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

• of hydrogen with a pressure of 1 bar, a good selectivity for the hydrogenation of the external alkene is achieved providing enone 27. The reaction mixture containing enone 27 is then mixed with tosylhydrazone and passed through a column with sulfonic acidic resin Amberlyst-15 to catalyze the

• -nonadien-1-al are nearly ubiquitous in modern perfumery for both women and men, even appearing in dark or woody fragrances such as Hugo Boss: Soul. In 2012, Barbaro and co-workers developed a synthesis for alkene 32 by selective hydrogenation of the corresponding alkyne (Scheme 7) [37]. Instead of using a

• . Optimization of process parameters revealed that at a conversion of 75% a good selectivity of 89% for hydrogenation of alkyne 31 to alkene 32 is achieved affording a mixture of (Z)- and (E)-isomers in a ratio of 80:20 [37]. Floral odorants Floral notes, such as rose, jasmine, orange blossom, or lavender, are

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

• and was supported by a CH3OD trapping experiment [13]. Thus, DPIBF in this reaction acts both as Diels−Alder trap reagent for reactive alkene [28] as well as radical anion quencher [29][30]. The N,N-Boc-protected N-amidinylpyrrole 28 [31] and 1-guanidinoanthracene (29) [10][32] have functional groups

• (conditions a), imide 44 was the major product accompanied by a small amount of janusene imide derivative 45 (7:1 ratio). The formation of the intermediate alkene 43 was observed spectroscopically only in the milling reaction of 42 alone (an indicative 1H NMR signal of bicyclo[2.2.1] moiety at 5.28 ppm

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

• reactions involving the formation of cationic intermediate species [41] like water elimination from an alcohol to provide the corresponding alkene, the isomerization of β-pinene and α-pinene and the cyclization of (S)-citronellal to secondary alcohols. The key point to interpret the action of the capsule in

• subsequent water elimination leading to a stable tertiary, bis-benzyl carbocation that evolves forming the corresponding alkene by proton elimination (Scheme 3). The reaction was carried out at 60 °C with 10 mol % of 16 (Table 2, entry 1), monitoring the formation of the products by 1H NMR and GC–MS (see

• ), with quantitative yield after 20 h at 60 °C in the presence of 10 mol % of the capsule. The same reaction carried out with the capsule 16 and in the presence of 3 as competitive guest led to complete inhibition of the formation of the corresponding alkene (Figure 2D, Table 2, entry 2). This provides

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

• achieved with just the rhodium catalyst, by which in contrast, the fully hydrogenated product was obtained. Other series of intermolecular comparative experiments also showed the selectivity of the hydrogenation for the sterically accessible alkene over other sites and even in the presence of inherently

• diterpenoid substrates have four C–C double bonds with a trisubstituted terminal one. Functionalization of these structures would result in mixtures of products derived from each potential alkene group without site-selectivity. The cage host A was proved to recognize organic molecules in water and pre

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

• oxabicyclic alkene. In IN1a, the chelated acyl group is positioned syn to the C1-methyl substituent while in IN1b, they are positioned anti to one another. IN1b is 1.8 kcal/mol higher in energy than its isomer which can be attributed to the increased steric interactions between the bulky COD ligand and the C1

• MeOBD as a potential competing reaction (Figure 3). There are two potential isomeric intermediates following endo-η2-coordination of MeOBD concerning the relative orientation of the COD ligand, acyl group, and C1-substituent on the oxabicyclic alkene. In IN1e, the chelated acyl group is positioned syn

• determined the stereoselectivity of the reaction arises from the unattractive interactions imposed from the sterically hindered endo-face of the bicyclic alkene. The mechanistic insights gained from this combined experimental and theoretical study will facilitate further future methodology development in

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

• Kian Donnelly and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27

• , without the need for further extensive optimisation. Oxadiazole product 2j was chosen as the target molecule for the scale-up reaction due to the potential for further diversification via the embedded alkene. Due to the large quantity of material, an increase in column size was required to house the

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

• which one would predict to be less stable and more stable, respectively, than the tert-butyl cation. These additional studies would be somewhat simplified in that an alkene, observed as a product from 2-methyl-2-propanesulfonyl chloride, would not be formed from the 1-adamantanesulfonyl or

Earth-abundant 3d transition metals on the rise in catalysis

• Nikolaos Kaplaneris and
• Lutz Ackermann

Beilstein J. Org. Chem. 2022, 18, 86–88, doi:10.3762/bjoc.18.8

• syntheses, crop protection or medicinal chemistry. Particularly, cross-coupling reactions [1], as well as alkene and alkyne metathesis [2][3], have considerably changed the art of molecular synthesis, with a major impact on neighboring disciplines, such as molecular biology or materials sciences. Despite of

