Robust and Scalable Approach to 1,3‐Disubstituted Pyridylcyclobutanes
An approach to all isomeric 3‐pyridylcyclobutane‐derived building blocks, i.e. ketones, alcohols and amines, is described. Synthesis of the title compounds relied on the five‐step reaction sequence including alkylation of isomeric pyridyl acetonitriles with 1,3‐dibromo‐2,2‐dimethoxypropane. Hydrolys...
Gespeichert in:
| Veröffentlicht in: | European journal of organic chemistry 2019-09, Vol.2019 (34), p.5937-5949 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 5949 |
|---|---|
| container_issue | 34 |
| container_start_page | 5937 |
| container_title | European journal of organic chemistry |
| container_volume | 2019 |
| creator | Demchuk, Oleksandr P. Hryshchuk, Oleksandr V. Vashchenko, Bohdan V. Radchenko, Dmytro S. Kovtunenko, Volodymyr O. Komarov, Igor V. Grygorenko, Oleksandr O. |
| description | An approach to all isomeric 3‐pyridylcyclobutane‐derived building blocks, i.e. ketones, alcohols and amines, is described. Synthesis of the title compounds relied on the five‐step reaction sequence including alkylation of isomeric pyridyl acetonitriles with 1,3‐dibromo‐2,2‐dimethoxypropane. Hydrolysis, decarboxylation and removal of the ketal moiety led to the key 3‐pyridylcyclobutanones (obtained on up to 120 g scale in a single run), which were transformed into the corresponding alcohols and amines with high diastereoselectivity. The title cyclobutanone derivatives were used to synthesize three isomeric nicotine analogues, as well as for parallel synthesis of a small lead‐like compound library via reductive amination.
Robust and scalable synthesis of functionalized 1,3‐disubstituted pyridylcyclobutanes (including nicotine analogues) is developed, which relies on double alkylation of pyridylacetonitriles. |
| doi_str_mv | 10.1002/ejoc.201901001 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2289419514</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2289419514</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3171-a350390f3b1878fb8ef68d3e85e2d5ec1be7f1c48a521d155580761488524bf13</originalsourceid><addsrcrecordid>eNqFkM9KxDAQxoMouK5ePRe82jqTNG1yXNZ1VRZW_APeQpKm2KVu1yZFevMRfEafxC4revQ0M_D9Zr75CDlFSBCAXrhVYxMKKGEYcY-MEKSMIZOwP_QpS2OU7PmQHHm_AgCZZTgi8_vGdD5Eel1ED1bX2tQummw2baPtSxSaCM_Z18fnZeU740MVuuCK6K5vq6KvbW_rgQ567fwxOSh17d3JTx2Tp6vZ4_Q6XiznN9PJIrYMc4w148AklMygyEVphCszUTAnuKMFdxaNy0u0qdCcYoGccwF5hqkQnKamRDYmZ7u9g8O3zvmgVk3XroeTilIhU5R8eHVMkp3Kto33rSvVpq1eddsrBLUNS23DUr9hDYDcAe9V7fp_1Gp2u5z-sd9kPW3V</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2289419514</pqid></control><display><type>article</type><title>Robust and Scalable Approach to 1,3‐Disubstituted Pyridylcyclobutanes</title><source>Wiley Journals</source><creator>Demchuk, Oleksandr P. ; Hryshchuk, Oleksandr V. ; Vashchenko, Bohdan V. ; Radchenko, Dmytro S. ; Kovtunenko, Volodymyr O. ; Komarov, Igor V. ; Grygorenko, Oleksandr O.</creator><creatorcontrib>Demchuk, Oleksandr P. ; Hryshchuk, Oleksandr V. ; Vashchenko, Bohdan V. ; Radchenko, Dmytro S. ; Kovtunenko, Volodymyr O. ; Komarov, Igor V. ; Grygorenko, Oleksandr O.</creatorcontrib><description>An approach to all isomeric 3‐pyridylcyclobutane‐derived building blocks, i.e. ketones, alcohols and amines, is described. Synthesis of the title compounds relied on the five‐step reaction sequence including alkylation of isomeric pyridyl acetonitriles with 1,3‐dibromo‐2,2‐dimethoxypropane. Hydrolysis, decarboxylation and removal of the ketal moiety led to the key 3‐pyridylcyclobutanones (obtained on up to 120 g scale in a single run), which were transformed into the corresponding alcohols and amines with high diastereoselectivity. The title cyclobutanone derivatives were used to synthesize three isomeric nicotine analogues, as well as for parallel synthesis of a small lead‐like compound library via reductive amination.
