{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:37:20Z","timestamp":1760143040696,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T00:00:00Z","timestamp":1705276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Polish Ministry of Science and Higher Education"},{"name":"Computational grant from Wroc\u0142aw Centre of Networking and Supercomputing (WCSS)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Symmetry"],"abstract":"<jats:p>The asymmetric formal [3 + 3] annulation process of (E)-2-(3-phenylacryloyl)pyridine N-oxide with benzyl methyl ketone was investigated. The possibility of a stereoselective outcome was checked using salts of natural amino acids, as well as chiral bifunctional derivatives containing amino groups and thiourea or squaramide fragments as organocatalysts. Different types of organocatalysts applied led to opposite enantiomers of 2-(3-oxo-4,5-diphenyl-cyclohex-1-en-yl)pyridine 1-oxide (up to 60% ee). Spectroscopic analysis of the isolated product and analysis of the reaction course was carried out, taking into account the obtained regio- and stereoselectivity. In order to verify the postulated results, calculations of the energy of the intermediate reaction products and the final product using the Kohn\u2013Sham Density Functional Theory (KS-DFT) were made.<\/jats:p>","DOI":"10.3390\/sym16010104","type":"journal-article","created":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T11:15:01Z","timestamp":1705317301000},"page":"104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Selectivity in Catalytic Asymmetric Formal [3 + 3] Annulation of 2-Enoyl-pyridine N-Oxide with Benzyl Methyl Ketone"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5519-5891","authenticated-orcid":false,"given":"Zuzanna","family":"Wrzeszcz","sequence":"first","affiliation":[{"name":"Department of Organic and Medicinal Chemistry, Faculty of Chemistry, Wroclaw University of Science and Technology, Wyb. Wyspianskiego 27, 50-370 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jakub A.","family":"Warachim","sequence":"additional","affiliation":[{"name":"Institute of Advanced Materials, Faculty of Chemistry, Wroclaw University of Science and Technology, Wyb. Wyspianskiego 27, 50-370 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5143-4621","authenticated-orcid":false,"given":"Renata","family":"Siedlecka","sequence":"additional","affiliation":[{"name":"Department of Organic and Medicinal Chemistry, Faculty of Chemistry, Wroclaw University of Science and Technology, Wyb. Wyspianskiego 27, 50-370 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"242","DOI":"10.3998\/ark.5550190.0002.116","article-title":"Recent trends in the chemistry of pyridine N-oxides","volume":"1","author":"Youssif","year":"2001","journal-title":"Arkivoc"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Alvarez-Builla, J., Vaquero, J.J., and Barluenga, J. (2011). Six-Membered Heterocycles: Pyridines in Modern Heterocyclic Chemistry, Wiley-VCH.","DOI":"10.1002\/9783527637737"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.bmc.2010.12.025","article-title":"Lyconadins D and E, and complanadine E, new Lycopodium alkaloids from Lycopodium complanatum","volume":"19","author":"Ishuichi","year":"2011","journal-title":"Bioorg. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1021\/np4003355","article-title":"Casuarinines A\u2013J, Lycodine-Type Alkaloids from Lycopodiastrum casuarinoides","volume":"76","author":"Tang","year":"2013","journal-title":"J. Nat. Prod."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"616","DOI":"10.2174\/1385272823666190408095257","article-title":"The Diversity of Heterocyclic N-oxide Molecules: Highlights on their Potential in Organic Synthesis, Catalysis and Drug Applications","volume":"23","author":"Li","year":"2019","journal-title":"Curr. Org. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3026","DOI":"10.1039\/C4OB00115J","article-title":"Insights into the mechanistic and synthetic aspects of the Mo\/P-catalyzed oxidation of N-heterocycles","volume":"12","author":"Larionov","year":"2014","journal-title":"Org. Biomol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1002\/chem.201303360","article-title":"2,2,2-Trifluoroacetophenone as an Organocatalyst for the Oxidation of Tertiary Amines and Azines to N-Oxides","volume":"20","author":"Limnios","year":"2014","journal-title":"Chem. Eur. