{"id":25415,"date":"2022-08-14T07:16:26","date_gmt":"2022-08-14T06:16:26","guid":{"rendered":"https:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=25415"},"modified":"2022-09-11T06:15:52","modified_gmt":"2022-09-11T05:15:52","slug":"unexpected-isomerization-of-oxetane-carboxylic-acids-substrate-design","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25415","title":{"rendered":"Unexpected Isomerization of Oxetane-Carboxylic Acids \u2013 substrate design."},"content":{"rendered":"
\n

Having established a viable model for the unexpected isomerism of oxetane carboxylic acids to lactones[1]<\/a><\/span>, and taken a look at a variation in the proton transfer catalyst needed to accomplish the transformation, I now investigate the substrate itself.\"\"<\/a><\/p>\n

R’ is set to have three values, R’=H (the original substituent), R’= CH3<\/sub> and R’= CF3<\/sub> (FAIR data DOI: 10.14469\/hpc\/10820<\/a>)<\/p>\n\n\n\n\n\n\n
R’<\/th>\n\u0394G\u2021<\/sup>, kcal\/mol<\/th>\n<\/tr>\n
H<\/th>\n27.0<\/th>\n<\/tr>\n
CH3<\/sub><\/th>\n29.1<\/th>\n<\/tr>\n
CF3<\/sub><\/th>\n39.6<\/th>\n<\/tr>\n<\/tbody>\n<\/table>\n

\"\"<\/p>\n

The inference is clear-cut; to inhibit the isomerisation to a lactone, CF3<\/sub> groups substituted onto the methylene groups of the oxetane will effectively do this, with CH3<\/sub> itself having a much weaker effect.<\/p>\n

\n

DOI: 10.14469\/hpc\/10861 and 10.14469\/hpc\/10862<\/a><\/p>\n

\n

References<\/h2>\n
  1. B. Chalyk, A. Grynyova, K. Filimonova, T.V. Rudenko, D. Dibchak, and P.K. Mykhailiuk, \"Unexpected Isomerization of Oxetane-Carboxylic Acids\", Organic Letters<\/i>, vol. 24, pp. 4722-4728, 2022. https:\/\/doi.org\/10.1021\/acs.orglett.2c01402<\/a>\n\n<\/li>\n<\/ol>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