Robust and scalable synthesis of functionalized 1,3‐disubstituted pyridylcyclobutanes (including nicotine analogues) is developed, which relies on double alkylation of pyridylacetonitriles.</description><identifier>ISSN: 1434-193X</identifier><identifier>EISSN: 1099-0690</identifier><identifier>DOI: 10.1002/ejoc.201901001</identifier><language>eng</language><publisher>Weinheim: Wiley Subscription Services, Inc</publisher><subject>Alcohol ; Alcohols ; Alkaloids ; Alkylation ; Amines ; Cyclobutane ; Decarboxylation ; Heterocycles ; Ketones ; Lead‐oriented synthesis ; Nicotine ; Pyridine ; Stereoselectivity</subject><ispartof>European journal of organic chemistry, 2019-09, Vol.2019 (34), p.5937-5949</ispartof><rights>2019 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3171-a350390f3b1878fb8ef68d3e85e2d5ec1be7f1c48a521d155580761488524bf13</citedby><cites>FETCH-LOGICAL-c3171-a350390f3b1878fb8ef68d3e85e2d5ec1be7f1c48a521d155580761488524bf13</cites><orcidid>0000-0002-6036-5859 ; 0000-0003-4575-2065</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%2Fejoc.201901001$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fejoc.201901001$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids></links><search><creatorcontrib>Demchuk, Oleksandr P.</creatorcontrib><creatorcontrib>Hryshchuk, Oleksandr V.</creatorcontrib><creatorcontrib>Vashchenko, Bohdan V.</creatorcontrib><creatorcontrib>Radchenko, Dmytro S.</creatorcontrib><creatorcontrib>Kovtunenko, Volodymyr O.</creatorcontrib><creatorcontrib>Komarov, Igor V.</creatorcontrib><creatorcontrib>Grygorenko, Oleksandr O.</creatorcontrib><title>Robust and Scalable Approach to 1,3‐Disubstituted Pyridylcyclobutanes</title><title>European journal of organic chemistry</title><description>An approach to all isomeric 3‐pyridylcyclobutane‐derived building blocks, i.e. ketones, alcohols and amines, is described. Synthesis of the title compounds relied on the five‐step reaction sequence including alkylation of isomeric pyridyl acetonitriles with 1,3‐dibromo‐2,2‐dimethoxypropane. Hydrolysis, decarboxylation and removal of the ketal moiety led to the key 3‐pyridylcyclobutanones (obtained on up to 120 g scale in a single run), which were transformed into the corresponding alcohols and amines with high diastereoselectivity. The title cyclobutanone derivatives were used to synthesize three isomeric nicotine analogues, as well as for parallel synthesis of a small lead‐like compound library via reductive amination.
Robust and scalable synthesis of functionalized 1,3‐disubstituted pyridylcyclobutanes (including nicotine analogues) is developed, which relies on double alkylation of pyridylacetonitriles.</description><subject>Alcohol</subject><subject>Alcohols</subject><subject>Alkaloids</subject><subject>Alkylation</subject><subject>Amines</subject><subject>Cyclobutane</subject><subject>Decarboxylation</subject><subject>Heterocycles</subject><subject>Ketones</subject><subject>Lead‐oriented synthesis</subject><subject>Nicotine</subject><subject>Pyridine</subject><subject>Stereoselectivity</subject><issn>1434-193X</issn><issn>1099-0690</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNqFkM9KxDAQxoMouK5ePRe82jqTNG1yXNZ1VRZW_APeQpKm2KVu1yZFevMRfEafxC4revQ0M_D9Zr75CDlFSBCAXrhVYxMKKGEYcY-MEKSMIZOwP_QpS2OU7PmQHHm_AgCZZTgi8_vGdD5Eel1ED1bX2tQummw2baPtSxSaCM_Z18fnZeU740MVuuCK6K5vq6KvbW_rgQ567fwxOSh17d3JTx2Tp6vZ4_Q6XiznN9PJIrYMc4w148AklMygyEVphCszUTAnuKMFdxaNy0u0qdCcYoGccwF5hqkQnKamRDYmZ7u9g8O3zvmgVk3XroeTilIhU5R8eHVMkp3Kto33rSvVpq1eddsrBLUNS23DUr9hDYDcAe9V7fp_1Gp2u5z-sd9kPW3V</recordid><startdate>20190915</startdate><enddate>20190915</enddate><creator>Demchuk, Oleksandr P.</creator><creator>Hryshchuk, Oleksandr V.</creator><creator>Vashchenko, Bohdan V.</creator><creator>Radchenko, Dmytro S.</creator><creator>Kovtunenko, Volodymyr O.</creator><creator>Komarov, Igor V.</creator><creator>Grygorenko, Oleksandr O.</creator><general>Wiley Subscription Services, Inc</general><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0002-6036-5859</orcidid><orcidid>https://orcid.org/0000-0003-4575-2065</orcidid></search><sort><creationdate>20190915</creationdate><title>Robust and Scalable Approach to 1,3‐Disubstituted Pyridylcyclobutanes</title><author>Demchuk, Oleksandr P. ; Hryshchuk, Oleksandr V. ; Vashchenko, Bohdan V. ; Radchenko, Dmytro S. ; Kovtunenko, Volodymyr O. ; Komarov, Igor V. ; Grygorenko, Oleksandr O.