Chemoselective N-acylation of indoles using thioesters as acyl source

• Tianri Du,
• Xiangmu Wei,
• Honghong Xu,
• Xin Zhang,
• Ruiru Fang,
• Zheng Yuan,
• Zhi Liang and
• Yahui Li

Beilstein J. Org. Chem. 2022, 18, 89–94, doi:10.3762/bjoc.18.9

• requires sensitive and reactive acyl chloride derivatives. Here, we report a mild, efficient, functional group tolerant, and highly chemoselective N-acylation of indoles using thioesters as a stable acyl source. A series of indoleamides have been obtained with moderate to good yields. In addition

• cannabinoid (hCB1) receptor [3] (Figure 1). Indole has multiple reactive sites, and chemoselective N- or C-functionalization of indoles is a challenging and important task [4][5]. Acylation of indoles frequently takes place at the C3 position because of the relatively strong electron cloud density. As N

• efficient method for the synthesis of N-acylindoles becomes much attractive [9][10][11][12]. In 2009, Scheidt developed a dehydrogenative approach using indoles and alcohols catalyzed by tetrapropylammonium perruthenate [13] (Scheme 1, A1). In 2012, Sarpong successfully carried out chemoselective acylation

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

• solvent-tuned [129]. In neat CH2Cl2, the reaction produced the expected β-trichloromethyl alkyl azide; however, the reaction was chemoselective for diazidation when tert-butanol was used as co-solvent. The authors hypothesized the presence of the alcohol suppresses the polar-unmatched HAT process from

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

• 402160, China 10.3762/bjoc.17.193 Abstract Chemoselective sulfonylation and isonitrilation reactions for the divergent synthesis of valuable diarylmethyl sulfones and isonitrile diarylmethanes starting from easy-to-synthesize para-quinone methides (p-QMs) and commercially abundant p

• synthetic utility of this protocol was also demonstrated in the synthesis of difluoroalkylated diarylmethane 5 and diarylmethane ketone derivatives 6 and 7, which are important core structures in natural products and medicines. Keywords: chemoselective reactions; diarylmethyl sulfones; dual role

• report the chemoselective sulfonylation and isonitrilation of p-QMs by changing the reaction conditions. This new general protocol allows, from the same substrates p-QMs 1 and p-tosylmethyl isocyanide (TosMIC, 2a), the formation of quite different products 3 or 4 in a simple and mild manner, which

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• (Scheme 10) [52]. The tandem reaction involved a regio- and chemoselective addition of the Blaise reaction intermediate to 1,3-enyne, and the following sequential processes: isomerization, cyclization, and aromatization. Both carbocyclic and acyclic 1,3-enyenes 28 were compatible to give the corresponding

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• into the PMB-protected α,β-unsaturated ester 97 in four steps adopting the literature procedure (Scheme 12). The chemoselective reduction of the olefin in 97 was furnished in 88% yield applying NiCl4·6H2O/NaBH4 as reagents in methanol followed by reduction of the ester part with DIBAL-H providing the

A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

• Zsanett Benke,
• Attila M. Remete and
• Loránd Kiss

Beilstein J. Org. Chem. 2021, 17, 2051–2066, doi:10.3762/bjoc.17.132

• . Some commercial Ru-based catalysts used in the current work. Synthesis of divinylated cyclopentane-fused isoxazolines [41]. Various fluorine-containing olefins used in the current work. Chemoselective CM reaction due to steric hindrance. Cross-metathesis of divinylated isoxazoline (±)-4 with

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

• reaction showed to be chemoselective, maintaining good yields with compounds bearing varied functional groups, whereas low yields were observed for benzylic fluorination. Preliminary mechanistic studies suggested the C–H abstraction to be the rate-determining step and the high oxygen sensitivity of the

• applied in some very sophisticated protocols including several examples reported by the White group. In 2015, White and co-workers reported a new catalytic method using manganese tert-butylphthalocyanine [Mn(t-BuPc)Cl] for the chemoselective intramolecular amination of various C(sp3)–H bond types like

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• azidation product 11. Upon regeneration, the catalyst participates in the next catalytic cycle. In this Mn-catalyzed azidation study, the azide/oxygenated product ratio was 2:1–4:1. Therefore, a chemoselective manner is of dire need to avoid unwanted C–H oxygenation. In 2020, the Lei group disclosed the

• molecules bearing unactivated Csp3–H bonds facilitated by electricity (Scheme 5) [43]. Several pharmaceutically active molecules were committed to the external oxidant-free reaction conditions and were shown to undergo chemoselective azidation. Azidation of ibuprofen methyl ester (14a) was selective for the

