{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T19:53:57Z","timestamp":1788551637667,"version":"build-2803163510"},"reference-count":91,"publisher":"Wiley","issue":"36","license":[{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"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":[[2022,6,27]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Direct reductive amination (DRA) is a ubiquitous reaction in organic chemistry. This transformation between a carbonyl group and an amine is most often achieved by using a super stoichiometric amount of hazardous hydride reagents, thus being incompatible with many sensitive functional groups. DRA could also be achieved by means of chemo\u2010 or biocatalysis, thereby attracting the interest of industry as well as academic laboratories due to the virtually perfect atom economy. Although DRAs are well\u2010established for substrate pairs such as aldehydes with either 1\u00b0 or 2\u00b0 amines as well as ketones with 1\u00b0 amines, the current methodologies are limited in the case of ketones with 2\u00b0 amines. Herein, we present a general DRA protocol that overcomes this major limitation by means of iridium catalysis. The applicability of the methodology is demonstrated by accessing an unprecedented range of biologically relevant tertiary amines starting from both aliphatic ketones and aliphatic amines. The choice of a disphosphane ligand (Josiphos <jats:bold>A<\/jats:bold> or Xantphos) is essential for the success of the transformation.<\/jats:p>","DOI":"10.1002\/chem.202201078","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T04:51:38Z","timestamp":1651035098000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Iridium\u2010Catalyzed Direct Reductive Amination of Ketones and Secondary Amines: Breaking the Aliphatic Wall"],"prefix":"10.1002","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4478-2502","authenticated-orcid":false,"given":"Matthieu","family":"Jouffroy","sequence":"first","affiliation":[{"name":"Chemical Process R&amp;D Discovery Process Research Janssen Pharmaceutica N.V.  Turnhoutseweg 30 2340 Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi\u2010Mo","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Rennes  CNRS, ISCR-UMR6226 Rennes 35000 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0917-2725","authenticated-orcid":false,"given":"Marie","family":"Cordier","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Rennes  CNRS, ISCR-UMR6226 Rennes 35000 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marielle","family":"Blot","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Rennes  CNRS, ISCR-UMR6226 Rennes 35000 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6088-4472","authenticated-orcid":false,"given":"Thierry","family":"Roisnel","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Rennes  CNRS, ISCR-UMR6226 Rennes 35000 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0961-4530","authenticated-orcid":false,"given":"Rafael","family":"Gramage\u2010Doria","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Rennes  CNRS, ISCR-UMR6226 Rennes 35000 France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,12]]},"reference":[{"key":"e_1_2_3_1_1","unstructured":"\u00a0"},{"key":"e_1_2_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/1615-4169(200212)344:10<1037::AID-ADSC1037>3.0.CO;2-3"},{"key":"e_1_2_3_3_2","doi-asserted-by":"publisher","DOI":"10.1039\/C9CS00286C"},{"key":"e_1_2_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.201900777"},{"key":"e_1_2_3_5_1","unstructured":"\u00a0"},{"key":"e_1_2_3_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.0c00248"},{"key":"e_1_2_3_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.9b00383"},{"key":"e_1_2_3_8_2","doi-asserted-by":"publisher","DOI":"10.1039\/b005777k"},{"key":"e_1_2_3_9_2","doi-asserted-by":"publisher","DOI":"10.1039\/D1CY00695A"},{"key":"e_1_2_3_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.0c02156"},{"key":"e_1_2_3_11_1","unstructured":"\u00a0"},{"key":"e_1_2_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/9783527629541"},{"key":"e_1_2_3_13_2","first-page":"261","volume-title":"Stereoselective Formation of Amines","author":"Wang C.","year":"2014"},{"key":"e_1_2_3_14_2","doi-asserted-by":"publisher","DOI":"10.1039\/D1QO00300C"},{"key":"e_1_2_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2020.131863"},{"key":"e_1_2_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14475-x"},{"key":"e_1_2_3_17_2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/9783527826186.ch5","volume-title":"Methodologies in Amine Synthesis: Challenges and Applications","author":"Cunillera A.","year":"2021"},{"key":"e_1_2_3_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.201500213"},{"key":"e_1_2_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41929-021-00671-5"},{"key":"e_1_2_3_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.1c00574"},{"key":"e_1_2_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202112671"},{"key":"e_1_2_3_21_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202112671"},{"key":"e_1_2_3_22_1","unstructured":"\u00a0"},{"key":"e_1_2_3_23_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1611788"},{"key":"e_1_2_3_24_2","doi-asserted-by":"publisher","DOI":"10.1039\/C6RA10494K"},{"key":"e_1_2_3_25_2","volume-title":"Reductions by the Alumino- and Borohydrides in Organic Synthesis","author":"J. 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These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum KarlsruheAccess Structures service."},{"key":"e_1_2_3_68_1","unstructured":"\u00a0"},{"key":"e_1_2_3_69_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1158140"},{"key":"e_1_2_3_70_2","unstructured":"G. Rishton S.\u2005M. Catalano G.\u2005C. 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This supports the initial steps of the catalytic cycle proposed in Scheme\u20053."},{"key":"e_1_2_3_78_1","unstructured":"\u00a0"},{"key":"e_1_2_3_79_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200603224"},{"key":"e_1_2_3_79_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200603224"},{"key":"e_1_2_3_80_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202111462"},{"key":"e_1_2_3_80_3","doi-asserted-by":"crossref","first-page":"e202111462","DOI":"10.1002\/ange.202111462","volume":"134","year":"2022","journal-title":"Angew. 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