{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:07:46Z","timestamp":1790420866891,"version":"4.1.0"},"reference-count":48,"publisher":"American Chemical Society (ACS)","issue":"30","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004349","name":"BASF","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100004349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/X026566\/1"],"award-info":[{"award-number":["EP\/X026566\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"publisher","award":["UF150533"],"award-info":[{"award-number":["UF150533"]}],"id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000835","name":"University of Bath","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100000835","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Piperidines are the most prevalent saturated nitrogen heterocycles in pharmaceuticals, yet efficient and general methods for accessing \u03b1-disubstituted and spirocyclic variants have remained a long-standing synthetic challenge. A broadly applicable annulation strategy from unprotected primary alkylamines would represent an important advance, enabling access to privileged piperidine scaffolds from the most accessible nitrogen feedstocks. Here we disclose a general photoredox\/hydrogen atom transfer dual catalytic annulation that converts primary amines into \u03b1-mono- and \u03b1-disubstituted \u03b4-lactams, versatile intermediates that provide streamlined access to diverse piperidines. The method proceeds under mild conditions, can be scaled to \u223c100 g in continuous flow, and affords products capable of downstream modification. This work provides a broadly applicable solution to a challenging problem in heterocycle synthesis, expanding the structural space accessible to drug discovery.<\/jats:p>","DOI":"10.1021\/acs.orglett.6c02237","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T18:10:32Z","timestamp":1784311832000},"page":"9603-9608","source":"Crossref","is-referenced-by-count":1,"title":["Photocatalytic\nAnnulation of Primary Amines to \u03b4-Lactams:\nAccess to Privileged (Spiro)piperidine Space"],"prefix":"10.1021","volume":"28","author":[{"given":"Jacob C.","family":"Turner-Dore","sequence":"first","affiliation":[{"name":"University of Bath , , Claverton Down , ,","place":["Bath, U.K., BA2 7AY"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph J.","family":"Bell-Tyrer","sequence":"additional","affiliation":[{"name":"University of Bath , , Claverton Down , ,","place":["Bath, U.K., BA2 7AY"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah E.","family":"Askey","sequence":"additional","affiliation":[{"name":"University of Bath , , Claverton Down , ,","place":["Bath, U.K., BA2 7AY"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren L.","family":"Richards","sequence":"additional","affiliation":[{"name":"University of Bath , , Claverton Down , ,","place":["Bath, U.K., BA2 7AY"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleksandr","family":"Polishchuk","sequence":"additional","affiliation":[{"name":"Enamine Ltd. , Winston Churchill Street 78 , ,","place":["Kyiv, Ukraine, 02094"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleksandr P.","family":"Datsenko","sequence":"additional","affiliation":[{"name":"Enamine Ltd. , Winston Churchill Street 78 , ,","place":["Kyiv, Ukraine, 02094"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5700-2790","authenticated-orcid":true,"given":"Jamie A.","family":"Cadge","sequence":"additional","affiliation":[{"name":"University of Bath , , Claverton Down , ,","place":["Bath, U.K., BA2 7AY"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Ciaccia","sequence":"additional","affiliation":[{"name":"Syngenta, Jealott\u2019s Hill International Research Centre , , ,","place":["Bracknell, Berkshire, U.K., RG42 6EY"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1821-9011","authenticated-orcid":true,"given":"Pavel K.","family":"Mykhailiuk","sequence":"additional","affiliation":[{"name":"Enamine Ltd. , Winston Churchill Street 78 , ,","place":["Kyiv, Ukraine, 02094"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4060-9657","authenticated-orcid":true,"given":"Alexander