• acetate as the base to deliver the corresponding peptide–sugar conjugates 31 at the late stage. Notably, the chemoselective glycoconjugation strategy was compatible with various sugar scaffolds, affording glycotryptophans bearing either furanose or pyranose motifs. In addition, a brevianamide F analogue

A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

• Greta Utecht-Jarzyńska,
• Karolina Nagła,
• Grzegorz Mlostoń,
• Heinz Heimgartner,
• Marcin Palusiak and
• Marcin Jasiński

Beilstein J. Org. Chem. 2021, 17, 1509–1517, doi:10.3762/bjoc.17.108

• (Scheme 5). The presence of ≈40% of unconsumed quinone 1e in the crude reaction mixture evidenced that the observed fully chemoselective cycloaddition reaction with the sterically congested C=C bond in 1e occurs less efficiently than in 2,3-unsubstituted 1,4-quinones, such as 1a and 1b. However, in that

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

Nitroalkene reduction in deep eutectic solvents promoted by BH₃NH₃

• Chiara Faverio,
• Monica Fiorenza Boselli,
• Patricia Camarero Gonzalez,
• Alessandra Puglisi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2021, 17, 1041–1047, doi:10.3762/bjoc.17.83

• ammonia borane in the chemoselective reduction of a variety of nitrostyrenes and alkyl-substituted nitroalkenes to the corresponding nitroalkanes, without any catalyst or additive [13]. We thought that the combination of an atom economic, very convenient and inexpensive reagent such as BH3NH3 in bio-based

• report the results of our explorative studies, aimed to develop a chemoselective nitroalkene reduction in DESs, with the goals to establish a reliable and reproducible protocol to isolate the product without the use of any organic solvent and to assess the recovery and the recyclability of the DES

• was efficiently used in the chemoselective reduction of nitroalkenes to afford the corresponding nitroalkanes in fair to good yield. The possibility to isolate the product without the addition of any organic solvent and to recycle the eutectic mixtures at least three times in further reactions was

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• complex based on previous work in 2017 [21]. The reaction is initiated by the formation of EDA complex between electron acceptor N-acyloxyphthalimide 90 and electron donor HE 79, completing regio- and chemoselective C(sp3)–H allylation or olefin bifunctionalization (Scheme 31). In 2018, Tang and Studer

Metal-free visible-light-enabled vicinal trifluoromethyl dithiolation of unactivated alkenes

• Xiaojuan Li,
• Qiang Zhang,
• Weigang Zhang,
• Jinzhu Ma,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2021, 17, 551–557, doi:10.3762/bjoc.17.49

• substrate scope of the disulfides (Scheme 2). Using borate-substituted olefins, the intermolecular trifluoromethylthio–thiolation induced by the sequential radical difunctionalization proceeded smoothly in a chemoselective fashion. Both, with electron-withdrawing and electron-donating groups substituted

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

• within continuous flow processes [17][18][19][20] to provide a greener and more chemoselective means for the synthesis of drug-like targets. Recently, we reported on an innovative telescoped process using immobilized CALB (Candida antarctica lipase B) to enable the conversion of residual benzyl alcohol

• immobilized CALB enzyme is reported. This approach enabled the chemoselective derivatization of benzyl alcohol into the readily removable benzyl butyrate thus simplifying the final purification stages. The resulting Cbz-carbamates were furthermore elaborated into derivatives of β-amino acids via biphasic flow

Hydrazides in the reaction with hydroxypyrrolines: less nucleophilicity – more diversity

• Dmitrii A. Shabalin,
• Evgeniya E. Ivanova,
• Igor A. Ushakov,
• Elena Yu. Schmidt and
• Boris A. Trofimov

Beilstein J. Org. Chem. 2021, 17, 319–324, doi:10.3762/bjoc.17.29

• nucleophilicity of the hydrazides diversifies the recyclization of 5-hydroxypyrrolines and results in the chemoselective formation of highly functionalized azaheterocyclic scaffolds. Such a short-cut to partially saturated azaheterocyclic scaffolds meets the interests of modern medicinal chemistry which today

• followed by the introduction of 140 mol % of TFA and additional reflux for 3 h (Table 1, entry 11). Next, the substrate scope and functional group tolerance of the protocols aimed to the chemoselective synthesis of di- and tetrahydropyridazines were investigated. Several features of the developed methods

• for the convenient chemoselective syntheses of highly functionalized azaheterocyclic scaffolds (di- and tetrahydropyridazines) with an acyl function at the nitrogen atom, thus having a substituent pattern similar to that of the known biologically active compounds of the pyridazine family. Moreover

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• selectively attacked the C-8 ketone moiety of 47 to give alcohol 49 in β-configuration in 80% yield [32]. Chemoselective and stereoselective reduction of the C-9 ketone of 49 was accomplished by treatment with NaBH(OAc)3 [33] and produced 50 after a two-step synthesis. Removal of the sulfoximine group in 50

