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

• was further studied in intramolecular processes. [(DPEphos)(bcp)Cu]PF6, as a photocatalyst, was applied in these transformations. In 2018, the Bissember group [91] reported the photoinduced and copper-catalyzed dual α-amino-C–H/C–F functionalization reaction (Scheme 24). 3.5 Alkyl C–H

Synthesis of new substituted 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids containing a tetracyclic tetrahydroisoquinoline core structure

• Agnieszka Grajewska,
• Maria Chrzanowska and
• Wiktoria Adamska

Beilstein J. Org. Chem. 2021, 17, 2511–2519, doi:10.3762/bjoc.17.168

• the intramolecular Friedel–Crafts double cyclization reaction and N,N-dibenzylaminoacetaldehyde dialkyl acetals [12][14][15][16] in the Pomeranz–Fritsch-type double cyclization reaction. There is also one example of employing p-quinol acetates as substrates for the synthesis of these compounds [17

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• pyridylic C(sp3)–H bond (Scheme 1b). For examples, Tunge et al. developed a Pd-catalyzed intramolecular decarboxylative coupling of heterocyclic ally esters via a tandem allylation/Cope rearrangement strategy [18]; Hartwig and co-workers reported a stereo-divergent allylic substitution with azaarene

• intramolecular SN2’ type reaction (path a) or an aza-Cope rearrangement under thermal conditions to generate product 3. Results and Discussion To evaluate our idea for the allylic alkylation reaction of MBH carbonates to 2-alkylpyridines, 2-picoline (1a) and MBH carbonate 2a were selected as the model substrates

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• pyridine derivatives have been developed through the intramolecular or intermolecular tandem addition annulation/functionalization of alkynes with some N-containing compounds, such as nitriles, oximes, and imines [15][16][17][18][19]. The pyrrole structural motif is also an invaluable five-membered N

• functionalized pyridines and pyrroles. Review Synthesis of pyridines via tandem annulation of 1,3-enynes In 2015, Reddy and co-workers reported the synthesis of substituted pyridines via Lewis acid-mediated aza-annulation of 2-en-4-ynyl azides 1 (Scheme 1) [49]. They discovered that Ag-mediated intramolecular

• trapped by Cu(II) to deliver the Cu(III) species 12, which undergoes intramolecular annulation and reductive elimination to afford the desired product 8 and regenerate the Cu(I) catalyst. Path b: vinyl radical intermediate 11 is oxidized by Cu(II) to give the cationic vinyl species 14. Finally, the

Synthesis and investigation on optical and electrochemical properties of 2,4-diaryl-9-chloro-5,6,7,8-tetrahydroacridines

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 2450–2461, doi:10.3762/bjoc.17.162

• . Their bands at lower energy may be attributed to the intramolecular charge transfer (ICT) from the electron-donating methoxy groups to the tetrahydroacridine core. The Stokes shifts of 4a–d were calculated based on their absorption and emission spectra. Derivative 4b, containing an electron-donating

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• (GFPP, C25) for sesterterpene biosynthesis. Type I terpene synthases (TPSs) activate these acyclic molecules by the abstraction of diphosphate to produce a reactive allyl cation that can initiate a cascade reaction through typical carbocation chemistry, including cyclisation reactions by intramolecular

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• -promoted intramolecular oxacyclization. After TBS protection, intermediate 32 was collected in 86% yield from epoxide 30. Basic methanolysis of the cyclic carbonate followed by treatment with NaH and N-tosylimidazole then afforded terminal epoxide 34 in 97% yield. Unfortunately, attempts to open the

• epoxidation protocol was applied to the double bond using (−)-DET to afford chiral oxirane 100 in 85% yield. The free primary alcohol was then protected as tosyl ester 101 and treated with p-TSA to induce intramolecular cyclization. The anticipated furan 95 was successfully isolated in 85% accompanied with

• introduced by the addition of a protected propargyl alcohol to the epoxide derived from triol 109. The furan ring is formed by an acid-catalyzed intramolecular cyclization of the alcohol intermediate obtained from the Noyori reduction of α,β-unsaturated ketone 110. This compound is eventually constructed

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

• literature. Utilization of Hg(II) salts in the intramolecular cationic cyclization of olefinic, acetylenic, and allenic substrates having aromatic rings, nucleophiles, and heteroatoms in the neighborhood were well documented. Hg(II) reagents were also often employed in the important cyclization step during