J.","family":"Cresswell","sequence":"additional","affiliation":[{"name":"University of Bath , , Claverton Down , ,","place":["Bath, U.K., BA2 7AY"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"2026073109265384700_cit1","doi-asserted-by":"publisher","DOI":"10.26434\/chemrxiv-2025-2cx97","article-title":"Scalable Photocatalytic Annulation\nof Primary Amines to \u03b4-Lactams: Access to Privileged (Spiro)Piperidine\nSpace","author":"Turner-Dore","year":"2025","journal-title":"ChemRxiv"},{"key":"2026073109265384700_cit2a","doi-asserted-by":"publisher","first-page":"11622","DOI":"10.1021\/acs.jmedchem.4c01122","article-title":"An update on the nitrogen heterocycle\ncompositions\nand properties of U.S. FDA-approved pharmaceuticals (2013\u20132023)","volume":"67","author":"Marshall","year":"2024","journal-title":"J. Med. Chem."},{"key":"2026073109265384700_cit2b","doi-asserted-by":"publisher","first-page":"8699","DOI":"10.1021\/acs.jmedchem.2c00473","article-title":"Rings in\nclinical trials and drugs: present and future","volume":"65","author":"Shearer","year":"2022","journal-title":"J. Med. Chem."},{"key":"2026073109265384700_cit2c","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1186\/s43094-021-00335-y","article-title":"Piperidine nucleus\nin the field of drug discovery","volume":"7","author":"Abdelshaheed","year":"2021","journal-title":"Future Journal\nof Pharmaceutical Sciences"},{"key":"2026073109265384700_cit2d","doi-asserted-by":"publisher","first-page":"44247","DOI":"10.1039\/D0RA09198G","article-title":"Prescribed\ndrugs containing nitrogen heterocycles: an overview","volume":"10","author":"Heravi","year":"2020","journal-title":"RSC Adv."},{"key":"2026073109265384700_cit3a","doi-asserted-by":"publisher","first-page":"2937","DOI":"10.3390\/ijms24032937","article-title":"Piperidine derivatives: recent advances\nin synthesis and pharmacological applications","volume":"24","author":"Frolov","year":"2023","journal-title":"Int. J. Mol. 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Chem."},{"key":"2026073109265384700_cit3d","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1016\/j.tet.2003.11.043","article-title":"Synthesis of piperidines","volume":"60","author":"Buffat","year":"2004","journal-title":"Tetrahedron"},{"key":"2026073109265384700_cit3e","doi-asserted-by":"publisher","first-page":"2953","DOI":"10.1016\/S0040-4020(03)00295-3","article-title":"Recent\nadvances in the synthesis of piperidones and piperidines","volume":"59","author":"Weintraub","year":"2003","journal-title":"Tetrahedron"},{"key":"2026073109265384700_cit3f","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1055\/s-2000-8218","article-title":"Stereoselective synthesis of piperidines","volume":"2000","author":"Laschat","year":"2000","journal-title":"Synthesis"},{"key":"2026073109265384700_cit4a","doi-asserted-by":"publisher","first-page":"21088","DOI":"10.1021\/jacs.2c07143","article-title":"Synthesis of stereoenriched\npiperidines via chemo-enzymatic dearomatization of activated pyridines","volume":"144","author":"Harawa","year":"2022","journal-title":"J. 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Chem."},{"key":"2026073109265384700_cit12d","doi-asserted-by":"publisher","first-page":"6663","DOI":"10.1039\/c8ob01272e","article-title":"Synthesis of highly substituted 2-spiropiperidines","volume":"16","author":"Griggs","year":"2018","journal-title":"Org. Biomol. Chem."},{"key":"2026073109265384700_cit12e","doi-asserted-by":"publisher","first-page":"6620","DOI":"10.1039\/c8ob01271g","article-title":"Strategies for the\nsynthesis of spiropiperidines \u2013 a review of the last 10 years","volume":"16","author":"Griggs","year":"2018","journal-title":"Org. Biomol. Chem."},{"key":"2026073109265384700_cit13a","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1039\/D5QO01507C","article-title":"Photoredox-enabled\nC(sp3)\u2013H functionalization of\namines through iminium ions, radicals, and carbanions","volume":"13","author":"Chen","year":"2026","journal-title":"Org. Chem. 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Chem."},{"key":"2026073109265384700_cit15a","doi-asserted-by":"publisher","first-page":"10290","DOI":"10.1021\/acscatal.6c01036","article-title":"Direct\n\u03b1-C\u2013H heteroarylation\nof unprotected primary amines","volume":"16","author":"Johnson","year":"2026","journal-title":"ACS Catal."