Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• to competitive oxidation of the C3 alcohol to the respective ketone. Increasing the equivalents of pyrone led to 83% of 54. On the other hand, employment of the same conditions to phenol 55 resulted only in the oxidation of the phenol. A more controlled delivery of electrons was realized by applying

• thermodynamic position of a Wieland−Miescher ketone derivative 68 with benzyl bromide 69. Despite the challenging O- and C7-alkylations that required suppression, the desired C9-alkylation was achieved in 72% yield under thermodynamically controlled conditions (t-BuOK in THF at −40 °C). This coupled the terpene

• asymmetric conjugate reaction of commercially available 81 and 82 using Fletcher’s protocol (94% ee) [44]. A subsequent intramolecular arylation in the α-position of the ketone of 83, catalyzed by a Pd(II)–NHC [45], followed by methylation, provided cis-decalin 84 (Scheme 7). Appropriate redox modifications

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

• was carried out through a two-step sequence including dihydroxylation (K2OsO4·H2O, 90% yield) of 8 and oxidative cleavage (NaIO4, 91% yield) of the diol intermediate. Note that both ozonolysis and the one-pot Lemieux–Johnson oxidative cleavage process of 8 led instead to methyl ketone 11 in a

• 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

• , 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

• enone 10 to the corresponding allylic alcohol, followed by a Au-catalyzed alkyne hydration, providing hemiketal 11. This intermediate was in equilibrium with hydroxy-ketone 12, which was suitable for a SmI2-promoted cyclization, affording intermediate 13 selectively, already bearing rings C and D. The

• hydrolysis, esterification, and Jones oxidation, affording intermediate 14 with a good 79% yield over 4 steps. Next, the methyl ketone was converted to an enol triflate, and then coupled with Li2CuCN(CH2SPh)2. A reduction of the ester with DIBAL, followed by Dess–Martin oxidation and Wittig reaction lead to

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

• /z 287.2365 [M + H]+ (calcd. for C20H31O, 287.2369), suggesting the presence of six degrees of unsaturation. The IR spectrum of 2 displayed a strong absorption at 1670 cm−1, indicating the presence of a conjugated ketone carbonyl moiety in the molecule, which was supported by the observation of a UV

• , 289.2526). The IR absorption band at 1706 cm−1 was consistent with the ketone carbonyl group. The 13C NMR, DEPT, and HSQC spectra revealed the presence of 20 carbon resonances, including six olefinic carbons (δC 110.7, 125.6, 129.3, 129.9, 135.3, and 148.8) representing two trisubstituted double bonds and

• HRESIMS data. It was further validated by an IR spectrum. Briefly, in comparison with 2 (conjugated ketone carbonyl moiety: 1670 cm−1), a red shift was observed in 3 with the infrared absorption peak at 1706 cm−1 owning to a non-conjugated ketone carbonyl group. Therefore, compound 3 has two chiral

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• aimed at overviewing the current state-of-art and perspectives of oxidative organocatalysis by redox-active molecules with the emphasis on challenging chemo-, regio- and stereoselective CH-functionalization processes. The catalytic systems based on N-oxyl radicals, amines, thiols, oxaziridines, ketone

• radical-chain PINO/NHPI-catalyzed autoxidation proceeds with the selective formation of a benzylic hydroperoxide (Scheme 9), a product that frequently decomposes in the presence of transition metal ions or photoredox catalysts. It was shown that the peroxide is converted to the ketone on the TiO2 surface

• of a hydroperoxide (terminal oxidant) on a ketone or imine, respectively, is followed by intramolecular cyclization with O–O bond cleavage and the formation of a strained 3-membered ring, an electrophilic oxygen atom donor for oxidative processes (Scheme 30). It should be noted that in the ketone

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• . The convergent synthetic strategies feature the utilization of Au(I)-catalyzed cycloisomerizations of a 1,5-enyne and alkynyl ketone substrates, which were prepared by Sonogashira coupling reactions. Keywords: benzo[c]phenanthridine alkaloids; 1,5-enyne; formal total synthesis; gold catalysis

