{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T05:08:06Z","timestamp":1775279286531,"version":"3.50.1"},"reference-count":31,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5898","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2008,10,3]]},"abstract":"<jats:p>\n                    Photoredox catalysis and organocatalysis represent two powerful fields of molecule activation that have found widespread application in the areas of inorganic and organic chemistry, respectively. We merged these two catalysis fields to solve problems in asymmetric chemical synthesis. Specifically, the enantioselective intermolecular \u03b1-alkylation of aldehydes has been accomplished using an interwoven activation pathway that combines both the photoredox catalyst Ru(bpy)\n                    <jats:sub>3<\/jats:sub>\n                    Cl\n                    <jats:sub>2<\/jats:sub>\n                    (where bpy is 2,2\u2032-bipyridine) and an imidazolidinone organocatalyst. This broadly applicable, yet previously elusive, alkylation reaction is now highly enantioselective and operationally trivial.\n                  <\/jats:p>","DOI":"10.1126\/science.1161976","type":"journal-article","created":{"date-parts":[[2008,9,4]],"date-time":"2008-09-04T21:55:02Z","timestamp":1220565302000},"page":"77-80","source":"Crossref","is-referenced-by-count":2329,"title":["Merging Photoredox Catalysis with Organocatalysis: The Direct Asymmetric Alkylation of Aldehydes"],"prefix":"10.1126","volume":"322","author":[{"given":"David A.","family":"Nicewicz","sequence":"first","affiliation":[{"name":"Contribution from Merck Center for Catalysis, Department of Chemistry, Princeton University, Princeton, NJ 08544, USA."}]},{"given":"David W. C.","family":"MacMillan","sequence":"additional","affiliation":[{"name":"Contribution from Merck Center for Catalysis, Department of Chemistry, Princeton University, Princeton, NJ 08544, USA."}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0010-8545(82)85003-0"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0010-8545(88)80032-8"},{"key":"e_1_3_1_4_2","doi-asserted-by":"crossref","unstructured":"P. Renaud M. P. Sibi Eds. Radicals in Organic Synthesis (Wiley-VCH Weinheim Germany 2001).","DOI":"10.1002\/9783527618293"},{"key":"e_1_3_1_5_2","doi-asserted-by":"crossref","unstructured":"A. Berkessel H. Gr\u00f6ger Eds. Asymmetric Organocatalysis: From Biomimetic Concepts to Applications in Asymmetric Synthesis (Wiley-VCH Weinheim Germany 2005).","DOI":"10.1002\/3527604677"},{"key":"e_1_3_1_6_2","doi-asserted-by":"crossref","unstructured":"P. I. Dalko Ed. Enantioselective Organocatalysis: Reactions and Experimental Procedures (Wiley-VCH Weinheim Germany 2007).","DOI":"10.1002\/9783527610945"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science. 1142696"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0719428"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja077212h"},{"key":"e_1_3_1_10_2","unstructured":"A SOMO activation mechanism has also been reported for the \u03b1-oxidation of aldehydes ( 10 )."},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja069245n"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.65.070196.002541"},{"key":"e_1_3_1_13_2","unstructured":"An intramolecular \u03b1-formyl alkylation has been reported ( 13 )."},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0392566"},{"key":"e_1_3_1_15_2","unstructured":"For a catalytic enantioselective alkylation of racemic \u03b1-bromoesters see ( 15 )."},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja8009428"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-1990-21190"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00011a007"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00511a007"},{"key":"e_1_3_1_20_2","unstructured":"Value was corrected from the Ag\/Ag + ClO \u2013 4 electrode ( 20 )."},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00376a024"},{"key":"e_1_3_1_22_2","unstructured":"Ru(bpy) 3 + has previously been shown to reduce phenacyl bromide ( 22 )."},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/j100365a039"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0009-2614(86)80542-5"},{"key":"e_1_3_1_25_2","unstructured":"The possibility of direct one-electron reduction of the \u03b1-bromocarbonyl by the \u03b1-amino radical as a propagation step cannot be excluded."},{"key":"e_1_3_1_26_2","unstructured":"DFT calculations were performed with the use of B3LYP\/6-311+G(2d 2p)\/\/B3LYP\/6-31G(d)."},{"key":"e_1_3_1_27_2","unstructured":"A conformer that positions the enamine olefin toward the tert -butyl group was also found to be energetically relevant in these calculations. Because of the pseudo C 2 -symmetric nature of catalyst 6 this enamine conformer also exists with the Si face open and the Re face blocked in a manner similar to DFT\u2013 8 ."},{"key":"e_1_3_1_28_2","unstructured":"Materials and methods are available as supporting material on Science Online."},{"key":"e_1_3_1_29_2","unstructured":"No rate enhancement was observed in the absence of Ru(bpy) 3 2+ with additive bpy or Bu 4 NCl."},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1246\/cl.1978.45"},{"key":"e_1_3_1_31_2","unstructured":"None of the remaining reaction components (aldehyde amine catalyst 2 6-lutidine or 2 6-lutidinium bromide) quenched *Ru(bpy) 3 2+ ."},{"key":"e_1_3_1_32_2","unstructured":"We thank S. Bernhard for his assistance in performing quenching experiments as well as many insightful discussions. Additionally we thank T. J. Rainey for performing DFT calculations. Financial support was provided by the NIH General Medical Sciences (grant R01 GM078201-01-01) and gifts from Merck Amgen and Bristol-Myers Squibb. D.A.N. is grateful for a NIH National Service Research Award fellowship (F32GM076816)."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1161976","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T04:44:51Z","timestamp":1704861891000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1161976"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10,3]]},"references-count":31,"journal-issue":{"issue":"5898","published-print":{"date-parts":[[2008,10,3]]}},"alternative-id":["10.1126\/science.1161976"],"URL":"https:\/\/doi.org\/10.1126\/science.1161976","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1126791.583879","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,10,3]]}}}