Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• -coumarins are a key intermediate for diverse natural products, and they have already been synthesized by various research groups with different procedures [132][133][134][135][136][137][138]. Inspired by previous work, Gomez and co-workers reported the preparation of benzo-3,4-coumarins using photoredox

Allylic cross-coupling using aromatic aldehydes as α-alkoxyalkyl anions

• Akihiro Yuasa,
• Kazunori Nagao and
• Hirohisa Ohmiya

Beilstein J. Org. Chem. 2020, 16, 185–189, doi:10.3762/bjoc.16.21

• ) species B. The 1,2-addition of silylcopper(I) B to the aromatic aldehyde 1 [15][16][17][18][19] and the subsequent [1,2]-Brook rearrangement from the obtained α-silyl-substituted copper(I) alkoxide C forms the key intermediate, an α-silyloxybenzylcopper(I) species D. The transmetallation between D and an

Attempted synthesis of a meta-metalated calix[4]arene

• Christopher D. Jurisch and
• Gareth E. Arnott

Beilstein J. Org. Chem. 2019, 15, 1996–2002, doi:10.3762/bjoc.15.195

• 5 in 44% yield which was comparable to the yields reported by Albrecht [20]. Synthesis of the calix[4]arene ruthenacycle Satisfied that the published methods worked in our hands, we then set about synthesizing the targeted mesoionic calix[4]arene ruthenacycle. Our first key intermediate was

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• grams without losing of yield) for the synthesis of key intermediate 8. In order to further improve the synthesis of the key intermediate triptophenolide methyl ether (8), van Tamelen and co-workers further developed a synthesis as shown in Scheme 4 (Figure 2, route F) [70]. This synthesis features two

• key cyclization precursor ketoester 15, which was cyclized in the presence of SnCl4 to give tricyclic intermediate 83, followed by steps of functional group modification to install the butenolide (D-ring), and to finish the racemic synthesis of the key intermediate triptophenolide methyl ether (8) in

• conversion of 89 to vinyl triflate 90, followed by reduction and palladium-catalyzed carbonylation–lactone formation to give key intermediate 8 [75][76][77]. After that, the three successive epoxides were installed by known procedures with some modification. The highlights were the introduction of the second

Application of chiral 2-isoxazoline for the synthesis of syn-1,3-diol analogs

• Juanjuan Feng,
• Tianyu Li,
• Jiaxin Zhang and
• Peng Jiao

Beilstein J. Org. Chem. 2019, 15, 1840–1847, doi:10.3762/bjoc.15.179

• well tolerate PTSA-catalyzed methanolysis. Conclusion In conclusion, we synthesized tert-butyl (3S,5R)-6-hydroxy-3,5-O-isopropylidene-3,5-dihydroxyhexanoate (16), which is enantiomeric to a key intermediate for atorvastatin, from a chiral 2-isoxazoline (3). The β-hydroxy ketone 7 obtained from 3 could

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• selective desilylation and N-debenzylation with simultaneous N-Boc protection and served as a key intermediate for installation of a dimethylhexylene fragment in Julia–Kocienski olefination [56]. Pyrrolidine alkaloids (−)-hygrine ((S)-61) and (−)-hygroline ((2S,2'S)-62) were isolated from many natural

• hydrolysis. Installation of the allyl group at the nitrogen atom required prior derivatization as an oxazolidin-2-one and Birch reduction to furnish 204. To construct a properly functionalized piperidine ring olefin metathesis was performed to supply the key intermediate 205. Taking advantage of the steric

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Enantioselective PCCP Brønsted acid-catalyzed aza-Piancatelli rearrangement

• Gabrielle R. Hammersley,
• Meghan F. Nichol,
• Helena C. Steffens,
• Jose M. Delgado,
• Gesine K. Veits and
• Javier Read de Alaniz

Beilstein J. Org. Chem. 2019, 15, 1569–1574, doi:10.3762/bjoc.15.160

• hypothesized that a PCCP-derived catalyst could be used. It is proposed that the chiral anion moieties serve to interact with the key intermediate 5 during the enantiodetermining electrocyclization step [35][36][37]. A tentative mechanistic hypothesis for the asymmetric aza-Piancatelli is shown in Figure 1

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• allyldioxazaborolidine 11), respectively. The tetronate building blocks 4 and 5 were further converted to the corresponding enolates using lithium diisopropylamide and allowed to react with the common key intermediate 3 to afford the hydroxyalkylated products 18 and 19, in 78% and 59% yield, respectively (Scheme 4

