{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T21:46:32Z","timestamp":1780609592953,"version":"3.54.1"},"reference-count":56,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T00:00:00Z","timestamp":1636070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2022,1,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nitriles are recurring motifs in bioactive molecules and versatile functional groups in synthetic chemistry. Despite recent progress, direct introduction of a nitrile moiety in heteroarenes remains challenging. Recent developments in electrochemical reactions pave the way to more practical cyanation protocols. However, currently available methods typically require hazardous cyanide sources, expensive mediators, and often suffer from narrow substrate scope and laborious reaction set\u2010up. To address the limitations of current synthetic methods, herein, an effective, sustainable, and scalable procedure for the direct C(sp<jats:sup>2<\/jats:sup>)\u2212H cyanation of aromatic N\u2010heterocycles with a user\u2010friendly flow\u2010electrochemical set\u2010up is reported. Furthermore, high substrate and functional\u2010group tolerance is demonstrated, allowing late\u2010stage functionalization of drug\u2010like scaffolds, such as natural products and pharmaceuticals.<\/jats:p>","DOI":"10.1002\/chem.202103384","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T14:27:01Z","timestamp":1634740021000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Expedient Access to Cyanated N\u2010Heterocycles by Direct Flow\u2010Electrochemical C(sp<sup>2<\/sup>)\u2212H Activation"],"prefix":"10.1002","volume":"28","author":[{"given":"Mary\u2010Ambre","family":"Carvalho","sequence":"first","affiliation":[{"name":"Discovery Chemistry Janssen Research and Development  Turnhoutseweg 30 2340 Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samu\u00ebl","family":"Demin","sequence":"additional","affiliation":[{"name":"Discovery Chemistry Janssen Research and Development  Turnhoutseweg 30 2340 Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Martinez\u2010Lamenca","sequence":"additional","affiliation":[{"name":"Discovery Chemistry Janssen Research and Development  Turnhoutseweg 30 2340 Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0997-478X","authenticated-orcid":false,"given":"Fedor","family":"Romanov\u2010Michailidis","sequence":"additional","affiliation":[{"name":"Discovery Chemistry Janssen Research and Development  Turnhoutseweg 30 2340 Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1481-9212","authenticated-orcid":false,"given":"Kevin","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemical and Environmental Sciences School of Science University of Greenwich  Chatham Maritime Kent ME4 4TB UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1986-0476","authenticated-orcid":false,"given":"Frederik","family":"Rombouts","sequence":"additional","affiliation":[{"name":"Discovery Chemistry Janssen Research and Development  Turnhoutseweg 30 2340 Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3420-2789","authenticated-orcid":false,"given":"Morgan","family":"Lecomte","sequence":"additional","affiliation":[{"name":"Discovery Chemistry Janssen Research and Development  Turnhoutseweg 30 2340 Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,5]]},"reference":[{"key":"e_1_2_2_1_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm100762r"},{"key":"e_1_2_2_2_1","doi-asserted-by":"publisher","DOI":"10.6023\/cjoc1202132"},{"key":"e_1_2_2_3_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc-2018-0252"},{"key":"e_1_2_2_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-018-1005-4"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.1358\/dot.2010.46.3.1437247"},{"key":"e_1_2_2_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M504144200"},{"key":"e_1_2_2_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b01305"},{"key":"e_1_2_2_8_1","unstructured":"I.\u2009G. Buntain L.\u2009R. Hatton D.\u2009W. Hawkins C.\u2009J. Pearson D.\u2009A. Roberts (Rhone Poulenc Agriculture)1988 EP0295117B1."},{"key":"e_1_2_2_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201303637"},{"key":"e_1_2_2_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol302070t"},{"key":"e_1_2_2_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.201301073"},{"key":"e_1_2_2_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.9b03861"},{"key":"e_1_2_2_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3cc49502g"},{"key":"e_1_2_2_14_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0CC07783F"},{"key":"e_1_2_2_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201409247"},{"key":"e_1_2_2_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201409247"},{"key":"e_1_2_2_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja511011m"},{"key":"e_1_2_2_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja204063z"},{"key":"e_1_2_2_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.5b00142"},{"key":"e_1_2_2_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2013.03.089"},{"key":"e_1_2_2_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.201401152"},{"key":"e_1_2_2_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo061820i"},{"key":"e_1_2_2_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol0476826"},{"key":"e_1_2_2_23_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc-2018-0252"},{"key":"e_1_2_2_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470771709.ch9"},{"key":"e_1_2_2_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.7b00271"},{"key":"e_1_2_2_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(00)00840-1"},{"key":"e_1_2_2_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.201901635"},{"key":"e_1_2_2_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.9b00512"},{"key":"e_1_2_2_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.0c00049"},{"key":"e_1_2_2_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.7b00397"},{"key":"e_1_2_2_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201711060"},{"key":"e_1_2_2_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201711060"},{"key":"e_1_2_2_32_1","doi-asserted-by":"publisher","DOI":"10.1039\/c39780001108"},{"key":"e_1_2_2_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00304a045"},{"key":"e_1_2_2_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0040-4020(79)85026-7"},{"key":"e_1_2_2_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)90008-X"},{"key":"e_1_2_2_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(01)99615-7"},{"key":"e_1_2_2_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00502a030"},{"key":"e_1_2_2_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00460a052"},{"key":"e_1_2_2_39_1","doi-asserted-by":"publisher","DOI":"10.1039\/c29700000711"},{"key":"e_1_2_2_40_1","doi-asserted-by":"publisher","DOI":"10.1039\/df9684500242"},{"key":"e_1_2_2_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja01043a028"},{"key":"e_1_2_2_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201802247"},{"key":"e_1_2_2_43_1","author":"Cui T.","year":"2021","journal-title":"J. Org. Chem."},{"key":"e_1_2_2_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.1c02063"},{"key":"e_1_2_2_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201200486"},{"key":"e_1_2_2_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201200486"},{"key":"e_1_2_2_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2011.10.087"},{"key":"e_1_2_2_47_1","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/S0090-9556(25)00217-X","volume":"8","author":"Guengerich F. P.","year":"1980","journal-title":"Drug Metab. Dispos."},{"key":"e_1_2_2_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/jhet.5570430322"},{"key":"e_1_2_2_49_1","unstructured":"Versatile conditions: also possible with dichloromethane and acetonitrile instead of 2-methyltetrahydrofuran. SincenBu4NCN is hydroscopic an excess of water was added to the mixture to obtain an accurate methodology."},{"key":"e_1_2_2_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/np970493u"},{"key":"e_1_2_2_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)99315-8"},{"key":"e_1_2_2_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)74740-X"},{"key":"e_1_2_2_53_1","unstructured":"Trapping experiments were conducted in the presence of 1 equivalent of TEMPO. Although we haven't observed the formation of the TEMPO adduct the electrochemical cyanation reaction is completely inhibited in the presence of TEMPO (see the Supporting Information)."}],"container-title":["Chemistry \u2013 A European Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chem.202103384","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/chem.202103384","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chem.202103384","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T12:31:27Z","timestamp":1760272287000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/chem.202103384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,5]]},"references-count":56,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1,3]]}},"alternative-id":["10.1002\/chem.202103384"],"URL":"https:\/\/doi.org\/10.1002\/chem.202103384","archive":["Portico"],"relation":{},"ISSN":["0947-6539","1521-3765"],"issn-type":[{"value":"0947-6539","type":"print"},{"value":"1521-3765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,5]]},"assertion":[{"value":"2021-09-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202103384"}}