• total syntheses of many natural products [34]. Despite its wide application in ring formation reactions, only a few review articles on Hg(II)-salt-mediated cyclization reactions are available in the literature [35]. This review describes the intramolecular cyclization of unsaturated compounds in the

• )-salt-mediated cyclization reactions. The generalized mechanism for cyclization reactions are, alkenes/alkynes 1 initially react with Hg(II) salts (HgX2) leading to the formation of a mercurial carbonium ion 2 followed by the attack of an intramolecular nucleophile giving rise to a cyclized mercuro

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• ], rhodium-mediated alkyne [2 + 2 + 2] cycloaddition reactions [3], and the palladium-catalysed aerobic domino Suzuki coupling/Michael addition reaction [4]. The most attractive and common strategies to phenanthridines rely on intramolecular cyclizations of various ortho-functionalized biaryl precursors

• , such as ionic liquid- and transition metal-catalyzed and other metal-free transformations [1]. A strategically diverse route to phenanthridines involves intramolecular cyclization of biaryl oximes, allowing for the formation of a new C–N bond. Such a strategy was explored by Deb and Yoshikai in the Fe

• (III)-catalyzed intramolecular cyclization of O-acetyloximes (Figure 2, reaction 1). However, this transformation was limited to ketoximes and yielded only 6-substituted phenanthridines [7]. Applying photochemical conditions, Rodrıguez and Walton were able to use benzaldehydes utilizing a similar

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

• . Based on this concept, the applicability of N-acyliminium chlorides in thiourea-catalyzed anion-binding reactions was further explored. In 2008, an intramolecular asymmetric Pictet–Spengler-type cyclization reaction with pyrrole derivatives 13 was reported. The authors were not only able to control the

• maintain due to the conformational lability of the seleniranium ion [52][53][54], this initial problem can be exploited through the addition of an anion-binding catalyst. In this way, the configurational scrambling is used for a dynamic kinetic resolution during the intramolecular nucleophilic opening of

• -catalyzed intramolecular Pictet–Spengler-type cyclization of hydroxylactam-derived N-acyliminium chlorides and b) thiourea-catalyzed intermolecular hydroxy lactam-derived N-acyliminium chlorides with indoles. Enantioselective Reissert-type reactions of a) (iso)quinolines with silyl ketene acetals, and b

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

• ) photocatalyst 10-III. The active iridium(III) photocatalyst 10-I is regenerated by a SET process between 10-III and the nickel(I) species 10-X. The addition of the tertiary radical 10-IV to the terminal alkyne 34 followed by an intramolecular 1,5-HAT results in a nucleophilic secondary alkyl radical species 10

• linear amides were alkylated selectively at the δ-methylene position through an intramolecular 1,5-HAT event in synergy with a nickel catalytic cycle. Interestingly, secondary C–H bonds are selectively functionalized in preference over primary C–H, in the case of multiple functionalizable sites were

Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• significance were synthesized by developing a new synthesis method. In order to obtain xanthene derivatives, the original alkene compounds to be used as the starting materials were synthesized in four steps using appropriate reactions. A cyclization reaction by intramolecular Friedel–Crafts alkylation was

• carried out in order to synthesize the desired xanthene derivatives using the alkenes as starting compounds. The intramolecular Friedel–Crafts reaction was catalyzed by trifluoroacetic acid (TFA) and provided some novel substituted 9-methyl-9-arylxanthenes with good yields at room temperature within 6–24

• hours. As a result, an alkene compound was used for activation with TFA in the synthesis of xanthene through intramolecular Friedel–Crafts alkylation for the first time. Keywords: alkene activation; intramolecular Friedel–Crafts alkylation; trifluoroacetic acid; xanthene; Introduction The interest in

Nomimicins B–D, new tetronate-class polyketides from a marine-derived actinomycete of the genus Actinomadura

• Zhiwei Zhang,
• Tao Zhou,
• Taehui Yang,
• Keisuke Fukaya,
• Enjuro Harunari,
• Shun Saito,
• Katsuhisa Yamada,
• Chiaki Imada,
• Daisuke Urabe and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2194–2202, doi:10.3762/bjoc.17.141

• intramolecular Diels–Alder reaction [20][25]. Compound 3 is very likely a biosynthetic precursor of 4. This is the first report on the isolation of a biosynthetic precursor of spirotetronate antibiotics as an innate metabolite from a wild-type strain, while such an intermediate was previously obtained from a

Facile and innovative catalytic protocol for intramolecular Friedel–Crafts cyclization of Morita–Baylis–Hillman adducts: Synergistic combination of chiral (salen)chromium(III)/BF₃·OEt₂ catalysis

