{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:31:36Z","timestamp":1790879496234,"version":"4.1.0"},"reference-count":146,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2008,5,13]],"date-time":"2008-05-13T00:00:00Z","timestamp":1210636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2008,6,20]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A general method for the regioselective Heck reaction of electron\u2010rich olefins is presented. Fast, highly regioselective Pd\u2010catalysed \u03b1\u2010arylation of electron\u2010rich olefins, vinyl ethers (<jats:bold>1\u2009a\u2013d<\/jats:bold>), hydroxyl vinyl ethers (<jats:bold>1\u2009e,\u2009f<\/jats:bold>), enamides (<jats:bold>1\u2009g,\u2009h<\/jats:bold>) and a substituted vinyl ether (<jats:bold>1\u2009i<\/jats:bold>) has been accomplished with a diverse range of aryl bromides (<jats:bold>2\u2009a\u2013r<\/jats:bold>), for the first time, in cheap, green and easily available alcohols with no need for any halide scavengers or salt additives. The reaction proceeds with high efficiency, leading exclusively to the \u03b1\u2010products, in 2\u2010propanol and particularly in ethylene glycol. In the latter, the arylation can be catalysed at a palladium loading of 0.1\u2005mol\u2009% and finish in as short a time as 0.5\u2005h. The remarkable performance of the alcohol solvents in promoting \u03b1 regiocontrol is attributed to their hydrogen\u2010bond\u2010donating capability, which is believed to facilitate the dissociation of halide anions from Pd<jats:sup>II<\/jats:sup>, and hence, the generation of a key ionic Pd<jats:sup>II<\/jats:sup>\u2013olefin intermediate responsible for the \u03b1 product. This belief is further strengthened by the study of a benchmark arylation reaction in 21 different solvents. The study revealed that exclusive \u03b1\u2010regioselective arylation takes place in almost all of the protic solvents, and there is a rough correlation between the \u03b1\u2010arylation rates and the solvent parameter <jats:italic>E<\/jats:italic><jats:sub>T<\/jats:sub><jats:sup>N<\/jats:sup>. The method is simpler, cleaner and more general than those established thus far.<\/jats:p>","DOI":"10.1002\/chem.200800411","type":"journal-article","created":{"date-parts":[[2008,5,13]],"date-time":"2008-05-13T11:49:12Z","timestamp":1210679352000},"page":"5555-5566","source":"Crossref","is-referenced-by-count":80,"title":["Hydrogen\u2010Bond\u2010Directed Catalysis: Faster, Regioselective and Cleaner Heck Arylation of Electron\u2010Rich Olefins in Alcohols"],"prefix":"10.1002","volume":"14","author":[{"given":"Zeynab","family":"Hyder","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiwu","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianliang","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,6,11]]},"reference":[{"key":"e_1_2_7_1_2","unstructured":"For reviews see:"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1039\/B611547K"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.200400711"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2004.06.012"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.200404203"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471212466.ch46"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(01)00665-2"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr9903048"},{"key":"e_1_2_7_9_2","volume-title":"Transition Metals in the Synthesis of Complex Organic Molecules","author":"Hegedus L. 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was presented at an AstraZeneca meeting on February 22 2007 and at GlaxoSmithKline on April 27 2007. Very recently two communication papers appeared reporting the Heck arylation ofN\u2010acyl\u2010N\u2010vinylamine and1\u2009a respectively in 2\u2010propanol:"},{"key":"e_1_2_7_113_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2008.02.144"},{"key":"e_1_2_7_114_2","first-page":"887","author":"He T.","year":"2008","journal-title":"Synthesis"},{"key":"e_1_2_7_115_2","unstructured":"For recent examples of coupling reactions in alcohols