Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• alkene 12 (30%) could be formed from terminal epoxide 5, using cyclopropylstannane 11 [16] (Scheme 5); in this case the presence of LTMP was also necessary as epoxide 5 was recovered (>80%) in its absence. A silyl-stabilised methoxymethyllithium, available by direct lithiation of (methoxymethyl

• -lithio terminal epoxides or N-Bus-aziridines with α-lithio ethers. Where 1,2-disubstituted alkenes are generated the E/Z stereoselectivity is modest, and preliminary results suggest the size of the leaving group does not play a significant role. However, the geometry of alkene formation might be

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

• carbohydrate alkene precursor 7 and Hg(OAc)2 proceeds with high stereoselectivity to give the α-ᴅ-C-glycopyranosyl derivative (1,5-trans-isomer) 8 as a single isomer [41]. Treatment of compound 8 with sodium borohydride (NaBH4) under phase transfer conditions (PTC) yields compound 9 as the only product. The

• manner as reductive elimination forms during the mercury removal process (Scheme 6). Mercury(II) salts had been effectively used to synthesize five-membered furanose derivatives with high stereoselectivity. Nicotra et al. developed Hg(OAc)2-mediated cyclization of hydroxy-alkene derivative 15 to form α-ᴅ

• positions of the starting material. It had been cited in many publications that the stereoselectivity of products formed due to Hg(II)-salt-mediated cyclization reactions of alkene-alcohol derivatives depends on several factors: the nature of the Hg(II) salts [46], the starting materials [47], and the

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

• regenerate the nickel(0) species 21-VI and the carboxylate product 21-IX. Olefin difunctionalization Nickel-catalyzed alkene 1,2-difunctionalization is considered as useful method for preparing complex molecules in a single-step reaction [137][138][139]. In this aspect, the groups by Kong [140] and Molander

• decatungstate 22-II undergoes a HAT process with the C(sp3)–H substrate to form a carbon-centered radical species 22-III and reduced decatungstate 22-IV. The thus formed alkyl radical 22-III adds to the alkene 92 affording the radical adduct 22-VI, which is intercepted by the nickel(0) species 22-X to generate

• the triplet-state diradical 23-I. A HAT process between 23-I and the alkane substrate generates the desired carbon-centered radical 23-II with concomitant formation of ketyl radical species 23-III. The thus formed alkyl radical 23-II undergoes Giese addition to alkene 94 resulting in the radical

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

• significance were synthesized by developing a new synthesis method. In order to obtain xanthene derivatives, the original alkene compounds to be used as the starting materials were synthesized in four steps using appropriate reactions. A cyclization reaction by intramolecular Friedel–Crafts alkylation was

• hours. As a result, an alkene compound was used for activation with TFA in the synthesis of xanthene through intramolecular Friedel–Crafts alkylation for the first time. Keywords: alkene activation; intramolecular Friedel–Crafts alkylation; trifluoroacetic acid; xanthene; Introduction The interest in

• development trials for the synthesis of xanthene derivatives were carried out. For this purpose, catalyst researches were carried out using compound 4a. An intramolecular Friedel–Crafts reaction was tried by activating the alkene with various organic Brønsted acids and Lewis acids (Table 1). In the reaction

Facile and innovative catalytic protocol for intramolecular Friedel–Crafts cyclization of Morita–Baylis–Hillman adducts: Synergistic combination of chiral (salen)chromium(III)/BF₃·OEt₂ catalysis

• Karthikeyan Soundararajan,
• Helen Ratna Monica Jeyarajan,
• Raju Subimol Kamarajapurathu and
• Karthik Krishna Kumar Ayyanoth

Beilstein J. Org. Chem. 2021, 17, 2186–2193, doi:10.3762/bjoc.17.140

• , 1640, 1548, 1470, 1442, 1215, 734; 1H NMR (CDCl3, 300 MHz) δH 7.99 (s, 1H, alkene-CH), 7.64–7.41 (m, 4H, Aro-H), 4.41 (s, 2H, -CH2), 3.87 (s, 3H, COOCH3); 13C NMR (CDCl3, 75 MHz) δC 168.03, 145.31, 134.67, 130.11, 129.53, 128.62, 128.25, 64.78, 52.24; HRMS (m/z): [M + H]+ calcd for C11H10O2, 174.0681

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

• selective functionalization of readily available norbornadiene across nitrile oxide cycloaddition/ROM/CM protocols in view of the access of various fluorine-containing molecular entities as well as to explore the chemical behavior of olefin bonds in the reaction with some fluorinated alkene derivatives in