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5237","DOI":"10.1002\/ejoc.201800152","article-title":"Heteroarene N-Oxides as Oxygen Source in Organic Reactions","volume":"38","author":"Petrosyan","year":"2018","journal-title":"Eur. J. Org. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/j.tetasy.2004.02.032","article-title":"Chiral pyridine N-oxides: Useful ligands for asymmetric catalysis","volume":"15","author":"Chelucci","year":"2004","journal-title":"Tetrahedron Asymmetry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/7081_2017_3","article-title":"Pyridine N-Oxides and Derivatives Thereof in Organocatalysis","volume":"Volume 53","author":"Larionov","year":"2017","journal-title":"Heterocyclic N-Oxides. Topics in Heterocyclic Chemistry"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wrzeszcz, Z., and Siedlecka, R. (2020). Heteroaromatic N-Oxides in Asymmetric Catalysis: A Review. Molecules, 25.","DOI":"10.3390\/molecules25020330"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e202204099","DOI":"10.1002\/slct.202204099","article-title":"Recent Progress on Pyridine N-Oxide in Organic Transformations: A Review","volume":"8","author":"Habib","year":"2023","journal-title":"ChemistrySelect"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"10435","DOI":"10.1021\/acs.joc.2c00904","article-title":"N-Oxide-Induced Ugi Reaction: A Rapid Access to Quinoline-C2-amino Amides via Deoxygenative C(sp2)-H Functionalization","volume":"87","author":"Anugu","year":"2022","journal-title":"J. Org. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"349","DOI":"10.5562\/cca2447","article-title":"Proton Affnities of Organocatalysts Derived from Pyridine N-oxide","volume":"87","author":"Kotora","year":"2014","journal-title":"Croat. Chem. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"8802","DOI":"10.1021\/jo301513x","article-title":"Enantioselective synthesis of coumarin derivatives by PYBOX-DIPH-Zn (II) complex catalyzed Michael reaction","volume":"77","author":"Ray","year":"2012","journal-title":"J. Org. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1039\/c3ob40246k","article-title":"Enantioselective synthesis of 3, 4-dihydropyran derivatives via a Michael addition reaction catalysed by chiral pybox\u2013diph\u2013Zn (II) complex","volume":"11","author":"Ray","year":"2013","journal-title":"Org. Biomol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6081","DOI":"10.1021\/cr4007208","article-title":"Enantioselectively-Catalyzed Reactions with (E)-2-Alkenoyl-pyridines, Their N-Oxides, and the Corresponding Chalcones","volume":"114","author":"Desimoni","year":"2014","journal-title":"Chem. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1002\/ejoc.202001115","article-title":"Recent Progress in Non-Catalytic C\u2013H Functionalization of Heterocyclic N-Oxides","volume":"2021","author":"Kutasevich","year":"2021","journal-title":"Eur. J. Org. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/adsc.202000910","article-title":"Recent Advances in the Synthesis of C2-Functionalized Pyridines and Quinolines Using N-Oxide Chemistry","volume":"363","author":"Wang","year":"2021","journal-title":"Adv. Synth. Catal."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9766","DOI":"10.1039\/D0CS01124J","article-title":"Recent applications of asymmetric organocatalytic annulation reactions in natural product synthesis","volume":"50","author":"Wang","year":"2021","journal-title":"Chem. Soc. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3798","DOI":"10.1021\/jo502904n","article-title":"Asymmetric Robinson-Type Annulation Reaction between \u03b2-Ketoamides and \u03b1,\u03b2-Unsaturated Ketones","volume":"80","author":"Huang","year":"2015","journal-title":"J. Org. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1016\/j.tetlet.2015.01.035","article-title":"Formal carbo [3 + 3] annulation and its application in organic synthesis","volume":"56","author":"Feng","year":"2015","journal-title":"Tetrahedron Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1021\/ol100350w","article-title":"A New Powerful Strategy for the Organocatalytic Asymmetric Construction of a Quaternary Carbon Stereogenic Center","volume":"12","author":"Inokoishi","year":"2010","journal-title":"Org. