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

• disclosed a visible light-mediated radical tandem cyclization of N-arylacrylamides with N-(acyloxy)phthalimides to access 3,3-dialkylated oxindoles in the presence of [Ru(bpy)3Cl2]·6H2O [46]. However, these seminal methods remain limited by the need of noble-metal-based photocatalysts, excess additives and

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• natural products was accessed in a single step from 145 through a scalable tandem [4 + 2]–[3 + 2] cascade in 74–84% yield in gram-scale quantities, known from previous studies [77]. Compound 145 was readily prepared in four steps from N-benzyltryptamine and 4-(2-t-butyldimethylsilyloxy)pent-4-enoic acid

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• synthetic route based on a convergent strategy to accomplish the synthesis of principinol E, grayanotoxin III and rhodomollein XX [34]. The key steps include i) a tandem reaction combining organocatalytic Mukaiyama aldol and intramolecular Hosomi–Sakurai reactions in a one-pot manner; ii) a 7-membered

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

• Anastasia Vepreva,
• Alexander Yanovich,
• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• (Figure 1). Herein, we report on a successful realization of this strategy. Results and Discussion To test the possibility of a tandem double cycloaddition reaction between 1, an alkyne-containing amine and an azide-containing aldehyde, we set up a reaction of 1 with o-azidobenzaldehyde (3a) and

• ]bis([1,2,3]triazolo)[1,5-a:1',5'-d][1,4]diazepine (5a), i.e., the product of the tandem three-component 1,2,3-triazole synthesis followed by intramolecular azide–alkyne click reaction which, apparently, proceeded at room temperature. Product 5a was isolated in respectable 78% yield; therefore, the

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• ][19][20][21]. Among them, triarylbismuth dichlorides (Ar3BiCl2) have been widely used as aryl group donors for the C- and O-arylation of phenol derivatives [22][23][24], N-arylation of pyridin-2-ones [25][26], α-arylation of α,β-unsaturated carbonyls [27][28], and tandem 1,3-bisarylation of

Ionic multiresonant thermally activated delayed fluorescence emitters for light emitting electrochemical cells

• Merve Karaman,
• Abhishek Kumar Gupta,
• Subeesh Madayanad Suresh,
• Tomas Matulaitis,
• Lorenzo Mardegan,
• Daniel Tordera,
• Henk J. Bolink,
• Sen Wu,
• Stuart Warriner,
• Ifor D. Samuel and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2022, 18, 1311–1321, doi:10.3762/bjoc.18.136

• to 3.08 eV compared to that of DiKTa-OMe (3.74 eV). The excited states were modelled using spin-component scaling second-order approximate coupled-cluster (SCS-CC2) in tandem with the cc-pVDZ basis set (Table S1 in Supporting Information File 1). Figure 2b shows the difference density plots for

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

• ) should be a key intermediate for this tandem reaction. On the basis of the above mechanistic studies and the previous works on iodide-mediated electrochemical transformation [37][38][39][40], a possible mechanism for this electrochemical reaction was proposed (Scheme 5). It is well known that amino acid

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• furnished a chiral thiosquaramide-catalyzed tandem Michael–Henry reaction of phenacylmalononitriles and nitroolefins for the enantioselective synthesis of cyclopent-3-ene-1-carboxamides [32] (reaction 2 in Scheme 1). Mohanan and co-workers reported a PBu3-catalyzed [3 + 2] annulation of

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• - and stereoselectivities in the tandem intramolecular nucleophilic dearomatization of diphenyl-N-alkyl-N-benzylphosphinamides and reactions with different electrophiles under various reaction conditions [47]. They used both racemic and enantiopure diphenyl-N-methyl-N-(1-phenylethyl)phosphinamides 124

• minor diastereoisomeric epimer in the phosphorus atom was also isolated in less than 8% yield (Scheme 23) [48]. The authors further performed detailed mechanistic investigations experimentally and theoretically [49][50]. Dinaphth-1-yl-N-alkyl-N-benzylphosphinamides 134 were also applied to the tandem

Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications

• Sadanobu Iwase,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2022, 18, 872–880, doi:10.3762/bjoc.18.88

