Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• alkyl PdI-radical species 115 which could then react with 1,4-butadiene (116) to form hybrid allyl PdI complex 117. Subsequently, it was suggested that the species 117 would lead to the formation of a π-allylpalladium intermediate 118 through radical recombination. Ultimately, nucleophilic attack by the

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• -carbonyl-based Michael acceptors. Results and Discussion Synthesis During our endeavors to identify potent Lewis-base catalysts for the oxa-Michael reaction [13][14], the triarylphosphine 1 was tested in a model reaction (2 equiv allyl alcohol, 1 equiv acrylonitrile, 0.05 equiv 1). However, no conversion

• with allyl alcohol (in both cases using a molar ratio of 1:1.05 and dichloromethane as the solvent). While in the latter case only the starting materials were observed after 24 h at room temperature, the reaction of 1 with acrylonitrile turned yellow during the same time and exclusively yielded the

Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to C,N-diheteroarylcarbamidines

• Pavel S. Silaichev,
• Tetyana V. Beryozkina,
• Vsevolod V. Melekhin,
• Valeriy O. Filimonov,
• Andrey N. Maslivets,
• Vladimir G. Ilkin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2024, 20, 17–24, doi:10.3762/bjoc.20.3

• -triazole-4-carbimidamides with alkyl, allyl, propargyl, benzyl, cycloalkyl, and indolyl substituents at the N1 position . Keywords: Cornforth rearrangement; cycloaddition reactions; 3,3-diaminoacrylonitriles; heterocyclic azides; 1,2,3-triazole; Introduction Heteroaryl amidines are widely used in the

• previously unknown 5-amino-1-substituted 1,2,3-triazole-N-heteroaryl-4-carboximidamides 3 bearing alkyl, allyl, propargyl, benzyl, cycloalkyl, and various heteroaryl substituents at the N1 postion of the carbimidamide group. Herein, we disclose our results on the cycloaddition reaction of 3,3

• 1a–j, various substituents at the nitrogen were tolerated including aryl, (substituted) benzyl and alkyl substituents (including tryptamine, cyclohexyl, propargyl, and allyl) and furnished the N-heteroaryl amidines 3a–u in high or moderate yields (46–98%) (Scheme 2). There was no apparent substituent

Beyond n-dopants for organic semiconductors: use of bibenzo[d]imidazoles in UV-promoted dehalogenation reactions of organic halides

• Kan Tang,
• Megan R. Brown,
• Chad Risko,
• Melissa K. Gish,
• Garry Rumbles,
• Phuc H. Pham,
• Oana R. Luca,
• Stephen Barlow and
• Seth R. Marder

Beilstein J. Org. Chem. 2023, 19, 1912–1922, doi:10.3762/bjoc.19.142

• been used by Murphy’s group and others for a variety of transformations, such as the formation of indolines from N-allyl-2-iodoanilines [1], indanones from 3-(2-halophenyl)propanoic esters [2][3], and 3-methyl-2,3-dihydrobenzofuran from 1-allyloxy-2-halobenzenes [4]. Related species have also been used

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• ]isoquinolines. The reaction of 2-bromobenzaldehydes, 2-aminoisobutyric acid, and maleimides in MeCN under the catalysis of AcOH at 110 °C for 6 h afforded the cycloaddition products 26. The purified intermediates were used for the one-pot N-allylation with allyl bromide to afford intermediate 25 followed by a

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• functionalization of optically active polymers [106]. Theato and co-workers introduced vinyl/alkyne-bearing poly(vinyl ether)s [107], poly(vinylcyclopropanes) [108], and poly(allyl 2-ylideneacetate) [109] as promising new platforms compatible to thiol–ene chemistry. Atom transfer radical addition (ATRA) is another

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• the NHC–CuN(SiMe3)2 complexes 42, 45, and 48, respectively. All synthesized complexes were characterized by TGA to explain their thermal behavior. The impact of the N-allyl substituent and backbone character on volatility and thermal stability of the copper amides were investigated and it was found

• isomerization-induced alkenylation of electron-rich heteroarenes 187 and 188 utilizing allyl halides as reactants. The same catalyst system was found to effectively promote double-bond migration of the initially formed allylarenes resulting in vinylarene products. This method has been successfully used to

• functionalities, applicability to a wide range of heteroarenes and allyl halides, and high stereoselectivity (Scheme 71). The enantioselective C(sp2)–H allylation of (benz)oxazoles and benzothiazoles with γ,γ-disubstituted primary allyl phosphates catalyzed by NHC–Cu(I) complexes was reported by Ohmiya, Sawamura

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• from allyl alcohol (Figure 7) [82]. The Sharpless asymmetric epoxidation of allyl alcohol followed by tosylation produced glycidyl tosylate 7.1a (Figure 7). The reaction of palmityl alcohol (C16H33-OH) in the presence of a catalytic amount of BF3 open regio- and stereoselectively the epoxide to produce

