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

• for the allylation of aldehydes promoted by a dual catalytic system comprising CrCl3 and an iridium-based photocatalyst that was recently developed by Schwarz and co-workers [119]. Similar conditions were further employed to synthesize monoprotected 1,2-homoallylic diols from aldehydes and silyl and

• full agonists (54 and 55, Scheme 20A) [139]. Ackermann and co-workers presented a manganese(I)-catalyzed C–H allylation, installing α,β-unsaturated esters in peptide analogues bearing indole motifs (Scheme 22B) [140]. Starting with tryptophan, the enantioselective allylation reaction afforded the

• product (98% yield) (Scheme 20C). More complex structures like dipeptides and substrates containing multiple Lewis-basic functionalities also presented good yields and chemoselectivities with this protocol. The robust allylation reaction was tested in even more complex structures, including steroid

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

• ruled out. Manganese-catalyzed late-stage C–H allylation The late-stage modification of peptides has received increasing attention due to the convenient and efficient modality. However, such protocols generally require substrate prefunctionalization and expensive metal catalysts, such as Pd [66][67][68

• ][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87], Rh [88][89][90][91], and Ru [92][93]. In 2019, the Ackermann group demonstrated that a manganese(I) catalyst enabled the late-stage C–H allylation of structurally complex peptides in a site-selective fashion (Scheme 10) [94

• ]. Based on an initial optimization study, manganese(I) pentacarbonyl bromide was deemed as the optimal catalyst, enabling a robust racemization-free allylation process. In addition to tryptophan-containing peptides, diazepam and nucleoside analogues were found to be viable allylation substrates, affording

Design, synthesis and photophysical properties of novel star-shaped truxene-based heterocycles utilizing ring-closing metathesis, Clauson–Kaas, Van Leusen and Ullmann-type reactions as key tools

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2021, 17, 1374–1384, doi:10.3762/bjoc.17.96

• -allylation sequences, which in turn was assembled from the commercially available 1-indanone (1) utilizing cyclotrimerization and subsequent alkylation reactions. On the other hand, the same compound 6 was generated form triaminotruxene 4 using three-fold Clauson–Kaas reaction which in turn was assembled

• , compound 2 was subjected to nitration followed by reduction to deliver triaminotruxene 4 in excellent yield. Later, compound 4 was subjected to six-fold N-allylation in the presence of NaH/allyl bromide to provide the required compound 3 which was directly treated with G-I catalyst (9) to afford the

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

• applicability of sulfinyl imines was also shown by Garcia Ruano and co-workers. (SS)-tert-Butanesulfinyl imine 17b provided better diastereoselectivity to obtain aziridines 18b than (SS)-tert-butanesulfinyl imine 17a to obtain aziridines 18a (Scheme 7) [65]. Allylation of N-tert-butanesulfinyl imines 14 with

• , when the allylation was performed in the presence of indium metal, in a saturated aqueous solution of sodium bromide, a mixture of the bromoallylation and allylation products 25 and 26, respectively, were obtained [69]. The addition of the allyl unit to the imines proceeded with total facial

• )-configuration. Excellent diastereoselectivities were also achieved in the indium-mediated allylation of chiral tert-butanesulfinyl glyoxylate imine derivatives 87 with ethyl 2-bromomethylacrylate (88). Working at room temperature without any additional solvent provided the highest yields in these coupling

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

• of indium metal to produce homoallylic alcohol 156 (Scheme 37), which underwent a silyl-Prins cyclization to form polysubstituted exo-methylene THPs 157 [72]. Tandem allylation–silyl-Prins cyclization Tetrahydropyran can also be synthesized stereoselectively by sequential allylation to an aldehyde

• , followed by silyl-Prins cyclization of the resulting homoallylic alcohol. For illustration, a facile enantioselective strategy for the synthesis of cis-2,6-disubstituted 4-methylenetetrahydropyran 161 (91% yield, dr = 5:1) was reported by Yu et al, utilizing, first, asymmetric allylation of an aldehyde by