• (±)-6 with alkene 7d were explored (Scheme 14 and Table 13). G-3 catalyst yielded (±)-21a as the sole monocoupled product, while HG-2 and G-2 catalysts gave both monocoupled (±)-21a and dicoupled (±)-21c. The best yield of (±)-21c was achieved with HG-2 catalyst (although G-2 catalyst also produced a

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

• ] cyclotrimerization reactions in the presence of nickel and cobalt catalysts [38]. First, they employed diyne 15 in the reaction with a series of alkynes (16) or nitriles (17) bearing a variety of functional groups including alkyl and alkene chains, hydroxy groups, and benzene and pyridine rings, to achieve the

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

• phenanthroindolizidine alkaloid boehmeriasin A (31) (Scheme 12A) [98], and phenanthroindolizidines through an intramolecular oxidative aryl–alkene coupling (Scheme 12B) [99], which is a far less common transformation in organic synthesis. This approach was employed to synthesize eight phenanthroindolizidines, including

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

• [104]. The manganese(I)-catalyzed intermolecular alkenylation of tryptophan-containing peptides 32 was performed under basic conditions, yielding hybrid peptides 34 without racemization, containing a trans-alkene linker bearing biologically active motifs in chemo- and site-selective manners assisted by

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

• , France 10.3762/bjoc.17.120 Keywords: amine–borane complex; pentafluorosulfanyl chloride; pentafluorosulfanyl substituent; radical addition; radical initiation; The stereochemistry of some alkene products (2i–k) in Scheme 4 of the original publication was misattributed. The corrected structures are

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

• expense of the olefin double bond. Review Olefin activation by transition metals Transition metals can act as π-acid catalysts in olefin double bond activation, as they weaken the alkene double bond through coordination to allow a nucleophilic attack on the sp2 carbon to form an alkylmetal intermediate

• than Pd(II)-catalytic types have also been explored. Pd(II)-catalyzed hydroalkylation reactions The σ-alkylpalladium species formed after a carbon nucleophilic attack on an alkene double bond (Scheme 1) have a marked tendency to undergo a hydride β-elimination process that leads to oxidative coupling

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• is formed than we isolate. The compound can react further. Simply treating it with silica and methanol during filtration leads to the conjugate addition of methanol to the doubly activated alkene to give a cyclohexenone cyclophane 14 (Scheme 3). Attempting to force this reaction with acid leads to a

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• give the tetralin product. Instead, we only isolated 30% yield of the difuranyl-substituted compound 15 as the major product. In addition, aldehydes 13e or 13f bearing a methyl group at the acetaldehyde side or the benzylic position of the alkene side were also suitable substrates for this cascade

• strategy: the 1,2,4-trisubsitituted tetralins 14ea and 14eb as well as the 2,4,4-trisubsitituted tetralins 14fa and 14fb were obtained in moderate to reasonable yields. The aldehyde 13g bearing a phenyl group at the benzylic position of the alkene side was also tried. Under the standard conditions, the

Fritsch–Buttenberg–Wiechell rearrangement of magnesium alkylidene carbenoids leading to the formation of alkynes

• Tsutomu Kimura,
• Koto Sekiguchi,
• Akane Ando and
• Aki Imafuji

Beilstein J. Org. Chem. 2021, 17, 1352–1359, doi:10.3762/bjoc.17.94

• reactive intermediates in which both magnesium and chlorine atoms are attached to an alkene carbon atom (Scheme 2a) [10]. Magnesium alkylidene carbenoids 3 can be generated from isopropylmagnesium chloride and 1-chlorovinyl p-tolyl sulfoxides 2, which are prepared from carbonyl compounds 1 and chloromethyl

• )magnesium chlorides, CH2=CXMgCl (X = F, Cl, and Br) << (1-chlorovinyl)lithium, CH2=CClLi. If the 1-heteroatom-substituted vinylmetal displays vinylidene characteristics, the FBW rearrangement occurs to give the alkyne. If not, the vinylmetal is simply protonated to give a heteroatom-substituted alkene. A

• reaction of (1-fluorovinyl)magnesium chloride with isopropylmagnesium chloride competed with the FBW rearrangement to give a mixture of alkyne 4a and alkene 10 in 69% and 13% yield, respectively (Table 1, entry 4, Scheme 4a, and Scheme 2c) [20]. Both the sulfoxide/magnesium exchange reaction and bromine

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

• radical A. The subsequent hydrogen abstraction by radical A yields the key alkyl radical B. The addition of radical B or A to the alkene 7a following by an intramolecular cyclization provides the radical intermediates C or E, which are oxidized by the hole of CN-K via SET delivering the product 8a or

