Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• reaction proceeding through aza-Friedel–Crafts reaction and lactonization steps. Main focus of this article was to demonstrate a racemic process between α-naphthol or phenol derivatives and in situ-generated N-acetyl ketimine from methyl 2-acetamidoacrylate (18) in the course of preparing 3-NHAc

• ) [65]. In 2019, Piersanti and co-workers reported an organocatalyzed enantioselective aza-Friedel–Crafts/lactonization domino reaction sequence as the key step in the course of synthesizing (+)- and (−)-fumimycin. (−)-Fumimycin was first isolated from Aspergillus fumisynnematus and exhibits

• utilizing cyclic N-sulfimines as electrophiles. Aza-Friedel–Crafts reaction involving N-unprotected imino ester as electrophile. Aza-Friedel–Crafts and lactonization cascade. One-pot oxidation and aza-Friedel–Crafts reaction. C1 and C2-symmetric phosphoric acids as catalysts. Aza-Friedel–Crafts reaction

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• undergoing reductive elimination to afford to [2 + 2] adduct, β-oxygen elimination followed by E/Z isomerization and intramolecular lactonization generates the annulated coumarin scaffold. In 2003, the Cheng lab extended on this Ni-catalyzed ring-opening strategy [31]. It was noted the addition of 1.5

• solely observed (Scheme 1). This unprecedented lactone is presumed to be generated through the expected reductive coupling to generate the ring-opened intermediate 5 which undergoes subsequent intramolecular lactonization with the distal ester group. In the same year, Cheng and co-workers observed the

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• several cases, a good regioselectivity was achieved for complex molecules. Quinuclidine cation radicals were also involved in the generation of nucleophilic α-hydroxyalkyl radicals from alcohols for the addition to the electron-deficient C=C bond of methyl acrylate followed by lactonization [107] (Scheme

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• , Scheme 6) [15]. Through a series of finely tuned CH oxidations, cedrol (31) was converted to the lactone 32. In a single step, using Riley oxidation conditions, the methyl ketone moiety was transferred to the α-ketoester 33. Reduction, lactonization, and elimination gave the ketoesters-derived enol 34

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

• treatment with 1 M HCl produces phthalide 4 through desilylation and following lactonization of F (path d). As can be seen from Scheme 5, the cyclization of D to E is the key step for the formation of compound 6. Therefore, we calculated the intermediates (D and E) and transition states (D–E TS) for this

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• H-7 and H-10 also showed weak correlation, which clearly supports the cis relation of the proton H-10. In this reaction, lactonization and hydrolysis of the Boc group to the corresponding amine were observed. The formation of lactone 8 as the major product can be explained by nucleophilic attack of

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• process that reached 96.5% ee through the combination of the reversible hemithioacetal transformation and the enantioselective lactonization catalyzed by the immobilized lipase from Trichosporon laibachii (Scheme 24). As a result, the desired stereochemistry of 1,3-oxathiolane precursors 71 and 72 was

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• reaction between 3-cyano-4-methylcoumarins 39 and MBH carbonates 40. Enantioselective synthesis of cyclopropa[c]coumarins 45. NHC-catalyzed lactonization of 2-bromoenals 46 with 4-hydroxycoumarin (1). NHC-catalyzed enantioselective synthesis of dihydrocoumarins 51. Domino reaction of enals 2 with

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• action of Meerwein’s salt (Me3OBF4) and a mild base (proton sponge) to afford a methoxy cedrene derivative. Next, oxidative cleavage of the double bond using NaIO4/RuCl3·xH2O enabled a ring opening, followed by lactonization promoted by CuBr2 via an intramolecular acyloxylation. The 5,5-fused ring system

• was then converted to a 5,6-fused seco-prezizaane scaffold through an α-ketol rearrangement promoted by a strong base and after secondary alcohol protection with TBSCl, a Fe-catalyzed C–H activation reaction promoted a second lactonization to afford (+)-pseudoanisatin (Scheme 28B). In 2016, Chirik and

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

• Rashmi Singh,
• Tomas Horsten,
• Rashmi Prakash,
• Swapan Dey and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79