• strain with the existing stereogenic center (pseudoaxial group), leading to the formation of cis-tetrahydropyran 161 rather than a trans-tetrahydropyran. Floreancig and co-workers utilized a tandem allylation–silyl-Prins cyclization strategy to afford 2,6-disubstituted tetrahydropyran 167 by ionizing α,β

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

•  27). It is worth noting that EDA complex has been firstly employed for the generation of alkoxy radicals under visible-light irradiation, achieving selective C(sp3)–C(sp3)-bond cleavage and allylation or alkenylation. In 2017, Li and colleagues [57] reported a reaction for the synthesis of

• iodide anion (Scheme 30). Various β-naphthols with different substituents in the 1- and 3-positions were tolerated, providing the corresponding products with excellent yield. In 2018, Chen and colleagues [18] reported a method to realize C(sp3)–H allylation by generating aryl carboxyl radical from EDA

• 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

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

• nitrone. Murahashi synthesis – 2000 Starting from secondary amines, Murahashi et al. developed a method for preparing homochiral β-sulfinyl nitrones [41]. Accordingly, (+)-euphococcinine (2) was prepared through allylation followed by the 1,3-dipolar cycloaddition of β-sulfinyl nitrone 20 derived from

• tetroxide and potassium periodate, to provide (−)-adaline (1) and (−)-euphococcinine (2). Originally, Yu et al. synthesized (−)-adaline (1) with good yields and high enantiomeric excess using catalytic asymmetric allylation from commercially available 58. Additionally, intramolecular allylic transfer led to

• acids as catalysts for C-allylation of unprotected oximes with allyl boronates [58]. After screening to find the best reaction conditions, oxime 103 was converted to α-tertiary acetal-protected hydroxylamine (±)-104 in the presence of 3,5-difluorophenylboronic acid and diisopropyl allyl boronate (108

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

• adduct 105 in 93% yield with 99% ee. The freshly prepared enantioenriched adduct 105 was subjected to ozonolysis [47] followed by decarboxylation to give bisoxindole 106 in 68% yield over two steps. Conversion of 106 to the corresponding acetal and subsequent allylation afforded 108 in 86% yield over two

• and AIBN to a refluxing solution of cyclopropane 155 afforded 156 in 38% yield. It was subjected to cleavage of the Boc group followed by N-allylation to give 157 in 73% yield over two steps. A ring-closing metathesis of freshly prepared 157 was effected by the second generation Hoveyda–Grubbs (HG II

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

• Tetsuya Sengoku,
• Koki Makino,
• Ayumi Iijima,
• Toshiyasu Inuzuka and
• Hidemi Yoda

Beilstein J. Org. Chem. 2020, 16, 2769–2775, doi:10.3762/bjoc.16.227

• 501-1193, Japan 10.3762/bjoc.16.227 Abstract New synthetic methods for spirolactams bearing an α-methylene-γ-butyrolactone or its analogous methylene-lactam have been developed. The allylation of γ-phenylthio-functionalized γ-lactams with 2-(acetoxy)methyl acrylamides was accomplished by using 2.5

• yields. On the other hand, methylene-lactone-fused spirolactams could be delivered from the allyl adducts in high yields through a sequential N-Boc protection/desulfinative lactonization. Keywords: bifurcated synthesis; electrophilic amide allylation; α-methylene-γ-butyrolactam; α-methylene-γ

• -lactone derivatives spiro-fused to an oxindole (A), one of which exhibited a potent cytotoxic activity [9]. Our research group succeeded the enantiopure synthesis of these compounds, in which enantioselective allylation of an isatin derivative with an amido-functionalized allylstannane was employed as a