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3171-a350390f3b1878fb8ef68d3e85e2d5ec1be7f1c48a521d155580761488524bf13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Alcohol</topic><topic>Alcohols</topic><topic>Alkaloids</topic><topic>Alkylation</topic><topic>Amines</topic><topic>Cyclobutane</topic><topic>Decarboxylation</topic><topic>Heterocycles</topic><topic>Ketones</topic><topic>Lead‐oriented synthesis</topic><topic>Nicotine</topic><topic>Pyridine</topic><topic>Stereoselectivity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Demchuk, Oleksandr P.</creatorcontrib><creatorcontrib>Hryshchuk, Oleksandr V.</creatorcontrib><creatorcontrib>Vashchenko, Bohdan V.</creatorcontrib><creatorcontrib>Radchenko, Dmytro S.</creatorcontrib><creatorcontrib>Kovtunenko, Volodymyr O.</creatorcontrib><creatorcontrib>Komarov, Igor V.</creatorcontrib><creatorcontrib>Grygorenko, Oleksandr O.</creatorcontrib><collection>CrossRef</collection><jtitle>European journal of organic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Demchuk, Oleksandr P.</au><au>Hryshchuk, Oleksandr V.</au><au>Vashchenko, Bohdan V.</au><au>Radchenko, Dmytro S.</au><au>Kovtunenko, Volodymyr O.</au><au>Komarov, Igor V.</au><au>Grygorenko, Oleksandr O.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Robust and Scalable Approach to 1,3‐Disubstituted Pyridylcyclobutanes</atitle><jtitle>European journal of organic chemistry</jtitle><date>2019-09-15</date><risdate>2019</risdate><volume>2019</volume><issue>34</issue><spage>5937</spage><epage>5949</epage><pages>5937-5949</pages><issn>1434-193X</issn><eissn>1099-0690</eissn><abstract>An approach to all isomeric 3‐pyridylcyclobutane‐derived building blocks, i.e. ketones, alcohols and amines, is described. Synthesis of the title compounds relied on the five‐step reaction sequence including alkylation of isomeric pyridyl acetonitriles with 1,3‐dibromo‐2,2‐dimethoxypropane. Hydrolysis, decarboxylation and removal of the ketal moiety led to the key 3‐pyridylcyclobutanones (obtained on up to 120 g scale in a single run), which were transformed into the corresponding alcohols and amines with high diastereoselectivity. The title cyclobutanone derivatives were used to synthesize three isomeric nicotine analogues, as well as for parallel synthesis of a small lead‐like compound library via reductive amination.
Robust and scalable synthesis of functionalized 1,3‐disubstituted pyridylcyclobutanes (including nicotine analogues) is developed, which relies on double alkylation of pyridylacetonitriles.</abstract><cop>Weinheim</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1002/ejoc.201901001</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-6036-5859</orcidid><orcidid>https://orcid.org/0000-0003-4575-2065</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1434-193X |
| ispartof | European journal of organic chemistry, 2019-09, Vol.2019 (34), p.5937-5949 |
| issn | 1434-193X 1099-0690 |
| language | eng |
| recordid | cdi_proquest_journals_2289419514 |
| source | Wiley Journals |
| subjects | Alcohol Alcohols Alkaloids Alkylation Amines Cyclobutane Decarboxylation Heterocycles Ketones Lead‐oriented synthesis Nicotine Pyridine Stereoselectivity |
| title | Robust and Scalable Approach to 1,3‐Disubstituted Pyridylcyclobutanes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T11%3A31%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Robust%20and%20Scalable%20Approach%20to%201,3%E2%80%90Disubstituted%20Pyridylcyclobutanes&rft.jtitle=European%20journal%20of%20organic%20chemistry&rft.au=Demchuk,%20Oleksandr%20P.&rft.date=2019-09-15&rft.volume=2019&rft.issue=34&rft.spage=5937&rft.epage=5949&rft.pages=5937-5949&rft.issn=1434-193X&rft.eissn=1099-0690&rft_id=info:doi/10.1002/ejoc.201901001&rft_dat=%3Cproquest_cross%3E2289419514%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2289419514&rft_id=info:pmid/&rfr_iscdi=true |