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

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• addition (if X = H) or proton cleavage in the case of X = OH. Amine mediators are also suitable for the generation of radical species from CH-acidic substrates, such as β-dicarbonyl compounds. This reactivity was used in the dehydrogenative annulation of N-allyl amides with β-dicarbonyl compounds with the

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• incompatibility with electron-withdrawing substituents can be attributed to lower nucleophilicity of the phenoxide ion and structural instability of the product, which could lead to unexpected reactions of 2h and 2i during the reaction or purification process. Phenols with allyl or vinyl substituents (3j and 3k

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

• reagents [22][23] to these substrates was uneventful and allowed for the preparation of 2-furylalkyl (see 3a–c, 4c), -aryl (see 5c, 6c), and -allyl carbinols (see 7c) having furan rings with various triorganosilyl substituents at C3 in a synthetically useful yield and on an appropriate scale (Scheme 2

• [25], afforded only the addition product 3b without any detectable formation of product 9, expected from 1,4-silyl migration/electrophilic substitution of 8 (Scheme 4, top). Conversely, treatment of alcohol 3a with t-BuOCu in the presence of allyl chloride, according to conditions developed by Takeda

• -methylfuryl carbinols. As such, products 23 and 24, arising from phenyl- and allyl-substituted substrates 6c and 7c, respectively, were isolated in 56% and 65% yield, respectively. Somewhat lower yields were noted with butyl- and phenyl-substituted carbinols 3c and 5c, respectively, bearing C5-unsubstituted

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

• reacted smoothly with thiourea 2a under the optimized conditions, giving the corresponding products in 30–80% yields (3a–d). In addition, allyl and benzyl acetoacetate were also suitable substrates to give the desired 2-aminothiazoles 3e and 3f in 78% and 52% yields, respectively. β-ketoesters containing

Electrogenerated base-promoted cyclopropanation using alkyl 2-chloroacetates

• Kouichi Matsumoto,
• Yuta Hayashi,
• Kengo Hamasaki,
• Mizuki Matsuse,
• Hiyono Suzuki,
• Keiji Nishiwaki and
• Norihito Kawashita

Beilstein J. Org. Chem. 2022, 18, 1116–1122, doi:10.3762/bjoc.18.114

• with the vinyl group did not occur (Table 3, entry 7), but the reaction of compound 15 with the allyl group formed 16 in 34% yield (Table 3, entry 8). Finally, benzyl 2-chloroacetate (17) produced the corresponding compound 18 in 31% yield (Table 3, entry 9). The current electrolysis reaction can be

Electrochemical hydrogenation of enones using a proton-exchange membrane reactor: selectivity and utility

• Koichi Mitsudo,
• Haruka Inoue,
• Yuta Niki,
• Eisuke Sato and
• Seiji Suga

Beilstein J. Org. Chem. 2022, 18, 1055–1061, doi:10.3762/bjoc.18.107

• reactor; Introduction Catalytic hydrogenation of α,β-enones is a significant transformation in organic synthesis [1]. Hydrogenation of enones can give ketones, allyl alcohols, and saturated alcohols, and the control of the chemoselectivity is important. Therefore, there have been numerous studies on the

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

• be seen that the C–C double bond is connected to two methoxycarbonyl groups. Though one hydroxy group exists on the reactive allyl position and benzyl position, it still is present in the molecule and did not give the cyclopentadiene by further elimination of water. In order to obtain the

Understanding the competing pathways leading to hydropyrene and isoelisabethatriene

• Shani Zev,
• Marion Ringel,
• Ronja Driller,
• Bernhard Loll,
• Thomas Brück and
• Dan T. Major

Beilstein J. Org. Chem. 2022, 18, 972–978, doi:10.3762/bjoc.18.97

• -phase calculations commenced with geranylgeranyl cation (A and A’) in a fully extended form. HP pathway The HP gas-phase pathway commences with a C1–C10 cyclization, which yields cation B, which is more stable than A by −11.4 kcal/mol. A subsequent 1,3-hydride transfer results in an allyl cation (C

• yields cation B’, which is more stable than A’ by −15.7 kcal/mol. A subsequent 1,3-hydride transfer results in an allyl cation (C’, −32.1 kcal/mol relative to A’), with a barrier of 5.4 kcal/mol. Cation C’ collapses into D’ via a barrierless 1,6-ring closure (ΔGr of −35.9 kcal/mol relative to A’). D’ can

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

• group and the nature of its terminal substituents (aromatic phenyl and aliphatic isopropyl) are the crucial factors impacting the diastereoselectivity. Generally, the substrates with bulky R and aromatic phenyl terminal substituent in their allyl groups gave rise to the desired 1,5-dihydro-1,2

• intramolecular nucleophilic dearomatization and protonation or electrophilic alkylation reactions, affording the corresponding dihydronaphthylene-fused γ-phosphinolactams 135–142. Methanol was used as the electrophile for protonation, while methyl iodide and allyl bromide were used as electrophiles for

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• excellent chemical trap for detecting parent cyclopropene. Having carried out the experiment with ylide 1 as a trap in a similar fashion, we found that PRP (1) is unreactive towards parent cyclopropene (2p) under these conditions. Cyclopropene 2p, generated in situ from allyl chloride [41] and driven into a

