All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• quaternary carbon stereocenters in 86% yield. Reduction of aldehyde 119 and subsequent transesterification produced a lactone (not shown). It was exposed to SeO2 to install the allylic hydroxy group to give 120 in 65% yield. Upon catalytic hydrogenation of 120, alcohol 121 was formed. This alcohol 120 was

• produce 135 and 136 in 85% yield in the ratio of 1:1.16. A six-step synthesis from the major product 136 gave lactone 137. This compond was subjected to successive desilylation, OsO4-mediated dihydroxylation and subsequent oxidative cleavage of the C=C double bond with Pb(OAc)4 to give ketoaldehyde 138 in

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• contained ithomiolide A (3), a pyrrolizidine alkaloid derived γ-lactone, I. s. derasa carried the sesquiterpene α-elemol (8) in the androconia. These differences might be important for the reproductive isolation of the two subspecies, in line with previously reported low gene exchange between the two

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

• Tetsuya Sengoku,
• Koki Makino,
• Ayumi Iijima,
• Toshiyasu Inuzuka and
• Hidemi Yoda

Beilstein J. Org. Chem. 2020, 16, 2769–2775, doi:10.3762/bjoc.16.227

• yields. On the other hand, methylene-lactone-fused spirolactams could be delivered from the allyl adducts in high yields through a sequential N-Boc protection/desulfinative lactonization. Keywords: bifurcated synthesis; electrophilic amide allylation; α-methylene-γ-butyrolactam; α-methylene-γ

• -lactone derivatives spiro-fused to an oxindole (A), one of which exhibited a potent cytotoxic activity [9]. Our research group succeeded the enantiopure synthesis of these compounds, in which enantioselective allylation of an isatin derivative with an amido-functionalized allylstannane was employed as a

• reaction conditions and led to methylene-lactone-fused spirolactams 5a–h in excellent yields without exception (88–98% two-step yields). Thus, we established the bifurcated synthetic routes toward lactams spiro-fused to α-methylene-γ-butyrolactone or α-methylene-γ-butyrolactam by using 3-phenylthiolactams

Nocarimidazoles C and D, antimicrobial alkanoylimidazoles from a coral-derived actinomycete Kocuria sp.: application of ¹J_C,H coupling constants for the unequivocal determination of substituted imidazoles and stereochemical diversity of anteisoalkyl chains in microbial metabolites

• Md. Rokon Ul Karim,
• Enjuro Harunari,
• Amit Raj Sharma,
• Naoya Oku,
• Kazuaki Akasaka,
• Daisuke Urabe,
• Mada Triandala Sibero and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 2719–2727, doi:10.3762/bjoc.16.222

• actinomycete origin. For example, salinosporamide A, an antitumor drug candidate in clinical trials, is a proteasome inhibitor with an unusual γ-lactam-β-lactone bicyclic core produced by marine Salinospora tropica [10]. Abyssomicin, another example of uncommon polycyclic frameworks, is an antibacterial

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• the absence of the reagent. It is also worth mentioning that the bromolactone (rac)-17a was surprisingly stable against lactone ring-opening: the compound remained intact after 20 hours of reflux in methanol in the presence of a catalytic amount of H2SO4. Presumably, the halogen cation attacks from

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

Synthesis of 1,4-benzothiazinones from acylpyruvic acids or furan-2,3-diones and o-aminothiophenol

• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2020, 16, 2322–2331, doi:10.3762/bjoc.16.193

• 5a at the lactone carbonyl group, and the product 4a, when o-aminothiophenol’s NH2 group attacked compound 5a at the lactone carbonyl group. The in situ formation of 5-phenylfuran-2,3-dione (5a) was indicated by the appearance of bright yellow color (characteristic for the 5-arylfuran-2,3-diones 5 [6

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• (+)-sclareolide (C2 and C3) are remote from the lactone EWG and both form secondary radicals. Thus, the fluorination of these positions is presumably dictated by hindrance, given that the C3 position is neighbored by a gem-dimethyl group and is fluorinated to a lesser extent (22%). In both reports, the C2/C3

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• hydrogenation over Pt2O and then low-temperature DIBAL reduction afforded the all-cis tetrasubstituted tetrahydropyran 27. In Koide et al.’s synthesis, the unsaturated lactone 29 was prepared via the Wittig methenylation of 24, followed by aminal hydrolysis, methallylation of the 2° alcohol 28, and ring-closing