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

• Alexander N. Reznikov,
• Anastasiya E. Sibiryakova,
• Marat R. Baimuratov,
• Eugene V. Golovin,
• Victor B. Rybakov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2019, 15, 1289–1297, doi:10.3762/bjoc.15.127

• ) complexes [56]. The above considerations lead to the use of β-ketosulfones in the Ni(II)-catalyzed reaction, since the proposed mechanism [47], that involves the formation of cyclic Ni enolate, and the high CH acidity of ketosulfones (pKa 9.8–10.5 [4]). The formation of the key intermediate can be provided

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• ). For this reason, another strategy of obtaining high % ee of d was employed. Chiral resolution of racemic-d with (R)-menthyl chloroformate gave a high % ee of this key intermediate d. After column chromatographic purification of the crude reaction mixture, the corresponding diastereomers (R)-e or (S)-e

Efficient synthesis of 4-substituted-ortho-phthalaldehyde analogues: toward the emergence of new building blocks

• Clémence Moitessier,
• Ahmad Rifai,
• Pierre-Edouard Danjou,
• Isabelle Mallard and
• Francine Cazier-Dennin

Beilstein J. Org. Chem. 2019, 15, 721–726, doi:10.3762/bjoc.15.67

• the addition of a protecting step of the unstable key intermediate 4,5-dihydroisobenzofuran-5-ol. Oxidation and deprotection steps were also studied in order to provide an effective availability of these two dialdehyde compounds that may increase their future applications. Keywords: demethylation

• ). To our delight, the remarkable stability of the methoxy group under the same synthesis conditions introduces the key intermediate 4-methoxyphthalaldehyde (5b) with an excellent conversion rate and minimal OPA formation (Table 2, entry 6). Compound 5b was then isolated by column chromatography in 63

• key intermediate 4,5-dihydroisobenzofuran-5-ol (3) before reaching the oxidation step. The methoxy protecting group and the DDQ oxidation reagent were found to be the most efficient. Moreover, deprotection of 4-methoxy-ortho-phthalaldehyde (5b) was successfully achieved using [Bmim]Br and p-TsOH on

Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

• -identical functional groups on the primary side. Three different types of reactions were investigated to obtain 6A-monoazido-6X-monotosyl-β-CD (a key intermediate for the preparation of various hetero-difunctionalized β-CDs), having three possible regioisomers and consequently three pairs of

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• as key intermediate. A [2 + 2] cycloaddition with a second olefin leads to the formation of intermediate IV, followed by a retro [2 + 2] cycloaddition that regenerates catalyst I and releases the metathesis product. This visionary mechanistic proposal was later confirmed by experimental studies [17

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• key intermediate of the domino sequence (Scheme 1, reaction 1). Taking into account the capability of 2-iminochromenes to perform as Michael acceptors [39][40][41], we envisioned the diversification of the substitution pattern at the chromene ring to be a realizable and an appealing target

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• yield for two steps. The silyl group of compound 22 was cleaved using tetrabutylammonium fluoride (TBAF) in THF to form alcohol 23 which was used directly in the next step [48]. At this stage, we envisioned that 23 could be also a key intermediate to access the ristosamine derivative by reversing the

• for access to 3-amino glycals. Synthesis of key intermediate 23 for the C-3 unbranched amino glycals preparation. Access to diastereoisomeric compounds 3 and 4 from 23. Supporting Information Supporting Information contains detailed experimental procedures with full characterization of all compounds

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• pyrrolidine-based hamamelitannin analogues is depicted in Scheme 1. The synthesis of 4 as a key intermediate allows to gain access to a diverse set of analogues by chemoselective late-stage derivatization of the pyrrolidine nitrogen. Previously, we used the iminosugar 5 to prepare a series of 2

Oxidative and reductive cyclization in stiff dithienylethenes

• Michael Kleinwächter,
• Ellen Teichmann,
• Lutz Grubert,
• Martin Herder and
• Stefan Hecht

Beilstein J. Org. Chem. 2018, 14, 2812–2821, doi:10.3762/bjoc.14.259

• ][47] as the key intermediate undergoing thermal cyclization or cycloreversion, typically in the context of so-called “ECE” and “EEC” mechanisms, respectively [48]. To contribute to this discussion, nonsymmetrical DAEs bearing two electronically distinct aryl moieties (CF3- and Me-thiazole) [5] or

