Dissecting Mechanochemistry III

• Lars Borchardt and
• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1454–1456, doi:10.3762/bjoc.18.150

• Margetić used dibrominated polycyclic imides as substrates to generate reactive alkenes, which could be trapped in situ by several dienes through Diels−Alder cycloadditions by ball milling (Scheme 3) [7]. Further, Moores and co-workers synthesized phosphorus-bridged heptazine-based carbon nitrides (g-h-PCN

• . Mechanochemical palladium-catalyzed borylation protocol of aryl halides. 1,2-Debromination of polycyclic imides, followed by in situ trapping of the dienophile by several dienes. Synthesis of g-h-PCN from sodium phosphide and trichloroheptazine mediated by mechanochemistry. Mechanochemical intra- and

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• reported extensive studies on the regio-and stereoselectivity of nitroso Diels–Alder reactions between various nitroso derivatives and functionalized dienes [23]. These studies led to the selection of enol phosphates as ketone precursors for the diene functionalization. Enol phosphates display several

• , we have shown that the Wightman reagent 6, a chiral chloronitroso derivative [27], led to a complete regio- and stereoselective reaction with functionalized dienes (Scheme 1). The chiral auxiliary contributes to both regioselectivity and stereoselectivity. After hydrolysis of the chiral auxiliary and

Dienophilic reactivity of 2-phosphaindolizines: a conceptual DFT investigation

• Nosheen Beig,
• Aarti Peswani and
• Raj Kumar Bansal

Beilstein J. Org. Chem. 2022, 18, 1217–1224, doi:10.3762/bjoc.18.127

• dienophiles and undergo Diels–Alder reactions with 1,3-dienes. However, the dienophilic reactivity is affected by the nature of the substituent groups on the two sides of the σ2,λ3-P atom and also by the presence of more nitrogen atom(s) in the five-membered ring. The conceptual density functional theory (DFT

Copper-catalyzed multicomponent reactions for the efficient synthesis of diverse spirotetrahydrocarbazoles

• Shao-Cong Zhan,
• Ren-Jie Fang,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 796–808, doi:10.3762/bjoc.18.80

• -methylindole utilizing CuSO4 as the catalyst in toluene at 110 °C. The desired product 4a was obtained in 82% with excellent diastereoselectivity (dr > 20:1). In this reaction, both dienes (o-QDMs) and dienophiles were in situ formed from the starting material. As shown in Scheme 4b, a wide range of aromatic

• '-indolines] 2a–h, in which the two phenyl groups exist in cis-position. This result clearly indicated that this reaction has a similar outcome of stereochemistry. Based on the success of the four-component reaction through in situ generation of dienes and dienophiles, we further considered whether more

• -known 3,3'-(arylmethylene)bis(2-methylindoles) 6. Conclusion In summary, we have developed a copper-catalyzed multicomponent Diels–Alder reaction of 2-methylindole, aromatic aldehydes and cyclic 1,3-diones through in situ generated dienes and dienophiles under the same conditions. These strategies are

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• can be highly beneficial. Therefore, Skowerski and co-workers constructed a tube-in-tube reactor for the ring-closing metathesis of dienes 62 and 63 to macrocycles 65 or 66, respectively, mediated by ruthenium catalyst 64 (Scheme 15) [53]. The substrate and the catalyst are mixed in a Q-piece and

• cyclohexanone in flow. Synthesis of macrocyclic olefine 60 by ring-closing metathesis of diene 58 in a continuously stirred tank reactor (CSTR). Synthesis of macrocycles 65 and 66 by ring-closing metathesis of dienes 62 or 63, respectively, in a tube-in-tube reactor removing the formed ethylene. Z-Selective

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

• Petar Štrbac and
• Davor Margetić

Beilstein J. Org. Chem. 2022, 18, 746–753, doi:10.3762/bjoc.18.75

• was replaced by the Zn/Cu couple which was prepared without any metal activation by in situ ball milling of zinc and copper dusts. The advantage of the ball milling process is that the whole procedure is operationally very simplified. The reactive alkene generated was trapped in situ by several dienes

• polycyclic molecules given in Figure 1 are interesting reactive intermediates which could be applied in the Diels−Alder reactions of less reactive or thermally susceptible dienes. Often, these are generated in situ and trapped with dienes in a single pot, such as 7-oxanorbornadiene imides 1–3. For instance

• its synthetic utility were investigated employing various dienes such as furan (18), 1,3-diphenylisobenzofuran (24) (DPIBF) and substituted anthracenes 31, 36 and 39 (Figure 3). Exclusive norbornene exo-π selectivity [24] was observed in all cycloadddition reactions. Selected five-membered dienes were

