Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• demand aza-Diels–Alder reaction (IEDADA) of β,γ-unsaturated ketones 23 and benzofuran-derived azadienes 11 [31]. The procedure enables the straightforward synthesis of benzofuran derivatives 24 bearing an additional tetrahydropyridine ring in good yields (51–94%) and excellent enantioselectivities (90–96

• covalent attachment of the catalyst had been previously reported for IEDADA reactions, this work reflects the first Brønsted acid-catalyzed IEDADA reaction of 1-azadienes. This methodology enables the synthesis of a variety of chiral tetrahydropyridine derivatives 46 in good yields (57–84%) and good to

Tenacibactins K–M, cytotoxic siderophores from a coral-associated gliding bacterium of the genus Tenacibaculum

• Yasuhiro Igarashi,
• Yiwei Ge,
• Tao Zhou,
• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku and
• Agus Trianto

Beilstein J. Org. Chem. 2022, 18, 110–119, doi:10.3762/bjoc.18.12

• ketene to give carboxylate was also detected as an ion at m/z 439. The fragment ions m/z 232, 199, 181, and 98 were commonly detected in the MS/MS spectra for compounds 1–3, which appeared to be derived from the right half of the molecule by sequentially losing hydroxyamine, water, and tetrahydropyridine

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• that the fluorinations with 1-1 were suppressed by the formation of perfluoro-3,4,5,6-tetrahydropyridine (1-5), which was reactive to the nucleophilic substrates existing in the reaction mixture. In 1986, Banks and co-worker reported the preparation of polymeric analogues of perfluoro-N

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

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• piperidine (17). The synthetic sequence performed by the authors is described in Scheme 3. Oxidation of 17 in the presence of hydrogen peroxide, catalyzed by selenium dioxide provided tetrahydropyridine N-oxide 18 in 88% yield. 18 was treated with (R)-p-tolylsulfinylmethyllithium 25 in THF at −78 °C to

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• aldehyde and an enol functionality, which was subsequently reacted with isocyanide 31 – derived from cholesterol – and 3,5-dimethoxyaniline leading to the steroid–tetrahydropyridine hybrid 32 in good yield and excellent diastereoselectivity. As previously proven by the authors in their synthetic program on

• steroidal isocyanide 31 to the imine (or aminal) leads to the stereoselective formation of the α-adduct intermediates, which rearranges to the final tetrahydropyridine ring 32. Besides the use of steroids as oxo, amine, carboxylic acid and isocyanide components, there is a very early report by Dumestre et

• ]. Synthesis of ecdysteroid derivatives by Ugi-4CR using a steroidal isocyanide [30]. Stereoselective multicomponent synthesis of a steroid–tetrahydropyridine hybrid using a chiral bifunctional substrate and a cholestanic isocyanide. DBA: 3,5-dinitrobenzoic acid [31]. Pd(II)-catalyzed three-component reaction

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• ). The corresponding tetrahydropyridine derivatives 124 were obtained in good to excellent yields but the enantioselectivity remained moderate. Calixarene phosphonic acid (cR,pR)-121 was also tested in the asymmetric ring opening of several cyclic meso epoxides 125 with benzoic acid (Scheme 41). Good

An air-stable bisboron complex: a practical bidentate Lewis acid catalyst

• Longcheng Hong,
• Sebastian Ahles,
• Andreas H. Heindl,
• Gastelle Tiétcha,
• Andrey Petrov,
• Zhenpin Lu,
• Christian Logemann and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2018, 14, 618–625, doi:10.3762/bjoc.14.48

• the IEDDA reaction. However, the yields were significantly lower in reactions catalyzed with B when compared to catalyst A (Table 1, entries 1–4). Nonetheless, when a more active dienophile 6-ethoxy-1-methyl-1,2,3,4-tetrahydropyridine (4f) was subjected to the IEDDA reaction of phthalazine (3), the

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• mechanism is reminiscent of the formation of a tetrahydropyridine ring by the berberine bridge enzyme in plant alkaloid biosynthesis. It starts with S-adenosyl-L-methionine (SAM)-dependent methylation of the secondary hydroxy group in 81 by the O-methyltransferase Leu14 (Scheme 14a) [71][72][73][74

Photoinduced 1,2,3,4-tetrahydropyridine ring conversions

• Baiba Turovska,
• Henning Lund,
• Viesturs Lūsis,
• Anna Lielpētere,
• Edvards Liepiņš,
• Sergejs Beljakovs,
• Inguna Goba and
• Jānis Stradiņš