• bearing a perfluoroalkyl or perfluoroacyl group [27][28][29][30]. Furthermore, they extended this methodology to tandem cyclization to provide fused difluoromethylene-containing heterocycles [31]. In consideration of these facts, we studied the cathodic reduction of 1 using a mediator. Indirect cathodic

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• their applications in the biological and pharmaceutical fields. The Cu-catalyzed tandem reaction for the synthesis of novel alkynyl imidazopyridinyl selenides is presented. A one-pot synthesis route afforded alkynyl imidazopyridinyl selenides in moderate to good yields. This was achieved by a two-step

• reagents and 1,3-dipolar azide–alkyne cycloaddition based on the alkyne moiety. Keywords: alkynyl imidazopyridinyl selenide; copper catalyst; imidazo[1,2-a]pyridine; selenium; tandem reaction; terminal alkyne; Introduction Imidazo[1,2-a]pyridines are important heterocycles that serve as key functional

Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity

• Jamshid Amiri Moghaddam,
• Huijuan Guo,
• Karsten Willing,
• Thomas Wichard and
• Christine Beemelmanns

Beilstein J. Org. Chem. 2022, 18, 722–731, doi:10.3762/bjoc.18.72

• presence of Mg2+ as co-factor. Product formation was monitored after 2 h using high-resolution tandem mass spectrometry (HRMS/MS). Membrane proteins obtained from E. coli BL21 cultures harboring the empty expression pET28 plasmid were used as negative control (Figure S3 in Supporting Information File 1

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• heated flow system [65][66][67][68][69][70][71]. This is exemplified for the tandem synthesis of benzofuran 47 and phenylindole 48 (Scheme 10, case B) starting from phenol 44 and aniline derivative 46, respectively. The latter reaction was carried out in a glass reactor filled with MagSilicaTM [53

DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• practice by applying the strategies like domino, cascade, or tandem [11][12][13]. These environmentally friendly approaches set forth the journey of facilitating sustainable systems by using mechanochemical methods to access small organic compounds [3]. Due to the high reduction potential of the quinone

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• dispirocyclopentanebisoxindoles from two molecules of 3-phenacylideneoxindoles, accomplished by reduction of one molecule of 3-phenacylideneoxindole by thiol [24]. In 2017, Thennarasu et al. [25] reported the tandem oxidation/Michel-aldol reaction of 3-phenacyloxindoles for the synthesis of dispirocycliopentanebisoxindoles

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• -caprolactam moiety. Since the splitting pattern of the corresponding proton signals is consistent with 1, the lactam nitrogen must be hydroxylated in 2. Tandem MS data is consistent with this assumption (Figure 3). Compound 3 (1.8 mg) was isolated as a clear oil. Its molecular formula was established as

• next to the ε-amino group in the lysine moiety. The assumption of a hydroxylamine function is consistent with tandem MS data, which showed mass shifts of 16 Da in the corresponding region in comparison to compound 3. Compound 5 (0.7 mg) was obtained as a clear oil. Its molecular formula of C36H53N5O10

• conditions. The structures of these natural products were verified by high-resolution mass spectrometry, tandem mass spectrometry as well as 1D and 2D NMR analyses. Their absolute configuration is consistent with the already known amamistatin B according to a comparison of optical rotation values and NOE

Synthesis of 5-unsubstituted dihydropyrimidinone-4-carboxylates from deep eutectic mixtures

• Sangram Gore,
• Sundarababu Baskaran and
• Burkhard König

Beilstein J. Org. Chem. 2022, 18, 331–336, doi:10.3762/bjoc.18.37

• -unsaturated ketoesters, such as (E)-ethyl 4-(4-nitrophenyl)-2-oxobut-3-enoate (17), afforded the corresponding 5-unsubstituted DHPM derivative 18 in good yield (entry 6, Table 1). Similarly, heteroaromatic aldehyde derived ketoester 21, also underwent the tandem reaction to give the corresponding 5

