Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• the alkyl hypochlorite IIa. The second mechanism (path b) requires a direct ligand exchange of I-OH with the alcohol and subsequent β-elimination of the alkoxy(hydroxy)iodane IIb to form the desired aldehyde 4. Conclusion In conclusion, this study has successfully introduced N-heterocycle-stabilized

• was investigated, potentially leading to the formation of a hydroxy(chloro)iodane intermediate. This intermediate either liberates hypochlorous acid as the terminal oxidant or undergoes a direct ligand exchange with the alcohol, followed by oxidative elimination to form the aldehyde. Thus, these

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• homo- and heteropolymeric forms. The 1,4-O-linkage in alginate is cleaved by alginate lyases, in a β-elimination manner (Figure 3). Alginate lyases can be either endolyases, or exolyases with preference for polyM or polyG present in the alginate matrix [110]. Alginate lyases have been isolated from

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• predominately considered to be stable to isolation conditions, secondary and tertiary suffer from the elimination of HF, especially in the presence of silica gel or glass vessels. Therefore, benzyl fluorides have been derivatised, for example in C–O, C–N and C–C bond-forming reactions [18][19][20], thereby also

• pervasive in organic synthesis and can also be used to efficiently fluorinate benzylic C(sp3)–H bonds. The general blueprint for this transformation follows a metal insertion into the C(sp3)–H bond followed by C–F reductive elimination [11][22][38]. In 2006, Sanford and co-workers published a seminal and

• palladacycle intermediate, defining the stereochemical outcome. Subsequent oxidation to the Pd(IV)–F species, which triggered reductive elimination, afforded the fluorinated product. The non-innocent behaviour of the isobutyrylnitrile co-solvent aided in stabilising the palladacycle through occupying the

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• then extrude CO2 to generate the alkyl radical. Concurrently, Cu(II)–CN species are produced in the presence of cyanide anion through anodic oxidation. At this stage, Cu(II)–CN species are believed to capture alkyl radicals and the product would be readily generated via reductive elimination from the

Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain

• Changjun Xiang,
• Shunyu Yao,
• Ruoyu Wang and
• Lihan Zhang

Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131

• obscured by the following dehydration by the DH domain. It is widely believed that an α,β-trans (E) double bond is generated from a ᴅ-β-hydroxy intermediate produced by a B-type KR, whereas a cis (Z) double bond is from an ʟ-β-hydroxy intermediate generated by an A-type KR via syn elimination [21]. However

• , based on the syn-elimination mechanism, the ʟ-α-methyl,ʟ-β-hydroxy substrate produced by A2-type KR can also result in a trans (E) double bond [18][22], and some DH domains are reported to have epimerase activity on the α-substitution [23]. Thus, the stereochemical outcomes of KRs in γ- and δ-modules

• been investigated in several DH domains, which all follow the syn-elimination mechanism [5][21][33]. Based on the product configuration, we classified DHs into two types, E-type DHs (trans-double bond) and Z-type DHs (cis-double bond) and analyzed sequence logos of the DH-associated KRs. The sequence

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• study began with the preparation of the (E)-2-arylidene-3-cyclohexenones 2 via DMAP-catalyzed elimination reaction of 2-cyclohexenone-MBH alcohols 1 and di-tert-butyl dicarbonate [22] as depicted in Scheme 2. Starting materials 2 were prepared in moderate to high yields. Next, we chose (E)-2

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• catalytic cycle. Similar to what was previously observed, the elimination of the trichloro(alkoxy)ferrate(III) anion from intermediate C provides the iminium ion D, susceptible to nucleophilic attack by a water molecule present in the reaction medium, leading to the carbinolamines 6. This latter synthesis

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• accessed from the respective amines or organohalides (5 and 6, Scheme 1) [14][16][17][18]. Few examples of triazole–pyrazole hybrids, such as 13, have also been synthesized through a modified Sakai reaction [19], a reaction cascade involving the elimination of an azole [20] or in the n-butyllithium

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• electron density, which facilitates a π–π interactions with the aryl iodide system and ultimately results in the production of an electron donor–acceptor (EDA) complex 21. Photoexcitation of this EDA complex furnishes an aryl iodide radical anion and a radical cation complex 22. Then, the elimination of

• excited-state photocatalyst oxidizes the cesium alkyl oxalate via SET, followed by elimination of two carbon dioxide molecules, generating a tertiary alkyl radical that easily combines with an electron-deficient alkene, providing the product. This protocol was well compatible with a wide range of acceptor

• mechanism involves C–O bond activation of tertiary oxalates. It requires [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 and NiCl2⋅DME along with dtbbpy ligand. The reaction commences with single-electron oxidation of cesium oxalate initiated by *[Ir(III)] photocatalyst. This transfer leads to the elimination of two CO2