Beilstein J. Org. Chem. 2015, 11, 2166–2170, doi:10.3762/bjoc.11.234

• , Langelandsgade 140, DK 8000 Aarhus, Denmark 10.3762/bjoc.11.234 Abstract Stable heterocyclic hydroperoxide can be easily prepared as a product of fast oxidation of a 1,2,3,4-tetrahydropyridine by 3O2 if the solution is exposed to sunlight. The driving force for the photoinduced electron transfer is calculated

• ; photoinduced electron transfer; pyrrolidine; tetrahydropyridine; Introduction Increased attention has been paid to the chemistry of cyclic organic peroxides since it was found that naturally occurring representatives of this group possess biological activity, particular antimalarial [1][2]. Significantly less

• been extensively investigated, in the same time little attention has been paid to the corresponding reactions of tetrahydropyridines. During the investigation of the electrochemical oxidation mechanism of tetrahydropyridine 1 [15], an extremely high sensitivity of the formed cation radicals towards

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• cyclopropenylcarbinyl ether 33 with catalyst 2 (Scheme 4). Cyclobutene systems Cyclobutene is also highly strained and prone to RRM very easily. Maougal and co-workers synthesized 3,3’-bipiperidine and 3,3’-bis(1,2,3,6-tetrahydropyridine) systems through a RRM sequence [9]. In this context, they have identified

The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde

• Volodymyr V. Tkachenko,
• Elena A. Muravyova,
• Sergey M. Desenko,
• Oleg V. Shishkin,
• Svetlana V. Shishkina,
• Dmytro O. Sysoiev,
• Thomas J. J. Müller and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2014, 10, 3019–3030, doi:10.3762/bjoc.10.320

• , and 6''a (Figure 3). Assignment of the structure 6a was achieved with the help of 2D NMR experiments (Figure 4). COSY and NOESY spectra showed correlations between the protons of the NH and CH3 groups in the tetrahydropyridine ring which should be absent in case of structure 6''a. Neither scalar nor

• tetrahydropyridine and dihydrooxine rings, respectively). Deviation of the C5 atom from the mean plane of the remaining atoms of the ring is 0.70 Å and −0.77 Å for these two rings. Conclusion In summary, the three-component heterocyclizations involving 5-amino-3-methylisoxazole, salicylaldehyde and N-aryl-3

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

• Yiyang Liu,
• Marc Liniger,
• Ryan M. McFadden,
• Jenny L. Roizen,
• Jacquie Malette,
• Corey M. Reeves,
• Douglas C. Behenna,
• Masaki Seto,
• Jimin Kim,
• Justin T. Mohr,
• Scott C. Virgil and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2014, 10, 2501–2512, doi:10.3762/bjoc.10.261

• (+)-vincadifformine (Scheme 14) [106]. The key step in the synthesis was an iminium ion cascade reaction that formed the fused ring systems by coupling 3,3-disubstituted tetrahydropyridine 57 with indole derivative 58. The former coupling partner was derived from chiral α-quaternary lactam 60, which was constructed

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• temperature, affording a broad spectrum of densely functionalized tetrahydropyridine derivatives, with exclusive 4,5-trans diastereoselectivity, excellent enantioselectivity, and good to excellent yields. The transformations tolerated a wide range of N-sulfonyl-1-aza-1,3-dienes with different C4-substituents

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• ]-cycloaddition/allylboration/retro-sulfinyl-ene sequence was performed to afford 1,2,5,6-tetrahydropyridine 31 with high regio- and diastereoselectivity (Scheme 23). Boron-substituted heterodendralene On the basis of these precedents, boronated 2-vinyl-α,β-unsaturated aldehydes 32 were designed to fully exploit

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• six-membered rings. Five-membered dihydrofuran rings lead to the synthesis of furanomycin D [35][36], norfuranomycin E [37], and the polyoxin family F [38]. The six-membered tetrahydropyridine G synthesized via this route can be used as an intermediate in the synthesis of iminosugars, e.g., of the

Tandem dinucleophilic cyclization of cyclohexane-1,3-diones with pyridinium salts

• Mostafa Kiamehr,
• Firouz Matloubi Moghaddam,
• Satenik Mkrtchyan,
• Volodymyr Semeniuchenko,
• Linda Supe,
• Alexander Villinger,
• Peter Langer and
• Viktor O. Iaroshenko

Beilstein J. Org. Chem. 2013, 9, 1119–1126, doi:10.3762/bjoc.9.124

• been proven to be a powerful method for the construction of various dihydropyridines [1][2][3][4], which are not only valuable intermediates in organic synthesis [5][6][7][8][9][10][11][12], but also interesting compounds in medicinal [13] and bioorganic chemistry [14][15][16]. The tetrahydropyridine

