Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• absorption and metabolism, and specific moieties like rhamnose can enhance CG potency markedly by more than 25 times [1][7]. In addition, the -OH groups on the steroids’ structure also play an important role on their activity. However, these compounds are mainly isolated from plants or animals, which not

• [19]. In addition, rhodexin A exhibits a strong antiproliferation activity due to the ability to inhibit the synthesis of hypoxia inducible factor 1 (HIF-1α) [20]. Thus, rhodexin A shows high value in medicinal research. Structurally, rhodexin A consists of two parts, the cardenolide aglycon

Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• ) [63]. Glacial acetic acid (AcOH) was initially selected as a hydrophilic (polar) protic solvent due to its high dipole moment, which makes it ideal for microwave reactions, as well as its ability to facilitate simple work-up procedures by simple addition of water [64]. Using sodium acetate (NaOAc) as

• an additive resulted in low reaction yields of the desired product 3a (Table 1, entries 1 and 2). The addition of an aliphatic amine (piperidine) to the reaction medium significantly improved the yields (Table 1, entries 3 and 4). In the absence of NaOAc, only a slight decrease in yield was observed

• condensation reactions involving rhodanine derivatives (26 examples). In addition, it requires a lower catalyst loading (10 mol %) and eliminates the need for further purification steps. EDDA has also been employed in reactions for the synthesis of heterocyclic compounds such as tetrahydroquinolines [67

Silica gel with covalently attached bambusuril macrocycle for dicyanoaurate sorption from water

• Michaela Šusterová and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2025, 21, 2604–2611, doi:10.3762/bjoc.21.201

• 1 M KOH, followed by addition of dicyanoaurate ([Au(CN)2]−) to the supernatant. It was shown previously that the absorption spectrum of dicyanoaurate in aqueous solution changes upon formation of an inclusion complex between the anion and a bambusuril macrocycle [17]. A solution of dicyanoaurate in

• is only physically adsorbed on SG. However, upon addition of chloride anions, either as tetrabutylammonium (TBA) or sodium salt, BnBU formed a complex with the anion and dissolved in chloroform and dichloromethane and even in methanol. Thus, SG-BnBU remained stable only in water in the absence and

• presence of salt showing it is suitable for applications in an aqueous environment. SG-BU1 proved to be stable in chloroform, dichloromethane, and methanol even after addition of TBACl or NaCl, respectively. We did not detect any release of BU1 from SG-BU1 in aqueous phosphate buffer by NMR, but we

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• system involves the efficient nucleophilic addition of an imidazolyl anion B to radical cation species A, generated via single-electron oxidation of electron-donating arenes 31. The azolide anion B is released from acylimidazole 9 through an addition/elimination sequence in the presence of an NHC

Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• enantioenriched compound 33, a nickel-catalyzed hydrocyanation of the terminal alkyne was performed. Subsequent protection of the tertiary alcohol with TESOTf and reduction of the resulting cyanide to an aldehyde afforded compound 34 (Scheme 4). Addition of isopropenyllithium to aldehyde 34, followed by TES

• , deprotonation, and intramolecular addition to ketone. Treatment of the silacycle with MeMgCl cleaved the Si–O bond and subsequent intramolecular nucleophilic substitution of the chloride with the adjacent hydroxy group yielded TMS-epoxide 41. Protonic acid-mediated opening of the TMS-epoxide, accompanied by TES

• -mediated N–O bond cleavage afforded carbamate 90. The carbamate was converted to a carbonyl group via Boc deprotection with TFA, oxidation of the resulting amine to the oxime with Na2WO4 and H2O2, and subsequent reduction with TiCl3·HCl to give 91. The LaCl3·2LiCl-mediated methyl addition to the carbonyl

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• -alkoxy bridgehead radical addition then installed an allyl fragment, and ring-closing metathesis (RCM) smoothly formed the C ring to complete the core skeleton. The total synthesis was finalized by installing the four remaining stereocenters (C2, C3, C9, and C10). The specific synthetic route is as

