Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• compounds 132a–e. Spiro androstanemorpholinones 133a–e were synthesized through the lactonization of the amino esters by treatment with sodium methoxide. Intramolecular transesterification was favored by a high volume of solvent and a low quantity of base, which helped to avoid undesired intermolecular side

• peroxide solution or a mixture of bis(trimethylsilyl)peroxide and trimethylsilyl trifluoromethanesulfonate. In any case, the spiro products were afforded as a mixture of diastereomers. Finally, tetraoxanes 167d and 168d were synthesized by basic hydrolysis of the methyl esters 167a and 168a (Scheme 43

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• the chemo-enzymatic approach for synthesizing this family of natural products [57]. Regioselective macrocyclization: tylactone and juvenimicins In the chemical synthesis of macrolides, macrolactone construction most generally involves the generation of activated esters from the corresponding

• monooxygenases JuvC and JuvD for post-macrocyclization oxidative modifications. Based on the successful cloning and high-level overexpression of the two key PKS modules, JuvEIV and JuvEV, cascade enzymatic conversions of 77 were conducted. The SNAC (N-acetylcysteamine) esters 78 and 79 were used as surrogates

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• -fructofuranosidase were expressed in E. coli [41]. Both enzymes can work together to effectively degrade inulin. Lipases are enzymes that can hydrolyze various fatty esters and find applications in the detergent, oil, and pharmaceutical industries. The lip4346 is a novel lipase-encoding gene cloned from the

• -Hydroxybenzoate esters The first group of secondary metabolites described from the genus Microbulbifer were 4-hydroxybenzoate (4HBA, 1) and three alkyl esters (butyl, heptyl, and nonyl, 2–4, Figure 6). Commonly known as parabens, these molecules were isolated from a tropical ascidian-derived Microbulbifer sp. A4B

• -695 showed antimicrobial activity against E. coli [14]. Bioassay-guided fractionation led to the isolation of two new acetamidobenzoate esters: bulbiferate A (13) and bulbiferate B (14, Figure 6). Their structures were established on the basis of comprehensive spectroscopic and spectrometric data

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• groups proceeded smoothly to afford the corresponding benzylamines 2b–d in moderate-to-good yields. Electron-withdrawing groups, such as esters, can be tolerated under these conditions. Unfortunately, the electrochemical reduction of 1,4-dicyanobenzene (1f) did not give the desired product 2f probably

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• positions was observed when both positions were present, as highlighted by the formation of 19 and 20 in equal yields from the same substrate. In the same year, Yoneda and co-workers reported the electrochemical benzylic fluorination of four phenylacetic acid esters and 1-tetralone (Figure 38) [96]. Et4N

• . Electrochemical benzylic C(sp3)–H fluorination with 1-ethyl-3-methylimidazolium trifluoromethanesulfonate ([emim][OTf]) and HF·amine reagents. Electrochemical benzylic C(sp3)–H fluorination of phenylacetic acid esters with HF·amine reagents. Electrochemical benzylic C(sp3)–H fluorination of triphenylmethane with

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• esters, the so called "Barton esters", for decarboxylative cyanation of aliphatic acids with tosyl cyanide as the nitrile source under visible light irradiation at room temperature [21][22]. Although two synthetic steps are required, this is the first practical decarboxylative cyanation protocol because

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• intramolecular synthetic strategies. Immense applications in the synthesis of hydroxy acids and esters, heterocycles, fused carbocycles, natural products, and others with broad substrate scope have raised profound interest from methodological and synthetic standpoints. The ongoing development of reagents

• enantioselective intramolecular Cannizzaro reaction of aryl and alkyl glyoxals 1a–h and alcohol 2 using trisoxazoline (TOX) ligand (4)/copper catalysts to furnish the requisite mandelic esters 3a–h in good yields (greater than 90%) and high enantioselectivity. This was observed in the wide substrate scope as

• represented below (Scheme 2) [34]. Morken and coworkers [36] set forth an intramolecular Lewis acid-mediated Cannizzaro reaction of aryl glyoxals 7 at room temperature using appropriate chromium or copper catalysts. The strategy afforded moderate to good yields of Mandelic esters 8 in the presence of Cr(ClO4

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• , such as iridium complexes or organic dyes, and activating agents, including dimethyl dicarbonate (DMDC) and PPh3. Redox-active esters are created when activating agents and carboxylic acids react. These esters can then be reduced using a photoredox catalyst to produce the acyl radical. In 2019, Doyle

• presence of alkene, alkyne, halogen, and ether moieties. N-Boc-protected amines and esters also provided a good to excellent yield. Unfortunately, α,β-unsaturated carboxylic acids and aliphatic carboxylic acids were ineffective using this method. In 2024, Liu and co-workers [31] introduced a photocatalytic