A trustworthy mechanochemical route to isocyanides

• Francesco Basoccu,
• Federico Cuccu,
• Federico Casti,
• Rita Mocci,
• Claudia Fattuoni and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 732–737, doi:10.3762/bjoc.18.73

• straightforward procedure. Keywords: green chemistry; isocyanide; isonitriles; mechanochemistry; Introduction Isocyanides were first discovered more than a century ago by Lieke in Göttingen after having handled allyl iodide and potassium cyanide to synthesize crotonic acid. This attempt, instead, brought to the

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• spin density is distributed over C13–C15. The allyl radical at C15 reacts with a second molecular oxygen to afford the C15 peroxyl radical. Finally, the transfer of a hydrogen atom from the catalytic Tyr385 residue quenches the C15 peroxyl radical to yield PGG2 and a tyrosyl radical for the next round

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

• temperature of the nanostructured particles (Figure 4B). The Claisen rearrangement of the electron-deficient aryl allyl ether 9 was chosen to compare the versatility and performance of inductive heating with conventional and microwave heating (Scheme 8A) [50]. The effectiveness of inductive heating is clearly

• comparable to microwave-induced heating. In continuation of these studies a two-step sequence was developed which showed that Claisen rearrangements can be accelerated in water as solvent (Scheme 8B) [51]. The phenolate salt 11 was mixed with allyl bromide in a static mixer and inductively heated to 110 °C

• at 110–160 bar to form the O-allyl phenol which was heated in a second reactor to 265 °C where the Claisen rearrangement under near-critical conditions occurred to yield 2-allyl-4,6-difluorophenol (12) in 64% yield. In this example, the two reactors made of steel were heated directly by the external

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

• indoline ring was also investigated. Varieties of N-protected (Me, Et, propyl, benzyl and allyl) 3-phenacylideneoxindoles were used and provide good to excellent yield of the dimerized products (Scheme 2, Scheme 3). During the detailed study of the reaction, we conducted the reaction with 2-(2-oxindole-3

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• ), p-cresol (2f), 4-methoxyphenol (2g), 4-bromophenol (2h), 4-allyl-2-methoxyphenol (2i) are commercial reagents. Commercially available starting materials were used without further purification. The structures of synthesized products have been proven by 1H, 13C and 2D (NOESY, 1Н,13С HSQC, 1Н,13С HMBC

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

• constructing carbon–carbon and carbon–heteroatom bonds in organic synthesis [8][9][10]. In the course of their diversity-oriented synthesis of indole-based peri-annulated compounds, You and co-workers in 2013 reported the intramolecular Tsuji–Trost reaction of indolyl allyl carbonates 1 under the catalysis of

• cyclization of β-carbonyl sulfoxonium ylides 34a,b in the presence of K2CO3 to access cyclopenta[e]indol-6-ones 35a,b in moderate yields (Scheme 12) [23]. The authors proposed that under the experimental conditions β-carbonyl sulfoxonium ylides 34a,b were isomerized to IV which then produced oxy-allyl cation

• or annulation of: (A) substituted arenes/heteroarenes and (B) 3,5-unsubstituted, 4-substituted indoles. Indole C3 regioselective intramolecular alkylation of indolyl allyl carbonates. Indole C3 regioselective Michael-type cyclization in the total synthesis of (−)-indolactam V. Synthesis of azepino

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• suitable protected linear precursor A (Scheme 2, PG: protecting group), the resulting carboxylic acid obtained can directly be activated and subjected to cyclization. If the glycine allyl ester is incorporated as the last building block into the C-terminus of the peptide, this concept should provide a high

• approach, 1 was mono-O-allylated to 2 under similar conditions reported previously for monobenzylation (Scheme 3) [50]. Iodination (3) and subsequent elimination of the iodide with zinc dust gave allylic alcohol 4 as a single enantiomer, which was esterified with Boc-protected glycine to allyl ester 5

• the peptide can have a significant effect on the Claisen rearrangement and therefore we synthesized the Cbz- as well as the Boc-protected peptides 8a and 8b. The tripeptide building blocks were previously also used in the Cyl-1 synthesis. Glycine allyl ester 5 was Boc-deprotected to give amine 7 as

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

Ligand-dependent stereoselective Suzuki–Miyaura cross-coupling reactions of β-enamido triflates

• Tomáš Chvojka,
• Athanasios Markos,
• Svatava Voltrová,
• Radek Pohl and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 2657–2662, doi:10.3762/bjoc.17.179

• isomerization of N-allyl amides [20], but still possess drawbacks, especially for stereoselective synthesis of tri- and tetrasubstituted enamides. Recently, we have reported a triflic acid-mediated reaction of N-fluoroalkyl-1,2,3-triazoles leading to (Z)-β-enamido triflates [21] and Lewis acid-mediated reaction

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

• with aryl iodides to generate intermediate D, which then undergoes reductive elimination to generate the desired products (Scheme 23). In 2017, Evano’s group [55] established a photoinduced, copper-catalyzed C–C cross-coupling of aryl halides, and heteroarenes. The cyclization of N-allyl-o-iodoanilines