Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• carried out in order to synthesize the desired xanthene derivatives using the alkenes as starting compounds. The intramolecular Friedel–Crafts reaction was catalyzed by trifluoroacetic acid (TFA) and provided some novel substituted 9-methyl-9-arylxanthenes with good yields at room temperature within 6–24

• of xanthenes and thioxanthenes by intramolecular FCA catalyzed with organic Brønsted superacid, which are our works [41][42]. According to the literature, there are also hydroarylation methods with FCA, which are made by unactivated alkenes instead of π-activated alcohols. In these studies, generally

• gold(III) [43], iridium(III) [44][45], iron(III) [46], or bismuth(III) [47][48] were used as catalysts for the intermolecular hydroarylation of unactivated alkenes. Organic Brønsted acids were also used as catalysts in a smaller number of studies [49][50]. In this work, we searched for some organic

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

• general model suitable for the prediction of product selectivity and olefin bond chemodifferentiation in cross metathesis. In general, regarding the reactivity of the olefin bond in CM, alkenes can be categorized by the relative ability to undergo homodimerization via CM and the possibility of the

• are considered as to be of type II, only a handful of literature data are available on the behavior of fluorine-containing olefins or perfluorinated alkenes. The incorporation of fluoroalkyl moieties (such as difluoromethyl, trifluoromethyl and perfluoroalkyl groups) into an organic molecule can often

• ) late-stage fluorination, when the fluorine atom is incorporated in the final step of the synthetic protocol (e.g., deoxofluorinations) or ii) application of various commercial fluorine-containing scaffolds (e.g., fluorine-containing amines, fluorine-containing alkenes etc.) [49][50][51][52][53][54][55

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

• and co-workers in 2018 [39]. In this work, the presence of [Sc-1] and several alkenes resulted in the successful scandium-C(sp3)–H alkylation of methyl thioethers (Scheme 4B), by which different activated internal thioethers were obtained in good yields (Scheme 4C). The transformation facilitates

• similar catalyst, [Sc-2], which bears a more electron-rich cyclopentadienyl ligand, in a scandium-catalyzed C–H [3 + 2] cyclization (Scheme 5B) [40]. In this transformation, several aminoindane derivatives were obtained from benzylimines in the presence of the catalyst [Sc-2], alkenes and [Ph3C][B(C6F5)4

• efficient antibacterial compounds (Scheme 24A) [146]. In 2021, a divergent silylation of alkenes via a manganese-catalyzed C–H activation was reported by Xie et al. by using a ligand-tuned metalloradical reactivity strategy (Scheme 24B and C) [147]. Using Mn2(CO)10 as a catalyst precursor, the authors

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• ], electron-rich alkenes (entry 3) [65][66], alkyl sulfides (entry 4) [65][67], 1,3-dicarbonyl compounds [65][68], phosphonate esters (entry 5) [65], steroidal silyl enol ethers and enol acetates (entry 6) [65], pyrimidine bases and nucleosides (entry 7) [67][69], phenylalkynes (entry 8) [70], anthraquinones

Correction: Amine–borane complex-initiated SF₅Cl radical addition on alkenes and alkynes

• Audrey Gilbert,
• Pauline Langowski,
• Marine Delgado,
• Laurent Chabaud,
• Mathieu Pucheault and
• Jean-François Paquin

Beilstein J. Org. Chem. 2021, 17, 1725–1726, doi:10.3762/bjoc.17.120

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• Li [38], who used a catalytic system of AuCl3/AgOTf to promote the addition of active methylene compounds like acetylcyclopentanone 8 to more reactive alkenes, such as styrenes 9. Two examples were reported by the authors for the synthesis of quaternary carbon centers without the necessity of

• cyclization of internal alkenes, such as 19c, were not generated by this methodology. Additional experiments in the presence of deuterated water corroborated the authors’ proposal of an involvement of gold catalysis in the enolization of the substrates (a hydrogen–deuterium [H–D] exchange in saturated

• hydroalkylation of styrenes 9 using FeCl3·H2O as a source of iron(III) (Scheme 13) [46]. This reaction required higher temperatures than those used in the gold(III) methodology reported previously by Li [38] and a considerable excess (10 equiv) of alkenes (Scheme 6) to achieve the products in practice yields

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• , alkyl N-arylideneglycinates have attracted much attention in recent years. For instance, the metal-catalyzed asymmetric [3 + 2] cycloaddition of ethyl N-benzylideneglycinates with electron-deficient alkenes has been reported to yield substituted pyrrolidines [30]. Recently, we reported the synthesis of

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

• .17.89 Abstract A visible light-mediated heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile has been established using K-modified carbon nitride (CN-K) as a recyclable semiconductor photocatalyst. This protocol, employing readily accessible alkyl N-hydroxyphthalimide (NHPI

• cyanomethylarylation of alkenes, most of them rely on the use of transition metals (such as catalytic amounts of Pd, Cu, Fe catalyst or stoichiometric amounts of Ag, Mn salts) and strong oxidants (including PhI(OPiv)2, DTBP, and t-BuONO) in the presence of various base additives under high reaction temperatures or