• hemiacetalization to construct the oxa[3.2.1]-bridged ring system, thereby forming the D and E rings. Subsequently, the introduction of a tertiary hydroxy thiocarbonate at C11 afforded compound 38. Under thermal conditions, 38 underwent smooth introduction of an allyl fragment via intermolecular radical addition

• route commenced from (−)-pulegone. After introducing oxidation states at C6 and C10 and installing an alkynyl group at C11, oxidative cleavage of a double bond yielded the key propargylic alcohol intermediate 66. This compound underwent a 1,2-addition with alkynyl Grignard reagent 67, and the resulting

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• Abstract The total synthesis of bioactive (+)-aglacin B was achieved. The key steps include an asymmetric conjugate addition reaction induced by a chiral auxiliary and a nickel-promoted reductive tandem cyclization of the elaborated β-bromo acetal, which led to the efficient construction of the

• aryltetralin[2,3-c]furan skeleton embedded in this natural product. Keywords: aryltetralin; conjugate addition; cyclolignan; nickel; reductive coupling; Introduction Proksch and co-workers isolated aglacins A, B, C, and E (1–4, Figure 1) from the methanolic extract of stem bark of Aglaia cordata Hiern from

• that the diarylmethine stereocenter at C7′ in 6 could be formed by an Evans’ auxiliary-induced asymmetric conjugate addition of α,β-unsaturated acyl oxazolidinone 7 with 3,4,5-trimethoxyphenylmagnesium bromide (8). Both of these two building blocks could be conveniently prepared from commercially

Pentacyclic aromatic heterocycles from Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles

• Kaylen D. Lathrum,
• Emily M. Hanneken,
• Katelyn R. Grzelak and
• James T. Fletcher

Beilstein J. Org. Chem. 2025, 21, 2524–2534, doi:10.3762/bjoc.21.194

• ring itself to also include benzophenanthridine, dibenzonaphthyridine, and benzophenanthroline heterocycles of previously unreported identity (Figure 2). In addition to studying how naphthalene, quinolone, and isoquinoline incorporation impact click and annulation efficiency, characterizing the

Isoorotamide-based peptide nucleic acid nucleobases with extended linkers aimed at distal base recognition of adenosine in double helical RNA

• Grant D. Walby,
• Brandon R. Tessier,
• Tristan L. Mabee,
• Jennah M. Hoke,
• Hallie M. Bleam,
• Angelina Giglio-Tos,
• Emily E. Harding,
• Vladislavs Baskevics,
• Martins Katkevics,
• Eriks Rozners and
• James A. MacKay

Beilstein J. Org. Chem. 2025, 21, 2513–2523, doi:10.3762/bjoc.21.193

• addition of the acyl chloride to excess 9 was important to avoid forming bis-acylation of the phenylenediamine. The carboxylic acid 13 was formed using a microwave-promoted ring opening of glutaric anhydride (11) and benzyl-protected PNA backbone 12 [38]. A series of optimizations was performed in a

• . Db3 Synthesis The synthesis of Db3 was originally envisioned to be completed with an unprotected aniline nitrogen, however, this proved problematic in the PNA synthesis. The ultimate route was developed to have an N-Boc protected monomer (Scheme 3). The synthesis started with a conjugate addition of m

Effect of a photoswitchable rotaxane on membrane permeabilization across lipid compositions

• Udyogi N. K. Conthagamage,
• Lilia Lopez,
• Zuliah A. Abdulsalam and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2498–2512, doi:10.3762/bjoc.21.192

• the total release observed upon addition of rotaxanes 1-E and 1-Z in the absence of light. In these highly disordered and fluid bilayers, incorporation of rotaxane 1 alone is sufficient to induce substantial membrane permeability, depleting the vesicles of most dye within the first minutes. Even

• rotaxane 1-Z would convert to 1-E over that timescale. Nevertheless, the results clearly show that heating above Tm enhances release. We next evaluated the effect of light irradiation on rotaxane 1 in DPPC. At 25 °C, the initial addition of 1-Z resulted in only a 3% release after 5 minutes. Irradiation at

• 8:2 LUVs without light irradiation. Rotaxane 4 caused significantly more release than 1, with 59% for 4-E versus 29% for 1-E, and 33% for 4-Z versus 16% for 1-Z after 70 minutes of exposure (Figure 8b). Both isomers, 4-E and 4-Z, caused substantial release immediately upon addition. For 4-Z, release