• ring is an essential building block for numerous natural products, synthetic pharmaceuticals, and various biologically active compounds [17]. The tetrahydropyridine scaffold is inherent for pharmacologically relevant representatives [18][19][20][21][22][23][24]. At the same time, heterocyclic systems

Development of peptidomimetic ligands of Pro-Leu-Gly-NH₂ as allosteric modulators of the dopamine D₂ receptor

• Swapna Bhagwanth,
• Ram K. Mishra and
• Rodney L. Johnson

Beilstein J. Org. Chem. 2013, 9, 204–214, doi:10.3762/bjoc.9.24

• ]. Peptidomimetic 2 was also more potent than PLG in in vivo assay systems, including (1) potentiation of apomorphine-dependent rotational behavior in 6-hydroxydopamine lesioned rats [25]; (2) protection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced degeneration of the nigrostriatal

Chimeric self-sufficient P450cam-RhFRed biocatalysts with broad substrate scope

• Aélig Robin,
• Valentin Köhler,
• Alison Jones,
• Afruja Ali,
• Paul P. Kelly,
• Elaine O'Reilly,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2011, 7, 1494–1498, doi:10.3762/bjoc.7.173

• were hydroxylated by all three P450cam-RhFRed mutants, with the double mutant Y96F/V247A showing >99% conversion after 24 h (only one hydroxylated product was detected in the extracts). Epoxidation of tetrahydropyridine 7a to compound 8a with P450cam(Y96A)-RhFRed was shown to occur with low conversion

• (12%) with carboxybenzyl as a protecting group. In order to optimise the epoxidation reaction further, the N-protection group was used as another variable in the screening and a variety of N-protecting groups were installed to generate a set of tetrahydropyridine derivatives 7. An increase in

• turned out to be the most efficient for the epoxidation of the tetrahydropyridine ring, with substrate 7b epoxidised to 8b in 73% conversion. Racemic epoxide 8b was synthesised to confirm the structure of the biotransformation product and to determine the enantiomeric excess. This was found to be 18% for

Multicomponent reaction access to complex quinolines via oxidation of the Povarov adducts

• Esther Vicente-García,
• Rosario Ramón,
• Sara Preciado and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2011, 7, 980–987, doi:10.3762/bjoc.7.110

• . Despite the loss of all stereochemical information, in this way it would be feasible to obtain a single product from a multicomponent process (Scheme 1). The oxidation step itself is challenging as it involves the formal removal of four hydrogens from a tetrahydropyridine moiety to reach the fully

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• (dichloromethane, 20 °C) in the presence of the 1st-generation Grubbs catalyst [(Cl2(Cy3P)2Ru=CHPh)] (2) to form the chiral tetrahydropyridine building block 72 in 97% yield. The stereochemistry of 72 was unambiguously confirmed by transformation into the known trans-3-hydroxy-2-hydroxymethylpiperidine. The

• tetrahydropyridine scaffold 72 allowed an efficient synthesis of 1-deoxynojirimycin 62, and its stereoisomers 65 and 66. Thus, acid hydrolysis of the epoxy ring in the anti isomer 73 (H2SO4/dioxane/H2O, 0.2:3:2) gave 1-deoxynojirimycin (62) and 1-deoxyaltronojirimycin (65) in a 1:1 ratio and in 89% yield. Conversely

• was derived from the methyl ester of natural, enantiopure L-alanine. Having built the tetrahydropyridine scaffold 82 by RCM of 81 using the 2nd-generation Grubbs catalyst (5; 85% yield), Park et al. [66] were able to effect its stereodivergent dihydroxylation, via a common epoxide intermediate, to

Diastereoselective synthesis of some novel benzopyranopyridine derivatives

• Pradeep K. Mohakhud,
• Sujeet M. R. Kumar,
• Vasanth M. R. Kumar,
• Ravi M. R. Kumar,
• Moses D. R. Babu,
• Vyas D. R. K and
• Om D. R. Reddy

Beilstein J. Org. Chem. 2006, 2, No. 25, doi:10.1186/1860-5397-2-25

• enantiomers 7a and 7b. The absolute configuration is determined by single crystal X-ray analysis of the mandelate salt. General structures A & B, Tetrahydro cannabinole derivatives. General structures C & D, Benzopyrano pyridine derivatives. Proposed mechanism of tetrahydropyridine formation, Proposed

• mechanism. Molecular structure of the mandalate salt. Structural elucidation. Synthetic sequence to tetrahydropyridine compounds. Resolution of enantiomers using D(-) mandelic acid. Supporting Information Supporting Information File 86: Supplementary experimental data. The file contains all experimental