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

• and subsequent oxidation yielded aldehyde 18, a precursor for the intramolecular ring closure of the eight-membered ring. Upon treatment of 18 with BF3·Et2O, diastereoselective Prins cyclization of 18 proceeded to generate secondary alcohol 19. Subsequent one-pot treatment with (n-Bu)4NF·HF resulted

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• (+)-2. If the biosyntheses of these natural products does occur through a common iminium ion intermediate, then our isolation of 11 suggests that the key aza-Prins cyclization is enzyme-mediated rather than spontaneous. Conclusion In summary, we have synthesized the enantiomers of halichonic acid and

• B ((+)-2). Synthesis of (−)-7-amino-7,8-dihydrobisabolene (4) and its conversion to cyclization precursor 7. Synthesis of the halichonic acids via a key intramolecular aza-Prins cyclization. Proposed intermediates for the intramolecular aza-Prins reaction leading to the formation of ethyl ester 8

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• alkynyl-Prins cyclization, Friedel–Crafts alkenylation, and dehydration/aromatization reaction between 1-aryl-3-hexyne-2,6-diol derivatives and aldehydes, that led to the formation of 1,4-dihydro-2H-benzo[f]isochromenes [16]. The Prins reaction-induced cyclization, inter alia, became a versatile tool for

• ). However, the reaction with AlMe3 as the promotor resulted in a competing reduction of 13a to 2-bromophenylethanol (12a) that was obtained as the major product (Table 1, entry 3). Switching to the weaker Lewis acid In(OTf)3 failed to induce any intramolecular Prins cyclization (Table 1, entry 4), whilst

• structure is shown in Figure 3 [27]. Conclusion In summary, a Prins cyclization and Friedel–Crafts cascade reaction strategy for the synthesis of 4-aryl-tetralin-2-ols and 5-aryl-tetrahydro-5H-benzo[7]annulen-7-ols has been established. The sequence involved the Prins cyclization of 2-(2-vinylphenyl

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

• number of classical methodologies have been used for their synthesis, in which the key step is the generation of the six-membered ring, including the aldol reaction, the reductive amination, Mannich reaction, ring closing metathesis, Diels–Alder reaction with imines as dienophiles, aza-Prins cyclization

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• Prins cyclization strategies, covering the literature reports of the last twenty years (from 2000 to 2019), with an aim to give an overview on exciting advancements in this area and designing new strategies for the total synthesis of related natural products. Keywords: asymmetric; natural products

• ; Prins cyclization; stereoselective; tetrahydropyran; Introduction 6-Membered saturated oxygen heterocycles, known as tetrahydropyran (THP), are recognized as privileged scaffolds, present in a variety of biologically important natural products, such as polyether antibiotics, marine toxins, pheromones

• of the THP key scaffold and its application towards the total synthesis of natural products. Many advancements were also taking place in Prins cyclization methodologies over that period of time. This appraisal aims to bring together the work of many research groups in the area of the development of

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• -promoted Prins cyclization reactions of 3-allyl-3-hydroxyoxindoles with aldehydes, accessing functionalized spirooxindole pyrans as single diastereoisomers in good yields (71–91%) under mild conditions [76]. Interestingly, when BF3·Et2O was used, they obtained the biologically important fluorinated

A practical way to synthesize chiral fluoro-containing polyhydro-2H-chromenes from monoterpenoids

• Oksana S. Mikhalchenko,
• Dina V. Korchagina,
• Konstantin P. Volcho and
• Nariman F. Salakhutdinov

Beilstein J. Org. Chem. 2016, 12, 648–653, doi:10.3762/bjoc.12.64

• appropriate halogen-containing Lewis acids or ionic liquids are usually used (Scheme 2) [10][11][12][13][14][15][16]. However, only a few examples of reactions for introducing a fluorine atom via the halo-Prins cyclization have been reported to date [15][16][17][18][19][20][21]. In these reactions, BF3·Et2O

Efficient, highly diastereoselective MS 4 Å-promoted one-pot, three-component synthesis of 2,6-disubstituted-4-tosyloxytetrahydropyrans via Prins cyclization

• Naseem Ahmed and
• Naveen Kumar Konduru

Beilstein J. Org. Chem. 2012, 8, 177–185, doi:10.3762/bjoc.8.19

• -tosyloxytetrahydropyrans was performed. The synthesis features an optimized Prins cyclization in which an aromatic homoallylic alcohol, an aromatic/aliphatic aldehyde, and p-toluenesulfonic acid (catalyst and reagent) are reacted in the presence of molecular sieves (MS) 4 Å at reflux in dichloromethane to afford excellent

• -hydroxytetrahydropyran in excellent yields (95–96%). Keywords: aromatic homoallylic alcohols; 2,6-disubstituted-4-tosyloxytetrahydropyrans; MS 4 Å; Prins cyclization; PTSA; Introduction Substituted tetrahydropyrans are common structural motifs in numerous biological molecules and natural products that include

• , economical and stereoselective synthesis. To introduce the desired substituents and stereochemistry at the 2, 4 and 6-positions of the tetrahydropyran ring, Prins cyclization has been considered to be the best approach. The reaction can be conducted either with Brønsted acid catalysts – namely TFA [12], AcOH

PEG-embedded KBr₃: A recyclable catalyst for multicomponent coupling reaction for the efficient synthesis of functionalized piperidines

• Sanny Verma,
• Suman L. Jain and
• Bir Sain

Beilstein J. Org. Chem. 2011, 7, 1334–1341, doi:10.3762/bjoc.7.157

• –Alder reactions [22][23], intramolecular Michael reactions [24], intramolecular Mannich reactions onto iminium ions [25], tandem cyclopropane ring-opening/Conia-ene cyclizations [26], and aza-Prins-cyclization [27][28][29], have been reported for the synthesis of piperidines. However, these methods

Synthetic applications of gold-catalyzed ring expansions

• David Garayalde and
• Cristina Nevado

Beilstein J. Org. Chem. 2011, 7, 767–780, doi:10.3762/bjoc.7.87

• already summarized in section 1 of this review, can offer further synthetic potential in combination with 1,6-enyne substrates. Echavarren successfully developed a gold-catalyzed Prins cyclization of enynes 70 to afford trans- and cis-octahydrocyclobuta[a]pentalene skeletons 71 and 72, respectively