Construction of CF₂ moieties in FDA-approved drugs (2016–2025): industrial routes, mechanisms, and scale-up considerations

• Wenyan Yao,
• Huanhuan Zhang,
• Xiaolong Yang and
• Feng Liu

Beilstein J. Org. Chem. 2026, 22, 1122–1150, doi:10.3762/bjoc.22.91

• esterification before fluorination. The yields for esterification and fluorination were 85% and 88% for the methyl ester [12], and 90% and 76% for the ethyl ester [13], respectively (the yield for the benzyl ester was not reported [14]). Route e proceeds via Curtius rearrangement first, followed by fluorination

Synthesis and acaricidal activity against Varroa destructor of α- and γ-costic acid dimers

• Alessandro Santarsiere,
• Ernesto Santoro,
• Maria Letizia Ciavatta,
• Marianna Carbone,
• Sonia Ganassi,
• Cosimo Tedino,
• Antonio De Cristofaro,
• Antonio Evidente and
• Stefano Superchi

Beilstein J. Org. Chem. 2026, 22, 1088–1096, doi:10.3762/bjoc.22.87

• homo- and heterodimers 4, 6, and 7 (Scheme 1). Accordingly, the formation of dimer of 6 with ethylene glycol was first attempted under classical acid-catalyzed Fischer esterification conditions, in the presence of p-toluenesulfonic acid (pTsOH) (Scheme 1). However, these conditions led to isomerization

• of 1 into γ-costic acid (3) which was isolated together with its dimeric ester 4. On the contrary, Steglich esterification, achieved under basic catalysis by treating α-costic acid (1) with 1.0 equiv of ethylene glycol in the presence of dicyclohexylcarbodiimide (DCC) and a catalytic amount of N,N

• -dimethylaminopyridine (DMAP), provided the monoester 5 and no trace of isomerization products. Finally, both the α-costic acid homodimer 6 and the α/γ-costic acid heterodimer 7 were obtained by Steglich esterification of 5 with α-costic acid (1) and γ-costic acid (3), respectively (Scheme 1). The acaricidal activity of

Amino acid-based surfactants: sustainable synthesis and antimicrobial mechanisms

• Rafaela Gomes Bezerra,
• Lourdes Pérez and
• Francisco Fábio Oliveira de Sousa

Beilstein J. Org. Chem. 2026, 22, 1067–1085, doi:10.3762/bjoc.22.85

• groups (e.g., Fmoc or Boc) to ensure precise amino acid incorporation, followed by amidation or esterification reactions to anchor the alkyl chain [65]. Such controlled synthetic pathways enable the creation of structurally refined surfactants, optimized for applications ranging from antimicrobial agents

Chiral cyclopropenimine-catalyzed enantioselective Michael reactions of phenol and benzofuran-derived α,β-unsaturated pyrazolamides with benzophenone-imine of glycine esters

• Ya Bai,
• Xue-Ying Wang,
• Si-Kai Zhu,
• Yan-Ting Shen,
• Sheng-Yong Zhang and
• Ping-An Wang

Beilstein J. Org. Chem. 2026, 22, 888–896, doi:10.3762/bjoc.22.69

• in organic synthesis. Many medicines and intermediates contain these two motifs and show diverse functions and bioactivities [1][2]. The esterification and etherification of phenols are some of their common modifications. 2-Substituted benzofurans are backbones for many medicines such as amiodarone

Preparation of 3-(alkylamino)imidazo[1,2-a]pyridine-2-carbaldehydes via Kornblum oxidation and unexpected ring-opening reactions of the corresponding alcohols under oxidative conditions

• Sandile J. Mkhize,
• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2026, 22, 763–770, doi:10.3762/bjoc.22.58

• isocyanide, the glyoxylic acid had undergone in situ esterification in the presence of methanol and the acid catalyst. On scaling the reaction (≈2 g aminopyridine), the originally anticipated unsubstituted products 12a–d were prepared as the sole products in yields ranging from 31% to 57%. Once again, only

• starting material was recovered from reaction of compound 9e. In order to prevent possible mixtures of the two products being formed with slight variation in reaction conditions, the reaction to prepare ester 13 was properly optimised to ensure that full in situ esterification of the glyoxylic acid had

Synthesis of depressin, cryptomeridiol and 4-epi-cryptomeridiol enabled by a terpenoid chiral pool-producing platform

• Yao Kong,
• Tao Wang,
• Chen Wang,
• Pengcheng Zhang,
• Yuanning Liu,
• Kaibiao Wang,
• Fen Liu,
• Hongli Jia and
• Zhengren Xu

