Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae

• Jia Tang,
• Yixiang Zhang and
• Yudai Matsuda

Beilstein J. Org. Chem. 2024, 20, 638–644, doi:10.3762/bjoc.20.56

• polyketide portion [11][12][13][14]. One exception has been found in funiculolide biosynthesis, in which a 5-MOA-derived phthalide undergoes dearomatizing prenylation catalyzed by the UbiA-like prenyltransferase FncB (Figure 1B) [15]. In addition to prenyltransferases, transmembrane terpene cyclases play a

• ring in 1 (Figure 2B). Taken together, this observation suggests that the desired production system was successfully established. Notably, although the native substrate of FncB is believed to be the phthalide form of 5-MOA (Figure 1B) [15], this result demonstrates that it can also efficiently accept 5

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• acid (17), the formation of a complex mixture was observed, the main component of which turned out to be phthalide (19). The use of 2-bromoethanol (20) gave a similar result – compound 21 was transformed under the action of DBU into a multicomponent mixture of unidentifiable compounds. Judging from the

• under basic conditions resulting in achiral product 25. No proton signals related to the expected cyclization product were detected in the proton NMR spectrum. The formation of phthalide from compound 18 under the action of base is difficult to explain. In this case, for some reason, the nucleophilic

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

• 1 M HCl without dehydration in refluxing cat. PPTS/toluene (Table 1, entries 2–4 and 7). From 5,6-dimethoxy substrate 1d, phthalide 4d was also formed together with naphthol 3d (Table 1, entry 4). In contrast, phthalides 4e and 4f were the sole products in the reactions of 6-methoxy and 4,5,6

• -trimethoxy substrates 1e and 1f (Table 1, entries 5 and 6). In the reaction of methyl 2-benzoylbenzoate (1h), the reduced product, 3-phenylphthalide (i), was formed mainly in 42% yield accompanied by phthalide 4h in 24% yield (Table 1, entry 8). On the other hand, the electroreduction of 1a–h with methyl

• acrylate (2c) is much less reactive as an acceptor in this reaction as shown in Scheme 6. The main product in this case was the same dimeric phthalide 9 as the product without the acceptor. These results suggest that this reaction proceeds with the radical addition of A to form anion D (path a). Next, the

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

• somewhat similar to coumarin is phthalide (50), having a sweet and powdery scent reminiscent of coconut and tonka bean [43]. Phthalide can be considered as a top note type of coumarin. Recently, Noël and co-workers developed a method for the photochemical, decatungstate-catalyzed C–H oxidation of activated

• and unactivated alkanes, including the transformation of isodihydrobenzofuran (47) to phthalide (50, Scheme 11) [44]. In this reaction, the decatungstate anion is activated by irradiation in a 3D-printed tube reactor using LED light with a wavelength of λ = 365 nm. It is assumed, that the photoexcited

• state of the decatungstate anion generates carbon-centered radical 48 which is trapped in a segmented flow with molecular oxygen provided by a mass flow controller. Peroxide 49 is formed as intermediate which further reacts to phthalide (50) in 71% yield. This method efficiently utilizes the advantages

Regioselective cobalt(II)-catalyzed [2 + 3] cycloaddition reaction of fluoroalkylated alkynes with 2-formylphenylboronic acids: easy access to 2-fluoroalkylated indenols

• Tatsuya Kumon,
• Miroku Shimada,
• Jianyan Wu,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2020, 16, 2193–2200, doi:10.3762/bjoc.16.184

• reaction of the CF3-containing phthalide B prepared from the 1,2-diester A with the Ruppert–Prakash reagent (TMSCF3) in the presence of a catalytic amount of CsF (Scheme 1a). According to this paper, phthalide B reacted smoothly with phenylthiomethyllithium to give the corresponding CF3-containing indanone

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• leads to the formation of isoindolinone derivative 13 in 55–65% global yields, without isolating any intermediate. Regarding the reaction mechanism, the authors have ruled out that phthalide must be an intermediate of the reaction and they proposed the two pathways illustrated in Scheme 3. In the first

