Stereoselective Nickel(II)-Catalyzed Addition of Aryl Grignards to Diphenylacetylene in the Synthesis of Zuclomiphene

Stereoselective synthesis of zuclomiphene was developed using nickel-catalyzed addition of 4-fluorophenylmagnesium bromide to 1,2-diphenylacetylene, followed by quenching with a chlorinating reagent. Since the aryl fluoride addition and chlorination reactions occur consecutively in one pot, the cis...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Organic process research & development 2022-04, Vol.26 (4), p.1124-1129
Hauptverfasser: Karadeolian, Avedis, Emmett, Michael, Souza, Fabio, Chung, Andrew, Blazecka, Peter, Le Sueur, Richard, Patel, Dineshkumar, Zhao, Yajun, Rey, Allan, Green, Stuart
Format: Artikel
Sprache:eng
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 1129
container_issue 4
container_start_page 1124
container_title Organic process research & development
container_volume 26
creator Karadeolian, Avedis
Emmett, Michael
Souza, Fabio
Chung, Andrew
Blazecka, Peter
Le Sueur, Richard
Patel, Dineshkumar
Zhao, Yajun
Rey, Allan
Green, Stuart
description Stereoselective synthesis of zuclomiphene was developed using nickel-catalyzed addition of 4-fluorophenylmagnesium bromide to 1,2-diphenylacetylene, followed by quenching with a chlorinating reagent. Since the aryl fluoride addition and chlorination reactions occur consecutively in one pot, the cis orientation of the two phenyl groups of 1,2-diphenylacetylene is conserved, leading to the highly selective synthesis of zuclomiphene. The use of the Grignard reagent resulted in the presence of bromide ions in the reaction mixture, which led to the formation of the bromo-analog of zuclomiphene. Alternative routes were then explored to overcome this issue to yield high-purity zuclomiphene.
doi_str_mv 10.1021/acs.oprd.1c00366
format Article
fullrecord <record><control><sourceid>acs_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1021_acs_oprd_1c00366</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>a959342702</sourcerecordid><originalsourceid>FETCH-LOGICAL-a195t-67043dc07cb8c9ae137e73ae5ed07af0dbd6921045f139786cdbe852f91f078e3</originalsourceid><addsrcrecordid>eNp1kMFLwzAUh4MoOKd3jzkq2PnSrkl7HFPnQPQwBfFSsuTVZWbNSDKh_vW2bldPvwfv9z0eHyGXDEYMUnYrVRi5rdcjpgAyzo_IgOUpJHnB34-7GYos4YzDKTkLYQ0AOWfpgOwWET26gBZVNN9In436Qns1n18nUxmlbX9Q04nWJhrXUFfTiW8tnXnz2UivA42O3pntCpvWSoWxtdggNQ2NK6SLtukimNBzHztl3eaviufkpJY24MUhh-Tt4f51-pg8vczm08lTIlmZx4QLGGdagVDLQpUSWSZQZBJz1CBkDXqpeZkyGOc1y0pRcKWXWORpXbIaRIHZkMD-rvIuBI91tfVmI31bMah6bVWnreq1VQdtHXKzR_rN2u180z34f_0XOFdzvA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Stereoselective Nickel(II)-Catalyzed Addition of Aryl Grignards to Diphenylacetylene in the Synthesis of Zuclomiphene</title><source>American Chemical Society Journals</source><creator>Karadeolian, Avedis ; Emmett, Michael ; Souza, Fabio ; Chung, Andrew ; Blazecka, Peter ; Le Sueur, Richard ; Patel, Dineshkumar ; Zhao, Yajun ; Rey, Allan ; Green, Stuart</creator><creatorcontrib>Karadeolian, Avedis ; Emmett, Michael ; Souza, Fabio ; Chung, Andrew ; Blazecka, Peter ; Le Sueur, Richard ; Patel, Dineshkumar ; Zhao, Yajun ; Rey, Allan ; Green, Stuart</creatorcontrib><description>Stereoselective synthesis of zuclomiphene was developed using nickel-catalyzed addition of 4-fluorophenylmagnesium bromide to 1,2-diphenylacetylene, followed by quenching with a chlorinating reagent. Since the aryl fluoride addition and chlorination reactions occur consecutively in one pot, the cis orientation of the two phenyl groups of 1,2-diphenylacetylene is conserved, leading to the highly selective synthesis of zuclomiphene. The use of the Grignard reagent resulted in the presence of bromide ions in the reaction mixture, which led to the formation of the bromo-analog of zuclomiphene. Alternative routes were then explored to overcome this issue to yield high-purity zuclomiphene.