Beilstein J. Org. Chem. 2026, 22, 683–690, doi:10.3762/bjoc.22.53

• the benzoate ester for reductive deoxygenation were not successful [63], and 13a/b decomposed in the esterification step. We have finally found that the 13-hydroxy group could be smoothly removed by the methyl oxalyl ester deoxygenation method [64][65]. Thus, 13a/b were esterified with methyl

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• epoxide 98. Deprotection of the alcohol motif of 98 enabled the cyclization towards tetrahydropyran 99. Next, 99 underwent an esterification with acrylic acid, was cyclized via Grubbs metathesis and the remaining double bond was hydrogenated leading to bicyclic core structure of 101. Notably, during the

• esterification with EtI were conducted to form 318. TBDPS-protection and reduction yielded alcohol 319 in 58%, which was further oxidized to the respective aldehyde and olefinated leading to a 4:1 (Z/E) mixture of 320. The isomers were separated via chromatography, then, (Z)-320 was deprotected under acidic

Recent advances in the cleavage of non-activated amides

• Eun-Sol Choi and
• Hyo-Jun Lee

Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23

• . Keywords: amide; amide activation; esterification; non-activated amide; transamidation; Introduction Serving as a cornerstone in organic chemistry, the amide bond is a fundamental and extensively utilized functional group, playing a central role in natural products, biomolecules, and functional materials

• employed as reliable tools to activate amide bonds through coordination with the amide oxygen lone pair [45]. Although the substrate scope of such methods remains limited, several successful examples with hindered amides have recently been reported. In 2019, Shimizu et al. reported the esterification of

• intermediate E, the carboxylic acid is formed, regenerating the acidic and basic surface sites of the Nb2O5 catalyst. In 2020, Mashima et al. reported an intriguing accelerating effect of potassium alkoxides on the manganese-catalyzed esterification of tertiary amides (Scheme 4) [48]. They found that potassium

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

• –Villiger oxidation to 95b and finally rearomatisation and esterification to give cephanolide D (96) from fortunolide A (95). The complex sesquiterpenoid illisimonin A (97, see Scheme 25) was isolated in 2017 and traced back biosynthetically to FPP (9) and the cedrane cation 97a [146]. From here a 1,2-alkyl

• isomers (128b) of the aldol addition is privileged to undergo intramolecular esterification to give alstoscholarinoid B (125). The configuration of the other isomer 128c has been reportedly isolated already in 2002 by Kuo and Chiang [182]. For alstoscholarinoid A (124) an analogous oxidative cleavage and

• (via cations 132c and 132d) and finally elimination to give 132e, with the full skeleton assembled. After selective oxidation of the C-16 position giving 132f, spiroacetal formation and esterification with the side-chain ketone affords spirochensilide A (131). The A-ring-seco triterpenoid holophyllane

A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives

• Dmitrii A. Grishin,
• Kseniia I. Sharkovskaia,
• Ilya G. Kolmakov,
• Daria A. Ipatova,
• Rostislav A. Petrov,
• Nikolai D. Dagaev,
• Dmitry A. Skvortsov,
• Maria G. Khrenova,
• Valeriy V. Andreychev,
• Sergei A. Evteev,
• Yan A. Ivanenkov,
• Roman L. Antipin,
• Olga А. Dontsova and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18

• conditions. Subsequent transformations afford isopropyl and cyclohexyl analogues via hydrolysis–esterification. A preliminary biological evaluation revealed low cytotoxicity and modest antibacterial activity against Escherichia coli ΔtolC strains. This sustainable synthetic approach constitutes the first

• the influence of esterification on biological activity. Preliminary results indicated that compounds of this chemotype may possess antibacterial potential, forming the basis for the present study on their synthesis and biological evaluation. A literature survey revealed that derivatives of 3-(4

• esterification of acids 11a–c afforded the isopropyl esters 12a–c in 71–98% yields. Similar attempts were made using cyclohexyl alcohol both as reagent and solvent in Fischer–Speier esterification; however, difficulties in purifying the reaction mixtures due to the large excess of alcohol prevented isolation of

Synthesis of diaryl phosphates using phytic acid as a phosphorus source

• Kazuya Asao,
• Seika Matsumoto,
• Haruka Mori,
• Riku Yoshimura,
• Takeshi Sasaki,
• Naoya Hirata,
• Yasuyuki Hayakawa and
• Shin-ichi Kawaguchi

Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15

• with a recovery of 4.2% and then conducted an esterification reaction using the extracted phytic acid and phenol. As a result, diphenyl phosphate with a yield of 44% was obtained. This work can facilitate the development of an environmentally friendly method for producing phosphate esters that does not

