru(bpy)3Cl2-catalyzed synthesis of N-Boc proline oxindole derivatives under visible-light assistance [47]. Therein, N-hydroxyphthalimide (NPhth) esters were utilized as alkyl radical precursors, which can be readily prepared from highly available carboxylic acids. In 2015, Cheng and co-workers

Digyalipopeptide A, an antiparasitic cyclic peptide from the Ghanaian Bacillus sp. strain DE2B

• Adwoa P. Nartey,
• Aboagye K. Dofuor,
• Kofi B. A. Owusu,
• Anil S. Camas,
• Hai Deng,
• Marcel Jaspars and
• Kwaku Kyeremeh

Beilstein J. Org. Chem. 2022, 18, 1763–1771, doi:10.3762/bjoc.18.185

• carbonyl carbons of seven amides, two carboxylic acids, and one ester. Also present were forty-one sp3-hybridized carbon signals which were assigned to fourteen methines, fifteen methylenes and twelve methyl groups The 1H NMR spectrum exhibited signals at δH 4.19 (ov., 1H, H-2), 4.08 (dd, J = 8.8, 6.0 Hz

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• used to trap carboxylic acids, from which the product can be released with diluted solutions of formic acid [95]. Another strategy that is applicable in the context of biocatalysis involves Ni–NTA resins used for protein purification which are commonly packed in cartridges to enable automated peptide

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• oxidation of substrates with activated CH-bonds, such as alkylarenes (Scheme 6). At higher temperatures, even unactivated alkanes can be functionalized [75][81]. The NHPI/Co(OAc)2 system was successfully employed for the selective oxidation of methylarenes to aromatic carboxylic acids [78] (in AcOH medium

• -oxyl (ACT) allows for the oxidation of alcohols and aldehydes to carboxylic acids by controlled potential electrolysis, while maintaining the stereocenter configuration in the R-substituent [102] (Scheme 14). The method is also suitable for molecules with chelating pyridine moieties. An outstanding

• -hydroxylation of lactams under phase-transfer organocatalysis conditions employing a chiral quaternary ammonium ion salt. Selective CH-oxidation of methylarenes to aldehydes or carboxylic acids. An example of the regioselective CH-amination by a sterically hindered imide-N-oxyl radical precursor. CH-amination

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• cycle can also lead to different reaction outcomes, e.g., rearrangements, desaturations or epoxidations. Multiple oxidation rounds, leading to aldehydes/ketones or carboxylic acids, are also commonly observed. Together, this versatile oxidative chemistry makes CYPs key enzymes in specialised metabolism

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• literature. Syntheses and utilization of the corresponding 4H-benzo[b][1,4]thiazine-3-carboxylic acids 7 are very rare. Part of our research program is the construction of chiral heterocyclic compounds of medicinal interest [33][34]. Recently, we have been involved in the synthesis of potential SARS-CoV-2

Heterogeneous metallaphotoredox catalysis in a continuous-flow packed-bed reactor

• Wei-Hsin Hsu,
• Susanne Reischauer,
• Peter H. Seeberger,
• Bartholomäus Pieber and
• Dario Cambié

Beilstein J. Org. Chem. 2022, 18, 1123–1130, doi:10.3762/bjoc.18.115

• as a model system. The catalyst was shown to be stable, with a very low decrease of the yield (≈1% per day) during a continuous experiment over seven days, and to be effective for C–O arylations when carboxylic acids are used as nucleophile instead of sulfinates. Keywords: flow chemistry

• light-mediated carbon–heteroatom cross-couplings of sodium sulfinates, carboxylic acids and sulphonamides with aryl halides (Figure 2) [28]. Although recyclable, batch reactions are characterized by long reaction times (24 h). Here, we present a detailed investigation of a continuous-flow strategy for

Scope of tetrazolo[1,5-a]quinoxalines in CuAAC reactions for the synthesis of triazoloquinoxalines, imidazoloquinoxalines, and rhenium complexes thereof

