Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• betaine form 1 is the most thermodynamically stable of all tautomers (ΔG = −4.9 kcal/mol). It is also not surprising that the O-protonated form 1', which is both a ketone and an enol, is found to be the most unfavorable (ΔG = 10.8 kcal/mol). In contrast to the O-protonated tautomer 1', both the N

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

• fixatives but also enhancing the perceptibility of a perfume [23]. Fruity odorants One of the most important odorants giving raspberries their characteristic scent is the so-called “raspberry ketone” (5) having a “sweet, fruity, and warm odor” which is frequently used for fruity perfumes and as a flavor [9

• ]. It is prominently used in, e.g., Tom Ford: Tuscan Leather along with notes of leather, muguet, and thyme, defining the character of this scent. The related methyl ether 6 (“raspberry ketone methyl ether”) is also used as odorant but is, in contrast to raspberry ketone (5), “intensely sweet, floral

• of up to 0.35 kg/h for enone 4. In the second step, the obtained 4-aryl-3-buten-2-ones 3 and 4 are selectively hydrogenated in flow using a packed-bed reactor with Raney nickel as catalyst affording raspberry ketone (5) in 91% yield and raspberry ketone methyl ether (6) in 94% yield, respectively

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

• included a carboxylation and a Parham cyclization and hence a Grignard alkylation of ketone 82 using reagent 81. The resulting alcohol 83 was subjected to thermolysis that led to water elimination. This step proceeded in just 30 s by employing the inductive heating technique. The crude elimination product

• 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

• heating and the residence time was only 12 minutes. The Macrolide® 89 was obtained in 14% together with the aliphatic macrocyclic 90, the latter can be oxidatively converted into the corresponding ketone, which is of practical importance in the fragrance industry. It is clear that this process could not

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• -phenylethylidene)indolin-2-one (1j) in acetonitrile with Et3N catalyst under refluxing conditions, and isolated the corresponding saturated ketone 1-methyl-3-(2-oxo-2-phenylethyl)indolin-2-one (4j) in 60% yield, which results from reduction of the double bond of α,β-unsaturated ketone (Scheme 5). The structure of

• compound 4j was determined by NMR spectral data. After that we conducted another reaction between saturated ketone 4j with unsaturated ketone (E)-1-methyl-3-(2-oxo-2-phenylethylidene)indolin-2-one (1j) under base-catalyzed conditions, gratifyingly we obtained our desired product

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• corresponding ketone (10 mmol) in ethyl acetate (20 mL). The reaction mixture was stirred at rt for 12 h. After the reaction was complete, as indicated by TLC, the mixture was carefully treated with 10% aqueous NH4Cl (30 mL) and the pH adjusted to 5 with a solution of hydrochloric acid (3 M). The aqueous phase

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

• after Cs2CO3 convertion to CsBr (because of the very poor solubility of CsBr in DMF) has an influence on the rate of diphenoxyketone formation. In addition, the suppression of the di(nitrophenoxy)ketone formation can be due to the lower basicity of a reaction mixture since nitrophenols 2d,e are more

Four bioactive new steroids from the soft coral Lobophytum pauciflorum collected in South China Sea

• Di Zhang,
• Zhe Wang,
• Xiao Han,
• Xiao-Lei Li,
• Zhong-Yu Lu,
• Bei-Bei Dou,
• Wen-Ze Zhang,
• Xu-Li Tang,
• Ping-Lin Li and
• Guo-Qiang Li

Beilstein J. Org. Chem. 2022, 18, 374–380, doi:10.3762/bjoc.18.42

• ketone carbonyl at C-6 and the double bond at C-17, respectively. Thus, the planar structure of 2 was established as shown in Figure 1. The relative configuration of 2 was deduced by the cross-peaks shown by a 2D NOESY spectrum (Figure 3). The NOE correlations of H-8 with H3-18 and H3-19, and H-9 (δH

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

A Se···O bonding catalysis approach to the synthesis of calix[4]pyrroles

• Qingzhe Tong,
• Zhiguo Zhao and
• Yao Wang

Beilstein J. Org. Chem. 2022, 18, 325–330, doi:10.3762/bjoc.18.36

• investigation on using an asymmetric ketone such as pentan-2-one as a reactant showed that the reaction gave an inseparable mixture of diastereomers. Meanwhile, upon using benzaldehyde as a reactant, the reaction system was complex and there was no major product. Proposed activation mode The chalcogen bonding

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

• a 61%, 52%, and 76% yield, respectively. A significant decrease in the yield was observed for electron-withdrawing C1-substituted OBDs with ketone- (15i) and ester- (15j) substituted adducts only being produced in a 5% and 9% yield, respectively; however, unreacted starting material was recovered

• determine the effect of the electron-withdrawing group on the efficacy of the reaction. Interested if the C1-substituted ketone OBD 13i was merely unreactive, we subjected it to a competition reaction against C1-substituted methyl OBD 13b (Scheme 3). In the presence of 13i, the C1-substituted methyl OBD 13b