• Karthikeyan Soundararajan,
• Helen Ratna Monica Jeyarajan,
• Raju Subimol Kamarajapurathu and
• Karthik Krishna Kumar Ayyanoth

Beilstein J. Org. Chem. 2021, 17, 2186–2193, doi:10.3762/bjoc.17.140

• .17.140 Abstract The chiral (salen)Cr(III)/BF3·OEt2 catalytic combination was found to be an effective catalyst for intramolecular Friedel–Crafts cyclization of electron-deficient Morita–Baylis–Hillman adducts. In presence of mild reaction conditions the chiral (salen)Cr(III)/BF3·OEt2 complex affords 2

• -substituted-1H-indenes from unique substrates of Morita–Baylis–Hillman adducts via an easy operating practical procedure. Keywords: boron trifluoride etherate; chiral (salen)chromium(III); intramolecular Friedel–Crafts cyclization; Morita–Baylis–Hillman adducts; substituted-1H-indenes; Introduction

• -deficient arenes [4][5][6][7]. Operating FC reactions in versatile synthons such as Morita–Baylis–Hillman (MBH) adducts is a challenging process. Inter/intramolecular Friedel–Crafts reactions of Morita–Baylis–Hillman adducts leads to a variety of products such as quinolinones [8], cycloheptene-6

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• of the spectrum, the largest shift of 2500 nm was displayed by the polymer 56. The origin of such absorption bands in the near-IR region can be attributed to an intramolecular charge transfer (ICT) process leading to the lowering of the HOMO–LUMO bandgap [34]. The azulene moiety plays a pivotal role

• here as it is polar resonance stabilized and protonation leads to a drift in its electron density from the seven-membered ring to the five-membered ring generating a stable tropylium cation making it a strong electron acceptor during the intramolecular charge transfer (ICT) process. These protonated

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

• interactions in the brush dominate over the intramolecular ones. As a result, the chain conformation within the brush structure is always stretched compared to unattached pendants. The first theoretical investigations into the swelling behavior of polymer brushes based on the work of de Gennes [119][120] and

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

• years (2008–2020) and focuses on direct and indirect methods to construct anthracene and anthraquinone frameworks. Keywords: anthracenes; anthraquinones; Friedel–Crafts cyclization; intramolecular cyclization; metal-catalyzed; Introduction Anthracene is an important aromatic hydrocarbon consisting of

• anthracene derivatives 33. The strategy involved a palladium(II)-catalyzed tandem transformation with diphenyl carboxylic acids 31 and acrylates 32 (Scheme 7) [41]. This new methodology involved a carboxyl-directed C–H alkenylation, a carboxyl-directed secondary C–H activation, an intramolecular C–C-bond

• tested, but only the one-step method with sodium borohydride in alkaline medium resulted in 2,3-disubstituted anthracene 74a, the precursor of anthracene target 75, in excellent yield (95%) [50]. Intramolecular cyclization Intramolecular cyclization is a broad category that covers several known

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• linear iterative [263] approaches were reported. A block coupling approach enabled access to a collection of free amino or N-acetylated structures up to 11mer [264]. Intramolecular glycosylation between a thioglycoside and a free C-6 hydroxy group at the non-reducing end enabled the synthesis of β(1–6

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

• acid (4) as catalyst [30]. Based on this pioneer work, our research group described an efficient, highly stereoselective, one-pot process comprising an organocatalytic conjugate addition of dimedone or 4-hydroxycoumarin 1 to α,β-unsaturated aldehydes 2 followed by an intramolecular isocyanide-based

• starting material in the asymmetric organocatalyzed reaction, the Enders group described the use of (S)-proline as catalyst in an intramolecular aldol reaction, enabling a new strategy to obtain coumarin natural products [34]. As for example, the total synthesis of (+)-smyrindiol (17), a linear

• dihydrocinchonine 26 in combination with trifluoracetic acid (TFA) as Brønsted acid [39]. The reaction provides pyranocoumarins 25 with three vicinal stereogenic centers in high regio-, diastereo- and enantioselectivities through a tandem allylic alkylation/intramolecular oxa-Michael addition (Scheme 7). 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

• activation [37][38][39][40][41]. Hou’s group presented various studies on this theme [42][43], such as a notable work recently published in which they promoted a scandium-catalyzed intramolecular cyclization on benzimidazole substrates, via a C–H activation at the C-2 position (Scheme 2B). In this process, a

