{"id":22011,"date":"2020-03-29T06:25:55","date_gmt":"2020-03-29T05:25:55","guid":{"rendered":"https:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=22011"},"modified":"2020-04-04T06:01:10","modified_gmt":"2020-04-04T05:01:10","slug":"substituent-effects-on-the-mechanism-of-michael-14-nucleophilic-addition","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=22011","title":{"rendered":"Substituent effects on the mechanism of Michael 1,4-Nucleophilic addition."},"content":{"rendered":"
\n

In the previous post<\/a>, I looked at the mechanism for 1,4-nucleophilic addition to an activated alkene (the Michael reaction). The model nucleophile was malonaldehyde after deprotonation and the model electrophile was acrolein (prop-2-enal), with the rate determining transition state being carbon-carbon bond formation between the two, accompanied by proton transfer to the oxygen of the acrolein.<\/p>\n

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

Here I look at the effect of changing one<\/strong> of the aldehyde groups on the malonaldehyde to a variety of others and in particular how this might affect the relative timing of the C-C formation and the accompanying proton transfer to oxygen. Will this vary with substituents?<\/p>\n

The activation free energies for TS2 are shown below, showing that as the acidity of the proton on the incipient nucleophile decreases along the series R=NO2<\/sub> to R=H, the free energy barrier goes up.\u00a0<\/p>\n\n\n\n\n\n\n\n\n
Substituent<\/th>\n\u0394\u0394G298<\/sub>\u2021<\/sup><\/a> (TS2)<\/th>\nAngle of approach<\/th>\n<\/tr>\n
\n

NO2<\/p>\n<\/td>\n

11.5<\/td>\n110.8<\/td>\n<\/tr>\n
\n

CHO<\/p>\n<\/td>\n

16.3<\/td>\n118.2<\/td>\n<\/tr>\n
\n

CN<\/p>\n<\/td>\n

16.7<\/td>\n111.2<\/td>\n<\/tr>\n
\n

OMe<\/p>\n<\/td>\n

31.9<\/td>\n121.8<\/td>\n<\/tr>\n
\n

H<\/p>\n<\/td>\n

35.8<\/td>\n116.7<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

The asynchrony of the C-C formation and the PT is clearly shown for R=NO2<\/sub>. This can be seen most clearly when the gradient norm along the reaction path is plotted. This has TWO maxima at IRC 0.5 and 1.4, with a hidden (zwitterionic) intermediate in-between.<\/p>\n

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

\"\"<\/a> \"\"<\/a> For R=H the gradient norm peaks are at IRC 0.8 and 2.1; the reaction is equally asynchronous. If you are wondering why the barrier looks smaller for R=H than for R=NO2<\/sub> it is because Int1<\/strong> is a lot less stable for R=H (= more reactive) than for nitro. \"\"<\/a>\"\"<\/a><\/p>\n

So this was a surprise in the end. Unlike substituent effects on electrophilic peracid epoxidation of an alkene,[1]<\/a><\/span> nucleophilic addition to an alkene does not seem to exhibit a large substituent effect on its choreography.<\/p>\n

References<\/h2>\n
  1. J.E.M.N. Klein, G. Knizia, and H.S. Rzepa, \"Epoxidation of Alkenes by Peracids: From Textbook Mechanisms to a Quantum Mechanically Derived Curly\u2010Arrow Depiction\", ChemistryOpen<\/i>, vol. 8, pp. 1244-1250, 2019. https:\/\/doi.org\/10.1002\/open.201900099<\/a>\n\n<\/li>\n<\/ol>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

    In the previous post, I looked at the mechanism for 1,4-nucleophilic addition to an activated alkene (the Michael reaction). The model nucleophile was malonaldehyde after deprotonation and the model electrophile was acrolein (prop-2-enal), with the rate determining transition state being carbon-carbon bond formation between the two, accompanied by proton transfer to the oxygen 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":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[2327,1086],"tags":[],"ppma_author":[2661],"class_list":["post-22011","post","type-post","status-publish","format-standard","hentry","category-curl-arrows","category-reaction-mechanism-2"],"yoast_head":"\nSubstituent effects on the mechanism of Michael 1,4-Nucleophilic addition. - 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=22011\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Substituent effects on the mechanism of Michael 1,4-Nucleophilic addition. - Henry Rzepa's Blog\" \/>\n<meta property=\"og:description\" content=\"In the previous post, I looked at the mechanism for 1,4-nucleophilic addition to an activated alkene (the Michael reaction). The model nucleophile was malonaldehyde after deprotonation and the model electrophile was acrolein (prop-2-enal), with the rate determining transition state being carbon-carbon bond formation between the two, accompanied by proton transfer to the oxygen of the […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=22011\" \/>\n<meta property=\"og:site_name\" content=\"Henry Rzepa's Blog\" \/>\n<meta property=\"article:published_time\" content=\"2020-03-29T05:25:55+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2020-04-04T05:01:10+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2020\/03\/michael2.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":"Substituent effects on the mechanism of Michael 1,4-Nucleophilic addition. - 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=22011","og_locale":"en_GB","og_type":"article","og_title":"Substituent effects on the mechanism of Michael 1,4-Nucleophilic addition. - Henry Rzepa's Blog","og_description":"In the previous post, I looked at the mechanism for 1,4-nucleophilic addition to an activated alkene (the Michael reaction). The model nucleophile was malonaldehyde after deprotonation and the model electrophile was acrolein (prop-2-enal), with the rate determining transition state being carbon-carbon bond formation between the two, accompanied by proton transfer to the oxygen of the […]","og_url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=22011","og_site_name":"Henry Rzepa's Blog","article_published_time":"2020-03-29T05:25:55+00:00","article_modified_time":"2020-04-04T05:01:10+00:00","og_image":[{"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2020\/03\/michael2.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=22011#article","isPartOf":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=22011"},"author":{"name":"Henry Rzepa","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#\/schema\/person\/2b40f7b9c872a4dc1547e040a11b6281"},"headline":"Substituent effects on the mechanism of Michael 1,4-Nucleophilic addition.","datePublished":"2020-03-29T05:25:55+00:00","dateModified":"2020-04-04T05:01:10+00:00","mainEntityOfPage":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=22011"},"wordCount":291,"commentCount":0,"image":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=22011#primaryimage"},"thumbnailUrl":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2020\/03\/michael2.svg","articleSection":["Curly arrows","reaction mechanism"],"inLanguage":"en-GB","potentialAction":[{"@type":"CommentAction","name":"Comment","target":["https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=22011#respond"]}]},{"@type":"WebPage","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=22011","url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=22011","name":"Substituent effects on the mechanism of Michael 1,4-Nucleophilic addition. - 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