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• benzothiazole, in which benzothiazole compounds have higher reactivity and regioselectivity than thiazole. In 2014, Lei et al. successfully realized the copper-catalyzed oxidative alkenylation of simple ethers to construct allyl ethers in the presence of di-tert-butyl peroxide and KI (Scheme 10) [60]. The

• afford allyl ethers. Alkyne C(sp)–H bonds are reactive, and the challenge in the cross-coupling of C(sp)–H and C(sp3)–H bonds is to control chemoselectivity. In this context, Liu et al. reported a Cu(I)/Ga(III)-catalyzed trityl ion-mediated direct CDC of the C(sp3)–H bond of THF with C(sp)–H bonds of

Metal catalyst-free N-allylation/alkylation of imidazole and benzimidazole with Morita–Baylis–Hillman (MBH) alcohols and acetates

• Olfa Mhasni,
• Jalloul Bouajila and
• Farhat Rezgui

Beilstein J. Org. Chem. 2023, 19, 1251–1258, doi:10.3762/bjoc.19.93

• , such alcohols were in situ converted into the corresponding O-allyl carbamates as leaving groups, followed by their reaction with imidazoles, affording the SN2’ products 3 (Scheme 1, reaction 1, iii). Correlatively, we have previously reported a direct amination of cyclic MBH alcohols 4 with morpholine

• ). Similarly, the five-membered acetate 5b reacted under the same conditions and gave the N-allyl-substituted imidazole 6b in 65% yield (Table 1, entry 2). Furthermore, treatment of the available secondary acetates 5c,d (R = Me) with imidazoles 2a and 2b (2 equiv) in refluxing toluene afforded the N

• biological evaluation [45][46][47] are underway in our laboratory. Experimental Typical procedure for the α-substitution of cyclic MBH adducts with imidazoles A mixture of allyl acetate 5a (2 mmol, 0.33 g) or allyl alcohol 4a (2 mmol, 0.25 g) and imidazole (2a, 4 mmol, 0.27 g) in toluene (25 mL) was heated

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• ]. Although not yet completely clarified, some previous studies on the detailed mode of closure of the C ring in ergot alkaloids from DMAT have been shown to involve, before decarboxylative cyclization, oxidation on the C4-prenyl chain to give the stable rearranged allyl alcohol and/or the relatively unstable

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• DFT calculation, a plausible mechanism (Scheme 10b) has been proposed. Initially, a reversible ligand-to-ligand H-transfer process occurs for C–H activation between the intermediates 46 and 47. Next, isomerization of the η1-allyl complex 47 forms the η3-allylic nickel complex 48, which on reductive

• . Subsequently, insertion of alkene 68 provides the cyclic Pd(II) intermediate 72 which undergoes β-hydride elimination to produce the desired product 69. In the same year, Ramana and Goriya [75] proposed an unexpected C-6 (C-2)-propenylation reaction of pyridine in the presence of allyl bromide (73) and a Ru

• catalyst using 2-arylpyridines (Scheme 15). Earlier reports described the propenylation took place on the ortho-position of the phenyl ring [76][77], whereas this group achieved the propenylation of the pyridine moiety. The authors screened different allyl halides and Ru complexes as catalysts. With the

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

• ) [77][78]. The allyl moiety in 144 allows for facile further functionalization. Amidation of the dihydrodibenzo[b,f]azepine (2a) derivatives with acyl halides 145 allowed for the introduction of variable length amide linkers by Kastrinsky et al. [3] (Scheme 33B). An industrial synthesis of opipramol (5

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

• bond formation through RCM reaction: Ring-closing metathesis (RCM) is an efficient strategy for the construction of common to large cyclic compounds via the formation of a C=C bond [26], which can be further reduced to a C–C bond. To prepare phostam-derived antitumor agents, ethyl N-allyl-N-(but-3-en-1

• -yl(4-phenoxyphenyl)phosphoryl)glycinate (1) and ethyl N-allyl-N-((4-ethoxyphenyl)(pent-4-en-1-yl)phosphoryl)glycinate (2) were prepared and cyclized into ethyl 2-(2-oxido-2-(4-phenoxyphenyl)-3,4,7-trihydro-1,2-azaphosphepin-1-yl)acetate (3) and ethyl 2-(2-(4-ethoxyphenyl)-2-oxido-3,5,8-trihydro-1,2

• 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

• ) [34]. Encouraged by this, they have also attempted an intramolecular tandem conjugate addition/Michael reaction sequence, which has resulted in the expected cyclization product 30 in a diastereopure form (Scheme 7B). Zinc enolates readily react with allyl iodides 31 or the structurally similar Stork