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

• borylmetallation across the alkene in a syn-fashion 58. Side-on coordination of the haloalkene’s π-bond can trigger a syn-carbometallation 59. A base-mediated 1,2- elimination will deliver the alkenylboration product as well as regenerate 56. The methodology was applied towards the synthesis of (±)-imperanene

• thermal conditions or through the Fe redox cycle, can abstract the aldehydic hydrogen to form the acyl radical 71. Subsequent radical addition to the alkene 68 to form 72 followed by cyclization with the nitrile affords the iminyl radical 73 which can abstract a hydrogen atom to form the more stable imine

• and 1,3-dicarbonyl compounds 84 via synergistic photoredox/iron catalysis (Scheme 14) [90]. This protocol parallels Li’s seminal report in 2007 [44]; however, under these reaction conditions, the reactive radical was propagated across an alkene before termination with the activated methylene unit

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

• nucleophilic addition to afford axially chiral aryl-alkene-indole frameworks (89) in up to 98% yield, >95:5 E/Z, and up to 97% enantioselectivity (Scheme 30). The nonbiaryl N–C atropisomer is an important structural scaffold, which is present in natural products, medicines. and chiral ligands due to the

• cycloaddition–oxidative chirality conversion process. Atroposelective synthesis of oxindole-based axially chiral styrenes via kinetic resolution. Synthesis of axially chiral alkene-indole frame works [45]. Proposed reaction mechanism for axially chiral alkene-indoles. Atroposelective C–H aminations of N-aryl-2

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• (p-TSA) catalyst at reflux (Scheme 1). Sadayoshi and co-workers [39] developed the synthesis of 1,3-oxathiolane derivative 8 (Scheme 2). The protected glycolic aldehyde 3b was isolated after ozonolysis of alkene 3ra. The reaction between an aldehyde 3b and 2-mercaptoacetic acid (3o) was carried out

• acid derivatives to test the impact of a chiral auxiliary on N-glycosylation. Compound 50 was synthesized by ozonolysis of alkene 3rb, followed by reaction of aldehyde (generated in situ from alkene) with 1,4-dithiane-2,5-diol (3q). The use of lactic acid derivatives provided both enantiomers of

Solvent-free synthesis of enantioenriched β-silyl nitroalkanes under organocatalytic conditions

• Akhil K. Dubey and
• Raghunath Chowdhury

Beilstein J. Org. Chem. 2021, 17, 2642–2649, doi:10.3762/bjoc.17.177

• ]. In addition, the C–Si bond can be oxidized to a hydroxy group by Tamao–Fleming oxidation [3][4] or to an alkene unit via protodesilylation [5][6]. Many complex natural products, bioactive molecules, and drug molecules have been synthesized on exploitation of the above-mentioned properties of

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• (Figure 15). Next, ring-expanding rearrangement is proposed to form 75. Finally, the C7 ketone is reduced, the C8–C9 bond is oxidized back to an alkene, the C5–C6 double bond is oxidized to an epoxide, and C15 is oxidized to a tertiary alcohol to yield 72. The authors not only structurally characterized

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

• complexes to photocatalysis are reported. Copper-photocatalyzed reactions, including alkene and alkyne functionalization, organic halide functionalization, and alkyl C–H functionalization that have been reported over the past 5 years, are included. Keywords: copper-photocatalyzed reactions; green chemistry

• ruthenium-based catalysts and copper-based catalysts are discussed, and the strong reduction ability of copper complexes is explained. Subsequently, mechanisms of the photoredox catalysis by CuI and CuII are summarized, and the copper-catalyzed reactions, including alkene functionalization, alkyne

• bonds and can be applied to radical chemistry. This review discusses copper-catalyzed reactions including alkene and alkyne, organic halide, and alkyl C–H functionalization. 3. Visible-light-mediated copper-catalyzed alkene and alkyne functionalization 3.1 Olefinic C–H functionalization and allylic

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• alkene 12 (30%) could be formed from terminal epoxide 5, using cyclopropylstannane 11 [16] (Scheme 5); in this case the presence of LTMP was also necessary as epoxide 5 was recovered (>80%) in its absence. A silyl-stabilised methoxymethyllithium, available by direct lithiation of (methoxymethyl

• -lithio terminal epoxides or N-Bus-aziridines with α-lithio ethers. Where 1,2-disubstituted alkenes are generated the E/Z stereoselectivity is modest, and preliminary results suggest the size of the leaving group does not play a significant role. However, the geometry of alkene formation might be