</description><identifier>ISSN: 1083-6160</identifier><identifier>EISSN: 1520-586X</identifier><identifier>DOI: 10.1021/acs.oprd.1c00366</identifier><language>eng</language><publisher>American Chemical Society</publisher><ispartof>Organic process research &amp; development, 2022-04, Vol.26 (4), p.1124-1129</ispartof><rights>2022 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a195t-67043dc07cb8c9ae137e73ae5ed07af0dbd6921045f139786cdbe852f91f078e3</citedby><cites>FETCH-LOGICAL-a195t-67043dc07cb8c9ae137e73ae5ed07af0dbd6921045f139786cdbe852f91f078e3</cites><orcidid>0000-0003-0801-678X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.oprd.1c00366$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.oprd.1c00366$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids></links><search><creatorcontrib>Karadeolian, Avedis</creatorcontrib><creatorcontrib>Emmett, Michael</creatorcontrib><creatorcontrib>Souza, Fabio</creatorcontrib><creatorcontrib>Chung, Andrew</creatorcontrib><creatorcontrib>Blazecka, Peter</creatorcontrib><creatorcontrib>Le Sueur, Richard</creatorcontrib><creatorcontrib>Patel, Dineshkumar</creatorcontrib><creatorcontrib>Zhao, Yajun</creatorcontrib><creatorcontrib>Rey, Allan</creatorcontrib><creatorcontrib>Green, Stuart</creatorcontrib><title>Stereoselective Nickel(II)-Catalyzed Addition of Aryl Grignards to Diphenylacetylene in the Synthesis of Zuclomiphene</title><title>Organic process research &amp; development</title><addtitle>Org. Process Res. Dev</addtitle><description>Stereoselective synthesis of zuclomiphene was developed using nickel-catalyzed addition of 4-fluorophenylmagnesium bromide to 1,2-diphenylacetylene, followed by quenching with a chlorinating reagent. Since the aryl fluoride addition and chlorination reactions occur consecutively in one pot, the cis orientation of the two phenyl groups of 1,2-diphenylacetylene is conserved, leading to the highly selective synthesis of zuclomiphene. The use of the Grignard reagent resulted in the presence of bromide ions in the reaction mixture, which led to the formation of the bromo-analog of zuclomiphene. Alternative routes were then explored to overcome this issue to yield high-purity zuclomiphene.</description><issn>1083-6160</issn><issn>1520-586X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp1kMFLwzAUh4MoOKd3jzkq2PnSrkl7HFPnQPQwBfFSsuTVZWbNSDKh_vW2bldPvwfv9z0eHyGXDEYMUnYrVRi5rdcjpgAyzo_IgOUpJHnB34-7GYos4YzDKTkLYQ0AOWfpgOwWET26gBZVNN9In436Qns1n18nUxmlbX9Q04nWJhrXUFfTiW8tnXnz2UivA42O3pntCpvWSoWxtdggNQ2NK6SLtukimNBzHztl3eaviufkpJY24MUhh-Tt4f51-pg8vczm08lTIlmZx4QLGGdagVDLQpUSWSZQZBJz1CBkDXqpeZkyGOc1y0pRcKWXWORpXbIaRIHZkMD-rvIuBI91tfVmI31bMah6bVWnreq1VQdtHXKzR_rN2u180z34f_0XOFdzvA</recordid><startdate>20220415</startdate><enddate>20220415</enddate><creator>Karadeolian, Avedis</creator><creator>Emmett, Michael</creator><creator>Souza, Fabio</creator><creator>Chung, Andrew</creator><creator>Blazecka, Peter</creator><creator>Le Sueur, Richard</creator><creator>Patel, Dineshkumar</creator><creator>Zhao, Yajun</creator><creator>Rey, Allan</creator><creator>Green, Stuart</creator><general>American Chemical Society</general><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0003-0801-678X</orcidid></search><sort><creationdate>20220415</creationdate><title>Stereoselective Nickel(II)-Catalyzed Addition of Aryl Grignards to