• last key step in the catalytic cycle involves the C–C bond-forming reductive elimination to form the final ketone intermediate IN3a or IN3b (Figure 1). Two possible transition states, 2aTS3a and 2bTS3b, can be located. The concerning free energy barrier about IN2a to IN3a, via 2aTS3a is 10.8 kcal/mol

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• -oxazoles are: the 1,3-dipolar cycloaddition of alkenes and alkynes with nitrile oxides, and the reaction of a three-carbon atom component, such as a α,β-unsaturated ketone or a 1,3-diketone with hydroxylamine hydrochloride [33]. Recently, Rosa et al. reported a useful procedure for the synthesis of various

• -HMBC spectra. The aforementioned enamine proton and protons 2’(4’)-H (δ 4.00-4.09 ppm) from the azetidine ring system shared the HMBC cross-peak with the ketone carbonyl carbon (δ 195.4 ppm). Finally, in the 1H,15N-HMBC spectrum of 3a, an expected long-range correlation between the enamine proton (δ

Efficient synthesis of ethyl 2-(oxazolin-2-yl)alkanoates via ethoxycarbonylketene-induced electrophilic ring expansion of aziridines

• Yelong Lei and
• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 70–76, doi:10.3762/bjoc.18.6

• different chemoselectivities. 2-Alkylideneoxazolidines and 2-alkyloxazolines are structural isomers and can possibly tautomerize each other. As a more electron-withdrawing group with more electron density on the carbonyl group, a ketone favors the conjugation of the double bond as well as the intramolecular

DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

• ). Surprisingly, decent amounts of product were observed when the reaction was performed without the use of DABCO (Table 1, entry 9). This result indicates an alternative mechanism can be possible for aryl ketone formation when there are no bicyclic amines in the reaction media. Recent works indicate a bromine

• aldehydes to generate acyl radicals. The coupling of this radical to the Ni(0) complex furnishes the acyl−Ni(I) complex, which then proceeds oxidative addition to aryl bromide to generate the pentavalent Ni(III) complex. Lastly, reductive elimination affords the desired ketone and the Ni(I) complex, which

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• methyl ethyl ketone (MEK) was as effective. In addition, in situ-generated α-bromo-δ-valerolactone was directly converted into a sulfur-substituted functional lactone without difficulty by reacting it with a sulfur nucleophile in one pot without isolation. This new bromination system is expected to

• is toxic and an environmental pollutant. Therefore, we further optimized the solvent combination to construct an eco-friendlier reaction system (Table 5). Various solvents were used as the organic layer instead of CHCl3, with 3a produced in good yield using methyl ethyl ketone (MEK) as the solvent

• -bromolactones in excellent yields. The use of methyl ethyl ketone (MEK) in the two-phase system led to an eco-friendly system amenable to large-scale synthesis. Furthermore, the α-bromolactones generated in situ by this method were transformed into functional molecules, such as α-thiolated lactones, in good

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

• conditions, both primary and secondary alcohols are oxidized to the corresponding aldehyde/ketone, so the chronology of the addition remains unclear whether the reaction proceeds exclusively via an alkyl radical followed by subsequent oxidation, an acyl radical, or a combination of both. Further, slight

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

• synthetic utility of this protocol was also demonstrated in the synthesis of difluoroalkylated diarylmethane 5 and diarylmethane ketone derivatives 6 and 7, which are important core structures in natural products and medicines. Keywords: chemoselective reactions; diarylmethyl sulfones; dual role

• acids via a triphenylphosphine-mediated deoxygenation process, followed by reaction with sulfonylated diarylmethane 3b to obtain diarylmethane ketone derivatives 6 and 7 [53]. To gain mechanistic insight into this C–S-bond cleavage sulfonylation reaction, some control experiments were conducted (Scheme

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• base; Introduction Schiff bases are an important class of organic compounds first reported by the German chemist Hugo Schiff in 1864 and are formed from the reversible condensation between a primary amine and an aldehyde or a ketone [1]. Also known as azomethines, aldimines, and more commonly as

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• different ketone and enone precursors from cholic acid, deoxycholic acid, and chenodeoxycholic acid was established. Newly obtained tetrazole derivatives were characterized by NMR and X-ray diffraction spectroscopy. In a number of cases, preliminary antiproliferative tests of new compounds showed strong and

• [21], this variation of the reaction draws considerably less attention in comparison to the usage in the synthesis of amides or lactams. As presented in Figure 2, after initial formation of the azidohydrine by addition of hydrazoic acid to the ketone, the reaction can undergo two pathways. In the

• . Results and Discussion In order to investigate possibilities for the synthesis of bile acid B-ring- and bile acid C-ring-fused tetrazoles by a variation of the Schmidt reaction, the appropriate ketone and enone derivatives were prepared firstly. This was achieved using cholic acid, deoxycholic acid (1