},{"key":"2026073109265384700_cit15b","doi-asserted-by":"publisher","first-page":"15936","DOI":"10.1021\/jacs.1c07401","article-title":"Photocatalytic\nhydroaminoalkylation of styrenes with unprotected primary alkylamines","volume":"143","author":"Askey","year":"2021","journal-title":"J. Am. Chem. Soc."},{"key":"2026073109265384700_cit15c","doi-asserted-by":"publisher","first-page":"14986","DOI":"10.1002\/anie.202005294","article-title":"Photocatalytic \u03b1-tertiary amine synthesis via C\u2013H alkylation of unmasked primary amines","volume":"59","author":"Ryder","year":"2020","journal-title":"Angew. Chem., Int. 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Chem.\nRes."},{"key":"2026073109265384700_cit18","unstructured":"SMILES\nstrings for the primary amines in the Enamine catalogue were\nretrieved from the Enamine website. https:\/\/enamine.net\/building-blocks\/functional-classes\/primary-amines(accessed September 2025, catalogue version 09\/07\/2025)."},{"key":"2026073109265384700_cit19","unstructured":"RDKit: Open-source cheminformatics, ver.\n2025.3.5\n(https:\/\/www.rdkit.org).10.5281\/zenodo.16996017."},{"key":"2026073109265384700_cit20","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.1802.03426","article-title":"UMAP: Uniform Manifold Approximation\nand Projection for Dimension Reduction","author":"McInnes","year":"2018","journal-title":"arXiv"},{"key":"2026073109265384700_cit21a","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.2210.02410","article-title":"The Vendi Score:\nA Diversity Evaluation Metric for Machine Learning","author":"Friedman","year":"2023","journal-title":"arXiv"},{"key":"2026073109265384700_cit21b","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.2310.12952","article-title":"Cousins\nOf The Vendi Score: A Family of Similarity-Based Diversity Metrics\nfor Science and Machine Learning","author":"Pasarkar","year":"2024","journal-title":"arXiv"},{"key":"2026073109265384700_cit21c","unstructured":"(c)\n          \n          https:\/\/github.com\/vertaix\/Vendi-Score."},{"key":"2026073109265384700_cit22","doi-asserted-by":"publisher","first-page":"1910","DOI":"10.1021\/acs.orglett.7b00683","article-title":"Nickel-catalyzed\nreduction of secondary and tertiary amides","volume":"19","author":"Simmons","year":"2017","journal-title":"Org. Lett."},{"key":"2026073109265384700_cit23","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1021\/acs.orglett.1c04079","article-title":"Direct hydrodecarboxylation\nof aliphatic carboxylic acids: metal- and light-free","volume":"24","author":"McLean","year":"2022","journal-title":"Org. Lett."},{"key":"2026073109265384700_cit24","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1126\/science.abn1885","article-title":"Accelerating reaction generality\nand mechanistic insight\nthrough additive mapping","volume":"376","author":"Kullmer","year":"2022","journal-title":"Science"},{"key":"2026073109265384700_cit25","unstructured":"Xu, M.; Sun, G.; Huang, E.; Liu, D.\n          Preparation of 1-Boc-2,2-dimethylpiperidin-4-one. CN 119874607 A, 2025."}],"container-title":["Organic Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.orglett.6c02237","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/orlef7\/article-pdf\/28\/30\/9603\/66014242\/acs.orglett.6c02237.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/orlef7\/article-pdf\/28\/30\/9603\/66014242\/acs.orglett.6c02237.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T13:27:07Z","timestamp":1785504427000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/orlef7\/article\/28\/30\/9603\/5214730\/Photocatalytic-Annulation-of-Primary-Amines-to"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":48,"journal-issue":{"issue":"30","published-online":{"date-parts":[[2026,7,17]]},"published-print":{"date-parts":[[2026,7,31]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.orglett.6c02237","relation":{},"ISSN":["1523-7060","1523-7052"],"issn-type":[{"value":"1523-7060","type":"print"},{"value":"1523-7052","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]}}}