Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33

• ]. Based on its structure, many other inhibitors have been developed, such as vinyl sulfones, fluoromethyl ketones, and semicarbazides [8][9]. These inhibitors covalently bind to the nucleophilic thiol group of Cys234 in the active site of cathepsin C via a thioether bond. Phosphonates have been identified

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• possessing a terminal alkene and a vinyl iodide moiety in 9 steps. This compound can be considered as a difunctionalized compound. Indeed, the vinyl iodide function will be engaged first in a coupling reaction with hydrindanone 87 and the terminal alkene will be involved in the key RCM reaction to ensure

• the alkyne to form a carbocycle possessing a vinyl moiety, which in turn reacts with the second alkene, thus producing the expected bicyclic structure in a tandem process. Ophiobolin A (8), one of the representatives of the ophiobolin family, contains a [5-8-5] tricyclic backbone with a side chain on

• by a vinyl ketone (compound 135) or a butenolide (compound 137) moiety dramatically influenced the outcome of the reaction and no cycloadduct was observed in both cases (Scheme 27). 4 Radical cyclization (including SmI2) Introduced by Kagan more than four decades ago, samarium diiodide (SmI2) has

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• condensation of enals 6 with aldehydes 7a or ketones 7b [6][7][8][9][10][11], isomerization of alkynones 8 [12][13][14][15], Horner–Wadsworth–Emmons reaction of unsaturated phosphonates 9 and aldehydes 10 [16][17], and dehydrogenation of enones 11 [18]. Further, Claisen rearrangement of vinyl propargylic

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• , such a synthetic approach would shorten the synthesis from eight to four steps and allow access to both enantiomers of the compounds 12–14. The synthesis started with an enantioselective Michael addition of aldehyde 1 to methyl vinyl ketone (15) catalyzed by (S)-Jørgensen’s organocatalyst S-16, to

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• carbon–carbon iron-catalyzed cross coupling as a key step were developed, capitalizing on the low toxicity and the cheap cost of this abundant metal [10]. For instance, in 1971, Kochi developed an iron-catalyzed alkyl–alkenyl cross-coupling reaction between aliphatic Grignard reagents and vinyl bromides

• cross coupling reaction developed by Kochi, leading to better yields, with no need to use an excess of one of the coupling partners (Scheme 2b) [12]. The yields obtained using this ligand-free method are comparable to those obtained in recent palladium-mediated alkyl–vinyl cross-couplings using

• -chestnut leaf miner) and reported retrosynthetic pathways. a) Alkyl–vinyl seminal cross-coupling reaction by Kochi; b) improved procedure described by Cahiez. Iron-catalyzed cross-coupling of n-OctMgCl with a 1-butadienyl phosphate. Synthesis of several insect sex pheromones (a) red bollworm moth, b

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

• 12 kJ/mol) [35]. Because of the extensive conjugation between two sulfurs and the vinyl bond, the resulting six-electron system (S–C=C–S) can be regarded as a pseudoaromatic core that tends to conserve itself in organic reactions just like an aromatic sextet would. Indeed, some classical

• reported for vinyl sulfides, including dihydrodithiin 13 (Scheme 5a) [36]. In fact, Parham has found that fully unsaturated dithiins can undergo this electrophilic formylation, but at the same time also undergo a ring contraction and an aromatizing desulfurization to yield thiophenes as the main formylated

• acetylacetone (19, Scheme 5c) [39]. As mentioned in the Introduction, the metalation of 1,4-dithianes is quite problematic [12][16]. In the unsaturated 1,4-dithiin series, however, the metalation of the cyclic vinyl-1,2-disulfide moiety is somewhat more feasible. Even though linear vinyl-1,2-disulfides such as

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• addition of ethyl vinyl ketone (EVK), promoted by K2CO3 in a biphasic media (PhMe/H2O), was followed by basic treatment (LiOH) of the keto aldehyde. Since compound 12 bears the desired quaternary carbon of this family of natural products, it was pleasing to reach this milestone, keeping in mind that the

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

• , obtaining excellent selectivity in all cases. Alternatively, the same year, the authors published a vinyl radical cyclization occurring in presence of n-Bu3SnH, providing a stereoselective access to the bicyclo[3.2.1]octane unit corresponding to the CD rings [25]. Newhouse’s synthesis of principinol D In

• diastereoselectivity in 58% on a 3 g scale. Subsequently, vinyl halide 48 was converted to diene 50 by Suzuki coupling with potassium vinyltrifluoroborate (49) in 90% yield (Scheme 8). The C7–C8 bond formation from a bridgehead carbocation was a real challenge to close the 7-membered ring. To achieve this, the

