Enantioselective α‐Benzylation of Acyclic Esters Using π‐Extended Electrophiles
The first asymmetric cooperative Lewis base/palladium catalyzed benzylic alkylation of acyclic esters is reported. This reaction proceeds via stereodefined C1‐ammonium enolate nucleophiles. Critical to its success was the identification of benzylic phosphate electrophiles, which were uniquely reacti...
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| Veröffentlicht in: | Angewandte Chemie International Edition 2018-09, Vol.57 (37), p.12102-12105 |
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| container_issue | 37 |
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| container_title | Angewandte Chemie International Edition |
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| creator | Schwarz, Kevin J. Yang, Chao Fyfe, James W. B. Snaddon, Thomas N. |
| description | The first asymmetric cooperative Lewis base/palladium catalyzed benzylic alkylation of acyclic esters is reported. This reaction proceeds via stereodefined C1‐ammonium enolate nucleophiles. Critical to its success was the identification of benzylic phosphate electrophiles, which were uniquely reactive. Alkylated products were obtained with very high levels of enantioselectivity, and this method has been applied toward the synthesis of the thrombin inhibitor DX‐9065a.
Cooperate to benzylate: Cooperative catalysis enables the direct enantioselective α‐benzylation of aryl‐ and alkenylacetic acid esters using π‐extended benzylic electrophiles. Critical to the successful development of this method was the identification of diphenylphosphate as a uniquely effective nucleofuge, which permits oxidative addition of palladium(0). |
| doi_str_mv | 10.1002/anie.201806742 |
| format | Article |
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Cooperate to benzylate: Cooperative catalysis enables the direct enantioselective α‐benzylation of aryl‐ and alkenylacetic acid esters using π‐extended benzylic electrophiles. Critical to the successful development of this method was the identification of diphenylphosphate as a uniquely effective nucleofuge, which permits oxidative addition of palladium(0).</description><edition>International ed. in English</edition><identifier>ISSN: 1433-7851</identifier><identifier>EISSN: 1521-3773</identifier><identifier>DOI: 10.1002/anie.201806742</identifier><identifier>PMID: 30011353</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Alkylation ; Ammonium ; benzylation ; Catalysis ; cooperative catalysis ; Enantiomers ; enantioselectivity ; Enzyme Inhibitors - chemical synthesis ; Enzyme Inhibitors - chemistry ; Esters ; Esters - chemical synthesis ; Esters - chemistry ; Lewis base ; Lewis bases ; Lewis Bases - chemistry ; Nucleophiles ; Organophosphonates - chemistry ; Palladium ; Palladium - chemistry ; Stereoisomerism ; Thrombin</subject><ispartof>Angewandte Chemie International Edition, 2018-09, Vol.57 (37), p.12102-12105</ispartof><rights>2018 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4682-b9e0ec62e237a6d8d0bed69f8dd6944211784208a97e57ed38ea5243eb3f7013</citedby><cites>FETCH-LOGICAL-c4682-b9e0ec62e237a6d8d0bed69f8dd6944211784208a97e57ed38ea5243eb3f7013</cites><orcidid>0000-0003-1119-0332</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fanie.201806742$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fanie.201806742$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30011353$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schwarz, Kevin J.</creatorcontrib><creatorcontrib>Yang, Chao</creatorcontrib><creatorcontrib>Fyfe, James W. B.</creatorcontrib><creatorcontrib>Snaddon, Thomas N.</creatorcontrib><title>Enantioselective α‐Benzylation of Acyclic Esters Using π‐Extended Electrophiles</title><title>Angewandte Chemie International Edition</title><addtitle>Angew Chem Int Ed Engl</addtitle><description>The first asymmetric cooperative Lewis base/palladium catalyzed benzylic alkylation of acyclic esters is reported. This reaction proceeds via stereodefined C1‐ammonium enolate nucleophiles. Critical to its success was the identification of benzylic phosphate electrophiles, which were uniquely reactive. Alkylated products were obtained with very high levels of enantioselectivity, and this method has been applied toward the synthesis of the thrombin inhibitor DX‐9065a.
