{"id":6708,"date":"2012-05-07T16:31:53","date_gmt":"2012-05-07T15:31:53","guid":{"rendered":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=6708"},"modified":"2012-05-08T08:56:22","modified_gmt":"2012-05-08T07:56:22","slug":"reductive-ozonolysis-the-interesting-step","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=6708","title":{"rendered":"Reductive ozonolysis: the interesting step."},"content":{"rendered":"
\n

The mechanism of the reaction of alkenes known as ozonolysis was first set out in its modern form by Criegee<\/a>. The crucial steps, (a), (b) and (d), are all pericyclic cycloaddition\/eliminations. The last step (e) is known as reductive ozonolysis, and this step is often treated as an afterthought, part of the work-up of the reaction if you like (it is not illustrated in Criegee’s review for example). Here, I will attempt to show that it is actually a very interesting mechanistic step.<\/p>\n

\"\"<\/a><\/p>\n

Step (e) reminded me of a mechanism we had recently investigated, involving desulfurization of epidithiodioxopiperazine fungal metabolites<\/a><\/em>\u00a0in which an S-S bridge is reduced by one sulfur atom by the action of triphenyl phosphine. Dimethyl sulfide in turn is used to reduce a O-O fragment of the trioxolane intermediate produced from ozonolysis by one oxygen. The transition state<\/a>\u00a0for path (e) is shown below (\u03c9B97XD\/6-311G(d)\/SCRF=dichloromethane).<\/p>\n

\"\"

Transition state geometry for step (e). Click for 3D.<\/p><\/div>\n

The reaction IRC for this step is shown below<\/p>\n\n\n\n\n
\"\"<\/a><\/td>\n\"\"<\/a><\/td>\n<\/tr>\n
\"\"<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
    \n
  1. Notice how the sulfur atom approaches more or less along the axis of the O-O bond.<\/li>\n
  2. At the transition state (IRC=0) the three atoms are almost collinear. This might have some steric consequences for sterically congested alkenes.<\/li>\n
  3. At IRC = -4, cleavage of the O-O bond is almost complete, an the system is starting to resemble the zwitterion shown below (the calculation is done with a solvent continuum field applied, to help stabilise any ionic intermediates that might form). One might be tempted to ask how this species could be stabilised to the extent of having a less transient existence.
    \"\"<\/a><\/li>\n
  4. Still, it is highly transient, since there is no actual minimum in the IRC energy profile. Instead, between IRC -4 and -15, the remaining bonds cleave to form the final product shown in the scheme above. As with the previous post<\/a>, which illustrated the Baeyer-Villiger rearrangement, this reductive elimination is also very asynchronous, with the pair of C-O bonds cleaving after the O-O.<\/li>\n<\/ol>\n

    This again illustrates the reactions where several bonds are either forming or cleaving, the relative dynamics can be quite unpredictable. It may even be strongly influenced by substituents and solvation. All text books of organic chemistry \u00a0I know of rarely if ever address this aspect of mechanism. With new generations of interactive and dynamic text books about to spring upon us<\/a>, it might be time to rethink what goes into them. I would hope it is not just a rehash of \u00a0what one might call the classical arrow pushing representations of mechanism.<\/p>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