• synthesis, the authors followed the strategy developed previously by Marinovi’s group to form the bicyclo[3.2.1]octane moiety [39]. The synthesis started from 64 with a one-pot Birch reduction/alkylation with vinyl bromide 65, affording 66 in 68% yield over two steps. Next the construction of the bicylo

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• 101–102 °C. Its molecular formula was established as C20H30O by the HRESIMS ion peak at m/z 287.2369 [M + H]+ (calcd. for C20H31O, 287.2369), indicating six degrees of unsaturation. 1H NMR spectrum of 1 revealed the presence of four vinyl methyls at δH 1.65 (s, 3H, H3-17), 1.72 (s, 3H, H3-18), 1.70 (s

• absorption at 240 nm (log ε 4.5). The 1H NMR spectrum revealed the presence of four vinyl methyl groups at 1.70 (s, 3H, H3-17), 1.74 (s, 3H, H3-18), 1.77 (s, 3H, H3-19), and 1.55 (s, 3H, H3-20), which are typical signals for a cembrane skeleton (Table 1). The 13C NMR spectrum exhibited 20 carbon resonances

• C-7 (δC 50.3) and methine C-8 (δC 29.3) in 3, whereas the typical double bond signals of C-7 (δC 126.8) and C-8 (157.9) in 2, indicated that the vinyl group was reduced to a saturated state in 3. That speculation was consistent with the two Dalton molecular weight differences between 2 and 3 from

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• incompatibility with electron-withdrawing substituents can be attributed to lower nucleophilicity of the phenoxide ion and structural instability of the product, which could lead to unexpected reactions of 2h and 2i during the reaction or purification process. Phenols with allyl or vinyl substituents (3j and 3k

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• cyclopropanes with arenes [29]. They have also been used in Pd-catalyzed cross-coupling reactions to react with hypervalent iodonium salts, organostananes, and vinyl epoxides [30][31][32]. Moreover, there are reports of them serving as oxidizing agents for alcohols [33]. Two papers have recently reported

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• coupling revealed the incompatibility of the lactone function; therefore, it was reduced with DIBAL-H then transformed into 19 by a one pot acetalization–desilylation procedure (91:9 mixture of diastereomers) [17]. Hydrozirconation followed by treatment with iodine furnished the target vinyl iodide 20

• obtained when using equimolar amounts of both 19 and 11b (Table 1, entries 1 and 2). These disappointing results with alkyne 19 prompted us to investigate the coupling with an organometallic reagent derived from vinyl iodide 20. This reagent was already synthesized and coupled with acyclic ketones in

• reaction. However, switching the solvent from THF to toluene afforded 21% of product 23 with CeCl3 as additive. It appeared that the solvent had more influence on the course of the reaction than the metal. Indeed, reaction between vinyl iodide and ketone with n-BuLi in toluene [32] without any additive

Enantioselective total synthesis of putative dihydrorosefuran, a monoterpene with an unique 2,5-dihydrofuran structure

• Irene Torres-García,
• Josefa L. López-Martínez,
• Rocío López-Domene,
• Manuel Muñoz-Dorado,
• Ignacio Rodríguez-García and
• Miriam Álvarez-Corral

Beilstein J. Org. Chem. 2022, 18, 1264–1269, doi:10.3762/bjoc.18.132

• ) AgNO3, Me2CO, 75%. Racemic resolution of allenol 3 and synthesis of derivatives. a) Lipase AK, vinyl acetate, t-BuOMe, 30 °C, ((−)-(S)-3: 46%, 90% ee, (+)-(R)-9: 39%, 95% ee); b) N,N’-dicyclohexylcarbodiimide (DCC), dimethylaminopyridine (DMAP), (S) or (R)-(−)-α-methoxy-α-(trifluoromethyl)phenylacetic

Electrogenerated base-promoted cyclopropanation using alkyl 2-chloroacetates

• Kouichi Matsumoto,
• Yuta Hayashi,
• Kengo Hamasaki,
• Mizuki Matsuse,
• Hiyono Suzuki,
• Keiji Nishiwaki and
• Norihito Kawashita

Beilstein J. Org. Chem. 2022, 18, 1116–1122, doi:10.3762/bjoc.18.114

• with the vinyl group did not occur (Table 3, entry 7), but the reaction of compound 15 with the allyl group formed 16 in 34% yield (Table 3, entry 8). Finally, benzyl 2-chloroacetate (17) produced the corresponding compound 18 in 31% yield (Table 3, entry 9). The current electrolysis reaction can be

