Efficient synthesis of ethyl 2-(oxazolin-2-yl)alkanoates via ethoxycarbonylketene-induced electrophilic ring expansion of aziridines

• Yelong Lei and
• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 70–76, doi:10.3762/bjoc.18.6

• alcohols [13][14][15] (Scheme 1a); (3) oxidative condensation of aldehydes with vicinal amino alcohols [16] (Scheme 1b); (4) cyclization of N-allylamides in the presence of electrophilic reagents or radical initiators or catalysts [17] (Scheme 1c); (5) direct synthesis from alkenes and amides or nitriles

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

• initiated, the reaction will propagate, which typically involves the insertion of a π-system (carbometallation of alkenes/alkynes) in the case of organoiron species (Scheme 2). Alternatively, the generated radical species may undergo radical addition to alkenes, alkynes, or aromatic arenes. The final step

• reaction. In the same year, the Gutierrez Lab reported the first three-component 1,2-dicarbofunctionalzation of alkenes 21 (Scheme 5) [66]. The authors noted π-systems bearing O- and S-heteroatoms had little to no compatibility with the transformation as well as sterically hindered Grignard reagents 2

• addition is paramount, this method is currently limited to the use of a large excess of olefins; however, activated alkenes could circumvent this requirement. In 2016, the Deng group studied a novel double carbomagnesiation of unsymmetrical internal alkynes 31 with alkyl Grignard reagents 32 producing 1,3

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

• combination of acidic α-carbon atoms, isocyano groups, and sulfonyl moieties [18]. In general, TosMIC undergoes base-mediated 1,3-dipolar cycloadditions with activated alkenes to provide pyrroles as products [18] (Scheme 1A). Recently, alternative functionalizations using TosMIC as a tosyl source of

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

• ][40] including from properly functionalized arenes and alkenes [41][42][43][44][45][46][47][48][49][50][51][52][53]. In the case of such substrates having oxygen-containing functional groups, PIFA attacked the double bond first [41][42][43]. With unsaturated amides or hydroxamates, oxidation of the

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• terminal alkenes bearing both an allylic and homoallylic-type hydroxy group, yielding a sole threo isomer, are rare [36]. The cyclization of 5 through an epoxide ring-opening reaction with boron trifluoride etherate in dichloromethane at 0 °C yielded pyrrolidine derivative 12 in 69% isolated yield [37

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• elimination as opposed to styrenyl selectivity. In addition, the methacrylates were used as allyl surrogates to overcome the reactivity problem caused by steric hindrance of 1,1,-disubstituted alkenes, and the electron-withdrawing esters enhance the migratory insertion to form palladacycle I-2. The CPA

• generates the chiral environment and played a crucial role in favoring of atropisomerism. A series of axially chiral biaryl-2-amines with 1,1-disubstituted alkenes 17 was efficiently synthesized in moderate to excellent yields (42–96%) with excellent enantioselectivities (up to >99% ee). 2. Enantioselective

• chiral phosphoric acids in the preparation of centrally chiral compounds, their application in the synthesis of axially chiral biaryls and heterobiaryls, axially chiral allene, atropisomeric aryl alkenes, and spirane moieties is still quite limited. Given the increasing importance of axially chiral

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

• thiocyanate to generate 4-alkyl/aryl-2-aminothiazoles. Mechanistic experiments demonstrated that the photocatalyst formed in situ from Cu(OAc)2 and ammonium thiocyanate promoted the intermolecular cyclization (Scheme 7). 3.2 Difunctionalization of alkenes The 1,2-difunctionalization of alkenes is a versatile

• strategy for the construction of complex molecules. The primary process involved in the 1,2-difunctionalization of alkenes catalyzed by copper complexes is an atom-transfer radical addition (ATRA). Copper complexes or copper-based photoredox-active complexes formed in situ serve as photocatalysts to

• -catalyzed trifluoromethylchlorosulfonylation of unactivated alkenes 4 under photochemical conditions. When used in place of [Cu(dap)2]Cl, ruthenium-based, iridium-based, and eosin Y catalysts promoted the trifluoromethylchlorination of alkenes with the extrusion of SO2 (e.g., product 6). Studies were

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

• alkoxide. Keywords: alkenes; aziridines; epoxides; lithiation; synthetic methods; Introduction Methods for the convergent generation of alkenes can be of significant utility in organic synthesis [1]. A relatively under-examined approach is through the interaction of two carbenoids [2]. Dimerisation of

• (Scheme 1). The eliminative cross-coupling of carbenoids can provide a way to unsymmetrical alkenes, provided the differential reactivity of the two carbenoids is suitably matched [2]. In the current letter, we report preliminary results on the latter strategy to form alkenes which possess an allylic

• -carbon homologation of an epoxide to an allylic alcohol (cf Scheme 3) can also be achieved using excess dimethylsulfonium methylide [12][13], although non-terminal alkenes have not been shown to be directly accessible by higher homologation. To examine the latter in the context of the current chemistry

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

• )-salt-mediated cyclization reactions. The generalized mechanism for cyclization reactions are, alkenes/alkynes 1 initially react with Hg(II) salts (HgX2) leading to the formation of a mercurial carbonium ion 2 followed by the attack of an intramolecular nucleophile giving rise to a cyclized mercuro

• –halide complex compound 3 (Scheme 1). Review Cyclization reactions involving stoichiometric amounts of Hg(II) salts Cyclization involving alkenes (>C=C<) In 1900 and 1901, the Sand and Biilmann group had first reported the Hg(II)-mediated cyclization of allyl alcohol using Hg(II) nitrate (Hg(NO3)2) in

• with HgCl2 (0.5 equiv) in presence of N-bromosuccinimide (NBS) undergoes cyclization yielding stable bromo alkenes 87 (Scheme 28) [80][81]. Atta et al. reported the specific cyclization of ethynyl phenols 88 in presence of HgCl2 at ambient temperature yielding benzofuran derivatives 89. They had

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

• reaction, TIPS-protected ynones, ynoates, and ynamides smoothly transformed into the corresponding trisubstituted alkenes 63 in high regio- and stereoselectivities. A possible mechanism was proposed similar to the one shown in Figure 15 to account for the observed high regioselectivity. Allylation The

• substrates 65 and the amide substrates 64. However, the role of the nickel catalyst in this process and the reaction mechanism pathway were not fully established. The photoredox nickel-catalyzed allylation of α-amino C(sp3)–H bonds with trifluoromethylated alkenes 68 has been more recently achieved by Martin

• alkanes 16, alkenes 92, and aryl bromides 3 (Scheme 48) [140]. Here, TBADT enables the generation of alkyl radicals from various alkane substrates via a HAT process under near-ultraviolet light irradiation. Both cyclic and linear alkanes were found to be suitable under the reaction conditions. Linear

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