    The mechanism of the reaction of alkenes known as ozonolysis was first set out in its modern form by Criegee. The crucial steps, (a), (b) and (d), are all pericyclic cycloaddition\/eliminations. The last step (e) is known as reductive ozonolysis, and this step is often treated as an afterthought, part of the work-up of the […]<\/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":false,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[4],"tags":[836,2651,2650,837],"ppma_author":[2661],"class_list":["post-6708","post","type-post","status-publish","format-standard","hentry","category-interesting-chemistry","tag-200th-post","tag-historical","tag-pericyclic","tag-s-bridge"],"yoast_head":"\nReductive ozonolysis: the interesting step. - 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=6708\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Reductive ozonolysis: the interesting step. - Henry Rzepa's Blog\" \/>\n<meta property=\"og:description\" content=\"The mechanism of the reaction of alkenes known as ozonolysis was first set out in its modern form by Criegee. The crucial steps, (a), (b) and (d), are all pericyclic cycloaddition\/eliminations. The last step (e) is known as reductive ozonolysis, and this step is often treated as an afterthought, part of the work-up of the […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=6708\" \/>\n<meta property=\"og:site_name\" content=\"Henry Rzepa's Blog\" \/>\n<meta property=\"article:published_time\" content=\"2012-05-07T15:31:53+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2012-05-08T07:56:22+00:00\" \/>\n<meta property=\"og:image\" content=\"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2012\/05\/ozonolysis.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=\"2 minutes\" \/>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Reductive ozonolysis: the interesting step. - 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=6708","og_locale":"en_GB","og_type":"article","og_title":"Reductive ozonolysis: the interesting step. - Henry Rzepa's Blog","og_description":"The mechanism of the reaction of alkenes known as ozonolysis was first set out in its modern form by Criegee. The crucial steps, (a), (b) and (d), are all pericyclic cycloaddition\/eliminations. 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In this case, replacing toxic ozone O3\u00a0as used to fragment an alkene into two carbonyl\u00a0compounds (\"ozonolysis\") by a relatively non-toxic simple nitro-group based reagent, ArNO2\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\/10\/ozr.gif?resize=350%2C200&ssl=1","width":350,"height":200},"classes":[]},{"id":11110,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=11110","url_meta":{"origin":6708,"position":1},"title":"Coarctate reactions as a third fundamental organic-mechanistic type.","author":"Henry Rzepa","date":"September 4, 2013","format":false,"excerpt":"According to Herges, the mechanism of single-step (concerted) reactions can be divided into three basic types; linear (e.g. substitution, elimination etc), pericyclic (e.g. Diels Alder) and a third much rarer, and hence very often overlooked type that was named coarctate. This is based on the topology of\u00a0bond redistribution patterns, an\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":"Click for 3D","src":"https:\/\/i0.wp.com\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2013\/09\/coarctate-ts.jpeg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":20354,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=20354","url_meta":{"origin":6708,"position":2},"title":"Epoxidation of ethene: a new substituent twist.","author":"Henry Rzepa","date":"December 21, 2018","format":false,"excerpt":"Five years back,\u00a0I speculated about the mechanism of the epoxidation of ethene by a peracid, concluding that kinetic isotope effects provided interesting evidence that this mechanism is highly asynchronous and involves a so-called \"hidden intermediate\". Here I revisit this reaction in which a small change is applied to the atoms\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.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2018\/12\/imine2.gif?resize=350%2C200&ssl=1","width":350,"height":200},"classes":[]},{"id":45,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=45","url_meta":{"origin":6708,"position":3},"title":"Pericyclic assistance for SN-1 solvolysis","author":"Henry Rzepa","date":"April 3, 2009","format":false,"excerpt":"\u00a0 The reaction above is ostensibly a very simple pericyclic ring opening of a cyclopropyl carbocation to an allyl cation, preceeded by a preparatory step involving SN-1 solvolysis. As a 2-electron thermal process, the second step proceeds with disrotation of the terminii. Can this stereochemistry be illustrated with a computed\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":"Pericylically assisted solvolysis. Click above to see model.","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2009\/04\/p23.gif?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":6543,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=6543","url_meta":{"origin":6708,"position":4},"title":"The Dieneone-phenol controversies.","author":"Henry Rzepa","date":"April 30, 2012","format":false,"excerpt":"During the 1960s, a holy grail of synthetic chemists was to devise an efficient route to steroids. R. B. Woodward was one the chemists who undertook this challenge, starting from compounds known as dienones (e.g. 1) and their mysterious conversion to phenols (e.g. 2 or 3) under acidic conditions. This\u2026","rel":"","context":"In "Chemical IT"","block_context":{"text":"Chemical IT","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=2"},"img":{"alt_text":"","src":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2012\/04\/patha.svg","width":350,"height":200},"classes":[]},{"id":6124,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=6124","url_meta":{"origin":6708,"position":5},"title":"Secrets of a university tutor: dissection of a reaction mechanism. Part 2, the stereochemistry.","author":"Henry Rzepa","date":"January 30, 2012","format":false,"excerpt":"In the previous post, I went over how a reaction can be stripped down to basic components. That exercise was essentially a flat one in two dimensions, establishing only what connections between atoms are made or broken. Here we look at the three dimensional arrangements. It all boils down to\u2026","rel":"","context":"In \"pericyclic\"","block_context":{"text":"pericyclic","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?tag=pericyclic"},"img":{"alt_text":"","src":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2012\/01\/pericyclic-tutorial_s.svg","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\/6708","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=6708"}],"version-history":[{"count":20,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/6708\/revisions"}],"predecessor-version":[{"id":6737,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/6708\/revisions\/6737"}],"wp:attachment":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=6708"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=6708"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=6708"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=6708"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}