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• -cd]indoles 21 from the intramolecular cyclization of Ugi adducts 20 in moderate to good yields and excellent chemo-, regio-, and diastereoselectivity (Scheme 7) [17]. Mechanistically, the reaction involves a tandem gold(I)-catalyzed dearomatization/ipso-cyclization/Michael addition sequence to

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• -substituted iodobenzenes catalyzed by in situ-generated α-Fe2O3 nanoparticles. One-pot synthesis of 2-arylbenzo[b]furans via tandem Sonogashira coupling–cyclization protocol. Suggested mechanism of the Fe(III) catalyzed coupling of o-iodophenol with acetylene derivatives. Fe3O4@SiO2/Schiff base/Fe(II

Tenacibactins K–M, cytotoxic siderophores from a coral-associated gliding bacterium of the genus Tenacibaculum

• Yasuhiro Igarashi,
• Yiwei Ge,
• Tao Zhou,
• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku and
• Agus Trianto

Beilstein J. Org. Chem. 2022, 18, 110–119, doi:10.3762/bjoc.18.12

• remaining four methylenes (H6, H7, H8, H9) were not assignable from the NMR data due to signal overlapping, but were expected to be placed between the isohexyl and the alkenyl fragments, thus establishing an isopentadecenoyl moiety. The connectivity between this aliphatic chain to the tandem

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

• reported [53]. In 2015, Kang and co-workers described a FeCl2-catalyzed tandem cyclization/cross-coupling reaction of alkyl iodides 1 with aryl Grignard reagents 2 to give arylmethyl-substituted pyrrolidines and tetrahydrofurans 3 in poor to excellent yield (Scheme 3) [54]. The concept of alkyl halide

• tandem cross-coupling reactions was first introduced by Fürstner in 2004 who disclosed specific iodoalkanes with pendant olefins undergo cyclization prior to the anticipated cross-coupling with Grignard reagents [55]. This has since been recognized by a number of other reports, indicating a SET process

• byproducts were detected which supports the absence of an initial oxidative addition between the alkyl iodide and the active Fe catalyst. The possibility of a radical process rather than ionic cross-coupling is supported by the tandem cyclization/cyclopropyl ring-opening reaction, similar to previous reports

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

• important C1 synthon. Its special reactivity, such as the ability to react with electrophilic, nucleophilic, and radical reagents [25][26][27][28], determines that it can participate in many types of reactions such as multicomponent reactions [29][30][31][32], tandem reactions [33][34], and insertion

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• asymmetric aza-Michael reaction (aza-MR) alone or in tandem with other organic reaction(s) is an important synthetic tool to form new C–N bond(s) leading to developing new libraries of diverse types of bioactive nitrogen compounds. The synthesis and application of a variety of organocatalysts for

• high enantioselectivities (up to 65–91%) [40]. Rajasekar et al. developed an efficient one-pot tandem rhodium(II)/chiral squaramide relay catalysis for the enantioselective construction of dihydro-β-carbolines 37 from the Michael reaction of suitably substituted indole derivatives 34 with N-sulfonyl

• tertiary amine-thiourea catalyst (cat. 82). This cascade reaction afforded aza-Michael adducts in 77–92% yields with high ee (up to 90%) (Table 19) [55]. Du et al. developed an enantioselective catalytic tandem aminolysis/aza-Michael addition for the asymmetric total synthesis of two natural Apocynaceae

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• , tandem reactions, and the total synthesis and biosynthesis of natural products. This review explores the use of α-ketol rearrangements in these contexts over the past two decades. Keywords: acyloin rearrangement; asymmetric synthesis; iminol rearrangement; ketol rearrangement; tandem reactions

• reactions through mid-2002 have been thoroughly discussed in a past review by Paquette [1]. The current review expands on that work by providing an updated account from mid-2002 through early 2021, including the following recently developed applications: asymmetric synthesis, total synthesis, tandem

• . Subsequent methanolysis yields α-hydroxy-β-ketoamide 23 (Figure 6). The overall reaction occurs diastereospecifically, with greater than 80% yield across each of 5 distinct amide derivatives [8]. Tandem α-ketol rearrangements Because α-ketol rearrangements can be initiated by simple reagents like a Brønsted