see:"},{"key":"e_1_2_7_116_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0701614"},{"key":"e_1_2_7_117_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcata.2006.12.003"},{"key":"e_1_2_7_118_2","doi-asserted-by":"publisher","DOI":"10.1039\/b314246a"},{"key":"e_1_2_7_119_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja039889k"},{"key":"e_1_2_7_120_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol0266673"},{"key":"e_1_2_7_121_2","doi-asserted-by":"publisher","DOI":"10.1039\/b310455a"},{"key":"e_1_2_7_121_3","doi-asserted-by":"publisher","DOI":"10.1016\/S0010-8545(03)00019-5"},{"key":"e_1_2_7_122_2","unstructured":"Larhed shows that the hydroxyl vinyl ether1\u2009ereacts with aryl bromides regioselectively in toluene and suggests this may be due to the dissociation of bromide from Ar\u2010Pd\u2010Br being facilitated by \u2010OH hydrogen bonding to the bromide.[18]"},{"key":"e_1_2_7_123_2","unstructured":"The hydroxy group of a substrate could also affect selectivities in the Heck reaction by coordinating to palladium:"},{"key":"e_1_2_7_124_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.200500540"},{"key":"e_1_2_7_125_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200460921"},{"key":"e_1_2_7_125_3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200460921"},{"key":"e_1_2_7_126_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo951923t"},{"key":"e_1_2_7_127_2","unstructured":"\u00a0"},{"key":"e_1_2_7_128_2","doi-asserted-by":"publisher","DOI":"10.1002\/poc.863"},{"key":"e_1_2_7_129_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(02)00858-4"},{"key":"e_1_2_7_130_2","doi-asserted-by":"publisher","DOI":"10.1039\/b101449h"},{"key":"e_1_2_7_131_2","doi-asserted-by":"publisher","DOI":"10.1002\/1099-1395(200010)13:10<591::AID-POC305>3.0.CO;2-2"},{"key":"e_1_2_7_132_2","volume-title":"Solvents and Solvent Effects in Organic Chemistry","author":"Reichardt C.","year":"2003"},{"key":"e_1_2_7_133_2","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.200303163"},{"key":"e_1_2_7_134_2","unstructured":"\u00a0"},{"key":"e_1_2_7_135_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol0266976"},{"key":"e_1_2_7_136_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2006.08.009"},{"key":"e_1_2_7_137_2","unstructured":"The effect of higher equivalents of salt was also investigated. However the reduced solubility of the salt in the solvent obscured the results obtained. On the other hand we note that the ionic strength of an ionic liquid such as [bmim][BF4] (bmim=1\u2010butyl\u20103\u2010methylimidazolium) is significantly higher than that of the solution we examined assuming the ionic strength can be calculated withI=0.5\u03a3Zi2\u2009Ci in whichZiis the charge of ion i andCiis the concentration of the ion and the salt is fully ionised in the solvent."},{"key":"e_1_2_7_138_2","unstructured":"The standard molar Gibbs energies of transfer of single bromide anions from water is \u0394G=7 to ethylene glycol 18.2 to EtOH 22.0 toiPrOH 27.4 to DMSO 36.2 to DMF 44.0 to DMA and 46.0 to HMPA (all in kJ\u2009mol\u22121).[35]This provides an estimate on how well the Br\u2212ions are solvated by the alcohols in comparison with the dipolar aprotic solvents commonly used in the Heck reaction."},{"key":"e_1_2_7_139_2","unstructured":"A solvato alcohol\u2013PdIIspecies could be formed before olefin coordination [14b]which may also facilitate bromide dissociation."},{"key":"e_1_2_7_140_2","doi-asserted-by":"publisher","DOI":"10.1016\/0013-4686(76)85034-7"},{"key":"e_1_2_7_141_2","doi-asserted-by":"publisher","DOI":"10.1351\/pac198355060977"}],"container-title":["Chemistry \u2013 A European Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fchem.200800411","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chem.200800411","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T13:58:51Z","timestamp":1760277531000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/chem.200800411"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,6,11]]},"references-count":146,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2008,6,20]]}},"alternative-id":["10.1002\/chem.200800411"],"URL":"https:\/\/doi.org\/10.1002\/chem.200800411","archive":["Portico"],"relation":{},"ISSN":["0947-6539","1521-3765"],"issn-type":[{"value":"0947-6539","type":"print"},{"value":"1521-3765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,6,11]]}}}