• to convert aliphatic alcohols into boronic esters. At first, aliphatic alcohols are functionalized into 2-iodophenyl thionocarbonates that can facilitate a visible-light-mediated Barton–McCombie radical deoxygenation (Scheme 7). The reaction is free from photocatalyst, radical initiators, or

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• conditions [113]. Both diene and dienophile systems are readily soluble in the reaction medium of interest under the conditions studied, in contrast to aqueous media. The non-polar aprotic nature of vegetable oils and wax esters makes them inert to many reagents, as in this study. The reaction was completed

• , which are readily available from a large number and variety of natural sources around the world, fatty acids and wax esters, can be excellent alternative reaction media to existing conventional and green solvents for IMDAF reactions. This study reveals the first utilization of these materials as

Oxidative hydrolysis of aliphatic bromoalkenes: scope study and reactivity insights

• Amol P. Jadhav and
• Claude Y. Legault

Beilstein J. Org. Chem. 2024, 20, 1286–1291, doi:10.3762/bjoc.20.111

• transformations, cementing their position as a go-to option for organic chemists. Based on our continued interest in iodine(III)-mediated chemistry, we have explored numerous strategies in oxidative transformations such as direct α-tosyloxylation of ketones [12][13][14], and the oxidation of enol esters [15][16

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• chromones, presumably due to the electron-donating character of the methoxy group and the lower electrophilicity of the chromone. But this trend was also not general. Similar yields were obtained for ketones (R3 = Me, Ph) or esters (R3 = OMe). Treatment of 2-(salicyloyl)furan 35a with iodine in the presence

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• , which leads to the formation of a considerable amount of waste [52][53][54]. The BH approach allows a sustainable way for building C–C bonds by coupling abundant and cheap alcohols with ketones, nitriles, esters, and amides [4]. C–C Bond formation via alkylation of ketones with alcohols Several

• the same year, Milstein and co-workers accomplished the α-alkylation of esters, ketones, and amides using alcohols as alkylating agents with a PNP-pincer-supported manganese catalyst [59]. First, the α-alkylation of ketones with benzylic and aliphatic alcohols was studied using Mn11 (1 mol %) as

• catalyst and t-BuOK as a base at 125 °C for 18 h in toluene which afforded up to 95% yield of the desired alkylated ketones (Scheme 28A). Later, the more challenging esters and amides were selectively alkylated with alcohols, however, required higher catalyst loading (5 mol %) and a stoichiometric amount

Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines

• Vladislav V. Nikol’skiy,
• Mikhail E. Minyaev,
• Maxim A. Bastrakov and
• Alexey M. Starosotnikov

Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94

• , for example a formyl group. Thus, the key isonitroso compounds 7 were synthesized from chlorides 1a–c via in situ formation of pyridylacetoacetic esters 2a–c followed by decarbonylation to give 2-methyl-3-nitropyridines 5a–c [24] which were used in the next step without purification. Their reactions

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• ., in two different periods, reported two paradigmatic examples for indole syntheses. In 2010, they developed the synthesis of 1-(alkoxyarylmethyl)indole-3-carboxylic esters from 2-alkynylaniline imines by using PdI2/KI as catalyst system and oxygen as oxidant [15]. In particular, the reaction was

• years later, they performed, using the same catalytic and oxidative conditions, another oxidative heterocyclization/alkoxycarbonylation process for the synthesis of N-substituted indole-3-carboxylic esters and N–H free indole-3-carboxylic esters from N-substituted 2-alkynylanilines and 2-alkynylanilines

• the formation of N-substituted indole derivatives from N-substituted anilines. The direct PdI2/KI oxidative carbonylation of 2-alkynylanilines does not lead to the formation of indole-3-carboxylic esters but to the formation of acyclic carbamates. For this reason, they performed the reaction in the

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• exhibiting comparable electrophilicity to activated esters; however, with considerably fewer steric restrictions [9][10]. Acylations with acyl fluorides also typically proceed with fewer side-reactions while derivatives bearing an α-stereocentre generally undergo little racemisation [11][12]. The combination

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• difunctionalization of alkynes with various heteroatom and carbon nucleophiles [27][28][29][30][31][32][33][34]. Specifically, intermolecular trans-iodo(III)functionalization of alkynes has been achieved using oxygen nucleophiles such as alcohols [28][32], ethers [33], carboxylic acids [31], phosphate esters [31

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• aryl ((±)-54a) and heteroaryl ((±)-54b) substituted 1,2-BCHs. As an alternative synthesis of 1,2-BCHs, and importantly also enantioenriched examples, Qin and co-workers developed an intramolecular coupling of cyclobutane-tethered sulfonylhydrazones and boronic esters (not shown) [41]. They also