• photocatalysts are used; and the scope remains limited to activated alkenes. Therefore, it is still highly desirable to develop a general, efficient, and practical protocol for the cyanomethylarylation of unactivated alkenes from readily available radical initiators under mild and environmentally benign

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• described the diastereoselective synthesis of aziridines 42 in one-step using the Cu(I)/ʟ-proline complex as a catalyst and N-tert-butasulfinylamide in an aminotrifluoromethylation reaction of alkenes. All the aziridines 42 were obtained with high diastereoselectivity (dr > 25:1) and good yields (56–98

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

• Rashmi Singh,
• Tomas Horsten,
• Rashmi Prakash,
• Swapan Dey and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79

• polycyclic derivatives was designed. The procedures towards such polycyclic building blocks include C–H-arylation strategies. In the classical Meerwein reaction, aryldiazonium salts are used as the reagents to couple aryl groups to electron-poor alkenes, and this process is assumed to proceed via a free

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• alcohols having unactivated and unsubstituted alkenes, whereas the substituent adjacent to the hydroxy group in the homoallylic alcohol controls the oxonia-Cope rearrangement (see 273a–c). The alkyl substituent favored the exclusive formation of crossed THP derivatives, whereas 2-oxonia-Cope rearrangement

Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions

• Dat Phuc Tran,
• Yuki Sato,
• Yuki Yamamoto,
• Shin-ichi Kawaguchi,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 866–872, doi:10.3762/bjoc.17.72

• reactivities. The method using V-40 as an initiator is successfully investigated for the regio- and stereoselective phosphinylphosphination of terminal alkynes giving the corresponding trans-isomers of 1-diphenylphosphinyl-2-diphenylthiophosphinyl-1-alkenes in good yields. The protocol can be applied to a wide

• using a radical initiator such as 1,1'-azobis(cyclohexane-1-carbonitrile) (V-40) (Scheme 1a) [45] or upon photoirradiation (Scheme 1b) [38] yields vic-bis(diphenylphosphino)alkenes in good yields. Unfortunately, this photoinduced reaction of Ph2PPPh2 was not applicable to alkenes [42]. To change the

• reactivity of the P–P bond, therefore, when the combination of pentavalent phosphorus and trivalent phosphorus was examined, it was found that the desired radical addition of Ph2P(X)PPh2 (X = O, S) to alkenes successfully occurred [42][43] (Scheme 1c and 1d). However, in the case of Ph2P(O)PPh2, its

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

• unactivated olefins and alkynes. This approach employed 68 and Togni reagent 69 (electron acceptor) as substrates, NMM as electron donor, and pyrrolidin-2-one as solvent to give hydrotrifluoromethylated product 70 at room temperature (Scheme 24). CF3 was added to a variety of terminal alkenes, leading to

• triethylamine as additive at 20 °C and under 405 nm irradiation (Scheme 40). A standard residence time of 5 min was required for the full conversion via the EDA complex that formed by alkene and perfluoroalkyl iodide in flow, while longer residence times were requisite for less reactive alkenes. Moreover, the

• that could react with olefin 120 with an electron-withdrawing group to give alkylation product 121 under irradiation with light (Scheme 41). The reaction is compatible with various substrates, including alkenes, secondary alkylpyridinium ions, benzylic pyridinium ions, and primary alkylpyridinium ions

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

• Ramazan Koçak and
• Arif Daştan

Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61

• electron-demand Diels–Alder cycloaddition reactions of alkenes with tetrazines are commonly used for the synthesis of dihydropyridazines and pyridazines [50][51][52][53][54]. In our previous study, we made a discovery that would form the basis of a new class of dyestuffs with skeletons unlike those of

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

• , Nanjing 210023, China School of pharmacy, Wannan Medical College, Wuhu, 241002, China 10.3762/bjoc.17.49 Abstract The difunctionalization of alkenes involving a trifluoromethylthio group (SCF3) for the conversion of versatile and readily available olefins into structurally more complex molecules has been

• successfully studied. However, the disproportionate dithiolation of alkenes is unknown. Herein, a transition-metal-free protocol is presented for the vicinal trifluoromethylthio–thiolation of unactivated alkenes via a radical process under mild conditions with a broad substrate scope and excellent tolerance

• . Keywords: alkenes; difunctionalization; metal-free; photoredox; trifluoromethylthiolation; Introduction The incorporation of fluorine atoms into drug molecules will significantly enhance the physical, chemical, and biological properties of the pharmaceuticals [1][2][3][4][5][6]. Modifying drug candidates

A new and efficient methodology for olefin epoxidation catalyzed by supported cobalt nanoparticles

• Lucía Rossi-Fernández,
• Viviana Dorn and
• Gabriel Radivoy

Beilstein J. Org. Chem. 2021, 17, 519–526, doi:10.3762/bjoc.17.46

• materials and it could be recovered and reused maintaining its unaltered high activity. Keywords: alkenes; cobalt nanoparticles; epoxides; oxidation; TBHP; Introduction Olefin oxidation reactions are key synthetic transformations in the production of oxygenated chemicals of high interest for both academic