• (Scheme 7A). Beckhaus and Doye reported cyclization processes mediated by titanium catalysis, that led to pyridinone derivatives or external cycloamines via an intramolecular titanium-catalyzed C–H hydroaminoalkylation [72][73][74]. In these works, two titanium catalysts were studied, tetrakis

• compounds and biaryl chiral auxiliaries. Also, the oxidative coupling of phenolic substrates has been reported to be mediated by vanadium complexes such as VCl4, VOCl3, and VOF3, among others. For instance, an intramolecular coupling of phenolic moieties using VOF3 has been reported as a final step in the

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

• intramolecular KIEs of C–H cleavage are 2.5 and 3.0, respectively). Next, the benzylic radical is trapped by the Mn–imido complex to afford aminated product 19. Based on additional mechanistic experiments, it was suggested that the MnIII(ClPc) (18)-catalyzed C–H amination process is regioselective for the more

• cyclic peptide motif (Scheme 11). Dipeptide substrate 26f decorated with a Morita–Baylis–Hillman carbonate underwent the intramolecular C–H allylation process to yield cyclic peptide 28f under dilute reaction conditions. This macrocyclization strategy introduces an exocyclic olefin motif onto the cyclic

• 31n, regarded as a potentially viable peptide-based biosensor. Manganese-catalyzed inter- and intramolecular C–H alkenylations Manganese(I)-catalyzed C–H alkenylation of 2-phenylpyridines or N-pyridinylindoles with alkynes is characterized by proximity-induced C–H activation through chelation

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• takes place to form intermediate 22, which subsequently converts to diazo-functionalized intermediate 23. Finally, the intramolecular annulation of intermediate 23 gives corresponding fully decorated 1,2,3-triazole 19 (Scheme 9) [42]. A domino coupling synthesis of fully decorated 1,2,3-triazole

• via intramolecular cyclization reaction of ketones 31, p-nitrophenyl azide (PNA, 32) and amino esters 33 has been described by Dehaen et al. The products were often obtained in good yield and in all cases with the retention of the configuration of the stereocenter. The reaction was carried out by

• . Finally, a reductive elimination takes place to give the corresponding final product and the catalyst for the next run [51]. A tandem Click/intramolecular sulfenylation procedure for the synthesis of sulfur-cycle-fused 1,2,3-triazoles 75 and 77 was described by Xu et al. The reaction was performed through

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

• intramolecular hydroamination in the presence of base. Conclusion In conclusion, we have reported on the chelation-assisted oxidative copper-promoted cascade C−H alkynylation and intramolecular annulation. The removable N-2-pyridylhydrazide was utilized to facilitate copper(II)-promoted C−H activations. Thus

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

• reported the use of active methylene compounds as suitable nucleophiles in intramolecular hydroalkylation reactions (Scheme 2) [25]. In the presence of PdCl2(CH3CN)2, the hydroalkylation of β-diketones 1 gave only 6-endo-trig cyclization products 2 in moderate to good yields (Scheme 2). The methodology

• developed by Widenhoefer [25][29] relied heavily on the acidity of the carbonyl substrate, and this hampered the use of less enolizable substrates, like alkenyl β-ketoesters. The same group addressed this limitation by proposing the use of trimethylsilyl chloride (TMSCl) as an additive in the intramolecular

• nucleophilic attack on the metal-complexed olefin (see Scheme 3, intermediate A). Taking advantage of HCl as an additive (or generated in situ by silyl chloride hydrolysis), Widenhoefer described the intramolecular hydroalkylation of even less reactive alkenyl ketones 4 under Pd(II) catalysis, with minor

Substituted nitrogen-bridged diazocines

• Pascal Lentes,
• Jeremy Rudtke,
• Thomas Griebenow and
• Rainer Herges

Beilstein J. Org. Chem. 2021, 17, 1503–1508, doi:10.3762/bjoc.17.107

• acetyl group at the CH2NR-bridge and bromo- or iodo-substituents at the distant phenyl ring. The photophysical properties were investigated in acetonitrile and water. As compared to previous approaches the yields of the intramolecular azo cyclizations were increased (from ≈40 to 60%) using an oxidative

• compounds with iron(III) to perform an intramolecular Baeyer–Mills reaction [15][21]. We found that a complete reduction of the nitro group to aniline 7 and oxidation with mCPBA is increasing the yield of the intramolecular cyclization from 39% to 62% (over two steps) for the unsubstituted diazocine 8c as