Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• first reported synthesis of imipramine (3) by Schindler and Häfliger [76] proceeded by alkylation of 2a by alkyl halides. Selected N-alkylations of 1a and 2a are included in Scheme 33. N-Allylation of 1a or 2a with allyl bromide (143) can be achieved by a base-promoted substitution reaction (Scheme 33A

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• synthesis of 1,2-oxaphosphaheterocycle 2-oxides. tert-Butyl 2-(bis(allyloxy)phosphoryl)pent-4-enoate (11) generated tert-butyl 2-(allyloxy)-3,4,7-trihydro-1,2-oxaphosphepine-3-carboxylate 2-oxide (12) in excellent 94% yield in the presence of the Grubbs catalyst in DCM. After further allylation with allyl

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• -mediated epimerization. Guénée et al. described the allylation, benzylation, and propargylation of magnesium enolates. These enolates were generated by a Cu-NHC-catalyzed conjugate addition of Grignard reagents to β-substituted cyclic enones (70) (Scheme 19) [51]. Fox and co-workers developed an intriguing

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• analogue synthesis, starting from (+)-β-citronellene. Key stereoselective transformations involve an asymmetric Krische allylation, an aldol reaction under 1,5-anti stereocontrol, and a Tishchenko–Evans reduction accompanied by a peculiar ester transposition, allowing to install key stereogenic centers of

• the natural products. Keywords: allylation; aldol reaction; latrunculins; stereocontrol; total synthesis; Introduction Latrunculins constitute a class of marine polyketide natural products isolated from Sponges like Negombata (= Latrunculia) magnifica [1][2]. They are characterized by the presence

• formed by the oxidation of an allyl moiety introduced by the asymmetric allylation of an aldehyde derived from (+)-β-citronellene. At this stage, we can speculate that the stereocontrol of this reaction could either follow a polar Felkin–Anh model [14][15][16] based on chiral aldehyde partner 8 [17], or

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• their anti-inflammatory activity (see Section 3). Reaction of compounds 166 and 167 gave the corresponding diaryl ether 168, which was converted to phenol 169 using a Baeyer–Villiger oxidation reaction followed by hydrolysis. Subsequent phenol allylation reaction followed by Claisen rearrangement led to

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• of allenes, using various boronates as the terminal reductant (Scheme 5) [68]. Experimental and computational studies suggested the reaction proceeded by hydroboration of the allene 14 by bis(pentafluorophenyl)borane to give an allylborane 15, which underwent allylation of a second equivalent of the

• to give aldol-type products 61. Thomas reported the borane-catalysed diastereo- and enantioselective allylation of ketones with allenes and HBpin to give diastereo- and enantioenriched allylic alcohols, after workup (Scheme 15) [78]. The mechanism was investigated by single-turnover experiments and

• isotopic labelling and proposed to proceed by hydroboration of the allene 62 by the borane catalyst (H-B-9-BBN or 10-phenyl-9-borabicyclo[3.3.2]decane [Ph-BBD]) followed by rapid isomerisation from the (Z)-63 to (E)-allylborane 64 which underwent allylation of the ketone 65 to give an allylic borinic ester

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• cation in (3 + 2) cycloadditions: 5,6-dihydro-1,4-dithiin-2-methanol as a stabilized allyl cation Allyl cations are versatile electrophiles for the allylation of various nucleophiles, but can also act as C3-π-systems in a range of cycloaddition reactions (Scheme 13) [84][85][86][87][88]. When combined

• (viz 106) was formed. In part, this was found to be due to decomposition (and self-condensation reactions) of the dimethylthio-substituted allyl alcohol 105. However, also the minor adducts that were formed with the olefins were shown to be mixtures of exclusively non-cyclic allylation products of the

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

• allylation using achiral H-PHOX followed to produce 16, without being isolated. From this point of divergence, Baran’s group managed to reveal the requisite phthalimide carboxylates for each precursor of the diverse natural products and transformed it carrying out Giese reactions or nickel-catalyzed radical

• further oxidized, and thus producing the respective benzylic cation. Intramolecular cyclization in the cationic position under participation of the methyl ester function provided the core for (+)-grandilodine C (191) and (+)-lapidilectine B (192), while allylation of the benzylic position allowed

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• -catalyzed cross-coupling reactions, such as arylation reactions catalyzed by Pd2(dba)3/CuI, as well as allylation and methylation reactions catalyzed by CuI⋅PPh3. C3-Benzyldimethylsilyl-appended furfurals are thus introduced as versatile platforms, providing a modular access to 3-substituted 2-furyl

• requirement for copper prompted us to test copper-catalyzed C(sp2)–C(sp3) cross-coupling reactions, as reported by Takeda et al., to achieve allylation reactions of benzyldimethyl(alkenyl)silanes [36]. Treatment of 4c with methallyl chloride in the presence of TBAF⋅(t-BuOH)4 (2.4 equiv), CuI (1.5 equiv), and

• furan rings, which gave products 25 and 26 in 42% and 40% yield, respectively. Electrophiles other than methallyl chloride could also be used. C3-Allylation of substrate 4c, leading to 27, was achieved in 52% yield by reaction with allyl chloride and in a better 61% yield using allyl bromide. It should