• ) and a subsequent addition of enolate 37 onto the aldehyde moiety in 33, with concomitant decarboxylation and cyclization to form a phthalide intermediate 38 (Scheme 10). Then, the known amine-substitution reaction would transform phthalide 38 into isoindolinone 36. A conceptually very similar

Nucleophilic fluoroalkylation/cyclization route to fluorinated phthalides

• Masanori Inaba,
• Tatsuya Sakai,
• Shun Shinada,
• Tsuyuka Sugiishi,
• Yuta Nishina,
• Norio Shibata and
• Hideki Amii

Beilstein J. Org. Chem. 2018, 14, 182–186, doi:10.3762/bjoc.14.12

• good yields. Keywords: cyclization; fluorine; lactone; phthalide; trifluoromethylation; Introduction Phthalides (1(3H)-isobenzofuranones) are frequently found in natural products and exhibit a range of bioactivity (Scheme 1) [1][2]. Substituted phthalides have been used as building blocks for the

• and hexafluoroacetone to give 3-(trifluoromethyl)phthalide derivatives [11]. In 2006, Pedrosa et al. reported the nucleophilic trifluoromethylation of protected ortho-phthalaldehyde, followed by deprotection and oxidation to afford 3-(trifluoromethyl)phthalide [12]. Pohmakotr et al. demonstrated the

• . An operational simple procedure for a short-step synthesis of 3-(trifluoromethyl)phthalide is required due to their great potential in a variety of applications. Herein, we wish to report a general and convenient synthesis of 3-(perfluoroalkyl)phthalides 1 by nucleophilic perfluoroalkylation of 2

Preparation and isolation of isobenzofuran

• Morten K. Peters and
• Rainer Herges

Beilstein J. Org. Chem. 2017, 13, 2659–2662, doi:10.3762/bjoc.13.263

• phthalic acid (2) or phthalic acid ester 3 to 1,2-bis(hydroxymethyl)benzene (4) [19], acid promoted ring closure, and subsequent oxidation with hypochlorite in the presence of methanol gives 7 in a moderate yield of 65% [18]. Alternatively, phthalide 5 has been reduced to 1,3-dihydroisobenzofuran-1-ol (6

Sustainable synthesis of 3-substituted phthalides via a catalytic one-pot cascade strategy from 2-formylbenzoic acid with β-keto acids in glycerol

• Lina Jia and
• Fuzhong Han

Beilstein J. Org. Chem. 2017, 13, 1425–1429, doi:10.3762/bjoc.13.139

• reaction; phthalide; Introduction The phthalides, also known as isobenzofuran-1(3H)-ones, are an important class of heterocycles which are of continued interest for chemists [1][2]. 3-Substituted phthalides, which are recognized as versatile building blocks found in a large number of bioactive compounds

Regiodefined synthesis of brominated hydroxyanthraquinones related to proisocrinins

• Joyeeta Roy,
• Tanushree Mal,
• Supriti Jana and
• Dipakranjan Mal

Beilstein J. Org. Chem. 2016, 12, 531–536, doi:10.3762/bjoc.12.52

• afforded phthalide 23 in 61% yield. NBS bromination of 23 afforded the 3-bromophthalide [33], which on treatment with dioxane/water furnished phthalaldehydic acid 24 in 69% yield over two steps [34]. Treatment of 24 with KCN furnished 3-cyanophathalide 12 in 75% yield analogously as described in references

• [35][36][37]. The structure of phthalide 12 was confirmed by the appearance of a singlet at δ 5.84 (s, 1H) in the 1H NMR spectrum and the appearance of a characteristic band for the C≡N stretching frequency at 2260 cm−1 in the IR spectrum. The characteristic carbon for the cyano functionality appeared

Electrocarboxylation: towards sustainable and efficient synthesis of valuable carboxylic acids