Rhodium-catalyzed homo-coupling reaction of aryl Grignard reagents and its application for the synthesis of an integrin inhibitor

• Kazuyuki Sato,
• Satoki Teranishi,
• Atsushi Sakaue,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai,
• Hiroyuki Takeda,
• Tatsuo Kinashi and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 1341–1347, doi:10.3762/bjoc.20.118

• elimination of ethylene. Further transmetalation between the complex 8 and another Grignard reagent gives Rh(III)–bis(aryl) complex 9. Finally, reductive elimination affords the desired homo-coupling product 3 and regenerates the Rh catalyst. We did not identify any cross-coupling products such as (2

• -bromoethyl)arenes or styrenes in this reaction. Unfortunately, we have not clarified the reason why a cross-coupling reaction did not proceed. At this stage, we speculate that the elimination rate of ethylene and reductive elimination rate of 3 might be fast in this reaction. Medicinal chemistry application

Oxidative hydrolysis of aliphatic bromoalkenes: scope study and reactivity insights

• Amol P. Jadhav and
• Claude Y. Legault

Beilstein J. Org. Chem. 2024, 20, 1286–1291, doi:10.3762/bjoc.20.111

• side products is proposed through path b (Scheme 3). The elimination of α-proton on the side chain of dialkyl bromoalkenes results in iodonium intermediate D, which on the expulsion of PhI gives a mixture of the allylic carbocation E, which ultimately gets trapped by MeCN in the presence of H2O, giving

Mechanistic investigations of polyaza[7]helicene in photoredox and energy transfer catalysis

• Johannes Rocker,
• Till J. B. Zähringer,
• Matthias Schmitz,
• Till Opatz and
• Christoph Kerzig

Beilstein J. Org. Chem. 2024, 20, 1236–1245, doi:10.3762/bjoc.20.106

• its photochemical reactivity. The main reaction class catalyzed by excited-state polyazahelicene Aza-H so far is the redox-neutral addition of sulfinates and cyanopyridines, under elimination of cyanide, to styrenes in a three-component reaction. The proposed mechanism was derived from the redox

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• rise to either diaryl selenoxide via dehydration or diaryl monoselenide via reductive elimination by eliminating H2O2 [39]. Observation of m/z peaks for compound 8 clearly confirmed the formation of diaryl selenoxide in the reaction. Mechanism for the formation of oxamides The possible reaction

• latter undergoes addition–elimination reaction with another molecule of o-anisidine to give 2-(phenylamino)cyclohexa-2,5-diene-1,4-dione. The third unit of o-anisidine is added to the quinone via 1,4-addition, followed by oxidation of the 1,4-dihydroxy compound to give 2,5-bis((2-methoxyphenyl)amino

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• complex Mn9-a via the debromination of the pre-catalyst Mn9 with the help of a strong base. Then, Mn9-a treated with an alcohol provided a manganese alkoxy complex Mn9-b, which then undergoes β-hydride elimination to give the manganese hydride complex Mn9-c and the corresponding aldehyde. Further, the azo

• intramolecular manganese amidate rather than the traditional β-hydride elimination process. In 2018, Maji’s group reported the α-alkylation of ketones with primary alcohols using a phosphine-free manganese catalyst generated in situ from Mn(CO)5Br and L3 [58]. Under optimized conditions (2 mol % Mn(CO)5Br, 10

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• . Useful alkenyl functional groups can also be obtained by means of elimination processes, if proper alkyl side chains are present. Additional opportunities offered by C(sp3)–Hal bonds arise from the ease of their homolytic cleavage, leading to the formation of reactive carbon-centred radicals. C(sp2)–Hal

Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

• –elimination pathway will dominate over hydrolysis. This preference was crucial to prevent the formation of undesired carboxylic acid products [28][30][31]. These results also align with the observations previously reported by Takeda and co-workers [24]. The reaction was carried out using a large excess (10

Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

• Luca Julianna Tóth,
• Kateřina Krejčová,
• Milan Dejmek,
• Eva Žilecká,
• Blanka Klepetářová,
• Lenka Poštová Slavětínská,
• Evžen Bouřa and
• Radim Nencka

Beilstein J. Org. Chem. 2024, 20, 1029–1036, doi:10.3762/bjoc.20.91

• , led to two crucial mesoionic compounds, 22 and 27. The recrystallized intermediates then underwent a formal cycloaddition with ethyl acrylate, followed by the elimination of H2S, forming the desired heterocyclic core structures (intermediates 23 and 28, respectively). A subsequent saponification step

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• reaction mechanism proceeds with an initial reduction of Pd(II) to Pd(0) followed by oxidative addition on the ArCH2–Cl bond to form the ArCH2–PdII–Cl complex. Then, insertion of CO, from TFBen, takes place followed by nucleophilic displacement and reductive elimination. The obtained compound undergoes