• heterogeneous [33][34][35][36][37] Co-based catalysts have been applied to the epoxidation of alkenes, however, most of the reported methods lead to unsatisfactory yield, low selectivity, or limited substrate scope. Suib et al. [38] reported on the synthesis of mesoporous Co3O4 for the catalytic epoxidation of

• a variety of alkenes as an interesting heterogeneous system. This cobalt oxide mesoporous nanomaterial showed good activity and selectivity to the epoxide product and could be recovered and reused, but the multistep (not straightforward) synthesis of the catalyst and the use of DMF as the solvent

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

• trichloride; dichloroalkenes; Friedel–Crafts alkylation; rearrangement; trifluoroalkanes; Introduction 1,1-Dichloro-1-alkenes are valuable synthetic intermediates and have been employed in Pd-mediated cross couplings of one or both chlorine atoms [1][2][3][4][5][6][7], carbonylation reactions [8], and C–H

• bond alkynylations of heteroarenes [9]. The 1,1-dichloro-1-alkenyl moiety is found in a number of pyrethroid insecticides including permethrin and marine natural products such as caracolamide A [10] (Figure 1). 1,1-Dichloro-1-alkenes 2 are commonly prepared from the corresponding aldehydes 1 in one

• dichloroalkenes [18][19][20]. The preparation of 1,1-dichloro-1-alkenes from hydrazones [21] and from 2,2,2-trichloroethyl carbonates [22] has also been reported. Internal difluoroalkanes have been used to generate chloroalkene products using AlEt2Cl [23][24]. In this article we describe the AlCl3-mediated

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

• utilizing electron-poor alkenes as the reaction partners that would undergo aza-Michael addition reactions on the Cbz-carbamates (Scheme 4). Driven by the desire to develop readily scalable routes towards the target products 8, continuous flow processing was again exploited. In a first approach the use of

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• (hetero)arenes [104][105] and alkenes [106] under Lewis acid activation but also with electron-rich arenes under thermal activation [107][108][109]. CF3-substituted hemiacetal 168 can react with amines to furnish the corresponding hemiaminal ethers, which can be further activated by a Lewis acid to

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

• . The carbene-based methods typically give the highest yields when alkenes with electron-donating substituents are used. There are few examples in which the cyclopropanation by carbene methods of electron-deficient alkenes containing substituents with a large −M effect (for example, CO2R, COR, CN, SO2R

• halodifluoromethanes and alkenes (Scheme 2). The elimination of hydrogen halide from the halodifluoromethane under basic conditions (metal alkoxide or alkyllithium) generated difluorocarbene [14][15]. The low yields of the product have been attributed to the facile addition of the strong bases to difluorocarbene. The

• yields were best in the reactions with electron-rich alkenes and when a low concentration of the base was used to minimize the destruction of difluorocarbene. The use of oxirane or epichlorohydrin as hydrogen halide scavengers avoided the need for a stoichiometric amount of the strong base [16][17]. The

Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodium S-organyl sulfurothioates under basic conditions

• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Thiago Barcellos,
• Claudio C. Silveira and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2021, 17, 234–244, doi:10.3762/bjoc.17.24

• sulfides by the acetamidosulfenylation of alkenes [12], among others [13][14][15]. Sulfur-containing compounds are important intermediates in organic synthesis, being able to act as an electrophile or nucleophile in many organic transformations [16][17][18]. Still, many of them are pharmacologically active

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• iii) an asymmetric Mukaiyama–Kiyooka aldol reaction (Scheme 16 and Scheme 17) [8]. The total synthesis was initiated with the preparation of two alkenes precursors (rac)-118 and 121. The tiglic aldehyde 115 was converted into silyl enol ether 116 followed by treatment with acetal 117 using a

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• acid in toluene. After 5 minutes, 1.2 equiv of tributyltin fluoride was added to intermediate A, and at the end of the process, 63a and 63b were obtained after chromatographic purification with 81% yield for 63a and 74% yield for 63b. Finally, the alkenes were oxidized in the presence of osmium

Silver-catalyzed synthesis of β-fluorovinylphosphonates by phosphonofluorination of aromatic alkynes

• Yajing Zhang,
• Qingshan Tian,
• Guozhu Zhang and
• Dayong Zhang

Beilstein J. Org. Chem. 2020, 16, 3086–3092, doi:10.3762/bjoc.16.258

• . Among the strategies for constructing diverse alkenes containing two-heteroatom bonds, such as disulfonylation [14][15][16], heterohalogenation [17][18][19][20], bis(trifluoromethyl)thiolation [21], and phosphorylation [22], the direct heterodifunctionalization of alkynes using three-component reactions

• others concerning the silver-catalyzed phosphonofluorination of alkenes [24][25][26], we herein present a general silver-catalyzed regio- and stereoselective phosphonofluorination of alkynes using Selectfluor® and phosphonates as reactants (Scheme 1). This new silver-catalyzed approach to fluorinated