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• the corresponding acetate (4%, not shown), the bromomethyllactone 15 (8%), and alkene Z-13 (1%). Only lactone 14 could be isolated in a pure form (58% yield). The amount of HBr/AcOH had little influence on the selectivity (Table 4, entry 2) of the reaction. However, in the presence of TBAB (2.5 equiv

• ) and CSA (2 equiv) an 84% conversion into mainly brominated lactone 15 (79%) with traces of hydroxylated lactone 14, and of bromoalkene Z-13 was determined by crude 19F NMR. The remaining 8% appeared to be the β-chloromethyllactone 19 (see Scheme 7 below), an analogue of 15 as determined by NMR

• ). The former, using an excess of acid (33% HBr in AcOH solution) favored the direct nucleophilic attack (path b) leading to lactone 14, whereas the latter in the presence of TBAB/CSA allowed bromide addition on the same side of the fluorine atom (path a) leading to lactone 15 [31]. However, the reaction

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization

• Dominik Göbel,
• Marius Friedrich,
• Enno Lork and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139

• reduction with NaBH4 to give the primary alcohol 19. In contrast to benzaldehyde 7, carbaldehyde 18 showed no decomposition at ambient temperature. While acidic hydrolysis of 19 provided exocyclic γ-lactone 20, the substitution reaction with DPPA/NaN3 yielded the primary azide in 87% yield. In accordance to

NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

• Alyn T. Davies,
• Mark D. Greenhalgh,
• Alexandra M. Z. Slawin and
• Andrew D. Smith

Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129

• -substituted β-lactone products in a high yield, diastereo-, and enantioselectivity (Figure 2A) [46]. Chi and co-workers have reported limited examples of oxidative [2 + 2] cycloadditions using hydrocinnamaldehyde as an azolium enolate precursor and the NHC precatalyst 2, giving β-lactone products in high

• -aroyloxyaldehyde 4 and trifluoromethylacetophenone (5) as reactants began using the NHC precatalyst 3, triethylamine as the base, and THF as the solvent (Table 1, entry 1). A moderate conversion (48%, as determined by NMR analysis) to the desired β-lactone product 6 as a 70:30 mixture of diastereoisomers was

• , diethyl ether, and toluene showed no improvement upon the yield obtained with THF (Table 1, entries 4–6). Unfortunately, attempts to isolate the desired β-lactone product 6 were unsuccessful, with 6 being unstable to chromatographic purification under a variety of different conditions. As such, following

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

Anthelmintic drug discovery: target identification, screening methods and the role of open science

• Frederick A. Partridge,
• Ruth Forman,
• Carole J. R. Bataille,
• Graham M. Wynne,
• Marina Nick,
• Angela J. Russell,
• Kathryn J. Else and
• David B. Sattelle

Beilstein J. Org. Chem. 2020, 16, 1203–1224, doi:10.3762/bjoc.16.105

• macrocyclic lactone is an effective microfilaricide but does not kill the adult nematodes. Ivermectin must therefore be administered annually or twice-annually for many years to eliminate the parasite in the population. Progress has been impressive: onchocerciasis has been largely controlled as a public

Activated carbon as catalyst support: precursors, preparation, modification and characterization

• Melanie Iwanow,
• Tobias Gärtner,
• Volker Sieber and
• Burkhard König

Beilstein J. Org. Chem. 2020, 16, 1188–1202, doi:10.3762/bjoc.16.104

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• with zincate 11 using a variety of catalysts and different reaction conditions, was unsuccessful. However, coupling of 4-[bis(dimethoxybenzyl)difluoromethyl]benzyl bromide (14) with the lithium enolate of William`s lactone 15 gave the protected amino acid 16 in 80% yield. The desired protected amino

Towards the total synthesis of chondrochloren A: synthesis of the (Z)-enamide fragment

• Jan Geldsetzer and
• Markus Kalesse

Beilstein J. Org. Chem. 2020, 16, 670–673, doi:10.3762/bjoc.16.64

• obtained through a seven-step sequence starting from ᴅ-ribonic acid-1,4-lactone. The (Z)-vinyl bromide 4 is accessible in four steps from 4-hydroxybenzaldehyde. The pivotal cross coupling between both fragments was achieved after extensive experimentation with copper(I) iodide, K2CO3 and N,N