Assembly strategy for thieno[3,2-b]thiophenes via a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate

• Roman A. Irgashev

Beilstein J. Org. Chem. 2025, 21, 2489–2497, doi:10.3762/bjoc.21.191

• addition to potassium thioacetate, the reactivity of ester 1 was investigated with other related S-nucleophiles, such as potassium ethyl xanthate (KSC(S)OEt), sodium diethyldithiocarbamate (NaSC(S)NEt2) as well as thioacetamide in the presence of K2CO3 and Na2S2 (Table 1, entries 2–5). In each case, the

• reactions, probably involving ester hydrolysis or alkylating agent decomposition, can be avoided by omitting the external base. In addition, Na2S2O4 was investigated as a reductant in a DMF/water 9:1 (v/v) mixture at room temperature (Table 2, entry 6). In the presence of both K2CO3 and the alkylating agent

• formation of carboxylic acid 9bA, isolated in 71% yield (Scheme 7). In addition, an attempt to cyclize 6b in the presence of DBU without a solvent at 110 °C led to significant destruction of the substrate and product 9b was obtained with a yield of about 20%. Cyclization of substrate 4a with NaH in toluene

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• addition to cross-coupling reactions, transition metal-catalyzed cyclization involving C–H activation approaches have also been reported [29][30][31][32][33][34][35][36]. Despite the significant advances in carbazole core constructions, the established protocols significantly lack access to selectively C1

• thoroughly characterized by 1H and 13C NMR spectroscopy, HRMS, and single-crystal X-ray diffraction analysis (Figure 1). A range of solvents was subsequently screened; however, none provided an improvement over 1,4-dioxane for this transformation (Table 1, entries 2 and 3). In addition to AgNO3, other silver

Synthesis of the tetracyclic skeleton of Aspidosperma alkaloids via PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction

• Ru-Dong Liu,
• Jian-Yu Long,
• Zhi-Lin Song,
• Zhen Yang and
• Zhong-Chao Zhang

Beilstein J. Org. Chem. 2025, 21, 2470–2478, doi:10.3762/bjoc.21.189

• leads to ketene D, which can undergo cycloaddition with an alkene to yield E. This fragmentation pathway dominates under various conditions (e.g., transition-metal catalysis, nucleophilic addition) and is driven by ring-strain release [11]. PET, an alternative to direct excitation and EnT, enables the

• formation of IN1. The radical cation IN1 served as the reference point for DFT investigations. As illustrated in Figure 2a, facilitated by a favorable radical cation–π interaction [31], IN1 proceeds to the first radical addition transition state (TS1), with an energy barrier of 8.3 kcal/mol. This leads to

Ex-situ generation of gaseous nitriles in two-chamber glassware for facile haloacetimidate synthesis

• Nikolai B. Akselvoll,
• Jonas T. Larsen and
• Christian M. Pedersen

Beilstein J. Org. Chem. 2025, 21, 2465–2469, doi:10.3762/bjoc.21.188

• of various trifluoromethyl-containing aza-heterocycles, such as pyridines [2], pyridinones and pyrimidinones [3], tetrazoles [4], tetrazapentalenes [5] and uracil [6]. In addition, it has also been used for the synthesis of fluoro-substituted ketones [7] and substituted trifluoroacetamides via the

• used building blocks in glycosylations. For the synthesis chamber (A) was loaded with trifluoroacetamide (6 equiv) in pyridine. In the other chamber (B), the hemiacetal (ca. 500 mg, 1 equiv) was dissolved in CH2Cl2 together with a catalytic amount of DBU. Upon addition of trifluoroacetic anhydride

• (TFAA, 5 equiv) to the acetamide in chamber A gas bubbles were observed within seconds. Hence the formation of trifluoroacetonitrile can easily be controlled by the speed of addition of TFAA. After complete addition the reaction was left for some time to ensure sufficient reaction time as TLC analysis

Catalytic enantioselective synthesis of selenium-containing atropisomers via C–Se bond formations