• Laura Holzhauer,
• Chloé Liagre,
• Olaf Fuhr,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2022, 18, 1088–1099, doi:10.3762/bjoc.18.111

• electron-withdrawing functional groups, such as carboxylic acids, were not tolerated in the reaction of 11 to 14, or led to lower yields (for not successful reactions, please see Supporting Information File 1). The highest yields could be observed for the compounds 14j–l (Scheme 3). To extend the scope of

A versatile way for the synthesis of monomethylamines by reduction of N-substituted carbonylimidazoles with the NaBH₄/I₂ system

• Lin Chen,
• Xuan Zhou,
• Zhiyong Chen,
• Changxu Wang,
• Shunjie Wang and
• Hanbing Teng

Beilstein J. Org. Chem. 2022, 18, 1032–1039, doi:10.3762/bjoc.18.104

• secondary amines), carboxylic acids and isocyanates. Besides, an interesting reduction selectivity was observed. Exploration of the reaction process shows that it undergoes a two-step pathway via a formamide intermediate and the reduction of the formamide intermediate to monomethylamine as the rate

• -determining step. This work can contribute significantly expanding the applications of N-substituted carbonylimidazoles. Keywords: amines; carboxylic acids; isocyanates; monomethylamines; N-substituted carbonylimidazoles; reduction; Introduction N-Methylamines are widely found in natural products, fine

• suitable stability for isolation or storage, and various good methods for their perparation have been developed by employing different starting materials such as amines [56][57][58], isocyanates [59][60][61] and carboxylic acids [62]. Since the carbonyl carbon atom of the carbonylimidazole moiety is easily

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• alcohols [24], methoxides [23][25][26], carboxylic acids [27], amides [28], ketones [29][30], an exo-olefin [31], and lactones [32]. Elucidating the mechanisms of structural diversification is essential when considering the synthesis of unnatural azoxides by a synthetic biology-based approach. However

Synthesis and HDAC inhibitory activity of pyrimidine-based hydroxamic acids

• Virginija Jakubkiene,
• Gabrielius Ernis Valiulis,
• Markus Schweipert,
• Asta Zubriene,
• Daumantas Matulis,
• Franz-Josef Meyer-Almes and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 837–844, doi:10.3762/bjoc.18.84

• of varying length and the evaluation of their HDAC inhibitory activity. Results and Discussion Chemistry Commonly, hydroxamic acids (N-hydroxyamides) are prepared by coupling activated carboxylic acids with O-protected hydroxylamine [23][24][25] or by treatment of esters with hydroxylamine [26][27

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• highly selective hydration/acylation of tertiary bromopropargylic alcohols with carboxylic acids promoted by alkali metal carbonates [24]. The reaction proceeds via the ring-opening of 1,3-dioxolan-2-one intermediates formed with hydroxy and alkynyl groups of bromopropargylic alcohol and alkali metal

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

• outcome, although electronic effects can be considered to play a role, especially with substituted α-amino acids. Lanfranchi and co-workers also studied the menadione (10) alkylation by oxidative decarboxylation using carboxylic acids containing nitrogenous heterocycles as substituents, and achieved very

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

• Kian Donnelly and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27

• anticancer agents [21][22][23]. Previous reports of the synthesis of 1,3,4-oxadiazoles in continuous flow focused on the reaction between tetrazoles and carboxylic acids (Huisgen synthesis) [24][25]. Continuous flow technology has also been exploited for the further functionalisation of 1,3,4-oxadiazoles [26

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• (apicidin [19], microsporin A [20]), carboxylic acids (azumamides [21]), α-hydroxy ketones (FR235222 [22]) or thioesters (largazole [23]). These cyclopeptides mainly differ in the amino acid sequence of the peptide backbone, which causes selectivity towards the different HDAC isoforms. In fact, many

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