    Having established a viable model for the unexpected isomerism of oxetane carboxylic acids to lactones, and taken a look at a variation in the proton transfer catalyst needed to accomplish the transformation, I now investigate the substrate itself. R’ is set to have three values, R’=H (the original substituent), R’= CH3 and R’= CF3 (FAIR […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"activitypub_content_warning":"","activitypub_content_visibility":"","activitypub_max_image_attachments":5,"activitypub_interaction_policy_quote":"anyone","activitypub_status":"","footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[1086],"tags":[],"ppma_author":[2661],"class_list":["post-25415","post","type-post","status-publish","format-standard","hentry","category-reaction-mechanism-2"],"yoast_head":"\nUnexpected Isomerization of Oxetane-Carboxylic Acids \u2013 substrate design. - Henry Rzepa's Blog<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25415\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Unexpected Isomerization of Oxetane-Carboxylic Acids \u2013 substrate design. - Henry Rzepa's Blog\" \/>\n<meta property=\"og:description\" content=\"Having established a viable model for the unexpected isomerism of oxetane carboxylic acids to lactones, and taken a look at a variation in the proton transfer catalyst needed to accomplish the transformation, I now investigate the substrate itself. R’ is set to have three values, R’=H (the original substituent), R’= CH3 and R’= CF3 (FAIR […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25415\" \/>\n<meta property=\"og:site_name\" content=\"Henry Rzepa's Blog\" \/>\n<meta property=\"article:published_time\" content=\"2022-08-14T06:16:26+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2022-09-11T05:15:52+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2022\/08\/oxetane2.svg\" \/>\n<meta name=\"author\" content=\"Henry Rzepa\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Henry Rzepa\" \/>\n\t<meta name=\"twitter:label2\" content=\"Estimated reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"1 minute\" \/>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Unexpected Isomerization of Oxetane-Carboxylic Acids \u2013 substrate design. - Henry Rzepa's Blog","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25415","og_locale":"en_GB","og_type":"article","og_title":"Unexpected Isomerization of Oxetane-Carboxylic Acids \u2013 substrate design. - Henry Rzepa's Blog","og_description":"Having established a viable model for the unexpected isomerism of oxetane carboxylic acids to lactones, and taken a look at a variation in the proton transfer catalyst needed to accomplish the transformation, I now investigate the substrate itself. R’ is set to have three values, R’=H (the original substituent), R’= CH3 and R’= CF3 (FAIR […]","og_url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25415","og_site_name":"Henry Rzepa's Blog","article_published_time":"2022-08-14T06:16:26+00:00","article_modified_time":"2022-09-11T05:15:52+00:00","og_image":[{"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2022\/08\/oxetane2.svg","type":"","width":"","height":""}],"author":"Henry Rzepa","twitter_card":"summary_large_image","twitter_misc":{"Written by":"Henry Rzepa","Estimated reading time":"1 minute"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25415#article","isPartOf":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25415"},"author":{"name":"Henry Rzepa","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#\/schema\/person\/2b40f7b9c872a4dc1547e040a11b6281"},"headline":"Unexpected Isomerization of Oxetane-Carboxylic Acids \u2013 substrate design.","datePublished":"2022-08-14T06:16:26+00:00","dateModified":"2022-09-11T05:15:52+00:00","mainEntityOfPage":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25415"},"wordCount":115,"commentCount":1,"image":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25415#primaryimage"},"thumbnailUrl":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2022\/08\/oxetane2.svg","articleSection":["reaction mechanism"],"inLanguage":"en-GB","potentialAction":[{"@type":"CommentAction","name":"Comment","target":["https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25415#respond"]}]},{"@type":"WebPage","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25415","url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25415","name":"Unexpected Isomerization of Oxetane-Carboxylic Acids \u2013 substrate design. - 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This is important because these types of compound\u2026","rel":"","context":"In "reaction mechanism"","block_context":{"text":"reaction mechanism","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=1086"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":25338,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25338","url_meta":{"origin":25415,"position":1},"title":"Unexpected Isomerization of Oxetane-Carboxylic Acids \u2013 a viable mechanism","author":"Henry Rzepa","date":"August 12, 2022","format":false,"excerpt":"In the previous post, I looked at the intramolecular rearrangement of the oxetane carboxylic acid to a lactone, finding the barrier to the Sn2 reaction with retention was unfeasibly high. Here I explore alternatives. This first attempt uses a second molecule of a carboxylic acid (modelled as formic acid for\u2026","rel":"","context":"Similar post","block_context":{"text":"Similar post","link":""},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2022\/08\/Rtn.gif?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2022\/08\/Rtn.gif?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2022\/08\/Rtn.gif?resize=525%2C300&ssl=1 1.5x"},"classes":[]},{"id":25391,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25391","url_meta":{"origin":25415,"position":2},"title":"Unexpected Isomerization of Oxetane-Carboxylic Acids \u2013 catalyst design.","author":"Henry Rzepa","date":"August 13, 2022","format":false,"excerpt":"Previously, a mechanism with a reasonable predicted energy was modelled for the isomerisation of an oxetane carboxylic acid to a lactone by using two further molecules of acid to transfer the proton and in the process encouraging an Sn2 reaction with inversion to open the oxetane ring. We are now\u2026","rel":"","context":"In "reaction mechanism"","block_context":{"text":"reaction mechanism","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=1086"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":25439,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25439","url_meta":{"origin":25415,"position":3},"title":"Unexpected Isomerization of Oxetane-Carboxylic Acids \u2013 an alternative autocatalytic mechanism evaluated.","author":"Henry Rzepa","date":"August 17, 2022","format":false,"excerpt":"Previously, I looked at autocatalytic mechanisms where the carboxyl group of an oxetane-carboxylic acid could catalyse its transformation to a lactone, finding that a chain of two such groups were required to achieve the result. Here I look at an alternative mode where the oxetane-carboxylate itself acts as the transfer\u2026","rel":"","context":"In "reaction mechanism"","block_context":{"text":"reaction mechanism","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=1086"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2022\/08\/saddle.gif?resize=350%2C200&ssl=1","width":350,"height":200},"classes":[]},{"id":18091,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=18091","url_meta":{"origin":25415,"position":4},"title":"The conformation of carboxylic acids revealed.","author":"Henry Rzepa","date":"April 11, 2017","format":false,"excerpt":"Following my conformational exploration of enols, here is one about a much more common molecule, a carboxylic acid. The components of the search are shown as four queries below, which will be combined in various Boolean senses (DOI:\u00a010.14469\/hpc\/2462). Query one defines the carboxylic acid, with 3-coordinate carbon specified at the\u2026","rel":"","context":"In "crystal_structure_mining"","block_context":{"text":"crystal_structure_mining","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=1745"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2017\/04\/051-1024x676.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":6361,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=6361","url_meta":{"origin":25415,"position":5},"title":"Spotting the unexpected. The trifluoromeric effect in the hydration of the carbonyl group.","author":"Henry Rzepa","date":"March 9, 2012","format":false,"excerpt":"The equilibrium for the hydration of a ketone to form a gem-diol hydrate is known to be highly sensitive to substituents. Consider the two equilibria: For propanone, it lies almost entirely on the left, whereas for the hexafluoro derivative it is almost entirely on the right. The standard answer to\u2026","rel":"","context":"In "Interesting chemistry"","block_context":{"text":"Interesting chemistry","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=4"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2012\/03\/diol.jpg?resize=350%2C200","width":350,"height":200},"classes":[]}],"jetpack_likes_enabled":false,"authors":[{"term_id":2661,"user_id":1,"is_guest":0,"slug":"admin","display_name":"Henry Rzepa","avatar_url":"https:\/\/secure.gravatar.com\/avatar\/897b6740f7f599bca7942cdf7d7914af5988937ae0e3869ab09aebb87f26a731?s=96&d=blank&r=g","0":null,"1":"","2":"","3":"","4":"","5":"","6":"","7":"","8":""}],"_links":{"self":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/25415","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=25415"}],"version-history":[{"count":13,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/25415\/revisions"}],"predecessor-version":[{"id":25436,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/25415\/revisions\/25436"}],"wp:attachment":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=25415"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=25415"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=25415"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=25415"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}