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

• the synthesis of chemical reagents with an endoperoxide bridge have been reported [77][78]. The classical method for endoperoxide synthesis is through cycloadditions of dienes and alkenes, using singlet oxygen. Furthermore, cyclizations of hydroperoxides with pendant alkenes or alkynes have also been

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• -nitro-1H-pyrazoles bearing a dichloromethyl and an amino or thio moiety at C3 and C5 has been prepared in yields up to 72% from the reaction of 1,1-bisazolyl-, 1-azolyl-1-amino-, and 1-thioperchloro-2-nitrobuta-1,3-dienes with 7-chloro-4-hydrazinylquinoline. A new way for the formation of a pyrazole

• acid. The next step of our investigation was the two-step synthesis of persubstituted aminopyrazoles 5 upon reaction of the benzotriazolyl derivative 2c with primary, secondary, aliphatic, or (het)aromatic amines (first step) and successive reaction of the obtained dienes 4 with 7-chloro-4

• -hydrazinylquinoline. Thus, the reaction of compound 2c with methylamine, 1,2,3,4-tetrahydroisoquinoline, 1-methyl-1,2,3,4-tetrahydroisoquinoline, (2-fluorophenyl)methylamine, and 5-methylisoxazolyl-3-amine proceeded smoothly under mild conditions (methanol, 0 °C to rt), similarly to the previously obtained dienes 4b

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• reaction, among pericyclic reactions, is a very important synthetic approach to obtain several molecular scaffolds, including naturally occurring molecules, drugs, polymers, and heterocycles with promising biological activity. Especially, Diels–Alder reactions involving quinones and dienes as starting

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• . Contemporaneously, the Rebek group illustrated another interesting site-selective monoepoxidation of α,ω-dienes mediated by the water-soluble cavitand host E (Figure 10) [71]. The α,ω-dienes were determined to adopt a yo-yo motion between two J-shaped conformations or the rapid tumbling of a coiled conformation

• . Site-selective monoepoxidation of α,ω-dienes mediated by the water-soluble cavitand host E. Site-selective ring-opening reaction of epoxides mediated by cavitand I with an inwardly directed carboxylic acid module. Site-selective nucleophilic substitution reaction of allylic chlorides mediated by cage

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

• ]. The group expanded the reaction to include 1,6-dienes 24 leading to 25 via the formation of three C–C bonds through a radical cyclization/arylation cascade, like that reported by Kang et al. (Scheme 3). The authors hypothesized the alkyl halide could react with aryl iron species 27 to form the alkyl

• Echeverria demonstrated a mechanistically distinct protocol for the synthesis of 1,3-dienes 36 (Scheme 7) [72]. Compared to previous Fe-catalyzed carbomagnesiation reactions (Scheme 6) where carbometallation occurs in a concerted syn-manner this protocol, instead, is initiated by the oxidative cyclization of

• Cheng investigated the cascade cyclization of dienes 119 with alkyl carbazates 117 for the synthesis of fused nitrogen heterocyclic compounds 120 (Scheme 25) [117]. Diene substrates possessing EDGs reacted smoothly under the optimized conditions while their electron-deficient counterparts delivered the

Efficient synthesis of polyfunctionalized carbazoles and pyrrolo[3,4-c]carbazoles via domino Diels–Alder reaction

• Ren-Jie Fang,
• Chen Yan,
• Jing Sun,
• Ying Han and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2021, 17, 2425–2432, doi:10.3762/bjoc.17.159

• , simple manufacture, high efficiency and atomic economy. The unusual feature of this reaction is the normal electron-demand Diels–Alder reaction between electron-deficient dienes such as (3-(indol-3-yl)maleimides and indole-chalcone to electron-deficient dienophilic chalcones. The potential applications

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• ) produces trans-2,5,5,9-tetramethylhexahydrochromene (53) while the cis-cyclized product was formed from cis-isoprenoid derivatives. Later, Hoye et al. used similar reaction conditions to cyclize dienes 54 with 1.1 equiv of Hg(TFA)2 to yield endocyclic enol ether 55 in almost quantitative yield [66]. They

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• oxidation of 1,3-dienes 159 and aroyl-substituted propiolates 160 (Scheme 36) [70]. Subsequently, the authors performed an intramolecular Friedel-Crafts cyclization of the corresponding derivatives 161 by using concentrated sulfuric acid. The authors noted that the more electron-donating alkyl or methoxy

• metathesis strategy to synthesize benz[a]anthracenes. Green synthesis of oxa-aza-benzo[a]anthracene and oxa-aza-phenanthrene derivatives. Triple benzannulation of substituted naphtalene via a 1,3,6-naphthotriyne synthetic equivalent. Zinc iodide-catalyzed Diels–Alder reactions with 1,3-dienes and aroyl