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• N-tosyl group was removed and the resultant amine protected to give the N-Boc tetrahydropyran 31. The Koide group had originally attempted the reduction–allylation–ionic reduction sequence on the Boc-protected amine 32, however, this gave lower overall yields due to the competing formation of a

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

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• imine-derived CF3-containing enyne, bearing the trifluoromethylethynyl group at the ortho position (Scheme 16) [55]. One of the key steps in the preparation of the starting 1,n-enynes was a highly diastereoselective allylation reaction of chiral Ellman’s sulfinylimines. Based on this strategy, chiral

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• Two kinds of [3 + 2] cycloaddition intermediates generated from the three-component reactions of 2-bromobenzaldehydes and maleimides with amino esters or amino acids were used for a one-pot N-allylation and intramolecular Heck reactions to form pyrrolidinedione-fused hexahydropyrrolo[2,1-a

• via sequential 1,3-dipolar cycloaddition, N-allylation, and intramolecular Heck cyclization reactions [50][51][52][53][54] (Scheme 2, K). Both stabilized and non-stabilized azomethine ylides could be used for the initial [3 + 2] cycloaddition. A multicomponent reaction was combined with one-pot

• with 2-bromobenzaldehydes 3 and maleimides 4 (Scheme 3) [30][37]. The cycloaddition reactions were diastereoselective (>20:1 dr for adducts 5 and >6:1 dr for adducts 6). The major diastereomers of 5 and 6 were isolated for following N-allylation and intramolecular Heck reactions. Adduct 5a generated

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• a suitable Michael acceptor 24.2 to obtain the corresponding allylation product 24.3 after a desulfonylation. Enones can also be subject to SET reductions through photoredox catalysis, and this can lead to [2 + 2] cycloadditions [2][108]. Similar intermediates can also be generated through the

Photocatalytic deaminative benzylation and alkylation of tetrahydroisoquinolines with N-alkylpyrydinium salts

• David Schönbauer,
• Carlo Sambiagio,
• Timothy Noël and
• Michael Schnürch

Beilstein J. Org. Chem. 2020, 16, 809–817, doi:10.3762/bjoc.16.74

• ], alkynation [17][18], or allylation [19]), this method has certain drawbacks, most importantly the frequent requirement of superstoichiometric amounts of an oxidant. Hence, alternative methods were investigated and photoredox catalysis proved to be a viable option [20][21][22]. By now, several different

• reaction time was kept at 6 h, or was even shortened to 3 h for 6,7-dimethoxy-N-phenyl-THIQ (products 37 and 38). Allylation of the unsubstituted phenyl-THIQ was again more efficient compared to the dimethoxylated substrate. Based on previous reports [45][47][52], we propose the following mechanism for the

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

• -metal-catalyzed transformations were needed to achieve the total synthesis of des-epoxy-amphidinolide N, including a palladium asymmetric allylic alkylation (Pd-AAA), a Mukaiyama aldol reaction (with Sn), and a Krische allylation (with Ir) [72]. As special feature of this procedure, an Evans aldol

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• catalysts in a similar transformation [17]. In another study, Reiser and co-workers described a related allylation process of organic halides with allyltributyltin in the presence of [Cu(I)(dap)2]Cl as the catalyst [16]. This reaction was applied to a broad range of substrates, including a para-nitrophenyl

• allylation reaction using the [Cu(I)(dpp)(binc)]BF4 complex (Scheme 16) [32]. The reaction of α-bromomalonates with allyl- and crotylsilanes afforded the allylated products in good yields. To explain the reaction outcome, the authors suggested a reduction of the α-bromomalonate by the excited Cu(I) complex

• allylation of α-haloketones. [Cu(I)(dap)2]Cl-photocatalyzed chlorosulfonylation and chlorotrifluoromethylation of alkenes. Photocatalytic perfluoroalkylchlorination of electron-deficient alkenes using the Sauvage catalyst. Photocatalytic synthesis of fluorinated sultones. Photocatalyzed

