{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T21:49:21Z","timestamp":1765057761844,"version":"build-2065373602"},"reference-count":63,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:00:00Z","timestamp":1647907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2022,4,27]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The development of an enantioselective enamine\u2010catalysed addition of masked acetaldehyde to nitroalkenes <jats:italic>via<\/jats:italic> a rational approach helped to move away from the use of chloroform. The presented research allows the use of water as a reaction medium, therefore improving the industrial relevance of a protocol to access very important pharmaceutical intermediates. Critical to the success is the use of chemometrics\u2010assisted \u2018Design of Experiments\u2019 (DoE) optimisation during the development of the presented new synthetic approach, which allows to investigate the chemical space in a rational way.<\/jats:p>","DOI":"10.1002\/chem.202104524","type":"journal-article","created":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T06:22:19Z","timestamp":1646115739000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["DoE\u2010Driven Development of an Organocatalytic Enantioselective Addition of Acetaldehyde to Nitrostyrenes in Water**"],"prefix":"10.1002","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6634-1620","authenticated-orcid":false,"given":"Valeria","family":"Nori","sequence":"first","affiliation":[{"name":"Department of Physical and Chemical Sciences Universit\u00e0 degli Studi dell'Aquila  via Vetoio 67100 L'Aquila Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0455-4049","authenticated-orcid":false,"given":"Arianna","family":"Sinibaldi","sequence":"additional","affiliation":[{"name":"Department of Physical and Chemical Sciences Universit\u00e0 degli Studi dell'Aquila  via Vetoio 67100 L'Aquila Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7180-9689","authenticated-orcid":false,"given":"Giuliana","family":"Giorgianni","sequence":"additional","affiliation":[{"name":"Department of Physical and Chemical Sciences Universit\u00e0 degli Studi dell'Aquila  via Vetoio 67100 L'Aquila Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6792-6292","authenticated-orcid":false,"given":"Fabio","family":"Pesciaioli","sequence":"additional","affiliation":[{"name":"Department of Physical and Chemical Sciences Universit\u00e0 degli Studi dell'Aquila  via Vetoio 67100 L'Aquila Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0633-9016","authenticated-orcid":false,"given":"Francesca","family":"Di Donato","sequence":"additional","affiliation":[{"name":"Department of Physical and Chemical Sciences Universit\u00e0 degli Studi dell'Aquila  via Vetoio 67100 L'Aquila Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6176-0535","authenticated-orcid":false,"given":"Emanuele","family":"Cocco","sequence":"additional","affiliation":[{"name":"Department of Physical and Chemical Sciences Universit\u00e0 degli Studi dell'Aquila  via Vetoio 67100 L'Aquila Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9461-9597","authenticated-orcid":false,"given":"Alessandra","family":"Biancolillo","sequence":"additional","affiliation":[{"name":"Department of Physical and Chemical Sciences Universit\u00e0 degli Studi dell'Aquila  via Vetoio 67100 L'Aquila Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8574-8568","authenticated-orcid":false,"given":"Aitor","family":"Landa","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica I Universidad del Pa\u00eds Vasco  Manuel Lardizabal 3 20018 \u2013 San Sebasti\u00e1n Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2983-6445","authenticated-orcid":false,"given":"Armando","family":"Carlone","sequence":"additional","affiliation":[{"name":"Department of Physical and Chemical Sciences Universit\u00e0 degli Studi dell'Aquila  via Vetoio 67100 L'Aquila Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,3,22]]},"reference":[{"key":"e_1_2_3_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17580-z"},{"key":"e_1_2_3_2_1","unstructured":"\u00a0"},{"volume-title":"Green Chemistry: Theory and Practice","year":"1998","author":"Anastas P. T.","key":"e_1_2_3_3_2"},{"key":"e_1_2_3_4_2","doi-asserted-by":"publisher","DOI":"10.1039\/B918763B"},{"key":"e_1_2_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/cssc.202100573"},{"key":"e_1_2_3_6_1","unstructured":"\u00a0"},{"key":"e_1_2_3_7_2","doi-asserted-by":"publisher","DOI":"10.1515\/psr-2018-0097"},{"key":"e_1_2_3_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/op200214d"},{"key":"e_1_2_3_9_1","unstructured":"\u00a0"},{"key":"e_1_2_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200704870"},{"key":"e_1_2_3_10_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200704870"},{"key":"e_1_2_3_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200801130"},{"key":"e_1_2_3_11_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200801130"},{"key":"e_1_2_3_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200800847"},{"key":"e_1_2_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200800847"},{"key":"e_1_2_3_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201006204"},{"key":"e_1_2_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201006204"},{"key":"e_1_2_3_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201302087"},{"key":"e_1_2_3_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/catal10111296"},{"key":"e_1_2_3_16_1","unstructured":"General reviews:"},{"key":"e_1_2_3_17_2","unstructured":"Organic Synthesis in Water(Eds.: P.