Cooperate to benzylate: Cooperative catalysis enables the direct enantioselective α‐benzylation of aryl‐ and alkenylacetic acid esters using π‐extended benzylic electrophiles. Critical to the successful development of this method was the identification of diphenylphosphate as a uniquely effective nucleofuge, which permits oxidative addition of palladium(0).</description><subject>Alkylation</subject><subject>Ammonium</subject><subject>benzylation</subject><subject>Catalysis</subject><subject>cooperative catalysis</subject><subject>Enantiomers</subject><subject>enantioselectivity</subject><subject>Enzyme Inhibitors - chemical synthesis</subject><subject>Enzyme Inhibitors - chemistry</subject><subject>Esters</subject><subject>Esters - chemical synthesis</subject><subject>Esters - chemistry</subject><subject>Lewis base</subject><subject>Lewis bases</subject><subject>Lewis Bases - chemistry</subject><subject>Nucleophiles</subject><subject>Organophosphonates - chemistry</subject><subject>Palladium</subject><subject>Palladium - chemistry</subject><subject>Stereoisomerism</subject><subject>Thrombin</subject><issn>1433-7851</issn><issn>1521-3773</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9OGzEQhy0EgkC59litxKWXDf6zu_ZeKoVoKUgRvZCz5XhnwWhjp_YmbXrKI_AqvEh5B54ERwkp7aUX29J882nGP4Q-EtwnGNNzZQ30KSYCFzyje6hHckpSxjnbj--MsZSLnByh4xAeIi8id4iOGMaEsJz10LiyynbGBWhBd2YBye-nl9XjBdhfy1bFgk1ckwz0UrdGJ1XowIdkHIy9S55XEax-dmBrqJNq3e_d7N60ED6gg0a1AU639wm6vaxuh1fp6NvX6-FglOqsEDSdlIBBFxQo46qoRY0nUBdlI-p4ZhklhIuMYqFKDjmHmglQOc0YTFjDMWEn6MtGO5tPplBrsJ1XrZx5M1V-KZ0y8u-KNffyzi1kkZUl4ywKPm8F3n2fQ-jk1AQNbassuHmQFHOSF4wQHNGzf9AHN_c2bhepaIsZlGuqv6G0dyF4aHbDECzXgcl1YHIXWGz49H6FHf6WUATKDfAjfuzyPzo5uLmu_shfAcYcpkE</recordid><startdate>20180910</startdate><enddate>20180910</enddate><creator>Schwarz, Kevin J.</creator><creator>Yang, Chao</creator><creator>Fyfe, James W. B.</creator><creator>Snaddon, Thomas N.</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1119-0332</orcidid></search><sort><creationdate>20180910</creationdate><title>Enantioselective α‐Benzylation of Acyclic Esters Using π‐Extended Electrophiles</title><author>Schwarz, Kevin J. ; Yang, Chao ; Fyfe, James W. B. ; Snaddon, Thomas N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4682-b9e0ec62e237a6d8d0bed69f8dd6944211784208a97e57ed38ea5243eb3f7013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Alkylation</topic><topic>Ammonium</topic><topic>benzylation</topic><topic>Catalysis</topic><topic>cooperative catalysis</topic><topic>Enantiomers</topic><topic>enantioselectivity</topic><topic>Enzyme Inhibitors - chemical synthesis</topic><topic>Enzyme Inhibitors - chemistry</topic><topic>Esters</topic><topic>Esters - chemical synthesis</topic><topic>Esters - chemistry</topic><topic>Lewis base</topic><topic>Lewis bases</topic><topic>Lewis Bases - chemistry</topic><topic>Nucleophiles</topic><topic>Organophosphonates - chemistry</topic><topic>Palladium</topic><topic>Palladium - chemistry</topic><topic>Stereoisomerism</topic><topic>Thrombin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schwarz, Kevin J.</creatorcontrib><creatorcontrib>Yang, Chao</creatorcontrib><creatorcontrib>Fyfe, James W. 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B.</au><au>Snaddon, Thomas N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enantioselective α‐Benzylation of Acyclic Esters Using π‐Extended Electrophiles</atitle><jtitle>Angewandte Chemie International Edition</jtitle><addtitle>Angew Chem Int Ed Engl</addtitle><date>2018-09-10</date><risdate>2018</risdate><volume>57</volume><issue>37</issue><spage>12102</spage><epage>12105</epage><pages>12102-12105</pages><issn>1433-7851</issn><eissn>1521-3773</eissn><abstract>The first asymmetric cooperative Lewis base/palladium catalyzed benzylic alkylation of acyclic esters is reported. This reaction proceeds via stereodefined C1‐ammonium enolate nucleophiles. Critical to its success was the identification of benzylic phosphate electrophiles, which were uniquely reactive. Alkylated products were obtained with very high levels of enantioselectivity, and this method has been applied toward the synthesis of the thrombin inhibitor DX‐9065a.
Cooperate to benzylate: Cooperative catalysis enables the direct enantioselective α‐benzylation of aryl‐ and alkenylacetic acid esters using π‐extended benzylic electrophiles. Critical to the successful development of this method was the identification of diphenylphosphate as a uniquely effective nucleofuge, which permits oxidative addition of palladium(0).</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30011353</pmid><doi>10.1002/anie.201806742</doi><tpages>4</tpages><edition>International ed. in English</edition><orcidid>https://orcid.org/0000-0003-1119-0332</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Angewandte Chemie International Edition, 2018-09, Vol.57 (37), p.12102-12105 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Alkylation Ammonium benzylation Catalysis cooperative catalysis Enantiomers enantioselectivity Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - chemistry Esters Esters - chemical synthesis Esters - chemistry Lewis base Lewis bases Lewis Bases - chemistry Nucleophiles Organophosphonates - chemistry Palladium Palladium - chemistry Stereoisomerism Thrombin |
| title | Enantioselective α‐Benzylation of Acyclic Esters Using π‐Extended Electrophiles |
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