{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:42:50Z","timestamp":1791574970363,"version":"4.3.4"},"reference-count":82,"publisher":"Wiley","issue":"47","license":[{"start":{"date-parts":[[2019,10,22]],"date-time":"2019-10-22T00:00:00Z","timestamp":1571702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["122483"],"award-info":[{"award-number":["122483"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["058160-17S1"],"award-info":[{"award-number":["058160-17S1"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002701","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2018R1A6A3A03011441"],"award-info":[{"award-number":["2018R1A6A3A03011441"]}],"id":[{"id":"10.13039\/501100002701","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2019,11,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Recently, CuH\u2010catalyzed reductive coupling processes involving carbonyl compounds and imines have become attractive alternatives to traditional methods for stereoselective addition because of their ability to use readily accessible and stable olefins as surrogates for organometallic nucleophiles. However, the inability to use aldehydes, which usually reduce too rapidly in the presence of copper hydride complexes to be viable substrates, has been a major limitation. Shown here is that by exploiting relative concentration effects through kinetic control, this intrinsic reactivity can be inverted and the reductive coupling of 1,3\u2010dienes with aldehydes achieved. Using this method, both aromatic and aliphatic aldehydes can be transformed into synthetically valuable homoallylic alcohols with high levels of diastereo\u2010 and enantioselectivities, and in the presence of many useful functional groups. Furthermore, using a combination of theoretical (DFT) and experimental methods, important mechanistic features of this reaction related to stereo\u2010 and chemoselectivities were uncovered.<\/jats:p>","DOI":"10.1002\/anie.201911008","type":"journal-article","created":{"date-parts":[[2019,9,25]],"date-time":"2019-09-25T07:39:35Z","timestamp":1569397175000},"page":"17074-17080","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":96,"title":["Engaging Aldehydes in CuH\u2010Catalyzed Reductive Coupling Reactions: Stereoselective Allylation with Unactivated 1,3\u2010Diene Pronucleophiles"],"prefix":"10.1002","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3904-0299","authenticated-orcid":false,"given":"Chengxi","family":"Li","sequence":"first","affiliation":[{"name":"Department of Chemistry Massachusetts Institute of Technology  Cambridge Massachusetts 02139 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1708-2351","authenticated-orcid":false,"given":"Kwangmin","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Chemistry Massachusetts Institute of Technology  Cambridge Massachusetts 02139 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0951-6487","authenticated-orcid":false,"given":"Richard Y.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Chemistry Massachusetts Institute of Technology  Cambridge Massachusetts 02139 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3875-4775","authenticated-orcid":false,"given":"Stephen L.","family":"Buchwald","sequence":"additional","affiliation":[{"name":"Department of Chemistry Massachusetts Institute of Technology  Cambridge Massachusetts 02139 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,10,22]]},"reference":[{"key":"e_1_2_6_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781118750421"},{"key":"e_1_2_6_2_1","unstructured":"For selected reviews on addition of organometallic reagents to carbonyl derivatives see:"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr000411y"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr020050h"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1039\/b617746h"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr078340r"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr1004474"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr400008h"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.7b00561"},{"key":"e_1_2_6_10_1","unstructured":"For selected reviews on reductive coupling of \u03c0-unsaturated pronucleophiles with carbonyl derivatives see:"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah5133"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.8b00213"},{"key":"e_1_2_6_13_1","unstructured":"For selected examples of Rh-catalyzed reductive coupling of olefin-derived pronucleophiles with carbonyl compounds see:"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200351986"},{"key":"e_1_2_6_14_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200351986"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0673027"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol901527b"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201905540"},{"key":"e_1_2_6_17_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201905540"},{"key":"e_1_2_6_18_1","unstructured":"For selected examples of Ru-catalyzed reductive coupling of \u03c0-unsaturated pronucleophiles with carbonyl compounds see:"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol800836v"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja801213x"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200801359"},{"key":"e_1_2_6_21_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200801359"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja904124b"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1219274"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja2046028"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja4087193"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b02279"},{"key":"e_1_2_6_27_1","unstructured":"For selected examples of Ir-catalyzed reductive coupling of \u03c0-unsaturated pronucleophiles with carbonyl compounds see:"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol800159w"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja902437k"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.201000599"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201200239"},{"key":"e_1_2_6_31_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201200239"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b09333"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b04374"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1039\/C8CC09706B"},{"key":"e_1_2_6_35_1","unstructured":"For selected examples of Ni-catalyzed reductive coupling of \u03c0-unsaturated pronucleophiles