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• substrates will be reviewed, so electron-deficient olefins like Michael acceptors and even conjugate dienes will not be included in this review. Some examples of hydroallylation reactions have been included since these reactions, like hydroalkylation reactions, also form a new C(sp3)–C(sp3) bond at the

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

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

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

• Ramazan Koçak and
• Arif Daştan

Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61

• reaction conditions. Inverse electron-demand Diels–Alder reactions are cycloadditions between electron-rich dienophiles and electron-poor dienes. EDGs raise the electron density of dienes and, in parallel, raise the LUMOdiene–HOMOdienophile energy gap, and consequently the reactivity decreases. Although

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• Chemistry, Russian Academy of Sciences Leninsky prosp. 47, Moscow 119991, Russian Federation Department of Chemistry Johannes Gutenberg-University, Duesbergweg 10–14, D-55128 Mainz, Germany 10.3762/bjoc.17.27 Abstract The Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic 1,3-dienes was

• mol−1 for endo-1h and 121.75 kJ mol−1 for exo-1h and were consistent with the predicted ones. Next, the reaction with some other cyclic dienes was investigated. The reaction with the unsymmetrical 1-methoxy-1,3-cyclohexadiene (Scheme 5) led to the formation of a mixture of four products (regioisomers

• (H5 or H6) and its coupling constant to fluorine (3JH5-F or 3JH6-F). The reaction with 7- and 8-membered cyclic dienes (1,3-cycloheptadiene and 1,3-cyclooctadiene) did not result in the formation of the corresponding cycloadducts confirming that the reaction is very sensitive to the structure of the

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• radical 127. Itoh et al. discovered the generation of 1,6-dienes 129 via the ring opening of bromomethyl-bearing gem-difluorocyclopropanes 130 due to the reaction with allyltributylstannane in the presence of AIBN (Scheme 56) [105]. The ring opening of the intermediate cyclopropylmethyl radical occurred

• with a cleavage of the distal C–C bond. The reaction proceeded regioselectively and in high yields. There was no difference observed between cis and trans-isomers in terms of the reactivity and yields. The resultant dienes 129 were used in ring-closing metathesis reactions to furnish gem

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

Formation of an exceptionally stable ketene during phototransformations of bicyclo[2.2.2]oct-5-en-2-ones having mixed chromophores

• Asitanga Ghosh

Beilstein J. Org. Chem. 2020, 16, 2297–2303, doi:10.3762/bjoc.16.190

• groups were bulkier than the earlier reported one. Results and Discussion 5,6-Dibenzoyl-4-phenylbicyclo[2.2.2]oct-5-en-2-one (7a) and 5,6-dibenzoyl-4-isopropenylbicyclo[2.2.2]oct-5-en-2-one (7b) have been prepared through Diels–Alder reaction between substituted silyloxycyclohexa-1,3-dienes 8a and 8b [17

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• , an excess of sodium thioalkoxide in 1,3-dimethyl-2-imidazolidinone 98 reacted with 94 at 100 °C to generate the required sumanene derivatives 99a–c. In another report, Sakurai’s group in situ generated sumanyne and treated it with different dienes (101a–d) in a Diels–Alder (DA) manner to produce the

• further reaction with dienes furnished the DA-adducts 102a–d. In 2012, another type of functionalized sumanene, namely tris(ethoxycarbonylethenyl)sumanene 108 was prepared by Sakurai's group through ROM–RCM as well as Horner–Wadsworth–Emmons (HWE) reactions as key transformations (Scheme 26) [59]. To this

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• consider the reactivity of the electrophilic (“electron-poor”) acetylenic bond toward 1,3-dienes, and show how the expected [4 + 2] or [2 + 2] cycloaddition products can enter subsequent cascade reactions toward carbocycles which incorporate a C(CF3)NMe2 structural unit. Results and Discussion The Diels

• presumably renders an ionic [2 + 2] cycloaddition pathway competitive with the Diels–Alder reaction. The few reported examples of cyclobutene formation from alkynes and unactivated 1,3-dienes include the sensitized photocycloaddition of phenylacetylene and DMBD [30] and the gold(I)-catalyzed reaction of

• -substituted iminium groups with electron-rich (hetero)aromatics are known [18][24]. Furthermore, 1-(trifluoromethyl)indenes have recently been generated by cationic cyclization of β-aryl trifluoromethyl enones under superacid conditions [42][43][44]. Styrenes are also known to behave as dienes in [4 + 2