• reductive elimination and the generated Pd(0) species gets oxidated by the oxygen to the active Pd(II) species (Scheme 7). Synthesis of indoles by metal-catalyzed reductive cyclization reaction of organic nitro compounds with carbon monoxide as reductant In the last 60 years, the metal-catalyzed

• ). The proposed mechanism, shown in Scheme 34, suggested that the process proceeded through a Pd(0) catalysis proceeding through first an intramolecular Heck reaction, followed by CO insertion, N-cyclization (anilines) or O-cyclization (phenols) and final reductive elimination. Carbonylative

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• elimination of methanol favored by the evaporation process. The instability of hemiaminal ethers was previously described in literature [19] during work-up. We then found that careful control of the drying conditions, thus avoiding complete drying of the crude mixture prevents degradation of the Heck products

• palladium(II)–N,N-ligand complex (II), to which the pyrrolidine substrate coordinates (III). Next, migratory insertion takes place generating the alkylpalladium species (IV), which upon a sequence of β-elimination (V) and hydride insertion leads to alkylpalladium intermediate (VI). Finally, upon

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• from a self-propagating process initiated by addition of an adventitious nucleophile to the electrophilic thioester. This results in elimination of a (trifluoromethyl)thiolate (−SCF3) anion (C, Scheme 4), which can subsequently undergo β-fluoride elimination, releasing a fluoride anion. Addition of F

• only 10 mol % of DIPEA (92% 19F NMR yield, Scheme 5b). This reaction could result from base-assisted nucleophilic attack of adventitious water present in the reaction mixture. In addition to addition/elimination of fluoride ions to thioesters 3, a second potential mechanistic pathway exists for the

• formation of acyl fluorides 2. Alongside a fluoride ion, β-fluoride elimination from a (trifluoromethyl)thiolate (−SCF3) anion (C) also generates a thiocarbonyl difluoride species D. As previously demonstrated by Schoenebeck and co-workers in a deoxyfluorination of carboxylic acids with NMe4SCF3, this

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• -workers, and was accessed over 8 steps from diene 161 (Scheme 17A) [51]. Diels–Alder reaction of diene 161 and di-tert-butyl azodicarboxylate (160) followed by palladium-assisted elimination of acetic acid gave diene 162. A sequence of 4π-electrocyclisation and electrophilic transcarbamation (to 163

Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• organoborane intermediate, which was formed by elimination of BH3 from IM-16 followed by re-addition of BH3 from the opposite β-face to the proposed C8–C9 double bond intermediate, would also be possible. To further advance the intermediate to crystalline hydrazone product (Scheme 2B), we have found that both

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• ) [78]. Another advantage of the MH HAT process is that the α-C–H bond in the corresponding radical is comparatively stable, whereas a carbocation has superacidic α-C–H bonds with a pKa of ≈ −17 [79]. Therefore, polar hydrochlorination reactions are in competition with elimination reactions which is not

• from Merck (Scheme 27) [88][89]. They observed that the reaction of 144 with Me2SiCl2 yielded the desired product 145 along with 5–10% of the undesired elimination byproduct 146. Subjecting the obtained mixture to the hydrochlorination conditions depicted in Scheme 27 transformed the alkene 146 into

• elimination, resulting in a Pd(II) complex and the corresponding alkyl chloride K. Conclusion Despite being regarded as uninteresting museum chemistry for a considerable time, recent advancements in the hydrochlorination of alkenes have significantly expanded its applicability. Approximately three decades ago

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• elimination of the organometallic intermediate would lead to the desired product (Scheme 1B, reaction 1). Unfortunately, this approach will not be compatible in the case of azidation since the copper, azides and alkynes present in the mixture are expected to undergo alkyne–azide cycloaddition reactions [28

• generate a large quantity of iodanyl radical from Ts-ABZ (3) homolysis and from the addition–elimination on Ph-EBX (2). Since no quencher is present in the mixture, we wondered if the accumulation of those radicals could be responsible for the low yields obtained. Addition of (TMS)3SiH, a H• donor

Enhanced reactivity of Li⁺@C₆₀ toward thermal [2 + 2] cycloaddition by encapsulated Li⁺ Lewis acid

• Hiroshi Ueno,
• Yu Yamazaki,
• Hiroshi Okada,
• Fuminori Misaizu,
• Ken Kokubo and
• Hidehiro Sakurai

Beilstein J. Org. Chem. 2024, 20, 653–660, doi:10.3762/bjoc.20.58

• , photoirradiation triggered the elimination of the addends, reforming the starting Li+@C60 (Figure 3). No other insoluble or undetectable products by HPLC were identified during the study. On the other hand, the reactions of 3 and 4 with Li+@C60 did not proceed significantly even under higher temperature reaction