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

• analysis of lactam 19l. In order to shed light on the details of the reaction mechanism, we have performed carefully designed mechanistic studies which consist of experiments on the effect of β-silicon stabilization, the alkene geometry of the α,β-unsaturated acyl chloride reactants, and adventitious water

• catalytic aza-Nazarov reaction starting from cyclic and acyclic imines and TMS-substituted α,β-unsaturated acyl chlorides to yield α-methylene-γ-lactam heterocycles with high diastereoselectivities. We also report the results of our detailed mechanistic studies along with the necessary control experiments

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

• intermediate radical reduction. The observed diastereoselectivity can be rationalized by referring to earlier mechanistic studies [79]. The same (−)-configured intermediate 147 was utilized in a HAT-initiated oxidation to access (−)-minovincinine (150) in 38% yield after deprotection (Scheme 12). Interestingly

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• products that can be purified by SiO2 column chromatography, other noteworthy advantages are the possibility of isolating side products that may aid in mechanistic studies, and the recyclability and robustness of the SiO2 columns. One of the main issues that can be found with this purification technique is

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• ]. Conclusion We have identified a new fungal FC-type DTS, which is responsible for the biosynthesis of talaro-7,13-diene (1). Further mechanistic studies revealed that 2,6-cyclization in the formation of 1 is likely to be triggered by protonation of the neutral intermediate 3, and Tyr91 in TadA plays a

B–N/B–H Transborylation: borane-catalysed nitrile hydroboration

• Filip Meger,
• Alexander C. W. Kwok,
• Franziska Gilch,
• Dominic R. Willcox,
• Alex J. Hendy,
• Kieran Nicholson,
• Andrew D. Bage,
• Thomas Langer,
• Thomas A. Hunt and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2022, 18, 1332–1337, doi:10.3762/bjoc.18.138

• relies upon stoichiometric reagents or transition-metal catalysis. Herein, a borane-catalysed hydroboration of nitriles to give primary amines is reported. Good yields (48–95%) and chemoselectivity (e.g., ester, nitro, sulfone) were observed. DFT calculations and mechanistic studies support the proposal

• is proposed to serve as the key turnover step in catalysis, supported by computational mechanistic studies. This approach uses both a commercially-available catalyst and turnover reagent, providing good user accessibility, and displays comparable chemoselectivity to current state-of-the-art catalysed

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

• ) should be a key intermediate for this tandem reaction. On the basis of the above mechanistic studies and the previous works on iodide-mediated electrochemical transformation [37][38][39][40], a possible mechanism for this electrochemical reaction was proposed (Scheme 5). It is well known that amino acid

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

• 72% yield with good selectivity (89%). Both 1f and 1g could be used in this reactions, and the corresponding alcohols 3f and 3g were obtained as major products. Mechanistic studies To gain further insight into the reaction mechanism of the chemoselectivity of a Pd/C cathode system, some additional

• . Charge was passed to the circulated solution until 1 was consumed. The yield was determined by GC analysis using n-dodecane as an internal standard. Values in parentheses show the chemoselectivity of 3, which was calculated as yield of 3 / yield of (2 + 3). Mechanistic studies. Electroreduction of 1a

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

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

• [59]. The authors proposed a plausible catalytic cycle based on a series of mechanistic studies (Scheme 3). First, FeCl2 will react with the aryl Grignard reagent to form an aryliron complex 8 which can undergo a SET with the iodoalkane to yield the radical substrate 9. A 5-exo-dig cyclization will

• sections: strictly carbon CDC reactions and heteroatomic CDC reactions. Iron-catalyzed carbon–carbon cross dehydrogenative coupling In 2013, Li and co-workers reported the FeCl3-catalyzed arylalkylation of activated alkenes 60 for the synthesis of oxindoles 62 (Scheme 10) [80]. Mechanistic studies

• -carbonyl alkyl bromides 147 and indole derivatives 146 (Scheme 30) [124]. Although the reaction operated in the absence of the iron catalyst, its use is crucial for high yielding reactions. Preliminary mechanistic studies suggest the reaction proceeds through a radical addition of the carbon-centered alkyl

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• mmol), MeCN (1.0 mL), 80 °C, under air atmosphere for 10 h; yields are reported for the isolated products. Synthetic applications of the synthesized compound 3b. Mechanistic studies and proposed mechanism. Optimization of the reaction conditions for the sulfonylation and isonitrilation of p-quinone

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

• process, suggesting that dynamic kinetic resolution could be used to accomplish enantioselective synthesis of axially chiral 3,3'-bisindoles. The mechanistic studies showed that the N–H group of 3,3′-bisindoles 47 played a crucial role in carrying out the addition reaction with substrates 52 possibly by

• -amino allenoates 101 was prepared in moderate to excellent yields (69–99%), dr (9:1 to >20:1), and excellent enantioselectivity (91–99% ee, Scheme 34). The mechanistic studies showed that the substituents at the second and third positions of the indole play a crucial role in the chemo- and

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

• ), which was due to the ability of copper to stabilize and interact with radical intermediates in its coordination sphere. Mechanistic studies revealed that the iodoperfluoroalkylation of alkenes and alkynes involved a rebound or ligand transfer cycle (section 3.1). In 2017, Wang and co-workers [54

• alkyl halides 14, olefins, and trifluoromethylthiolate 15. Mechanistic studies demonstrated that the photoexcited CuI/binap/SCF3 complex generated in situ engages in electron transfer with the alkyl halides, thereby providing an alkyl radical and the CuII/binap/SCF3 species. Subsequently, the alkyl