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5568","DOI":"10.1021\/ol5025794","article-title":"Asymmetric Direct Vinylogous Michael Addition to 2-Enoylpyridine N-Oxides Catalyzed by Bifunctional Thio-Urea","volume":"16","author":"Rout","year":"2014","journal-title":"Org. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"15835","DOI":"10.1039\/C5CC06383C","article-title":"Diastereo-and enantioselective direct vinylogous Michael addition of \u03b3-substituted butenolides to 2-enoylpyridines catalyzed by chiral bifunctional amine-squaramides","volume":"51","author":"Wang","year":"2015","journal-title":"Chem. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1039\/C7QO00796E","article-title":"L-Phenylalanine Potassium Catalyzed Asymmetric Formal [3 + 3] Annulation of 2-enoyl-Pyridine N-Oxides with Acetone","volume":"5","author":"Xu","year":"2018","journal-title":"Org. Chem. Front."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1021\/acs.orglett.8b03612","article-title":"Enantioselective Construction of Pyridine N-Oxides Featuring 2,3-Dihydrofuran Motifs via Phosphine-Catalyzed [4 + 1]-Annulation of 2-Enoylpyridine N-Oxides with Morita-Baylis-Hillman Carbonates","volume":"21","author":"Zhang","year":"2019","journal-title":"Org. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9790","DOI":"10.1021\/acs.orglett.9b04068","article-title":"Rhodium-Catalyzed Pyridine N-Oxide Assisted Suzuki\u2013Miyaura Coupling Reaction via C(O)\u2013C Bond Activation","volume":"21","author":"Zhong","year":"2019","journal-title":"Org. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1021\/ol0705752","article-title":"2-Alkenoyl Pyridine N -Oxides, Highly Efficient Dienophiles for the Enantioselective Cu(II)-Bis(oxazoline) Catalyzed Diels-Alder Reaction","volume":"9","author":"Barroso","year":"2007","journal-title":"Org. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4151","DOI":"10.1021\/ol701669b","article-title":"Annulation for the Direct Construction of Bicyclic Skeletons with Four Stereogenic Centers","volume":"9","author":"Cao","year":"2007","journal-title":"Org. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"11384","DOI":"10.1002\/chem.200900696","article-title":"An Organocatalytic Asymmetric Tandem Reaction for the Construction of Bicyclic Skeletons","volume":"15","author":"Cao","year":"2009","journal-title":"Chem. Euro. J"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1055\/s-0036-1588976","article-title":"Primary-Secondary Diamine Catalyzed Enantioselective Synthesis of Substituted Cyclohex-2-enones by Cascade Michael\u2013Aldol\u2013Dehydration of Ketones with Chalcones","volume":"28","author":"Wagh","year":"2017","journal-title":"Synlett"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6752","DOI":"10.1002\/chem.201701315","article-title":"Direct Noncovalent Activation of \u03b1, \u03b2-Unsaturated Aldehydes for the Stereodivergent Synthesis of Substituted Cyclohexenes","volume":"23","author":"Xie","year":"2017","journal-title":"Chem. Eur. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/j.tet.2017.01.004","article-title":"Highly enantioselective Michael-aldol-dehydration reaction for the synthesis of chiral 3,5-diaryl-cyclohexenones catalyzed by primary amine","volume":"73","author":"Tang","year":"2017","journal-title":"Tetrahedron"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"13295","DOI":"10.1002\/chem.200901541","article-title":"Chiral Primary\u2013Secondary Diamines Catalyzed Michael\u2013Aldol\u2013Dehydration Reaction between Benzoylacetates and \u03b1,\u03b2-Unsaturated Ketones: Highly Enantioselective Synthesis of Functionalized Chiral Cyclohexenones","volume":"15","author":"Yang","year":"2009","journal-title":"Chem. Eur. J."}],"container-title":["Symmetry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-8994\/16\/1\/104\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:47:20Z","timestamp":1760104040000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-8994\/16\/1\/104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,15]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["sym16010104"],"URL":"https:\/\/doi.org\/10.3390\/sym16010104","relation":{},"ISSN":["2073-8994"],"issn-type":[{"type":"electronic","value":"2073-8994"}],"subject":[],"published":{"date-parts":[[2024,1,15]]}}}