• )-bromide 4 we decided to use a (Z)-selective Buchwald-type reaction encouraged by the previous works of the Buchwald group on producing (E)-enamide coupling products [13][14][15]. The synthesis of the amide 3 started with TIPDS-protection of commercially available ᴅ-ribonic acid-1,4-lactone (5) (Scheme 1

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• the best copper-based photocatalyst, Collins and co-workers reported the synthesis of a bicyclic lactone by a PCET reaction manifold (Scheme 32) [39]. Using their methodology, the authors discovered the [Cu(I)(quinitri)(xantphos)]BF4 catalyst as the best one, which afford the cis-lactone in 79

• lactone synthesis using a copper-photocatalyzed PCET reaction. Photocatalytic Pinacol coupling reaction catalyzed by [Cu(I)(pypzs)(BINAP)]BF4. The ligands of the copper complex are omitted for clarity. Azide photosensitization using a Cu-based photocatalyst. Funding This work was partially supported by

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

• distributes in literature but is wrong because protons do not exist alone and data related to pH-values relate only to aqueous solutions. Ring opening by rhodamine B lactone quantitatively probed formation conjugate acid by formation of rhodamine B [5]. We interpret the term conjugate acid as a species in

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

• Kaj M. van Vliet,
• Nicole S. van Leeuwen,
• Albert M. Brouwer and
• Bas de Bruin

Beilstein J. Org. Chem. 2020, 16, 398–408, doi:10.3762/bjoc.16.38

• form in case of fac-[Ir(ppy)3]), which was proven by mass spectrometry and EPR spectroscopy for one of the catalysts (N,N-5,10-di(2-naphthalene)-5,10-dihydrophenazine) used in this work. The generation of HCl resulting from lactone formation could be an additional problem for organometallic photoredox

• catalysts used in this reaction. In an attempt to trap one of the radical intermediates with TEMPO, we observed a compound indicating the generation of a chloromethyl radical. Keywords: ATRA; catalysis; chloroacetic acid; lactone; photoredox; Introduction Monochloroacetic acid is an industrially important

• , Kokotos and co-workers published a visible light photoredox catalyzed lactone formation from iodoacetic acid and alkenes [29] (Scheme 1). In addition, it has been shown that monochloroacetic acid can be reduced by hydrated electrons [30][31]. The group of Goez developed a strategy for the photoredox

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• enantioenriched products (up to 99% ee) were successfully converted to relevant molecules, such as trans-whisky lactone [43]. In 2003, Hoveyda and Hird reported the first 1,4-addition of alkylmetal nucleophiles to α,β-unsaturated N-acyloxazolidinones (Scheme 19) [47]. The chiral triamidophosphane ligand L15a as a

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• lactone with the lithium salt of dimethyl methylphosphonate followed by an elimination step of the resulting hemiketal, leading to the corresponding exo- and endo-glycal derivatives. The ensuing selective monodemethylation and hydrogenolysis of the benzyl groups and reduction of the 4-azido group gave the

• Ara4N transferase reacted with the equatorial phosphodiester lipid, we opted to use lactone 4 as a suitable precursor for C-glycosyl phosphonates, based on literature precedents [10][20][21]. Thus, a modified Swern oxidation of lactol 3 with acetic anhydride in DMSO afforded a near-quantitative yield of

• lactone 4, which, however, was unstable towards chromatographic purification and used as crude material after lyophilization to remove the solvent. Coupling of 4 with the lithium salt of dimethyl methylphosphonate (5) in THF afforded the β-anomeric ketol phosphonate derivative 6 in 57% yield. The axial

A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones

• Daniel P. Pienaar,
• Kamogelo R. Butsi,
• Amanda L. Rousseau and
• Dean Brady

Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287

• solubility of both the KOt-Bu base and the acetonitrile derived KCH2CN salt. This effectively accelerates the generation of the latter and as such, its reaction with the lactone (or ester) carbonyl carbon. By increasing the solubility of the conjugate base salt, the pKa of acetonitrile in the ethereal

• alkoxide anions. This reduces the occurrence of undesirable side-reactions, e.g., intermolecular aldol reaction, lactone/ketonitrile product dimerization and ring-opening polymerization. The application of this method to produce the analogous hemiketal 6 from γ-butyrolactone was not as efficient. Although

• from lactone to 20% (Scheme 2). Due to the interest in the potential preparation of pyrimidines from β-ketonitriles and guanidine [18], we wanted to test the general applicability of this method for access to a variety of alkyl and aryl-substituted β-ketonitriles (as summarized in Table 1). When we