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

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• progresses under neutral conditions. The authors postulated that the vacancy on the square-planar Pd(II) species allows a faster alkene insertion in comparison to Pd(0). The cationic Pd(II) enolate exists as a dynamic mixture of C- and O-bound enolate and is highly susceptible to hydrolysis. This means that

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

• Lewis acid (Scheme 53). Recently Xu et al. reported the homoallylic silyl alcohol 224 containing a multisubstituted (Z)-alkene reacting with an aldehyde in the presence of TMSI and InCl3 to afford 226 in high diastereoselectivity [96]. The authors assumed that the Prins cyclization proceeded through

• Alder’s chair-like transition state 227 in which the (Z)-alkene accounts for the trans-stereocontrol at the C3 position and equatorial iodide addition accounts for the cis-stereocontrol at the C4 position, as shown below in Scheme 54. The one-pot synthesis of tetrahydropyran by utilizing the Babier–Prins

• activation via DDQ oxidation, followed by nucleophilic attack of an unactivated olefin to obtain all-cis-trisubstituted Prins products with high stereochemical precision [111]. A single-electron transfer (SET) mechanism was proposed for the above transformation (Scheme 69). A SET from an arene or alkene to

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

• perfluoroalkyl iodide form a halogen-bond adduct, and then light-induced electron transfer happens in order to give a perfluoroalkyl radical. The protocol can realize alkene- and alkyne iodide perfluoroalkylation and C–H perfluoroalkylation of electron-rich heteroaromatic hydrocarbons, providing a novel protocol

• trifluoromethyl alkynylation product 84 with alkynyl sulfone 83, alkene 81, and Togni reagent 82 as substrates catalyzed by 2,4,6-trimethylpyridine (TMP). The EDA complex formed by electron donor TMP and electron acceptor Togni reagent 82 facilitated electron transfer, yielding trifluoromethyl radical to initiate

• 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

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• substituents at C3 and C4 of the formed 2-pyrrolidone ring predominated with moderate selectivity (Table 3, entries 2–7). The diastereomeric ratio is more or less independent of the nature of the amide substituent R1 or the substituent R4. Amide 9f with a methyl group at the internal position of the alkene

• alkene units furnished 4-isopropenylpyrrolidones 12g,k in very good yields as mixtures of inseparable diastereomers (Table 3, entries 7 and 11); no alkoxyamine-containing products were isolated. Lactam 12h with a defined hydroxy group configuration in the side chain at C3 of the lactam as well as

• (2R*,4S*)-9l as the major product (Scheme 8). The outcome of the thermal radical cyclizations of the dioxygenated amides 9 is dependent on the structure of the alkene unit, but the general trend is similar (Scheme 9). Amides with a terminal alkene unit furnished dioxygenated pyrrolidones 12a–f,h–j as

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

• use of molecular oxygen as oxidant but require the use of high amounts (400–500% excess) of isobutyraldehyde as co-reductant. Therefore, there remains a need to develop and improve catalytic systems for alkene epoxidation by using low cost and easy to prepare supported cobalt nanoparticles as reusable

• very low conversion (pulegone, 22%) or did not react under the optimized conditions, even after 24 h of reaction time (methyl cinnamate, methyl acrylate, methyl methacrylate, isobutyl acrylate). For cycloalkenes (Table 2, entries 10–12) different oxidation patterns were observed depending on the alkene

• 2l coming from the α-oxidation of the starting alkene. It is known that the product selectivity in the oxidation of cyclohexene could be influenced by the catalyst and reaction conditions (solvent, temperature, catalyst loading, oxidant) [14]. Based on our experimental observations and those

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

• , with an HMBC cross-peak between the aryl ring and the alkene moiety proving most illuminating (see Supporting Information File 1). The geometry of the double bond was determined from a NOE interaction between the alkene proton and the ring hydrogen atoms. This molecule could not however be detected by

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

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

• disubstituted alkene 13 in refluxing diglyme or triglyme at 190 °C (Scheme 7) [23]. The method has been widely used for the difluorocyclopropanation of allylic alcohol derivatives [24], steroids [25], and N-Boc-protected enamides [26]. Boron-substituted difluorocyclopropanes 16 can be also obtained from 12

• there was an opportunity to control the temperature, pressure, and to make the heat transfer more efficient [40]. The separate injection of a solution of the carbene precursor and of the alkene premixed with the activator did not lead to any improvement. Rullière et al. also tested this method on simple

• reaction of 54 with AlCl3 and an alkene at −20 °C (Scheme 22). The difluorocyclopropane 55 was obtained in 75% yield [63]. A bis(trifluoromethyl)zinc reagent was employed as the difluorocarbene source for the gem-difluorocyclopropanation of alkenes or alkynes via thermal decomposition [64]. The reagent was