• Qi-Sen Gao,
• Zheng-Wei Wei and
• Zhi-Min Chen

Beilstein J. Org. Chem. 2025, 21, 2447–2455, doi:10.3762/bjoc.21.186

• phenyl-substituted benzoisoquinoline derivatives. Two plausible reaction mechanisms were proposed in the study: one involving oxidative addition of Int 4, a five-membered rhodium cyclic intermediate, followed by reductive elimination and the other proceeding via a bimolecular nucleophilic substitution

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• comparative study of two effective and practical oxidizing agents, hydroxy(tosyloxy)iodobenzene (HTIB) and thallium nitrate trihydrate (TTN·3H2O), was presented in the ring contraction reaction of protected 1,2-dihydronaphthalenes using trimethylorthoformate (TMOF). In addition, various protective groups were

• from 18% to 34% (Scheme 20). Analysis of literature data [58] indicated that the thallium(III) salt is a much better oxidizing agent than iodine(III) for indane syntheses. Similarly, the TTN-mediated reactions are less prone to form addition by-products compared to the HTIB-mediated reactions of 1,2

• phase. Benzyl esters were cleaved, and the resulting carboxylic acids were converted into corresponding benzylammonium salts by addition of two equivalents of benzylamine. Subsequent irradiation of these salts in the form of a crystalline suspension in hexane led to ring-contraction products with a 95

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• scaffolds. From the standpoint of organic chemistry, it is evident that these compounds can be efficiently converted into a variety of versatile organic intermediates through the application of ring-opening reactions [49][50][51][52]. In addition to the aforementioned useful properties, the current methods

• days). In addition, it can be seen that out of these three solvents, only methyl laurate is readily biodegradable on the basis of environmental risk factors (in the OECD 301C modified MITI (I) test, a substance can be considered ready biodegradable if 60% of the substance is mineralized in 28 days (in

• given in Supporting Information File 1, Figure S1). In addition to the calculations already outlined, a series of toxicity properties of methyl laurate were calculated using ADMETLab 3.0 in comparison with common organic solvents and some green solvents. The obtained results were visualized with a

An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives

• Elizaveta V. Gradova,
• Nikita A. Ozhegov,
• Roman O. Shcherbakov,
• Alexander G. Tkachenko,
• Larisa Y. Nesterova,
• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183

• , a highly diastereoselective method for the synthesis of dihydrospiro[indoline-3,2'-pyrrole]-2-ones has been developed (Scheme 1, path a) [7]. This transformation proceeds via a Lewis acid-mediated conjugate addition of vinyl azides to electron-deficient alkenes, followed by denitrogenative

• yield substituted spiropyrrolidines (Scheme 1, path b) [9]. Additionally, an organocatalytic, enantioselective Michael addition/cyclization sequence of 3-aminooxindole Schiff bases with terminal vinyl ketones, catalyzed by a cinchona-derived base, has been reported to afford chiral spiroindolylpyrroles

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• featuring a novel Pd-catalyzed β-lactone formation [29]. In addition to these approaches, Nelson and co-workers reported a very concise and impressive total synthesis of vibralactone involving photochemical valence isomerization of substituted pyrone, cyclopropanation, and ring expansion [30]. Zeng, Liu and

Conformational effects on iodide binding: a comparative study of flexible and rigid carbazole macrocyclic analogs

• Guang-Wei Zhang,
• Yong Zhang,
• Le Shi,
• Chuang Gao,
• Hong-Yu Li and
• Lei Xue

Beilstein J. Org. Chem. 2025, 21, 2369–2375, doi:10.3762/bjoc.21.181

• spectroscopy. Results and Discussion Partial 1H NMR spectra of PBG and WDG after binding to tetrabutylammonium iodide (TBAI) are presented in Figure 2a and 2b, respectively. All 1H NMR titrations were conducted at a fixed concentration of 8.7 mM. With the addition of 2 equivalents TBAI, the NH peak on the PBG

• groups inside the macrocycle and thus causes the NH peak to be shifted downfield. At the same time, after the addition of TBAI to the PBG solution, both proton signals c/d and e/f were shifted downfield, while protons a/b moved slightly to higher field, confirming the interaction between the anion and