\u2005A. Grieco) Blackie Academic & Profesional London 1998;"},{"key":"e_1_2_3_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr010122p"},{"key":"e_1_2_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0010-8545(02)00306-5"},{"key":"e_1_2_3_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr030009u"},{"key":"e_1_2_3_21_2","doi-asserted-by":"publisher","DOI":"10.1039\/B507207G"},{"key":"e_1_2_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2007.12.006"},{"key":"e_1_2_3_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.200800731"},{"key":"e_1_2_3_24_2","doi-asserted-by":"publisher","DOI":"10.1039\/b910861k"},{"key":"e_1_2_3_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr100162c"},{"key":"e_1_2_3_26_2","doi-asserted-by":"publisher","DOI":"10.1039\/c004970k"},{"key":"e_1_2_3_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/9783527658862.ch24"},{"key":"e_1_2_3_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201705499"},{"key":"e_1_2_3_29_2","doi-asserted-by":"publisher","DOI":"10.1039\/D0SC06000C"},{"key":"e_1_2_3_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0573312"},{"key":"e_1_2_3_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200601156"},{"key":"e_1_2_3_31_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200601156"},{"key":"e_1_2_3_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200704161"},{"key":"e_1_2_3_32_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200704161"},{"key":"e_1_2_3_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.7b06453"},{"key":"e_1_2_3_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja060338e"},{"key":"e_1_2_3_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200604952"},{"key":"e_1_2_3_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200604952"},{"key":"e_1_2_3_36_1","unstructured":"\u00a0"},{"key":"e_1_2_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-7439(98)00065-3"},{"key":"e_1_2_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemolab.2004.04.005"},{"key":"e_1_2_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2009.06.015"},{"key":"e_1_2_3_40_2","doi-asserted-by":"publisher","DOI":"10.1021\/op500169m"},{"key":"e_1_2_3_41_2","doi-asserted-by":"publisher","DOI":"10.1039\/C5OB01892G"},{"key":"e_1_2_3_42_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1588654"},{"key":"e_1_2_3_43_2","doi-asserted-by":"publisher","DOI":"10.1080\/10408347.2020.1848517"},{"key":"e_1_2_3_44_2","doi-asserted-by":"publisher","DOI":"10.1055\/a-1736\u20136703"},{"key":"e_1_2_3_45_1","unstructured":"For selected examples on the application of DoE in academia see:"},{"key":"e_1_2_3_46_2","first-page":"1603","author":"Jamieson C.","year":"2000","journal-title":"Synlett"},{"key":"e_1_2_3_47_2","doi-asserted-by":"publisher","DOI":"10.1021\/op010108e"},{"key":"e_1_2_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2003.10.055"},{"key":"e_1_2_3_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.200500870"},{"key":"e_1_2_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2007.12.056"},{"key":"e_1_2_3_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201301493"},{"key":"e_1_2_3_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201402380"},{"key":"e_1_2_3_53_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00706-015-1486-8"},{"key":"e_1_2_3_54_2","doi-asserted-by":"publisher","DOI":"10.1039\/C4OB02694B"},{"key":"e_1_2_3_55_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.9b01148"},{"key":"e_1_2_3_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200703261"}],"container-title":["Chemistry \u2013 A European Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chem.202104524","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/chem.202104524","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chem.202104524","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T19:59:51Z","timestamp":1760299191000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/chem.202104524"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,22]]},"references-count":63,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2022,4,27]]}},"alternative-id":["10.1002\/chem.202104524"],"URL":"https:\/\/doi.org\/10.1002\/chem.202104524","archive":["Portico"],"relation":{},"ISSN":["0947-6539","1521-3765"],"issn-type":[{"type":"print","value":"0947-6539"},{"type":"electronic","value":"1521-3765"}],"subject":[],"published":{"date-parts":[[2022,3,22]]},"assertion":[{"value":"2021-12-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202104524"}}