• enolate-trapping tandem sequence using various vinylsilanes 33 (Scheme 8B), allyl halides 35, and benzyl bromide (37) (Scheme 8C) [36]. Although the asymmetric conjugate addition step routinely provided excellent selectivity (93–96% ee), only a moderate to good diastereomeric ratio was achieved

• reagents required the presence of 1,3-dimethyltetrahydropyrimidine-2(1H)-one (DMPU) (Scheme 21). Reactive alkylating reagents such as iodomethane, benzyl bromide, allyl iodide, propargyl bromide, or bromoacetate reacted well and afforded the products 80 in good yields. In an attempt to expand the available

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• the reaction with tert-butyl-N-allyl carbamate 7g (1:6) while the reaction with allylcyclohexane resulted with the lowest yield (7f, 28%), probably due to the steric hindrance of the reagents. In the case of N-Boc-allylamine, improved diastereoselectivity might result from the coordination of the

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• into the C–O bond of the oxabicyclic alkene 30a to afford the σ-allyl intermediate 38 which can isomerize to the more stable π-allyl intermediate 39. Addition of the α-amino radical to the Ni(II) center generates the Ni(III) complex 41. Reductive elimination, followed by protodemetalation, leads to the

• state, followed by coordination to the alkyne generates intermediate 109. Migratory insertion of the alkyne results in the ruthenacycle 110. Subsequent reductive elimination generates putative allyl vinyl ether 111 and regenerates the active ruthenium complex. The allyl vinyl ether intermediate

• alkene of the azabicycle producing 154. A C–N bond cleavage occurs creating π-allylrhodium 155. Subsequently, the phenol oxygen then adds to the π–allyl species in a cis fashion, furnishing 156 which is proposed to be the enantiodetermining step. The carbonyl–rhodium species 156 inserts into the alkene

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

• 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

• 11 in 78% yield (Scheme 1). Due to easier purification, this alcohol was preferred to the aldehyde in our synthetic route, allowing a key stereoselective Krische allylation [21][22] to be envisaged. Applying reported conditions for this allylation – in presence of allyl acetate (10 equiv), [Ir(COD)Cl

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

• ) methoxide (102) underwent Ga‒O/B‒C exchange with allyl-Bpin 103 to give MeOBpin and an allylic gallium(I) species 104, which reacted with the oxocarbenium 103 to give the allylic ether 105 and regenerate the GaI catalyst 99 (Scheme 25). Using allenylBpin, the selective propargylation of acetals was also

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• this multistep process is initiated by the abstraction of diphosphate to produce an allyl cation that subsequently undergoes typical cation reactions such as cyclisations by intramolecular attack of an olefin to the cationic centre, Wagner–Meerwein rearrangements, hydride or proton shifts. The process

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

• give difficulties (Scheme 11a) [42]. The reactivity of the oxy-electrophiles can be enhanced by adding a Lewis acid catalyst such as titanium(IV) isopropoxide [59]. In this way, also epoxides can be smoothly reacted with lithiated dithiins, and both allyl and homoallyl alcohols can thus be prepared in

• this approach in a number of elegant stereocontrolled syntheses of polyhydroxy compounds and (derivatives of) natural carbohydrates, centering around Palumbo’s versatile building block 66 (Scheme 11c) [62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80]. The PMB-protected allyl

• -fused dihydrodithiin ring is first hydrodesulfurized and then dehydroxylated in a stereospecific and stereoselective manner [62]. The dihydrodithiin building block 66 thus acts as a synthetic equivalent of an allyl alcohol anion and serves as a versatile synthon for de novo carbohydrate synthesis [63

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• -Nazarov cyclization of the allyl-substituted imine substrate afforded α-methylene-γ-lactam product 19m in 56% yield. In our previous study, the relative stereochemistry of a tricyclic aza-Nazarov product obtained from a 3,4-dihydroisoquinoline derivative was secured by single-crystal X-ray analysis [35

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

• a semipinacol rearrangement leading to 95, followed by subsequent cyclization to natural products guignardone A (96) and C (97). This process involved 1,2-allyl migration and C–O bond formation through a semipinacol rearrangement and a cyclodehydration cascade reaction (Scheme 8). Following the same

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• carbanions of 1,3-dithiane [27], allyl [27], and methyldienylbenzene groups [31] to compound 2 were demonstrated, this result amounts to the first grafting of an aromatic nucleophile to the motif. The construction of the vicinal quaternary carbon of 6b was next investigated by methylation of the highly

• allyltitanocene reagents to carbonyl compounds was described by Sato which were prepared from the corresponding allyl carbonates exposed to the combination of [Cp2TiCl2]/n-BuLi [40]. Pleasingly, conducting the coupling of carbonate 20 to 5 in conditions inspired from Carreira’s study (Scheme 7b) led to the