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Probably due to the relatively low reactivity of ketones as electrophiles (aldol acceptors), its propensity for retro\u2010aldol reaction. The reactions often suffer from unsatisfactory chemoselectivity (self\u2010 vs. crossed aldol products) and regioselectivity (thermodynamic <jats:italic>vs<\/jats:italic>. kinetic enolate). In this quest, we report here for the first time selective cross\u2010coupling reaction of ketones to <jats:italic>\u03b2<\/jats:italic>\u2010branched <jats:italic>\u03b2, \u03b3<\/jats:italic>\u2010unsaturated ketones by using ruthenium catalysis. Interestingly, single crossed aldol condensation products are formed even in reactions where a mixture of products is possible. Reaction is highly chemoselective, regioselective and produces H<jats:sub>2<\/jats:sub>O as the only byproducts making the protocol environmentally benign. Method is compatible with a wide variety of sensitive functional group and applicable for even problematic aliphatic ketones as substrates. Notably, acetone was found as a three\u2010carbon feedstock for the syntheses of simple \u03b2, \u03b3\u2010unsaturated ketone compounds. The process can further be extended to the gram\u2010scale reaction and late\u2010stage functionalization of natural products. With the help of DFT calculations, several control experiments, and deuterium\u2010labeling experiments, the mechanistic finding demonstrated that initial aldol\u2010condensation of ketones to a \u03b2, \u03b2\u2010disubstituted \u03b1, \u03b2\u2010unsaturated ketone, which further isomerizes to a \u03b2, \u03b3\u2010 unsaturated ketone <jats:italic>via<\/jats:italic> \u03b7<jats:sup>3<\/jats:sup>\u2010allyl ruthenium complex.<\/jats:p>","DOI":"10.1002\/chem.202303206","type":"journal-article","created":{"date-parts":[[2023,12,23]],"date-time":"2023-12-23T03:18:55Z","timestamp":1703301535000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Chemo\u2010 and Regioselective Catalytic Cross\u2010Coupling Reaction of Ketones for the Synthesis of <i>\u03b2<\/i>, <i>\u03b3<\/i>\u2010Disubstituted <i>\u03b2<\/i>, <i>\u03b3<\/i>\u2010Unsaturated Ketones"],"prefix":"10.1002","volume":"30","author":[{"given":"Priyanka","family":"Adhikari","sequence":"first","affiliation":[{"name":"Department of Chemistry Indian Institute of Technology Guwahati  Guwahati Assam India 781039"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dipanjan","family":"Bhattacharyya","sequence":"additional","affiliation":[{"name":"Department of Chemistry Indian Institute of Technology Guwahati  Guwahati Assam India 781039"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kritartha","family":"Deori","sequence":"additional","affiliation":[{"name":"Department of Chemistry Indian Institute of Technology Guwahati  Guwahati Assam India 781039"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bikash Kumar","family":"Sarmah","sequence":"additional","affiliation":[{"name":"Department of Chemistry Indian Institute of Technology Guwahati  Guwahati Assam India 781039"},{"name":"Department of Chemistry Sonari College  Assam India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2178-7116","authenticated-orcid":false,"given":"Animesh","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Chemistry Indian Institute of Technology Guwahati  Guwahati Assam India 781039"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,1,26]]},"reference":[{"key":"e_1_2_9_1_1","unstructured":"\u00a0"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm001040g"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2011.01.073"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.300"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/ci500531r"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.20223"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.298"},{"key":"e_1_2_9_8_1","unstructured":"\u00a0"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201210113"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201509160"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja501780w"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.200606106"},{"key":"e_1_2_9_13_1","unstructured":"\u00a0"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.9b00025"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.0c02787"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38743-8"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201202798"},{"key":"e_1_2_9_18_1","unstructured":"\u00a0"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00267a036"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.7b00228"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.6b02458"},{"key":"e_1_2_9_22_1","unstructured":"\u00a0"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.1039\/C6CC08392G"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol5017965"},{"key":"e_1_2_9_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5b02945"},{"key":"e_1_2_9_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201505895"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja806929y"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja512015w"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol0159470"},{"key":"e_1_2_9_30_1","unstructured":"\u00a0"},{"key":"e_1_2_9_31_2","first-page":"203","volume":"28","author":"Mukaiyama T.","year":"1982","journal-title":"Org. 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