• mechanism, while rigid WDGs are limited by the preorganization effect and can only achieve weak hydrogen bonding through conformational selection. In addition, the changes in the chemical shifts of the above two structures lead us to believe that the two structural analogs undergo conformational changes

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• temporal precision in activating systems, and the ability to fine-tune responses by adjusting wavelength, intensity, and exposure time. Additionally, photoswitchable molecules can often operate reversibly without generating chemical waste or requiring the addition of chemical fuels [4][5]. In the last

• fluorescence quenching phenomena with aggregate-induced emission (AIE) in aqueous media. They synthesized a [2]rotaxane with one dithienylethene unit as a stopper, and one BAA and one urea binding site, as well as one DB24C8 macrocycle with a tetraphenylethene (TPE) fluorophore [16] (Figure 7). Addition of

• base results in the deprotonation of the ammonium site and shuttling of the macrocycle to the urea site. Whereas, upon addition of acid, the macrocycle returns to the protonated BAA site. Notably, the rotaxane exhibited high fluorescence intensity due to aggregation in acetonitrile with high water

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• -oxidized analog and complanadines D and E are partially reduced analogs. In addition, natural analogs such as lycoplatyrine A (6), isolated as a mixture of diastereomers, were discovered as derivatives of lycodine and an amino acid [11]. Biosynthetically, lysine was proposed to be the starting point of

• in four steps. Subsequent conjugate addition of the lithium anion of TMS-acetonitrile to 15, followed by careful one-pot protonation of the resulting enolate with ethyl salicylate and TMS removal with CsF, gave 16 bearing three properly arranged substituents. Grignard 1,2-addition to ketone 16

• alkyne-nitrile partner, the undesired regioisomer (2,2’-bipyridyl product) was obtained as the major product. Switching the alkyne-nitrile partner from 19, bearing a benzyl group, to the formyl-substituted partner 23, combined with addition of 8 equivalents of PPh3, successfully inverted the

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• (C6F5)3B triggered a Meinwald rearrangement, generating aldehyde 66. Nucleophilic addition, oxidation of the resulting alcohol, and base-promoted epimerization at C6 of 67' delivered 67. Subsequent dihydroxylation of the alkene in 67 and protection of the resulting 1,2-diol as a cyclic carbonate

• delivered 68. A one-pot desilylation/oxidation of 67 produced an aldehyde, which was subject to selective nucleophilic addition in the presence of a ketone, allowing for access to the furan precursor 68 [37]. Oxidation–cyclization–aromatization of 68 with Dess–Martin periodinane (DMP) constructed the

• (50) and D (52), respectively. Alternatively, nucleophilic addition of MeOH to 54a and 56a, followed by ring-opening elimination, arrived at the corresponding γ-keto aldehyde intermediates 72/73. Subsequent intramolecular aldol cyclization of these intermediates furnished gracilisoids C/G (51/55) and

Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• that β-cyclodextrin (Figure 1)-based polymers could remove organic micropollutants from water [15][16]. For example, in 2021, Sessler and co-workers reported the synthesis of a calix[4]pyrrole (Figure 1)-based porous organic polymer, which exhibits the rapid uptake of dyes from water [17]. In addition

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• infections. The preparation of 2-halo-2-deoxy-ᴅ-ribose derivatives can be achieved via the modification of the parent sugar [9][10] or chain-elongation strategies from lower homologues. For example, Castro and co-workers have demonstrated the synthesis of a dichlorinated 2-deoxypentose via the addition of

• morpholine via an aza-Michael addition and condensation (Scheme 3). It was envisaged that the β-amino group could act as a stable functional group resulting in Baylis–Hillman-like reactivity. An extensive survey of reaction conditions using Selectfluor and N-fluorobenzenesulfonimide (NFSI) as the sources of

• between was biased to 16 and not 5, gave full consumption of the starting material in 2 hours and the fluorinated product 7c was obtained in 18% yield. Attempts to combine the methanol addition reaction and the fluorination starting with LGO proceeding through 16 were unsuccessful. Although the yield was