Unprecedented nucleophile-promoted 1,7-S or Se shift reactions under Pummerer reaction conditions of 4-alkenyl-3-sulfinylmethylpyrroles

• Takashi Go,
• Akane Morimatsu,
• Hiroaki Wasada,
• Genzoh Tanabe,
• Osamu Muraoka,
• Yoshiharu Sawada and
• Mitsuhiro Yoshimatsu

Beilstein J. Org. Chem. 2018, 14, 2722–2729, doi:10.3762/bjoc.14.250

• key intermediate 15, of which the sulfanyl group would intramolecularly migrate to produce 16 stereoselectively (path c, not d). The hydrolysis of 16 using TBAH yields diol 17. We further confirmed the mechanism of the 1,7-S shift reaction by performing density functional theory (DFT)-based

• calculations (Table 2) [36]. Whether the reactions lead to the formation of pyrroloazepines or diols clearly depends on the substituents in the alkenyl group. We performed DFT calculations for the reaction pathways starting from the key intermediate 14 bearing methyl and phenyl groups. The DFT-calculated ΔG

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• key intermediate 13 removing the p-methoxybenzyl group [24][26][27][28] from 11 failed. Finally, compound 13 was successfully obtained by modifying the sequence of reactions. Deprotection of compound 10 with TFA [24], followed by selective alkylation with benzyl tosylate as previously described

A novel and practical asymmetric synthesis of eptazocine hydrobromide

• Ruipeng Li,
• Zhenren Liu,
• Liang Chen,
• Jing Pan,
• Kuaile Lin and
• Weicheng Zhou

Beilstein J. Org. Chem. 2018, 14, 2340–2347, doi:10.3762/bjoc.14.209

• ][12][13]. In our prior publication [14], this method was selected as the technology for the development of a process to prepare (R)-(+)-1-(5’-bromopentyl)-1-methyl-7-methoxy-2-tetralone, a key intermediate of dezocine, and N-(p-trifluoromethylbenzyl)cinchonidinium bromide (3) among 17 cinchona

Studies towards the synthesis of hyperireflexolide A

• G. Hari Mangeswara Rao

Beilstein J. Org. Chem. 2018, 14, 2106–2111, doi:10.3762/bjoc.14.185

• cyclopentane 5, a functionalized key intermediate, is presented. Compound 5 is involved in hydrolysis, α-allylation at C-8 and α-methylation at C-10 stereoselectively from the convex face. Then it is subjected to cross metathesis to give α,β-unsaturated ketone 11 as precursor in the total synthesis of

A switchable [2]rotaxane with two active alkenyl groups

• Xiu-Li Zheng,
• Rong-Rong Tao,
• Rui-Rui Gu,
• Wen-Zhi Wang and
• Da-Hui Qu

Beilstein J. Org. Chem. 2018, 14, 2074–2081, doi:10.3762/bjoc.14.181

• [36] were synthesized according to the previous literature. The key intermediate compound 5, containing a prior DBA recognition station and possessing alkynyl and ethylenic groups at two terminals respectively, was prepared from aldehyde 1 and amine 2. A “Schiff base” reaction was introduced at first

• alcohol with saturated NH4PF6 solution to obtain compound 5. For another key intermediate 8, containing an amide site for stabilizing the DB24C8 macrocycle, a 1,2,3-tris(dodecyloxy) benzene group as a stopper and an azide group which is used for the reaction with other moieties, was prepared through the

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• the sulfonamidation of other heterocycles and was not successful. The authors attribute this lack of reactivity to the limited oxidising power of the excited acridinium salts and to the relative instability of the heterocyclic radical cation, which is a key intermediate in the proposed mechanism

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• using PIDA (15) at 4 °C (Scheme 41). This oxidative cyclization of enamide substrate 113 afforded synthetically useful spiroenamide 114, which was used as key intermediate for total synthesis of annosqualine (1). The synthesis of natural product 1 was achieved in two steps starting from synthesized

• compound 136 was achieved in 87% yield by the reaction of PIDA (15) with the naphthol derivative 135 in trifluoroethanol at room temperature. Additionally, synthesized compound 136 was used as key intermediate in the total synthesis of natural products 137 and 138 (Scheme 50). Additionally, more analogues

• -mediated radical cyclization wherein the oxazaspiroketal moiety is formed which is further used as key intermediate for the synthesis of the natural product cephalostatin. Additionally, spiroketals 159 were also synthesised by enatioselective spirocyclization of ortho-substituted phenols 158 using similar