• , 18 (Scheme 10 and Scheme 11). Based on previous mechanistic studies [41], the authors found that the photoexcited ligand–CuI−amido species transferred electrons to alkyl halides to produce alkyl radicals, which reacted with alkenes and amines to generate the three-component coupling products. In the

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

• preparation of ferrocene–drug conjugates effectively. Mechanistic studies indicated that the C–H activation step was the rate-determining step. 3d-Transition-metal-catalyzed C–H functionalization to access functionalized ferrocenes. Scope of ferrocenes with morpholine. Scope of various amines with 1a

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

• , right). However, based on the freshly coined concept of anion-binding activation [30][31] and as the exact interaction mode of the catalyst remained elusive, Jacobsen’s group focused their attention towards mechanistic studies of thiourea-catalyzed reactions. In 2007, they reported a Pictet–Spengler

• species. However, the cationic counterpart can have important effects on the kinetics of the systems. This hypothesis has evidently been identified in enzymatic reactions [68]. Mechanistic studies have shown that in such processes, cationic species are stabilized through various attractive interactions

• crucial, while the urea analog of the catalysts proved less efficient and led to diminished reactivity and stereoselectivity. Further mechanistic studies corroborated this hypothesis as more electron-rich allylsilane derivatives were consumed slower despite being inherently more nucleophilic. Another

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

• similar reaction conditions with moderate to good yields. Based on their detailed mechanistic studies, the authors proposed a possible catalytic cycle involving a C–H cleavage via a HAT process between the triplet excited ketone photocatalyst 24 and the C(sp3)–H substrates (Figure 8) [66]. Thus, the

• enantioselectivities. A wide range of aryl bromides 3 were tested with alkylbenzenes 25 under ambient reaction conditions and afforded the desired products 26 in moderate yields and good enantioselectivities. Based on their control experiments and mechanistic studies, it was postulated that a bromine radical might be

• radical source via a nickel/photoredox-catalyzed HAT processes (Scheme 28) [92]. The method was also compatible with other chlorine-containing electrophiles such as acyl chlorides 45 to afford methyl ketones 47 in moderate yields. Based on the detailed mechanistic studies, the authors proposed a catalytic

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• mechanisms occur in parallel, which results in the formation of the Michael adduct as a byproduct and the desired spirocyclopentanes 104. It is noteworthy that the mechanistic studies showed that the product is formed through a concerted mechanism and therefore is not part of an intermediate adduct. A

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

• reaction showed to be chemoselective, maintaining good yields with compounds bearing varied functional groups, whereas low yields were observed for benzylic fluorination. Preliminary mechanistic studies suggested the C–H abstraction to be the rate-determining step and the high oxygen sensitivity of the

• reaction suggested it goes through a radical pathway. Similar to the oxidation of alkanes to give alcohols and carbonyl compounds, vanadium complexes have been reported to mediate the hydroxylation of arenes, including the obtaining of phenol from benzene. However, most mechanistic studies provided

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

• and loxoprofen underwent regioselective azidation at the secondary benzylic sites over tertiary benzylic sites (see 13d and 13e). Additional mechanistic studies support the reaction pathway depicted in Figure 4. The azide anion is oxidized to a radical species on the anodic surface, where Mn(II)/L–N3

Cerium-photocatalyzed aerobic oxidation of benzylic alcohols to aldehydes and ketones

• Girish Suresh Yedase,
• Sumit Kumar,
• Jessica Stahl,
• Burkhard König and
• Veera Reddy Yatham

Beilstein J. Org. Chem. 2021, 17, 1727–1732, doi:10.3762/bjoc.17.121

• this cerium-photocatalyzed aerobic oxidation of alcohols prompted us to conduct some preliminary mechanistic studies (Figure 1). As anticipated, the ON/OFF irradiation experiments confirmed that our reaction required a continuous blue light irradiation (see Supporting Information File 1). The

• and secondary benzylic alcohols were converted into the corresponding aldehydes and ketones in good to moderate yields using commercially available and inexpensive CeCl3·7H2O as a photocatalyst and air as an oxidant. Mechanistic studies. (A): UV–vis spectra of the CeIV(OBn)Cln complex in CH3CN under

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• ). Notable advantages of our protocol include: 1) removable MHP auxiliary used for copper-mediated oxidative C–H activations, 2) excellent functional group tolerance and compatibility with valuable heterocycles, and 3) mechanistic studies toward copper-mediated oxidative C−H alkynylations. Results and

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

• methylcycloalkanes (94a and 94b) and the terminal olefin 93 (Scheme 37A). Both examples showed perfect regioselectivity for the functionalization of the tertiary C(sp3)–H bond. Mechanistic studies carried out by the authors revealed a strong kinetic isotope effect (KIE = 11.5:1) when a competitive reaction was

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

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• chromone derivative for the total syntheses of (−)-caesalpinnone A and (−)-caesalpinflavan B (Scheme 12) [9]. Mechanistic studies of this catalytic system were also made by Stoltz’s group. A linear relationship between the ee of the catalyst and the product has been found [48]. That means that the

• catalytically relevant species is monomeric Pd–PyOx. This was further supported by a mass spectrometric study [52]. The catalytic cycle was also suggested in accordance with DFT calculations and mechanistic studies (Scheme 13) [48][49]. The key step for both, the enantioselectivity and turnover, is the

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

• carbonyl electrophilicity [105]. The use of chiral Lewis acids can induce asymmetry [106]. Yoon et al. applied this well-known form of catalysis to a photocatalytic system using enones 269 and 270 (Scheme 43a) [107]. Mechanistic studies of a closely related achiral reaction [20], showed this reaction