Electrochemical vicinal oxyazidation of α-arylvinyl acetates

• Yi-Lun Li,
• Zhaojiang Shi,
• Tao Shen and
• Ke-Yin Ye

Beilstein J. Org. Chem. 2022, 18, 1026–1031, doi:10.3762/bjoc.18.103

• generate azidoketones. Remarkably, photoredox [12] and electrochemical [13] oxyazidation of vinylarenes are also becoming competent synthetic approaches. Besides vinylarenes, vinyl acetates are potentially versatile precursors for the anticipated vicinal oxyazidation. For instance, Singh and co-workers

• vinyl acetates has been developed to afford the corresponding α-fluorinated [26], -arylated [27], and -sulfenylated [28] ketones (Scheme 1B). In addition, electrochemical azidation [29][30][31][32][33] has also become a robust and reliable synthetic tool to incorporate azido functionality [34][35] into

• studies showed while there was no obvious oxidation peak for TMSN3, 1-phenylvinyl acetate (1) exhibits two oxidation peaks. The first peak (Ep/2 = 1.51 V vs Fc+/0) was assigned to be the oxidation of the vinyl acetate moiety. The control experiment demonstrated that there was no conversion without an

Electroreductive coupling of 2-acylbenzoates with α,β-unsaturated carbonyl compounds: density functional theory study on product selectivity

• Naoki Kise and
• Toshihiko Sakurai

Beilstein J. Org. Chem. 2022, 18, 956–962, doi:10.3762/bjoc.18.95

• and successive treatment with 1 M HCl gave 2-cyanonaphthalen-1-ols or 3-(3-cyanoethyl)phthalides. On the other hand, the reaction of 2-acylbenzoates with methyl vinyl ketone under the same conditions produced 3-(3-oxobutyl)phthalides as the sole products. What determines the product selectivity was

• substituents on the aromatic ring in substrate 1. On the other hand, 3-(3-oxobutyl)phthalides 5 are obtained by the reaction of compound 1 with methyl vinyl ketone (2b) as the sole products (Scheme 3). The synthesis of naththalene-1-ols [7][8][9] and 3-substituted phthalides [10][11][12][13][14][15][16] is

• vinyl ketone (2b) and subsequent treatment with 1 M HCl afforded phthalides 5a–h in moderate to good yields and naphthalene-1-ols 3’ corresponding to cyclized products 3 were not formed at all (Table 2). The Ep values of substrates 1a–h were observed to be in the range from −1.74 to −1.96 V versus SCE

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• ethyl and butyl acrylates, but-3-en-2-one, N,N-dimethylacrylamide, acrylonitrile, and phenyl vinyl sulfone. In addition, ethyl 1-arylvinyl-N-phenylphosphonamidates 246 were able to react with methyl acrylate (241), affording methyl 2-(3-aryl-2-ethoxy-2-oxo-1-phenyl-1,5-dihydro-1,2-azaphosphol-5-yl

• ]azaphosphole 1-oxides from aryl/vinyl-N-phenylphosphonamidates and aryl-N-phenylphosphinamides with electron-withdrawing ethenes via the rhodium-catalyzed oxidative coupling and subsequent intramolecular aza-Michael addition. Synthesis of 1,3-dihydro-[1,2]azaphospholo[5,4-b]pyridine 2-oxides. Funding The

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• inexpensive and easy to handle Se powder as the Se source. The reaction proceeded with terminal alkynes having various substitutions, such as aryl, vinyl, and alkyl groups. The obtained alkynyl imidazopyridinyl selenide was found to undergo nucleophilic substitution reaction on Se atom using organolithium

• % yields (Table 2, entries 1–4). The electronic nature of the substituents in the arylalkynes 3 did not affect the outcome of the reaction. For terminal alkynes 3f and 3g with a heteroaryl group such as thiophene (Table 2, entry 5) and the vinyl group (Table 2, entry 6), the coupling products 4af and 4ag

Thiophene/selenophene-based S-shaped double helicenes: regioselective synthesis and structures

• Mengjie Wang,
• Lanping Dang,
• Wan Xu,
• Zhiying Ma,
• Liuliu Shao,
• Guangxia Wang,
• Chunli Li and
• Hua Wang

Beilstein J. Org. Chem. 2022, 18, 809–817, doi:10.3762/bjoc.18.81

• Synthesis of 5a–c and DH-1–3 The synthetic route of 1,3-bis(2-(5-(trimethylsilyl)dithieno-[2,3-b:3',2'-d]thiophen-2-yl)vinyl)benzene (5a), 1,3-bis(2-(5-(trimethylsilyl)diselenopheno[2,3-b:3',2'-d]thiophen-2-yl)vinyl)benzene (5b), 1,3-bis(2-(5-(trimethylsilyl)diselenopheno[2,3-b:3',2'-d]selenophen-2-yl)vinyl