• esterification with alcohols using sustainable biomass-derived phytic acid as a phosphorus source (Figure 2E). This approach can facilitate the development of environmentally friendly phosphate ester production as well as phosphorus recovery and recycling techniques. To date, the preparation of phosphate esters

• stopcock for water removal. The reaction conditions for this synthesis procedure were based on the results of our previous study dedicated to the esterification of phosphoric acid and phenols [15] (see Scheme 2). Under the optimized reaction conditions in our previous work, the reaction yield of phosphate

Circumventing Mukaiyama oxidation: selective S–O bond formation via sulfenamide–alcohol coupling

• Guoling Huang,
• Huarui Zhu,
• Shuting Zhou,
• Wanlin Zheng,
• Fangpeng Liang,
• Zhibo Zhao,
• Yifei Chen and
• Xunbo Lu

Beilstein J. Org. Chem. 2026, 22, 158–166, doi:10.3762/bjoc.22.9

• PIDA-mediated oxidative esterification of sulfenamides, rely on stoichiometric hypervalent iodine reagents and have not demonstrated broadly efficient reactivity with sterically demanding or chiral alcohols such as ʟ-menthol, where only modest conversion was observed in our hands. Motivated by these

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

• this dual catalytic strategy (Scheme 9) [59]. Organic dual catalysis enabled by visible-light-induced NHC and photoredoxcatalysts In 2018, Miyabe et al. reported an innovative organocatalytic method for the oxidative esterification of functionalized cinnamaldehydes 24. Dual photocatalysis, employing

• NHC (5 mol %) and rhodamine 6G (5 mol %), promoted the facile esterification of arylvinyl aldehydes 24 with BrCCl3 (3 equiv) and K2CO3 (2.5 equiv) in MeOH under visible-light irradiation. In contrast, oxidative esterification of the formyl group was also achieved via dual photocatalysis. Furthermore

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

• protected prior to the RCM step. Oxidative cleavage of the cyclopentene followed by Pinnick oxidation of the resulting aldehyde to the carboxylic acid and esterification yielded ketoester 56. Dieckmann condensation of 56, esterification of the resulting enolate with 57, and subsequent one-pot partial

• trans-esterification to give lactone 78. The resulting tertiary alcohol was protected as its benzyl ether to afford 79. A two-step oxidation protocol, analogous to Yang’s method, introduced the C8 carbonyl group, yielding 80. The final ring was closed via an intramolecular aldol reaction following

• starting materials [32]. This synthesis features a pentafulvene-based intramolecular [6 + 2] cycloaddition [41][42] and a nitroso-Diels–Alder reaction [43] as key steps. The route began with the esterification of pentafulvenol 82 to give β-ketoester 83, which was subsequently converted to the sterically

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

• )allylium tetrafluoroborate, which was then coupled to the C3 hydroxy group via Yamaguchi esterification. Global deprotection subsequently afforded ryanodine (1) in 10 steps, thus achieving this critical synthetic transformation. Although the interaction of ryanodine with intracellular calcium release

• , and introduction of an isopropenyl group afforded compound 75. Subsequent protection of the vicinal diol as a boronic ester and diastereoselective reduction of the C3 carbonyl group yielded compound 76. Esterification with acylating reagent 77 under basic conditions, followed by boronic ester removal

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

• ketal moiety was removed and the resulting intermediate underwent Wittig olefination to yield vinyl chloride 20. Subsequent hydrolysis and intramolecular esterification furnished intermediate 21, which was then subjected to C–H insertion [42][43][44]. To our disappointment, this ring closure still did

A chiral LC–MS strategy for stereochemical assignment of natural products sharing a 3-methylpent-4-en-2-ol moiety in their terminal structures

• Rei Suo,
• Raku Irie,
• Hinako Nakayama,
• Yuta Ishimaru,
• Yuya Akama,
• Masato Oikawa and
• Shiro Itoi

Beilstein J. Org. Chem. 2025, 21, 2243–2249, doi:10.3762/bjoc.21.171

• Discussion Our degradation strategy of natural products bearing an MPO moiety includes (1) acylation of hydroxy group, (2) oxidative cleavage of olefin to generate 3-acyloxy-2-methylbutanoic acid, and (3) its methyl esterification (Scheme 1A). We initially investigated derivatization strategies to enable LC

• obtained suffered from co-evaporation during solvent removal under reduced pressure, which led us to consider that degradation of the natural product to obtain the corresponding fragment would be challenging. Accordingly, esterification of the hydroxy group at C3 in 3, and suitable acyl groups were then