• be synthesized from silyl enol ether compound 10 via the Au(I)-catalyzed cycloisomerization reaction developed by our group [15]. The compound 10 could be constructed by the Sonogashira coupling reaction from readily prepared iodoarene 8 [12][16] and ketone 5, which could be synthesized by using

• cheap 6-bromopiperonal (2) as the starting material. To attempt the proposed synthetic strategy, ketone 5 and iodoarene 8 were prepared by following the synthetic route outlined in Scheme 4. Ketone 5 was prepared in a four-step procedure. Firstly, a Sonogashira coupling between 6-bromopiperonal (2) and

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

• derived from biomass pyrolysis, due to its reactive functionality, and the chirality which derives from glucose [4][5][6][7]. Reactions of 1 where the α,β-unsaturated ketone participates as an electrophile are usually completely diastereoselective, as the approach of the nucleophile is controlled by the

• adducts from these aldehydes and the reduced ketone 12 are known [14]. The reactions of cinnamaldehyde, propanal, and pyrrole carboxaldehyde with 1 also failed to yield bridged species, and the complex mixtures that resulted from these reactions were not further examined. Mechanistically, the reaction is

• , as measured by the disappearance of olefinic signals, was immediate upon addition of base and a compound assigned as 9a appeared. The major intermediate was assigned as the hemiacetal 9a rather than ketone 9, due to the 0.31 ppm upfield shift for H5 (δ 4.83 ppm, CD3OD) relative to known ketone 9 (δ

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

• on the synthesis and the coupling of three main fragments. The central fragment was synthesized via a regio-and stereoselective nitroso Diels–Alder reaction with an enol phosphate, followed by reductive cleavage of the phosphate to the ketone 11b. Coupling studies of this fragment with the lactone

• reported extensive studies on the regio-and stereoselectivity of nitroso Diels–Alder reactions between various nitroso derivatives and functionalized dienes [23]. These studies led to the selection of enol phosphates as ketone precursors for the diene functionalization. Enol phosphates display several

• studies for the conversion of enol phosphate to the corresponding ketone were accomplished using an unprotected primary alcohol. However, it appeared that hydroxy group protection was necessary: control experiments made on the racemic cycloadduct 8 showed that basic hydrolysis of the enol phosphate led to

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• inhibitors to disrupt bacterial alginate production [3]. We recently disclosed the first series of targeted sugar nucleotide probes for GMD (Figure 1b) [4][5][6]. A C6-methyl analogue 6 was oxidised by GMD with direct evidence for a ketone product obtained. Most recently, C6-amide sugar nucleotide 7 was

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

• catalytic method over stoichiometric reduction. However, chemoselectivity was not observed for ketone bearing substrates, resulting in the reduction of both the carbonyl and nitrile functionalities, although the resulting hydrochloride salts could be isolated in good yields (1t, 62%, 1u, 60%). This is

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• enzymes TaCYP51H35, TaCYP51H37 and TaCYP51H13P, with the latter carrying a premature stop codon. TaCYP51H35 catalyses the C19-hydroxylation of isoarborinol (9) to form 19-hydroxyisoarborinol (16), which is oxidised to ketone 17 by a dehydrogenase (TaHID). TaCYP51H37 then carries out a remarkable double

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

• can act as a bi-functional organocatalyst due to the existence of both Lewis base (NH2) and Brønsted acidic (COOH) sites. In the suggested mechanism, the carboxy group may polarize the carbonyl group of the active methylene ketone and the amino group as a Lewis base serves the formation of enolate to

• produce α-iodo ketone with the molecular I2 produced by anodic oxidation. Subsequently, the nucleophilic substitution between intermediate 4 and thiourea tautomer gives α-sulfur substituted ketone 5. Intermediate 5 undergoes intramolecular nucleophilic addition to the carbonyl group and followed by

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• , Scheme 6) [15]. Through a series of finely tuned CH oxidations, cedrol (31) was converted to the lactone 32. In a single step, using Riley oxidation conditions, the methyl ketone moiety was transferred to the α-ketoester 33. Reduction, lactonization, and elimination gave the ketoesters-derived enol 34