• (82) on multigram scale (Scheme 8) [48]. As in Camps' synthesis, their approach starts from dinitrile 83. However, while Camps and co-workers directly accessed the stellane scaffold from 83, Ryabukhin, Volochnyuk and co-workers first transformed the nitrile groups into esters before forming stellane

• -cubanes (Scheme 9B) [51]. Partial deprotection of diester 88 led to acid 89 as a key intermediate and in situ activation of the acid as the hypervalent iodine complex enabled a photoredox decarboxylative amination to 1,2-cubane 90. Alternatively, conversion of the acid moiety of 89 to redox active esters

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• oxidation, whereas in Nicewicz's report, the alkene is oxidized. This modification allows for a significantly larger reaction scope (Scheme 29). Terminal alkenes and several functional groups such as ethers (163), esters (165), ketones (166), nitriles (167), and enones (170) are tolerated. The

Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• biosynthesis of crocins in C. sativus [103]. Nagatoshi et al. identified GjUGT75L6 and GjUGT94E5 from G. jasminoides. GjUGT75L6 could catalyze the glycosylation of crocetin (1) to produce crocetin glycosyl esters 2c and 2e, and GjUGT94E5 catalyzed downstream glycosylation reactions [104]. Unexpectedly, the

Substrate specificity of a ketosynthase domain involved in bacillaene biosynthesis

• Zhiyong Yin and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2024, 20, 734–740, doi:10.3762/bjoc.20.67

• conjunction with 13C NMR to investigate substrate acceptance by BaeJ-KS2 from module 4 of the bacillaene PKS. Results and Discussion Synthesis of N-acetylcysteamine thioesters Previous studies have shown that N-acetylcysteamine thioesters (SNAC esters) can be uploaded to KS domains [22][23][24][25]. Therefore

• have established a new method based on stable isotope (13C) labelling to investigate the KS domain substrate specificity that makes use of simple 13C NMR analysis of protein preparations obtained by a buffer exchange after enzyme incubations with substrate surrogates (SNAC esters), and its application

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• thiophenol-activated esters. (b) Macrocyclization of daptomycin and A54145 catalyzed by A54145 PCP-TE. Chemoenzymatic synthesis of surugamide B and related natural products. (a) Three synthetic strategies of surugamide B. (b) Biocatalytic macrocyclization of desprenylagaramide C and wollamide B1 mediated by

• ethylene glycol-linked esters. Chemoenzymatic synthesis of the pikromycins. (a) Macrocyclization of 10-deoxymethynolide catalyzed by Pik TE. (b) Biocatalytic synthesis of pikromycin, methymycin, and related natural products. Chemoenzymatic synthesis of the juevnimicins. Chemoenzymatic synthesis of the

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• -light-mediated palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines, affording unsaturated γ- and ε-amino acid derivatives with diverse structures. In this methodology, the diazo compound readily transforms into a hybrid α-ester

• reactant ratio produced the desired product 4a in 84% yield as optimal conditions for this protocol (Table 1, entry 13). With the optimized conditions obtained, we examined the generality of our palladium-catalyzed regioselective carboamination of 1,3-dienes with diazo esters and amines (Scheme 2). First

• chemoselectivity (1,2-/1,4-addition = 4:1). Diazo esters suitable for this transformation were examined next. The MCRs with diazo substrates equipped with different substitution patterns were accommodated under the mild photocatalytic conditions to generate the desired 1,4-addition products in moderate to good

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• , acetonitrile, and the triflate counterion [66]. Theoretical calculation of binding constants predict that esters coordinate more strongly than alkynes, and water [68]. Alkenes have been shown in some cases to coordinate more strongly than alkynes, but the trend depends on substitution pattern (alkynes can

• coordinate more strongly) [69]. A more recent study of alkyne activation demonstrates that esters coordinate relatively weakly compared to alkynes, while amides coordinate relatively strongly [70]. Analysis of 31P chemical shift of the catalyst under reaction conditions does not provide strong conclusions

(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene

• Nataliia V. Kirij,
• Andrey A. Filatov,
• Yurii L. Yagupolskii,
• Sheng Peng and
• Lee Sprague

Beilstein J. Org. Chem. 2024, 20, 452–459, doi:10.3762/bjoc.20.40

• 1b. Wherein various alkyl and aryl olefins, including those that contain Lewis basic esters, carbamates and amines or α-branched moieties, may be used in efficient and exceptionally Z-selective cross-metathesis reactions [6][7][8]. A few years ago, some publications devoted to the cleavage of the C–F