• presence of a catalytic amount of piperidine afforded pyridopsoralen 22 in 46% yield. Analogously, pyridopsoralen 23 was prepared from 16 by Knoevenagel condensation with diethyl malonate and subsequent lactonization with 62% yield (Scheme 4) [13]. To the best of our understanding, the scaffolds 21–23 are

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

• the construction of the spiro skeleton of 4 and 5. For this purpose, we initially attempted to transform 3b to 5a through the reaction sequence consisting of copper-mediated hydroxylation and acid-mediated lactonization based on our previous reports [10][11][14][21]. Substitution of the phenylthio

• equivalents of n-butyllithium and 1.1 equivalents of Boc2O in THF at −78 °C, 5a was obtained as a mixture including unreacted starting material (<11% yield), indicating that installation of an N-Boc group on the terminus amide should trigger the desired lactonization. Therefore, we next examined the

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

• )-10 and the bicyclic lactam (rac)-14, the formation of fluoroselenated products in low amounts could be detected, but the isolation in a pure form failed. The treatment of the diester 16 with PhSeBr caused lactonization regardless of the presence or absence of Deoxo-Fluor®. The yield was better when

• )-1 and 4. PhSe+-induced lactonization of the diester 16. Relevant NOESY interactions are marked with two-headed arrows. Oxidation of the fluoroselenide (rac)-30 under acidic and basic conditions. Oxidation of the fluoroselenide mixture (rac)-31 under acidic and basic conditions. Supporting

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

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

• Kitahara’s synthesis [8][9], the Wittig olefination of 24, followed by a catalytic hydrogenation, removal of the dimethylaminal protecting group, and lactonization gave 25 as a mixture of diastereomers (Scheme 2). The further transformation of 25 afforded the dihydropyran 26, which upon catalytic

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• of the dienic compound through a Suzuki–Miyaura coupling and Julia–Kocienski olefination, followed by a Yamaguchi lactonization, and an asymmetric epoxidation in the presence of (+)-diethyl tartrate, conveniently produced (−)-amphidinolide K (4, Scheme 7). In a remarkable work, Trost et al. [72

• synthesis of the (−)-exiguolide enantiomer (25) was reported by Roulland et al. [94]. The method is a mechanistically distinct alternative to the enyne metathesis since it involves a Trost’s Ru-catalyzed enyne cross-coupling reaction associated with a Yamaguchi lactonization, a Grubbs Ru-catalyzed cross

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• triflyl chloride (64) by SET gives the highly energetic compound 66, which combines with 88 to give 94. The oxidation of 94 by 92 generates an intermediate 95, which, upon further deprotonation, produces the desired product 89 (Figure 14). C–H lactonization: synthesis of benzo-3,4-coumarins Benzo-3,4

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• felt electrodes for successful application in asymmetric electroorganic transformations, Kashiwagi’s group came up with two distinct protocols for asymmetric electrochemical lactonization of differently substituted diols. In 1996, they disclosed an asymmetric electrocatalytic method for lactonization

• lactonization of diols 51. However, in this method instead of a chiral base, they used 1-azaspiro[5.5]undecane N-oxyl 52 as a radical mediator for modifying the electrodes which resulted in optically active lactones 53 with enantiopurity of up to 99% (conditions B, Scheme 20) [52]. Chiral medium In this section

• formation of (S)-63 over (R)-63. Hence, (S)-63 would be converted to ketone 62 via hydride transfer, whereas (R)-63 might be predominantly retained. Very recently, Wirth’s group demonstrated the use of chiral iodoarene 67 as a redox mediator for the electrochemical lactonization of diketo acid derivatives

Characterization of two new degradation products of atorvastatin calcium formed upon treatment with strong acids

• Jürgen Krauß,
• Monika Klimt,
• Markus Luber,
• Peter Mayer and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2085–2091, doi:10.3762/bjoc.15.206

• structures of the degradation products. Here we report the identification of two novel degradation products of atorvastatin, which are formed only under drastic acidic conditions. While treatment with conc. sulfuric acid led to a loss of the carboxanilide residue (accompanied by an expectable lactonization

• process (stereoisomers, products resulting from impure starting materials or side reactions), and only one of these impurities, lactone 2, is most likely a degradation product, resulting from acid-mediated lactonization of the 3,5-dihydroxyheptanoate side chain. A couple of previous publications deal with