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

• carbohydrate alkene precursor 7 and Hg(OAc)2 proceeds with high stereoselectivity to give the α-ᴅ-C-glycopyranosyl derivative (1,5-trans-isomer) 8 as a single isomer [41]. Treatment of compound 8 with sodium borohydride (NaBH4) under phase transfer conditions (PTC) yields compound 9 as the only product. The

• manner as reductive elimination forms during the mercury removal process (Scheme 6). Mercury(II) salts had been effectively used to synthesize five-membered furanose derivatives with high stereoselectivity. Nicotra et al. developed Hg(OAc)2-mediated cyclization of hydroxy-alkene derivative 15 to form α-ᴅ

• positions of the starting material. It had been cited in many publications that the stereoselectivity of products formed due to Hg(II)-salt-mediated cyclization reactions of alkene-alcohol derivatives depends on several factors: the nature of the Hg(II) salts [46], the starting materials [47], and the

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

• decatungstate 22-II undergoes a HAT process with the C(sp3)–H substrate to form a carbon-centered radical species 22-III and reduced decatungstate 22-IV. The thus formed alkyl radical 22-III adds to the alkene 92 affording the radical adduct 22-VI, which is intercepted by the nickel(0) species 22-X to generate

• the triplet-state diradical 23-I. A HAT process between 23-I and the alkane substrate generates the desired carbon-centered radical 23-II with concomitant formation of ketyl radical species 23-III. The thus formed alkyl radical 23-II undergoes Giese addition to alkene 94 resulting in the radical

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

• 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

• development trials for the synthesis of xanthene derivatives were carried out. For this purpose, catalyst researches were carried out using compound 4a. An intramolecular Friedel–Crafts reaction was tried by activating the alkene with various organic Brønsted acids and Lewis acids (Table 1). In the reaction

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

• , 1640, 1548, 1470, 1442, 1215, 734; 1H NMR (CDCl3, 300 MHz) δH 7.99 (s, 1H, alkene-CH), 7.64–7.41 (m, 4H, Aro-H), 4.41 (s, 2H, -CH2), 3.87 (s, 3H, COOCH3); 13C NMR (CDCl3, 75 MHz) δC 168.03, 145.31, 134.67, 130.11, 129.53, 128.62, 128.25, 64.78, 52.24; HRMS (m/z): [M + H]+ calcd for C11H10O2, 174.0681

A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

• Zsanett Benke,
• Attila M. Remete and
• Loránd Kiss

Beilstein J. Org. Chem. 2021, 17, 2051–2066, doi:10.3762/bjoc.17.132

• selective functionalization of readily available norbornadiene across nitrile oxide cycloaddition/ROM/CM protocols in view of the access of various fluorine-containing molecular entities as well as to explore the chemical behavior of olefin bonds in the reaction with some fluorinated alkene derivatives in

• (±)-6 with alkene 7d were explored (Scheme 14 and Table 13). G-3 catalyst yielded (±)-21a as the sole monocoupled product, while HG-2 and G-2 catalysts gave both monocoupled (±)-21a and dicoupled (±)-21c. The best yield of (±)-21c was achieved with HG-2 catalyst (although G-2 catalyst also produced a

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

• ] cyclotrimerization reactions in the presence of nickel and cobalt catalysts [38]. First, they employed diyne 15 in the reaction with a series of alkynes (16) or nitriles (17) bearing a variety of functional groups including alkyl and alkene chains, hydroxy groups, and benzene and pyridine rings, to achieve the

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

• phenanthroindolizidine alkaloid boehmeriasin A (31) (Scheme 12A) [98], and phenanthroindolizidines through an intramolecular oxidative aryl–alkene coupling (Scheme 12B) [99], which is a far less common transformation in organic synthesis. This approach was employed to synthesize eight phenanthroindolizidines, including

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

• [104]. The manganese(I)-catalyzed intermolecular alkenylation of tryptophan-containing peptides 32 was performed under basic conditions, yielding hybrid peptides 34 without racemization, containing a trans-alkene linker bearing biologically active motifs in chemo- and site-selective manners assisted by

Correction: Amine–borane complex-initiated SF₅Cl radical addition on alkenes and alkynes

• Audrey Gilbert,
• Pauline Langowski,
• Marine Delgado,
• Laurent Chabaud,
• Mathieu Pucheault and
• Jean-François Paquin

Beilstein J. Org. Chem. 2021, 17, 1725–1726, doi:10.3762/bjoc.17.120

• , France 10.3762/bjoc.17.120 Keywords: amine–borane complex; pentafluorosulfanyl chloride; pentafluorosulfanyl substituent; radical addition; radical initiation; The stereochemistry of some alkene products (2i–k) in Scheme 4 of the original publication was misattributed. The corrected structures are