• that at C8–C9, and (3) methyl esterification (Scheme 2). The resulting C9–C12 fragment 7 was successfully detected at m/z 304.1 [M + Na]+ by LC–MS, as expected (see Figure 2b for the chromatogram). We then proceeded with the stereoselective synthesis of four diastereomers; 4-methoxy-3-methyl-4-oxobutan

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• solvent and Pd as catalyst played a vital role for achieving a high yield. Efficient subsequent esterification and quaternarization to diesterquat fabric softeners demonstrated that high-value chemicals could be produced fully biobased from GCA as the starting platform (Scheme 2). GCA can also be used as

• irradiation was proven to be thermally, chemically and sunlight stable. The esterification of trans-3-(2-furyl)acrylic acid with ethanol, provided (1α,2α,3β,4β)-2,4-di(furan-2-yl)cyclobutane-1,3-dicarboxylic acid (CBDA-5) via a solvent-free [2 + 2] photodimerization from ethyl 2-furanacrylate and subsequent

• , amides, lactones, acrylic acid, etc. (Scheme 72) and is therefore a key intermediate in the synthesis of pharmaceuticals, agrochemicals, and other specialty chemicals. Levulinate esters, used as a solvent or as biofuels, are obtained by esterification under acid catalysis, e.g., with a sulfuric acid

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• underwent the 1,2-addition of isopropenyllithium reagent (prepared from n-BuLi/tetraisopropenyltin (67) [55]) and DMP oxidation to afford ketone 68. A three-step transformation including RCM, Mukaiyama hydration, and esterification, 68 was converted to methyl oxalate 69. Irradiation of the reaction mixture

Measuring the stereogenic remoteness in non-central chirality: a stereocontrol connectivity index for asymmetric reactions

• Ivan Keng Wee On,
• Yu Kun Choo,
• Sambhav Baid and
• Ye Zhu

Beilstein J. Org. Chem. 2025, 21, 1995–2006, doi:10.3762/bjoc.21.155

• the other hand, if the bond formation/cleavage is within the macrocycle, the stereochemical differentiation atoms are traced to the stereogenic arene. Therefore, the CALB-mediated esterification to cyclophenes [21] is [53], regardless of the length of the linkage (CH2)n (Scheme 5D). In recent years

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• . Lipases commonly share typical sequences of α-helices and β-strands and possess a catalytic triad consisting of serine (Ser), histidine (His), and aspartate (Asp) or glutamate (Glu). These three amino residues function as a nucleophile-base–acid catalytic system to facilitate esterification, and the

• general mechanism of a reaction catalyzed by lipases is illustrated in Scheme 1. Additionally, the diverse three-dimensional structures of lipases confer enantioselectivity in lipase-catalyzed esterification [24][25]. Moreover, their commercial availability makes lipases an attractive option for preparing

• 103 in two steps. With the fragments 100 and 106 in hand, the synthesis of (−)-rasfonin proceeded via Yamaguchi esterification between the two fragments to obtain lactone 107 (Scheme 15c). A subsequent two-step transformation yielded compound 108, which underwent Stille coupling with (E)-2-bromobutene

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• acid substrates 43 which, upon treatment with ynamide 44, yielded the vinyl acetate intermediate INT-A (Scheme 13). Subsequently, the one-pot CPA-catalyzed intramolecular esterification of this intermediate afforded the planarly chiral macrocycles 45 with good yield and high enantioselectivity

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

Calcium waste as a catalyst in the transesterification for demanding esters: scalability perspective

• Anton N. Potorochenko and
• Konstantin S. Rodygin

Beilstein J. Org. Chem. 2025, 21, 1520–1527, doi:10.3762/bjoc.21.114

• of δ-valerolactone (4e) successfully led to the opening of the ring structure of the lactone and the formation of methyl 5-hydroxypentanoate (5e) in 91% yield at a catalyst loading of 1 wt % and for 3 h. The transesterification of triglycerides obtained from the esterification of linear saturated C5

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• hydrostatic pressure (HHP) was found to be an efficient activation method in several catalyst- and solvent-free reactions and has found application for the syntheses of heterocycles and the preparation of active pharmaceutical ingredients (APIs) via acylation and acid- and solvent-free esterification. The

• Mannich reactions [20], lipase-catalyzed esterification [21], nitro-aldol [22], Michael [23], and aza-Michael reactions [24][25], Diels–Alder reactions [26][27] and Friedel–Crafts alkylation of indoles [28]. Many high pressure reactions were applied in natural product synthesis [29]. The high pressure

• of important heterocycles, the synthesis of well-known APIs, such as acetaminophen and acetylsalicylic acid, a variety of esterification reactions and the successful scale up (up to 100 g scale) of the Paal–Knorr reaction. The use of HHP appears to provide several advantages, for example, resulting