• Roman Matthessen,
• Jan Fransaer,
• Koen Binnemans and
• Dirk E. De Vos

Beilstein J. Org. Chem. 2014, 10, 2484–2500, doi:10.3762/bjoc.10.260

• already been implemented on an industrial scale, like for example the electrohydrodimerisation of acrylonitrile (Scheme 4) [32], or the production of p-methoxybenzaldehyde [33]. Another interesting industrial process is the simultaneous production of phthalide and tert-butylbenzaldehyde dimethylacetal

• reaction [16][17][18][19][20]. Electroreduction of carbon dioxide to formic acid, methanol or methane. Electrochemical fixation of CO2 in olefins. Electrohydrodimerisation of acrylonitrile to adiponitrile [32]. Parallel paired electrosynthesis of phthalide and tert-butylbenzaldehyde dimethylacetal [34

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• envisioned. Respective silyl-substituted diynes 16 can be traced back to phthalide (17). To differentiate between the insertion of two differently substituted silylacetylenes, the lactone 17 had to be first converted into a monoprotected diol for further transformations. Synthesis of dialkyne building blocks

• strategy. We started our investigation with the reduction of commercially available phthalide (17) by LiAlH4 into dialcohol 18 in quantitative yield [28] (Scheme 4). The polar compound was easily converted into the mono-TBS-protected substrate by utilization of 1 equivalent of TBSCl [29]. Column

Marilones A–C, phthalides from the sponge-derived fungus Stachylidium sp.

• Celso Almeida,
• Stefan Kehraus,
• Miguel Prudêncio and
• Gabriele M. König

Beilstein J. Org. Chem. 2011, 7, 1636–1642, doi:10.3762/bjoc.7.192

• 10.3762/bjoc.7.192 Abstract The marine-derived fungus Stachylidium sp. was isolated from the sponge Callyspongia sp. cf. C. flammea. Culture on a biomalt medium supplemented with sea salt led to the isolation of three new phthalide derivatives, i.e., marilones A–C (1–3), and the known compound silvaticol

• ]. During our search for new natural products produced from the marine-derived fungus Stachylidium sp., several phthalide derivatives, i.e., marilones A–C, were isolated from a culture on agar-BMS media supplemented with artificial sea salt (Scheme 1). Albeit phthalide-like structures are not rare, the

• carbonyl carbon C-1. Ring double bond equivalents required a second ring within compound 1, and together with heteronuclear correlations of 8-H to C-1 and the carbon resonance of C-1 at δC 168.2 indicating the presence of a carbonyl group, this gave evidence for a C-8-methylated phthalide skeleton, i.e

Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

• Charles Dylan Turner and
• Marco A. Ciufolini

Beilstein J. Org. Chem. 2011, 7, 1475–1485, doi:10.3762/bjoc.7.171

• as the sole product. The aldehyde underwent tandem addition of the anion of simple phthalide (a model for 20; prepared from the parent compound by deprotonation with LDA) and dehydration via mesylate 26 to provide 27, which upon reaction with EtOLi (EtOH + BuLi) in THF rearranged to diketone 28

Total syntheses of oxygenated brazanquinones via regioselective homologous anionic Fries rearrangement of benzylic O-carbamates

• Glaucia Barbosa Candido Alves Slana,
• Mariângela Soares de Azevedo,
• Rosângela Sabattini Capella Lopes,
• Cláudio Cerqueira Lopes and
• Jari Nobrega Cardoso

Beilstein J. Org. Chem. 2006, 2, No. 1, doi:10.1186/1860-5397-2-1

• condensed aromatics. We found this route very attractive and envisaged that by in situ treatment of intermediate 4 with the third equivalent of sec-BuLi, the cyclization to the desired quinone 1a-d would be obtained. One unexpected result was the formation of the phthalide 9 when the dimethoxy carbamate 2d

• described. This methodology could be expanded in the future for the construction of new molecules with similar structures. Examples of carbanionic aromatic chemistry rearrangements. Retrosyntheses of Brazanquinones (1). Total syntheses of brazanquinones (1 a-c). Total syntheses of phthalide (9). Supporting