• were not characterized in this [6] and several other reports, which only determined the downsizing of the atorvastatin peak in HPLC after treatment with acid [7][8][9][10]. The most prominent decomposition product upon acidic treatment, compound 2, results from lactonization of the 3,5

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• -catalyzed lactonization, and iii) construction of the epoxides by a newly developed methodology. The synthesis commenced from the alkylation of tetralone 22 with 3-(2-iodoethyl)dihydrofuran-2(3H)-one (23) to give diastereomeric lactones that subsequently reacted with dimethylamine to afford a 1:1 mixture of

• -phenylethylamine (49) to generate key tricyclic intermediates 51 and 52, a Pd(II)-catalyzed carbonylation–lactonization reaction of 9 to construct the butenolide (D-ring), and a Friedel–Crafts isopropylation to install the C-13 isopropyl group. Still, the construction of the C-5 trans junction A-/B-ring was

• corresponding carboxylic acid followed by hydrogenolysis with H2/Pd-C led in spontaneous lactonization to give the key butenolide 66. Oxidation of 66 with CrO3/AcOH–H2O, followed by saponification and reduction afforded known benzyl alcohol 46 (19% from 66). Then, phenol 46 was converted to the corresponding

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• diastereoisomers (2S,4S)-68 and (2S,4R)-68, respectively (Scheme 17) [77][78]. A mixture of (2S,4S)-3 and (2S,4R)-3 obtained after hydrolysis was separated taking advantage of two phenomena: the preferential lactonization of (2S,4S)-3 to produce 69 and much better solubility of (2S,4R)-3 in water when compared

• intramolecular lactonization to form 83 by implementation of the Mitsunobu reaction. After opening of the lactone ring with trichloroethanol and silylation of the hydroxy group oxidation at C5 was performed in the usual way to give a pyroglutamate 84. Benzyl or p-methoxybenzyl esters 85a or 85b were next

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• ). Possibly another ligand exchange between E and KOAc regenerates the Rh complex A (step e). The desired product (35) is obtained after lactonization. Hydrocarboxylation of arylalkenes Hydrocarboxylation is an essential carboxylation reaction. To date, transition-metal-catalyzed hydrocarboxylation reactions

Studies towards the synthesis of hyperireflexolide A

• G. Hari Mangeswara Rao

Beilstein J. Org. Chem. 2018, 14, 2106–2111, doi:10.3762/bjoc.14.185

• with 2-bromopropene followed by lactonization. Enone 3 could be synthesized from 4 by installation of the methyl group at C-10 followed by cross metathesis reaction. Compound 4 could be obtained from the γ-lactone-fused cyclopentane 5 by deprotection of C-9 followed by allylation at C-8. Previously, we

• of the proposed synthetic sequence. Future studies will include the stereoselective epoxidation of 11 followed by opening of the epoxide and lactonization or 1,4-nucleophilic addition to the α,β-unsaturated ketone 11 followed by epoxidation of the resulted enolate with subsequent lactonization to

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• intramolecular lactonization of p-substituted phenols 82 to spirooxindoles 83 using 10 mol % of iodobenzene (35) as precatalyst, mCPBA as an external oxidant and TFA as additive. All the catalytic reactions were performed in dichloromethane and spirolactams 83 were isolated in good to excellent yields (Scheme 29

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

• assuming the pathway shown in Scheme 2. The formyl group in aldehyde 2 undergoes nucleophilic trifluoromethylation triggered by a catalytic amount of KF to give the ortho-cyanobenzyl silyl ether 3. Upon treatment with aq HCl, the subsequent lactonization of 4 takes place to afford trifluoromethylphthalide

• considerable importance in chemistry [26][27][28][29][30][31][32]. Enantioselective fluoroalkylation/lactonization reactions are worth investigating since a new stereogenic carbon center next to the fluoroalkyl groups is generated in products 1. To the best of our knowledge, only one successful example of an

•  2, entries 3–5). By employing catalyst 9b, the reaction proceeded at −60 °C to give phthalide 1a in 51% yield with 12% ee (Table 2, entry 4). To improve the enantioselectivity of the present nucleophilic trifluorometylation/lactonization, we surveyed suitable conditions for the catalytic asymmetric