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

• alkylations. Herein, the lithiated sulfur-heterocycles act as a cis-vinyl anion equivalent, a strategy that was developed by Palumbo and co-workers. The method shows some complementarity to the more classical acetylene alkylations, followed by partial hydrogenation to the cis-olefin (see Scheme 10 and Scheme

• reported far less commonly than their use in (4 + 3) cycloadditions [94]. Simple hydrocarbon allyl cations can also undergo (3 + 2) cycloadditions through a purely stepwise cation olefin cyclization-type pathway, but these generally give complex mixtures and low yields and show unpredictable substrate

• suppress homodimerization, via a stepwise (3 + 2) cycloaddition of the initially generated cumyl cation across the olefin in amylene. Our group became intrigued by the potential of dihydrodithiins to act as carbocation-stabilizing groups, as these would represent a synthetic equivalent of ‘naked’ allyl

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

• differences between acyl chlorides 23 and 6 in the examined aza-Nazarov cyclizations can be understood when the electron densities on the two olefin moieties are considered. Indeed, while both of the proposed intermediates 29 and 9 (Scheme 1) can benefit from the β-silicon stabilization effect, the olefinic

• -Nazarov product 7b, albeit in a lower yield (24%). The fact that the other diastereomer of the aza-Nazarov product 7b, which would be formed via the reaction of acyl chloride 6bb with (Z)-olefin configuration, was not observed in this transformation points to a potential E–Z isomerization during the

• reaction. This type of olefin E–Z isomerization is likely to take place after the N-acyliminium formation, possibly via a Michael/retro-Michael addition sequence between the chloride (Cl−) anion and the electron-deficient olefin of the N-acyliminium intermediate at 80 °C (Scheme 9c). In conclusion, these

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• , olefin, ketone or epoxide functionalities. From a biosynthetic point of view, grayananes arise from an oxidative rearrangement of the ent-kaurane skeleton (Scheme 1). The diversity is generated by cytochromes P450 (CYP) enzymatic oxidation of the grayanane skeleton [17]. The biological activities and low

• -disubstituted olefin and reductive epoxide ring-opening giving triol 18. After oxidation of the primary and the secondary alcohols with Dess–Martin periodinane, the remaining tertiary alcohol was protected as a MOM ether and the silyl ether protecting group was removed. The obtained intermediate 19 was then a

• 2019, Newhouse’s group published a total synthesis of principinol D [26], a compound isolated from Rhododendron principis in 2014 [27][28]. Compared to grayanotoxin III, principinol D displays an inverse configuration at C1 as well as an exo-olefin at C10–C20. The strategy developed by the group relied

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• )-protected ᴅ-serine 12 (Scheme 2). Treatment of the olefin 15 with trifluoroacetic acid (TFA) cleaved the Boc protecting group and the acetonide to deliver unsaturated amino alcohol 16. The amino group in 16 was protected by the fluorenylmethyloxycarbonyl (Fmoc) protecting group for solid-phase peptide

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• elimination of methanol rather than exocyclic elimination of water, and regioisomeric Rauhut–Currier reaction. Compound 7 was found to be unstable after isolation, possibly due to intermolecular reactions of the electron-poor olefin and furan ring. When a slight excess of 1 was used, only 6n was isolated

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

• strategies [27]. Both of these used non-commercially available catalysts prepared over multiple steps, the first an N-heterocyclic olefin [22], and the second a bicyclic (alkyl)(amino)carbine [23]. Both displayed limited tolerance to reducible functionalities. NaHBEt3 is the only known boron-based catalyst

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• alcohols [24], methoxides [23][25][26], carboxylic acids [27], amides [28], ketones [29][30], an exo-olefin [31], and lactones [32]. Elucidating the mechanisms of structural diversification is essential when considering the synthesis of unnatural azoxides by a synthetic biology-based approach. However

• , their enzymatic basis has remained elusive except for the exo-olefin formation in valanimycin biosynthesis, which is mediated by the phosphorylation of a serine moiety by VlmJ and the subsequent dehydration by VlmK [33]. To obtain insights into the late-stage diversification mechanisms, we focused on

• installation of a cis-olefin on the 1,2-positions of the alkyl side chain would afford azodyrecins A–C (1–3), in a reaction likely to be mediated by Ady9, a putative fatty acid desaturase. Nevertheless, the possibility that the desaturation occurs prior to the methyl esterification could not be excluded. The

Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications

• Sadanobu Iwase,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2022, 18, 872–880, doi:10.3762/bjoc.18.88

• performed at room temperature. As expected, product 3 was formed in moderate yield of 67% as shown in Scheme 7. It is known that difluorocarbene has generally low reactivity towards olefins; however, it can be trapped with electron-rich olefins [32]. In order to trap difluorocarbene with an olefin, we tried