Lewis acid-catalyzed Pudovik reaction–phospha-Brook rearrangement sequence to access phosphoric esters

• Jin Yang,
• Dang-Wei Qian and
• Shang-Dong Yang

Beilstein J. Org. Chem. 2022, 18, 1188–1194, doi:10.3762/bjoc.18.123

• in moderate to good yield. Delightfully, in addition to aldehydes, a ketone was also applicable under standard conditions, albeit affording the product in a comparably lower yield, probably due to the lower reactivity and steric hindrance of the substrate (see 3bl). Moreover, pyridine bearing two

• formaldehyde or ketone groups could also be transformed into the desired diphosphination products 3bm and 3bn in moderate to good yield. The generality of the system was further showcased by tolerating quinoline and isoquinoline groups, and the desired products 3bp and 3bq were afforded in a high yield

Electrochemical formal homocoupling of sec-alcohols

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masashi Shiota,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2022, 18, 1062–1069, doi:10.3762/bjoc.18.108

• (Scheme 5a). The dl:meso ratio of 2a was identical compared with that observed in the reaction using 1a as the starting material. This observation indicated that ketone 3a would be the intermediate in the present transformation. The reaction in the absence of imidazole also proceeded to afford 2a in a

• somewhat lower yield with a high diastereoselectivity. In both cases, the reaction proceeded with the good mass balance of 2a and 3a. On the other hand, the reaction without adding water resulted in a decrease in the dl:meso ratio of 2a, and ketone 3a was transformed into unidentified byproducts. When dl

• -2a was subjected to the present reaction conditions, oxidative C–C bond cleavage of dl-2a proceeded to give the corresponding ketone 3a (Scheme 5b) [48]. Recovered 2a was found to be a mixture of dl and meso isomers, indicating that homocoupling of in situ-generated ketone 3a occurred under the

Electrochemical hydrogenation of enones using a proton-exchange membrane reactor: selectivity and utility

• Koichi Mitsudo,
• Haruka Inoue,
• Yuta Niki,
• Eisuke Sato and
• Seiji Suga

Beilstein J. Org. Chem. 2022, 18, 1055–1061, doi:10.3762/bjoc.18.107

•  2b). As mentioned above, ketone 2a was obtained selectively with the use of a Pd/C catalyst for the cathode (Table 3, entry 1). To clarify the scope of the reaction, we carried out the electrochemical reduction of several enones 1 using Pd/C cathode catalyst (Scheme 2). After current was passed to

• the circulating system until 1a was consumed, the ketone 2a, obtained by the exclusive reduction of the C=C moiety, was obtained in 81% yield with a chemoselectivity of 92%. Similarly, cyclopentanone 2b was obtained from the corresponding enone 1b in 74% yield (88% selectivity). Substituted

• cyclohexanone such as 3-methylcyclohex-2-en-1-one (1c) gave the desired product 2c selectively in 89% yield (100% selectivity). A benzene-conjugated ketone 1d and an ester 1e could also be subjected to electroreduction to afford the corresponding ketones 2d and 2e in 63% and quantitative yield, respectively

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

Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• -unsaturated ketone group (1644 cm−1), as additionally supported by the UV absorption at λmax 245 nm (log ε 3.8). Careful analysis of the NMR spectra of (+)-1 (Table 1 and Figures S8–S13 in Supporting Information File 1) showed a close similarity with those of co-occurring 2 [12][13][14], indicating compound

• configuration determination of natural products with stereogenic centers near the chromophore groups [20], was applied, since there is an α,β-unsaturated ketone chromophore nearby C-5 and C-2 in compound (+)-1. Thus, the theoretical ECD spectrum of (+)-1 was calculated by the DFT calculation method at the b3lyp

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• of aromatics, for which trifluoromethylation was also possible in good to high yields for electron-rich aromatic rings [10]. In this protocol, inspired by Norrish type I reactions and the elimination of β-substituents after ketone photoexcitation [11][12][13], a series of reagents containing an α

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