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

• consisting of O-allylation and Claisen rearrangement for the continuous synthesis of 2-allyl-4,6-difluorophenol (SiC = silicon carbide) [52]. Continuous flow reactions and comparison with batch reaction (oil bath). A. Pd-catalyzed transfer hydrogenations using ethanol in cyclohexene [53], B. multicomponent

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

• tolerates a variety of substituents in both 22 and 23. From a mechanistic point of view, the reaction proceeds through a domino azomethine ylide formation/allylation/Pictet–Spengler reaction sequence. Recently, An and Xiao and co-workers disclosed high-yielding syntheses of a wide range of indole-3,4-fused

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

• interactions with the substrates. Moreover, the SPA ligand loading of 1 mol % is effective for this reaction under mild conditions [50]. Moreover, Shi, Lin and co-workers reported the first Pd(II)-catalyzed directed atroposelective C–H allylation of 2-(naphthalen-1-yl)aniline derivatives 14 with methacrylates

• atroposelective C–H allylation. Enantioselective synthesis of axially chiral (a) aryl indoles and (b) biaryldiols. Asymmetric arylation of indoles enabled by azo groups. Proposed mechanism for the asymmetric arylation of indoles. Enantioselective synthesis of axially chiral N-arylindoles [38]. Enantioselective [3

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

• alkylation Under mild conditions, copper salts are able to catalyze olefinic C–H functionalization or allylic alkylation, thus allow introducing alkenyl or allyl groups into organic molecules. Alkenylation and allylation reactions have been extensively investigated under thermal conditions. However, only few

• studies included visible-light catalysis. In 2012, Reiser’s group [44] reported the allylation of α-haloketones 1 with olefins under irradiation (λ = 530 nm) in the presence of [Cu(dap)2Cl] (dap = 2,9-di(p-anisyl)-1,10-phenanthroline) as the catalyst. They conducted control experiments to establish that

• [Cu(dap)2Cl] and visible light are necessary for this transformation. In 2013, Ollivier and co-workers [45] successfully applied the same strategy to the allylation of diphenyliodonium 2. In 2017, Liu’s group [46] reported the copper salt-catalyzed cyclization of vinyl azides 3 with ammonium

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• in the reaction to give the allylation products in 26–91% yields. The developed method provides a straightforward and operational simple strategy for the allylic functionalization of 2-alkypyridine derivatives. Keywords: 2-alkylpyridines; allylic alkylation; aza-Cope rearrangement; catalyst-free

• pyridylic C(sp3)–H bond (Scheme 1b). For examples, Tunge et al. developed a Pd-catalyzed intramolecular decarboxylative coupling of heterocyclic ally esters via a tandem allylation/Cope rearrangement strategy [18]; Hartwig and co-workers reported a stereo-divergent allylic substitution with azaarene

• reported C(sp3)–H allylic substitution reactions were mainly applied on the 2-alkyl-azaarenes containing strong electron-withdrawing groups. While the reactions with inactive alkyl-aza-arenes were rare [30][31]. Kim et al. have reported a K2CO3-promoted one-pot allylation reaction of 2-alkylpyridines with

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• ferrocenes with alkynes by using an unprecedented half-sandwich Sc catalyst [36]. Very recently, Shi and Zhang demonstrated a Cp*Co-catalyzed ortho-C–H allylation of ferrocenes assisted by thioamide using allyl carbonates and vinylcyclopropanes as allylating partners [37]. Meanwhile, Zhang and co-authors

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• Jin’s one step dihydroxylation–oxidation protocol using a NaIO4/(cat.) OsO4 system. Allylation of the resulting aldehyde 74 was best performed under Brown’s protocol at low temperature utilizing a chiral allyl reagent prepared from allylmagnesium bromide and (+)-B-chloro-diisopinocampheylborane. By this

• ). The olefin moieties can be installed via stereoselective allylation and cinnamic acid esterification of 94, which is derived from symmetrical alcohol 95. The right-hand side portion of this molecule can be constructed by epoxidation of the allylic alcohol derived from α,β-unsaturated ester 96 and the

• ether 94 (90%) and the PMB ether was cleaved to liberate the primary alcohol. After being oxidized with IBX, the aldehyde 103 was isolated in 68% yield over two steps. Application of the asymmetric Brown’s allylation afforded 104 in 80% yield (dr 95:5) that was readily esterified to its cinnamate ester

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• . Enantioselective tail-to-head cyclization of neryl chloride derivatives. Cation–π interactions in anion binding-catalyzed asymmetric addition reactions: a) addition of indoles to pyrones and b) allylation of α-chloro glycinates. Bisthiourea catalyzed oxa-Pictet–Spengler reaction of indole-based alcohols and

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

• transition-metal-catalyzed direct allylation of unactivated C–H bonds is considered as the prevalent strategy in organic synthesis. Despite significant advances were accomplished in the allylation of (hetero)aromatic and alkenyl C(sp2)‒H bonds [109], related reactions of C(sp3)–H are less explored [110][111

• ]. In this context, Tambar developed a δ-selective C(sp3)–H allylation of aliphatic amides 64 using allyl chlorides 65 under visible light photoredox nickel catalysis (Scheme 34) [112]. The optimized reaction conditions exhibited good tolerance to a variety of substitutions on the allyl chloride

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