{"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":"2020-03-29T06:25:55","modified_gmt":"2020-03-29T05:25:55","slug":"substituent-effects-on-the-mechanism-of-michael-14-nucleophilic-addition","status":"publish","type":"post","link":"https:\/\/www.rzepa.net\/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>\n<\/tr>\n
\n

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

11.5<\/td>\n<\/tr>\n
\n

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

16.3<\/td>\n<\/tr>\n
\n

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

16.7<\/td>\n<\/tr>\n
\n

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

31.9<\/td>\n<\/tr>\n
\n

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

35.8<\/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,"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":[2336,1085],"tags":[],"class_list":["post-22011","post","type-post","status-publish","format-standard","hentry","category-curl-arrows","category-reaction-mechanism-2"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p1gPyz-5J1","jetpack_likes_enabled":true,"_links":{"self":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts\/22011","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=22011"}],"version-history":[{"count":0,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts\/22011\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=22011"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=22011"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=22011"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}