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• ., Flemingovo nám. 2, 166 10 Prague 6, Czech Republic 10.3762/bjoc.16.226 Abstract The prochiral 4-(allyloxy)hepta-1,6-diynes, optionally modified in the positions 1 and 7 with an alkyl or ester group, undergo a chemoselective ring-closing enyne metathesis yielding racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

Azidophosphonium salt-directed chemoselective synthesis of (E)/(Z)-cinnamyl-1H-triazoles and regiospecific access to bromomethylcoumarins from Morita–Baylis–Hillman adducts

• Soundararajan Karthikeyan,
• Radha Krishnan Shobana,
• Kamarajapurathu Raju Subimol,
• J. Helen Ratna Monica and
• Ayyanoth Karthik Krishna Kumar

Beilstein J. Org. Chem. 2020, 16, 1579–1587, doi:10.3762/bjoc.16.130

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• discovered two new applications of BTMS, providing new mild methods for the synthesis of oxazoles and an α-bromoacetamide. Even though the former synthesis was not completely chemoselective, the pure oxazoles could be easily isolated in good yields, and the proposed procedure constitutes an interesting

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• , mild, and chemoselective radical catalysts that deserve more attention. The present review highlights the recent progress in the field of disulfide-catalyzed and -cocatalyzed photocatalytic reactions for different reaction types. Keywords: cycloaddition; disulfide catalyst; isomerization; oxidation

• variety of reactions, renders them a class of green, economic, mild, and chemoselective radical catalyst. Apart from this, they are also excellent HAT catalysts in photoredox catalysis systems [2][3]. In various types of organic photochemistry reactions, such as cyclizations, anti-Markovnikov additions

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• wavelength afforded better results. The irradiation of dinuclear derivatives 3a–f and 3h–j in CH2Cl2 solution with blue light (465 nm), provided by low-power LED lamps, took place with chemoselective [2 + 2] photocycloaddition of the oxazolone exocyclic C=C bonds and formation of the corresponding ortho

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• chemoselective manner. Regarding porphyrin-mediated reduction reactions, we have selected one representative example reported by Nagaraja and co-workers. They have shown a heterogeneous photocatalytic reduction of nitroaromatic compounds to the corresponding anilines using a Ni(II)-MOF, [Ni3(Ni-TCPP)2(µ2-H2O)2

• enantioselective and chemoselective oxidations of many organic compounds. Notably, the Gryko’s group recently described an enantio- and diastereoselective approach involving a porphyrin-based photooxygenation of aldehydes with sequential reduction to yield chiral diols in yields up to 91% and significant er (up to

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• [44]. Among the various embodiments of olefin metathesis, the highly chemoselective enyne metathesis reaction [45][46][47][48][49] has led to some of the most striking advances in the development of modern, efficient synthetic protocols [50][51]. Thus, the present account focuses on the impressive

• metathesis (RCM) [67][68]. Starting from 3-cyanocyclohex-2-enone, the authors obtained a versatile intermediate able to provide the appropriate dienyne precursors (A–C, Scheme 4) by multicomponent Grignard addition-alkylations. Through divergent cyclizations involving a chemoselective enyne metathesis

• dienyne precursors in three steps, from (S)- and (R)-citronellal, through a diastereoselective Michael addition, chemoselective dibromoolefination, and a one-pot Wittig olefination/alkyne-bond formation. The enantiopure dienynes were then converted into the enantiomeric hydroazulenes in 53% and 55% yield

Efficient synthesis of 3,6,13,16-tetrasubstituted-tetrabenzo[a,d,j,m]coronenes by selective C–H/C–O arylations of anthraquinone derivatives

• Seiya Terai,
• Yuki Sato,
• Takuya Kochi and
• Fumitoshi Kakiuchi

Beilstein J. Org. Chem. 2020, 16, 544–550, doi:10.3762/bjoc.16.51

• effectively provided various tetrabenzo[a,d,j,m]coronenes in short steps from readily available starting materials. Tetrabenzo[a,d,j,m]coronenes possessing two different types of substituents were obtained selectively by sequential chemoselective C–O arylation and C–H arylation. The 1H NMR spectra of the

• introduction of two different aryl groups at the ortho-positions can be achieved by chemoselective C–O arylation of aromatic ketones possessing both C–H and C–O bonds and subsequent C–H arylation. We envisioned that the application of this strategy to the anthraquinone template would provide its derivatives

• . Tetraarylanthraquinones containing two different aryl groups were also prepared via the above-mentioned chemoselective C–O arylation and subsequent C–H arylation. The chemoselective C–O diarylation of 1,4-dimethoxyanthraquinone to form 1,4-diarylanthraquinones has been previously reported by our group [19], and 1,4-bis(4