with carbonyl compounds see:"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0491735"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0521831"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja060580l"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0608904"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1039\/c3sc22051f"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1039\/b414322a"},{"key":"e_1_2_6_42_1","unstructured":"For recent examples of Cu-catalyzed stereoselective addition of \u03c0-unsaturated pronucleophiles to carbonyl derivatives reported by our research group see:"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b06299"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf7720"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201608446"},{"key":"e_1_2_6_45_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201608446"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b12271"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b13907"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.9b01784"},{"key":"e_1_2_6_49_1","unstructured":"For selected reports by other research groups see:"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja3036916"},{"key":"e_1_2_6_51_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b10149"},{"key":"e_1_2_6_52_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b12213"},{"key":"e_1_2_6_53_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b04750"},{"key":"e_1_2_6_54_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.8b03216"},{"key":"e_1_2_6_55_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.9b00979"},{"key":"e_1_2_6_56_1","unstructured":"The barriers provided for comparison in Figure\u20051\u2009A are computed standard Gibbs free energy barriers using B3LYP\/6-31G(d)-SDD. In these calculations L*=(S S)-Ph-BPE was employed. The barriers provided are relative to infinitely separatedL*CuH and carbonyl derivative since all optimized precomplexes were less stable."},{"key":"e_1_2_6_57_1","unstructured":"\u00a0"},{"key":"e_1_2_6_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(99)01098-4"},{"key":"e_1_2_6_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-328X(00)00903-7"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol062398v"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201806937"},{"key":"e_1_2_6_61_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201806937"},{"key":"e_1_2_6_62_1","unstructured":"\u00a0"},{"key":"e_1_2_6_63_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-1991-20797"},{"key":"e_1_2_6_64_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00076a005"},{"key":"e_1_2_6_65_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja9603315"},{"key":"e_1_2_6_66_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200461312"},{"key":"e_1_2_6_66_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200461312"},{"key":"e_1_2_6_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2007.02.014"},{"key":"e_1_2_6_68_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol400498a"},{"key":"e_1_2_6_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11844"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr000427o"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol902784q"},{"key":"e_1_2_6_72_1","unstructured":"We note that that electron-deficient aldehydes can be problematic substrates under these reaction conditions. For instance the reaction of 4-chlorobenzaldehyde provided unsatisfactory yield (49\u2009% as assessed by1H\u2005NMR analysis of the crude reaction mixture) and selectivity (2:1 dr and 91:9 er for the major diastereomer). For more detail see the Supporting Information. We believe that the lower yield might be due to faster reduction of the electron-deficient aldehyde which accounts for the remainder of the mass balance."},{"key":"e_1_2_6_73_1","unstructured":"In contrast to allylation reactions using most 2-substituted 1 3-dienes the reaction of 2-unsubstituted (1 3-butadiene) and methyl-substituted (isoprene) reagents both resulted in low diastereo- and enantioselectivities (see the Supporting Information for more detail). These results suggest that the presence of a large substituent at 2-position of 1 3-diene substrate is beneficial for high stereoselectivity. Although the exact origin of this effect has not been thoroughly determined it is apparent in our proposed stereochemical model (see the discussion of stereoselectivity in the Supporting Information) that the 2-substituent of the diene might engage in steric interactions with both the phosphine ligand and the aldehyde in the selectivity-determining transition states."},{"key":"e_1_2_6_74_1","unstructured":"In general away from equilibrium the Gibbs free energy of reaction (\u0394G) differs from the standard free energy of reaction (\u0394G\u00b0) by a quantity related to the reaction quotientQ: \u0394G\u2212\u0394G\u00b0=RTlnQIn our system of interest the aldehyde concentration is presumably maintained at a very low value meaning that states involving free aldehyde are lowered in free energy relative to those involving the aldehyde bound to the catalyst. Although this effect is not reflected in Figure\u20052 which shows only the standard free energies it is a useful mnemonic to associate the effect of decreasing the steady-state aldehyde concentration with raising the energies of the grey-highlighted states relative to the white ones."},{"key":"e_1_2_6_75_1","unstructured":"See the Supporting Information for the detailed DFT studies on the origin of stereoselectivity in the addition step."}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fanie.201911008","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.201911008","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.201911008","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.201911008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T17:24:04Z","timestamp":1694021044000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.201911008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,22]]},"references-count":82,"journal-issue":{"issue":"47","published-print":{"date-parts":[[2019,11,18]]}},"alternative-id":["10.1002\/anie.201911008"],"URL":"https:\/\/doi.org\/10.1002\/anie.201911008","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.26434\/chemrxiv.8977673.v1","asserted-by":"object"}]},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,22]]},"assertion":[{"value":"2019-08-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}