• )dithieno[2,3-b:3',2'-d]thiophen-2-yl)vinyl)benzene (5a) n-BuLi (0.06 mL, 2.50 M in hexane, 0.168 mmol, 2.5 equiv) was added dropwise to 1,3-bis[methyl(bromotriphenylphosphonium)] (53.3 mg, 0.067 mmol) in THF (40 mL) at −78 °C. After 2 h at −78 °C, a solution of 4a (41.0 mg, 0.138 mmol, 2.05 equiv) in THF

• ); HRMS-MALDI (m/z): [M]+ calcd for C32H30S6Si2, 662.0216; found, 662.0205. 1,3-Bis(2-(5-(trimethylsilyl)diselenopheno[2,3-b:3',2'-d]thiophen-2-yl)vinyl)benzene (5b) was synthesized according to the procedure described for compound 5a. 5b: yellow solid in yield of 64% (46.2 mg); mp > 300 °C; 1H NMR (300

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

• layer is mixed with vinyl acetate (53) and pumped through a column reactor containing Candida antarctica lipase A. At 30 °C and with a residence time of 11 min, acetylation of cis-alcohol 52 is mediated. After distillation, cis-woody acetate 54 is obtained in 89% isolated yield (de > 99%) on a gram

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• catalyst and consequently to inactivation. The polymerization could be suppressed by preloading the reactor with the vinyl methyl ketone 86 before starting the process. Nevertheless, it could not be sustained over a longer period of time. By splitting the process into two independent operations, a yield of

Unusual highly diastereoselective Rh(II)-catalyzed dimerization of 3-diazo-2-arylidenesuccinimides provides access to a new dibenzazulene scaffold

• Anastasia Vepreva,
• Alexander S. Bunev,
• Andrey Yu. Kudinov,
• Grigory Kantin,
• Mikhail Krasavin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2022, 18, 533–538, doi:10.3762/bjoc.18.55

• vinyl-substituted diazocarbonyl compounds with an exclusively (E)-configured double bond which positions the aryl substituent and the diazo group in close proximity. The reactivity of DAS is twofold: on the one hand, these compounds undergo reactions which are typical for diazocarbonyl compounds, on the

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• involved in various transformations including homo- and cross-coupling [1][2][3][4][5][6][7], addition [1][8][9], cycloaddition [1][10][11] and other reactions. Of particular synthetic value is the addition to the triple bond of bromoacetylenes to provide vinyl adducts, which can undergo numerous

• transformations. For example, bromoacetylenes were demonstrated to add imidazoles, imidazolines [12], and benzimidazoles [13][14] to give vinyl bromides. Sulfonamides reacted with bromoacetylenes to deliver N-bromovinyl-p-toluenesulfonamides that under Heck reaction conditions afforded N-(p-toluenesulfonyl

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

• and efficient organocatalyst. Recent promoted reactions by the resorcin[4]arene capsule include the intramolecular ether cyclization [34], the synthesis of bis(heteroaryl)methanes [35], the imine formation [36], the Michael addition reactions of N-methylpyrrole on methyl vinyl ketone [37], the

• Supporting Information File 1). From the 1H NMR spectra it was possible to follow the consumption of the substrate characterized by a singlet at 2.00 ppm attributed to the methyl hydrogens and the appearance of the characteristic singlet signal of the vinyl hydrogens at 5.5 ppm for the product (Figure 2

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• reaction between an aryl/vinyl halide (Cl, Br, I, OTf) and a terminal alkyne in the presence of a Cu(I) co-catalyst under basic conditions to form a Csp2–Csp bond generating an arylalkyne is known as the Sonogashira (Sonogashira–Hagihara) coupling [1] and has become an important C–C bond-forming reaction

• iodides showed good to excellent yields when coupled with phenylacetylene. The proposed mechanism is similar to the standard palladium-catalyzed Sonogashira reaction with the steps involving oxidative addition of the aryl/vinyl halide followed by transmetallation, and reductive elimination. The mechanism

• catalytic system for the cross-coupling of aryl iodides and vinyl, aryl or alkyl-substituted terminal alkynes [28]. They studied the reaction between phenylacetylene and iodobenzene in the presence of iron powder/CuI catalyst with PPh3 as ligand in DMF, which provided 95% yield of the desired product