Diphenylacetylene in the Synthesis of Zuclomiphene</title><author>Karadeolian, Avedis ; Emmett, Michael ; Souza, Fabio ; Chung, Andrew ; Blazecka, Peter ; Le Sueur, Richard ; Patel, Dineshkumar ; Zhao, Yajun ; Rey, Allan ; Green, Stuart</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a195t-67043dc07cb8c9ae137e73ae5ed07af0dbd6921045f139786cdbe852f91f078e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Karadeolian, Avedis</creatorcontrib><creatorcontrib>Emmett, Michael</creatorcontrib><creatorcontrib>Souza, Fabio</creatorcontrib><creatorcontrib>Chung, Andrew</creatorcontrib><creatorcontrib>Blazecka, Peter</creatorcontrib><creatorcontrib>Le Sueur, Richard</creatorcontrib><creatorcontrib>Patel, Dineshkumar</creatorcontrib><creatorcontrib>Zhao, Yajun</creatorcontrib><creatorcontrib>Rey, Allan</creatorcontrib><creatorcontrib>Green, Stuart</creatorcontrib><collection>CrossRef</collection><jtitle>Organic process research &amp; development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Karadeolian, Avedis</au><au>Emmett, Michael</au><au>Souza, Fabio</au><au>Chung, Andrew</au><au>Blazecka, Peter</au><au>Le Sueur, Richard</au><au>Patel, Dineshkumar</au><au>Zhao, Yajun</au><au>Rey, Allan</au><au>Green, Stuart</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stereoselective Nickel(II)-Catalyzed Addition of Aryl Grignards to Diphenylacetylene in the Synthesis of Zuclomiphene</atitle><jtitle>Organic process research &amp; development</jtitle><addtitle>Org. Process Res. Dev</addtitle><date>2022-04-15</date><risdate>2022</risdate><volume>26</volume><issue>4</issue><spage>1124</spage><epage>1129</epage><pages>1124-1129</pages><issn>1083-6160</issn><eissn>1520-586X</eissn><abstract>Stereoselective synthesis of zuclomiphene was developed using nickel-catalyzed addition of 4-fluorophenylmagnesium bromide to 1,2-diphenylacetylene, followed by quenching with a chlorinating reagent. Since the aryl fluoride addition and chlorination reactions occur consecutively in one pot, the cis orientation of the two phenyl groups of 1,2-diphenylacetylene is conserved, leading to the highly selective synthesis of zuclomiphene. The use of the Grignard reagent resulted in the presence of bromide ions in the reaction mixture, which led to the formation of the bromo-analog of zuclomiphene. Alternative routes were then explored to overcome this issue to yield high-purity zuclomiphene.</abstract><pub>American Chemical Society</pub><doi>10.1021/acs.oprd.1c00366</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0003-0801-678X</orcidid></addata></record>
fulltext fulltext
identifier ISSN: 1083-6160
ispartof Organic process research & development, 2022-04, Vol.26 (4), p.1124-1129
issn 1083-6160
1520-586X
language eng
recordid cdi_crossref_primary_10_1021_acs_oprd_1c00366
source American Chemical Society Journals
title Stereoselective Nickel(II)-Catalyzed Addition of Aryl Grignards to Diphenylacetylene in the Synthesis of Zuclomiphene
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T01%3A51%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-acs_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Stereoselective%20Nickel(II)-Catalyzed%20Addition%20of%20Aryl%20Grignards%20to%20Diphenylacetylene%20in%20the%20Synthesis%20of%20Zuclomiphene&rft.jtitle=Organic%20process%20research%20&%20development&rft.au=Karadeolian,%20Avedis&rft.date=2022-04-15&rft.volume=26&rft.issue=4&rft.spage=1124&rft.epage=1129&rft.pages=1124-1129&rft.issn=1083-6160&rft.eissn=1520-586X&rft_id=info:doi/10.1021/acs.oprd.1c00366&rft_dat=%3Cacs_cross%3Ea959342702%3C/acs_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true