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• –91%) with excellent levels of stereocontrol (≈92% ee, >20:1 dr in all cases). The ketone group in the cascade product was reduced asymmetrically to a chiral secondary hydroxy group (Table 1) [26]. In this case, the role of Ph3CCO2H as additive is to furnish the conjugate base Ph3CO2− anion which

• of carbamates, sulfonamides and acetamides 13 bearing an α,β-unsaturated ketone to synthesize a series of 2-substituted five- and six-membered heterocycles in good yields (up to 99%) and excellent enantioselectivity (92–97.5% ee) (Table 3). As in an earlier case [29], several acids were tested as co

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

• features the 1,2-shift of an alkyl or aryl group. In the process, the hydroxy group is converted to a carbonyl and the aldehyde/ketone or imine is converted to an alcohol or amine. Such α-ketol/α-iminol rearrangements are used in a wide variety of synthetic applications including asymmetric synthesis

• use of aldehydes (R′ = H), which are usually less stable than their ketone counterparts; (2) ring expansion (Z, R = cyclic) or contraction (Z, R′ = cyclic) of strained cyclic α-ketols; (3) the use of α-dicarbonyl compounds (R′ = acyl, ester, amide, etc.), which lead to more stable β-dicarbonyl

• -moderate yields but with ≥74% ee, while the α-amino ketone products 15 could be obtained in nearly quantitative yields and variable ee, from 53% to 98% [6]. A fifth example of an enantioselective α-ketol rearrangement provides a twist by demonstrating the ability to function on substrates protected as

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• -trig interactions of both the enol nucleophile and the ketone in the transient intermediate 21 bring about formation of the new five-membered ring intermediate 22. Finally, acid-induced dehydration of 22 completes the formation of the pyrrole ring, resulting in conversion into the dihydropyrrolizine

Synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and their transformations under superelectrophilic activation conditions

• Andrey I. Puzanov,
• Dmitry S. Ryabukhin,
• Anna S. Zalivatskaya,
• Dmitriy N. Zakusilo,
• Darya S. Mikson,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2417–2424, doi:10.3762/bjoc.17.158

• ), oxadiazole 3a gave the product of hydration of the acetylene bond (4d, yield of 65%) existing in solution as equilibrium between ketone and enol forms in a ratio of 1.2:1 according to NMR data (see Supporting Information File 1). Then, reactions of 5-acetylenyl-1,2,4-oxadiazole 3a–d with arenes (benzene and

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

• acid (17) (Scheme 4). The β-hydroxy moiety in 44 can be installed via Sharpless dihydroxylation of the silyl enol ether derived from ketone 45. The 5,6-dihydro-α-pyrone group in ketone 45 is envisaged from protected diol 46 by the sequence of Mitsunobu esterification, ring-closing metathesis, and base

• -promoted double bond migration. The cyclopropyl functionality in 46 can be assembled from the reaction of sulfur ylide and the α,β-unsaturated ketone 47, which in turn can be realized from the cross metathesis between commercially available ethyl vinyl ketone (48) and the C2-symmetrical diene-diol 49. The

• afforded in 78% yield as an (E)-isomer exclusively after reaction with excess ethyl vinyl ketone (48) in the presence of a catalytic amount of Grubbs II catalyst and CuI. The free secondary alcohol in 51 required a protection prior to the next transformation. For this purpose, MEMCl was chosen instead of

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

• enol ether derivative 79 forming carbocyclic compounds 81 with good yields via intermediate 80 [78]. The cyclization of compounds 79 undergo regioselective addition with the triple bond in exocyclic alkene position leading to the formation of α-mercury ketone 80, which were later functionalized by

• ) [101]. Later it was shown that alkynyl diol 150 when treated with 20 mol % Hg(OTf)2 followed by Et3SiH afforded bispyranoyl ketone 151, but when Hg(OTf)2 was increased (1 equiv) then fused pyran-oxocane derivative 152 was isolated [102]. Six-membered morpholine derivatives were also synthesized by

Phenolic constituents from twigs of Aleurites fordii and their biological activities

• Kyoung Jin Park,
• Won Se Suh,
• Da Hye Yoon,
• Chung Sub Kim,
• Sun Yeou Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2021, 17, 2329–2339, doi:10.3762/bjoc.17.151

• ′)], and two methylenes [δH 3.23 (t, J = 6.0 Hz, 2H, H-8) and 3.96 (t, J = 6.0 Hz, 2H, H-9)]. The 13C NMR spectrum of compound 15 (Table 2) revealed 14 peaks for 17 carbons including a ketone carbon (δC 200.0), a 1,3,4,5-tetrasubstituted aromatic ring [δC 154.4 (×2), 140.7, 134.6, and 107.5 (×2)], two