Allylic cross-coupling using aromatic aldehydes as α-alkoxyalkyl anions

• Akihiro Yuasa,
• Kazunori Nagao and
• Hirohisa Ohmiya

Beilstein J. Org. Chem. 2020, 16, 185–189, doi:10.3762/bjoc.16.21

• ) afforded the linear allylation product 3aa with complete regioselectivity. The symmetric secondary allylic carbonate was converted to the corresponding homoallylic alcohol derivative in 50% yield (3af). To gain understanding into the mechanism of this synergistic palladium/copper-catalyzed allylic cross

Rapid, two-pot procedure for the synthesis of dihydropyridinones; total synthesis of aza-goniothalamin

• Thomas J. Cogswell,
• Craig S. Donald and
• Rodolfo Marquez

Beilstein J. Org. Chem. 2020, 16, 135–139, doi:10.3762/bjoc.16.15

• described above. Rewardingly, Hosomi–Sakurai allylation of the conjugated imine intermediate proceeded to afford the desired diene 10 in working yield (35%). The formation of diene 10 is significant as the corresponding α,β-enones and α,β-enals undergo exclusive conjugate addition under Hosomi–Sakurai

Indium-mediated C-allylation of melibiose

• Christian Denner,
• Manuel Gintner,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2019, 15, 2458–2464, doi:10.3762/bjoc.15.238

• Christian Denner Manuel Gintner Hanspeter Kahlig Walther Schmid Institute of Organic Chemistry, University of Vienna, Währinger Straße 38, A-1090, Vienna, Austria 10.3762/bjoc.15.238 Abstract The indium-mediated allylation reaction has been applied to melibiose, a disaccharidic substrate. This

• the elongated unit at the reducing end of the disaccharide. Keywords: carbohydrates; C–C bond formation; indium-mediated allylation; melibiose; ozonolysis; Introduction The tin and indium-mediated allylation (IMA) proved to be useful synthetic tools for the chain elongation of unprotected

• reported for the first time a tin-mediated allylation of unprotected carbohydrates followed by ozonolysis allowing for easy accessibility of the corresponding elongated sugars [2]. In the same year, Chan and Li introduced indium for the allylation of aldehydes and furthermore demonstrated the applicability

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• intermediates, building blocks 4 and 5 (4, R = Me and 5, R = CH2CH2Ph) were synthesized starting with allyldioxazaborolidine 11, an allyl-transfer reagent that was prepared as previously reported (Scheme 3) [27]. Allylation of methyl pyruvate (12) or 13 (synthesized from dimethyl oxalate and phenethylmagnesium

Switchable selectivity in Pd-catalyzed [3 + 2] annulations of γ-oxy-2-cycloalkenones with 3-oxoglutarates: C–C/C–C vs C–C/O–C bond formation

• Yang Liu,
• Julie Oble and
• Giovanni Poli

Beilstein J. Org. Chem. 2019, 15, 1107–1115, doi:10.3762/bjoc.15.107

• -2-cycloalkenones, simply differing on the reaction temperature, are disclosed. These domino transformations allow C–C/O–C or C–C/C–C [3 + 2] annulations at will, via an intermolecular Pd-catalyzed C-allylation/intramolecular O- or C-1,4-addition sequence, respectively. In particular, exploiting the

• -one bis-nucleophiles. Keywords: 1,4-addition; annulation; decarboxylation; palladium; Pd-catalyzed allylation reaction; Introduction The development of new strategies for the synthesis of complex carbocyclic and heterocyclic structures remains a general topic for the synthetic chemists [1]. In the

• , resonance-stabilized acetamides and cyclic α,β-unsaturated-γ-oxicarbonyl derivatives are used as bis-nucleophile and bis-electrophile partners, respectively. This process involves an intermolecular Pd(0)-catalyzed C-allylation (Tsuji–Trost reaction)/intramolecular nitrogen 1,4-addition sequence (Scheme 1