• 1,1-diphenylethylene as a more electron-rich olefin compared to α-methylstyrene was carried out similarly. As expected, the adduct 6 was formed in a high yield of 90% as shown in Scheme 10. Isopropanol can serve as both a proton and a hydrogen radical source while cumene serves only as a hydrogen

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

• ]. Therefore, Roberge, Fogg, and co-workers investigated the advantages of continuously stirred tank reactors (CSTR) and tube reactors in comparison to the corresponding batch reaction for the ring-closing metathesis of diene 58, producing macrocyclic olefin 60 (Scheme 14) [52]. Although, macrocycle 60 is not

• conditions. In contrast, when a continuously stirred tank reactor was used, its head space was continuously flushed with argon to keep the concentration of ethylene in solution as low as possible. In this case, full conversion to macrocyclic olefin 60 (99% yield, detected be GC-FID) could be achieved after

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

A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• synthesis of sesquiterpene natural product derivatives [38][39] and the carbonyl olefin metathesis leading to 2,5-dihydropyrroles [40]. Herein we present our investigation on the ability of the hexameric capsule 16 to act as a supramolecular self-assembled organocatalyst for a series of unimolecular

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

• -organize them with certain confined conformations. In this case, the linear diterpenoid substrate 29 possessed a folded U-shaped conformation within the cavity, with the terminal trisubstituted olefin exposed to the solution while the other three internal ones were protected by the cage host. The structure

• of the host–guest complex was determined by NMR and X-ray crystallographic analysis. Accordingly, the terminal trisubstituted olefin moiety was site-selectively transformed to the corresponding nitratobrominated compound 30 (Figure 9a) or epoxide 31 (Figure 9b) by NBS or m-CPBA, respectively. The

• terminal was exposed to the aqueous solution and the more hydrophobic olefin terminal was buried deep in the cavitand hence protected from the further functionalization. This methodology could be expanded generally to the systems of converting symmetrical hydrophobic guests to unsymmetrical, amphiphilic

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

• diastereo- and enantioselectivities (up to >20:1 dr and >99% ee) (Scheme 8) [18]. The optimized reaction conditions for the annulation reaction were as follows: [Ir(cod)Cl]2 (4 mol %), Carreira’s P/olefin ligand (S)-L3 (16 mol %), Zn(OTf)2 (100 mol %), and 4 Å MS in CH2Cl2 at rt. The synthetic protocol

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• regioselectivity. The mechanism and origins of selectivity in the iridium-catalyzed hydroacylation reaction has been examined at the M06/Def2TZVP level of theory. The catalytic cycle consists of three key steps including oxidative addition into the aldehyde C–H bond, insertion of the olefin into the iridium

• hydroacylation reactions [74][75][76][77][78], we propose a catalytic cycle utilizing iridium that proceeds with three key steps: (1) iridium(I) oxidative addition into the aldehyde C–H bond, (2) insertion of the olefin into the iridium hydride, and (3) C–C bond-forming reductive elimination. The hydroacylation

• substrate, the active catalyst Ir(COD)OH will undergo oxidative addition into the aldehyde C–H bond. Next, the iridium hydride species will undergo exo-η2-coordination with the olefin of MeOBD to generate intermediates IN1a and IN1b (Figure 1). It is typically assumed exo-η2-coordination is preferential

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• -naphthoquinones 35 and β-lapachone (11) for hCE1 (Scheme 9). It is important to note that 35 can be obtained from other reagents, such as 2-naphthol, in a cascade of reactions involving oxidation to 1,2-naphthoquinones followed by Michael addition to the olefin and reoxidation [85]. In addition, Yang and co

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins

• Jiang-Song Zhai and
• Da-Ming Du

Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3

• . Results and Discussion To verify the feasibility of the reaction, the domino Michael addition/cyclization reaction of 2-isothiocyanato-1-indanone (1a) and barbiturate-based olefin 2a was used as a model reaction, which was carried out in dichloromethane (DCM) with 5 mol % quinine-derived squaramide C1 at

Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes

• Shun Saito,
• Kanji Indo,
• Naoya Oku,
• Hisayuki Komaki,
• Masashi Kawasaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2939–2949, doi:10.3762/bjoc.17.203

• from a triplet methyl H-8 to an olefinic methine H-5 via two methylenes H-7 and H-6, which revealed a propyl-substituted olefin moiety (Figure 2). In addition, HMBC correlations (Table 2) from the allylic methyl H-10 to C-5, C-4, and C-3 and from the other allylic methyl H-9 to C-3, C-2, and C-1

• larger by C2H4 than 1. Analysis of a COSY spectrum identified a 1,2-disubstituted (E)-olefin fragment H-2/H-3 (3JH-H = 15.0 Hz), a four-carbon fragment containing a methyl-substituted olefinic methine H-5/H-6/(H-12)/H-7, and an ethyl group H-9/H-10 (Figure 2, Table 1 and Table 2). The connectivity of the

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• -formyl amide products have unique properties and reactivity, but are difficult or impossible to access by traditional synthetic approaches. Keywords: formyl peptide; nitroaryl compound; nitroso compound; olefin cleavage; photocleavage; Findings The photochemistry of nitroaromatic functional groups has

• then account for the isolation of the acetylated analogue 9. The photochemical pathway described here represents a formal oxidative olefin cleavage of vinylogous nitroaryl-modified amides and ethers. The pathway adds to the diversity of photochemical pathways known for 2-nitrophenyl systems, and the

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

• first three-component alkenylboration of alkenes 50 (Scheme 9) [78]. The authors noted the described methodology regioselectively installs both the boryl functionality and olefin across both activated and unactivated π-systems 50; however, the later required the use of (dppe)FeBr2 in DMF to deliver

• an Fe(II) species and S2O82−, a cascade of SET reactions between the alkylcarbazate and the Fe catalyst will lead to the formation of the alkoxycarbonyl 125. Regioselective addition of the radical across the electron-neutral olefin will generate the radical intermediate 126, followed by the 6-endo

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

• radical reacts with the olefin generating a new alkyl radical, which is trapped by CuII/binap/SCF3 to provide the coupling product (Scheme 10). In 2019, Zhang and co-workers [58] reported the photoinduced copper-catalyzed carboamination of alkenes that involved organic halides 16, alkenes, and amines 17

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

• necessary for this transformation. Recently, copper hydride (CuH) catalysis has been a wonderful procedure for olefin hydrofunctionalization via the formation of nucleophilic alkylcopper intermediate. In 2016, Buchwald and co-workers described a CuH-catalyzed asymmetric addition of olefin to ketones [65

• -aryl-substituted pyrroles 55 in moderate to good yield. In addition, the method could tolerate a wide range of functional groups, such as phenolic hydroxy, aryl bromide, ester, terminal olefin, aryl chloride, and silyl-protected alcohol moieties. Furthermore, both aromatic and aliphatic nitriles

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

• synthesis commenced with the monoprotection of the known diene-diol ent-49 as TBS ether affording compound 50 in 76% yield, which served as an excellent strategy to direct the later cross metathesis reaction to one site of the olefin over another (Scheme 5). Thus, the desired α,β-unsaturated ester 51 was

• Michael-initiated ring closure cyclopropanation at the more electrophilic olefin. The α-keto cyclopropyl intermediate 53 was formed in 79% yield with a dr value of >20:1. Reducing the proportion of DMF to 5% with respect to THF in the reaction mixture was hypothesized as the key factor for maximizing the

• all the centers of the stereochemical brevipolides but in the mirror image of the natural configuration. After sequential ring-closing metathesis, base-promoted olefin migration, and MEM removal, the ent-brevipolide H (ent-8) was obtained. This compound showed inhibition activity in the preliminary

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

• in the key step for the synthesis of (±)-thallusin (207, Scheme 62). A complex mixture of Hg(OTf)2 and N,N-dimethylaniline (DMA) (1.2 equiv) was initially used for olefin cyclization to produce a regio- and a stereoisomeric mixture of acetate 205 after reduction and acetylation of the crude product

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

• regenerate the nickel(0) species 21-VI and the carboxylate product 21-IX. Olefin difunctionalization Nickel-catalyzed alkene 1,2-difunctionalization is considered as useful method for preparing complex molecules in a single-step reaction [137][138][139]. In this aspect, the groups by Kong [140] and Molander

• [141] independently demonstrated photoredox/nickel-catalyzed approaches to olefin difunctionalizations involving C(sp3)–H activation. Thus, Kong devised a synthetic method combining nickel catalysis with tetrabutylammonium decatungstate (TBADT) as photocatalyst for the three component reaction of

• substituted diaryl ketone, 4-(4-methoxybenzoyl)benzonitrile (96) serves as the HAT photocatalyst to activate the C(sp3)–H bonds for olefin functionalization. It was identified that the use of nonpolar, aprotic solvents, such as benzene and α,α,α-trifluorotoluene (TFT) is critical for the formation of the

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

• alcohols with diaryliodonium salts [26], the Sc(OTf)3-catalyzed domino reaction [27], and the iodine-catalyzed nucleophilic substitution reaction of xanthen-9-ol [28]. As an example of an intramolecular hydroarylation of an olefin, 9,10-dihydroacridines, which are N derivatives of xanthenes, were