{"id":6921,"date":"2012-06-10T18:33:45","date_gmt":"2012-06-10T17:33:45","guid":{"rendered":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=6921"},"modified":"2012-06-11T11:24:06","modified_gmt":"2012-06-11T10:24:06","slug":"transition-state-models-for-baldwin-digonal-ring-closures","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=6921","title":{"rendered":"Transition state models for Baldwin dig(onal) ring closures."},"content":{"rendered":"
\n

This is a continuation of the previous post<\/a> exploring the transition state geometries of various types of ring closure as predicted by \u00a0Baldwin’s rules. I had dealt with bond formation to a trigonal<\/em> (sp2<\/sup>) carbon; now I add a digonal<\/em><\/strong> (sp) example (see an interesting literature <\/a>variation).\u00a0<\/p>\n

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

As before, I have added two solvent (water) molecules to the model, since the immediate product of the closure is a zwitterionic intermediate, which is likely to be stabilised by the solvent. I also used the same nucleophile as before to facilitate comparison.<\/p>\n\n\n\n
\n
\"\"

5-exo-dig transition state. Click for 4D.<\/p><\/div><\/td>\n

\n
\"\"

6-endo-dig transition state. Click for 4D.<\/p><\/div><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

The digonal angle of attack is 121\u00b0 for the \u00a0exo<\/em> form<\/a>, and 116\u00b0 for the endo<\/a>, <\/em>both larger than was the case in the trig<\/em> systems.<\/em>\u00a0The relative free energies of the two transition states is 3.6 kcal\/mol in favour of the\u00a0exo<\/em>\u00a0isomer.\u00a0The hydrogen bond network is somewhat strained, since two solvent molecules cannot quite reach the forming carbanion at the optimal angle to form a good hydrogen bond to it. Instead, the water has to content itself with a \u03c0-facial hydrogen bond between the alkyne and the H-O. As a result, proton transfer to the carbon requires a separate activation step (or a stronger acid than water).\u00a0<\/p>\n\n\n\n\n
5-exo-dig<\/em> transition state<\/th>\n<\/tr>\n
\"\"<\/a><\/td>\n\"\"<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n\n\n
6-endo-dig<\/em> transition state<\/th>\n<\/tr>\n
\"\"<\/a><\/td>\n\"\"<\/a><\/td>\n<\/tr>\n
\"\"<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

The IRC for the 6-endo-dig pathway has features worth commenting upon.<\/p>\n

    \n
  1. At IRC -12, the two solvent molecules form a triangular network with the nucleophilic amine.<\/li>\n
  2. By IRC -9, one of the water molecules has split itself off from this triangle, and started to move towards the triple bond, which is gradually becoming a better acceptor of a hydrogen bond.<\/li>\n
  3. At IRC -3, this water molecule is now forming a\u00a0\u00a0\u03c0-facial hydrogen bond to the alkyne, which is still largely in place at the end of this step of the mechanism.<\/li>\n<\/ol>\n

    To complete the mechanism, I have added the final step in the reaction, a proton transfer from the amine to the carbon recipient, as facilitated by the bridge of solvent molecules connecting the start and end of the process. The free energy<\/a> of this transition state is 0.3 kcal\/mol higher than the N-C bond forming reaction, making it (just) the rate determining step.<\/p>\n\n\n\n\n\n
    Proton transfer<\/th>\n<\/tr>\n
    \n
    \"\"

    Transition state for proton transfer. Click for 4D<\/p><\/div><\/td>\n

    		\"\"<\/a><\/td>\n<\/tr>\n
    \"\"<\/a><\/td>\n\"\"<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
      \n
    1. The feature at IRC = 0.0 (the transition state) is the first proton transfer, from \u00a0C to O.<\/li>\n
    2. The second feature at \u00a0IRC -2.5\u00a0is an O to\u00a0O proton transfer<\/li>\n
    3. At IRC -4, the third and final proton transfer can be seen, from\u00a0O to N.<\/li>\n
    4. At\u00a0IRC -6.5,\u00a0a weak\u00a0\u03c0-OH hydrogen bond forms.<\/li>\n<\/ol>\n

      There is one more common type of cyclisation covered by Baldwin’s rules, this time involving tet<\/em>(rahedral) or sp3<\/sup>\u00a0centres. This turns out to be the most interesting of the lot; reporting on this will have to wait a little!<\/p>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

      This is a continuation of the previous post exploring the transition state geometries of various types of ring closure as predicted by \u00a0Baldwin’s rules. I had dealt with bond formation to a trigonal (sp2) carbon; now I add a digonal (sp) example (see an interesting literature variation).\u00a0 As before, I have added two solvent (water) […]<\/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":[],"tags":[844,40,852,851,843],"ppma_author":[2661],"class_list":["post-6921","post","type-post","status-publish","format-standard","hentry","tag-baldwins-rules","tag-free-energy","tag-hydrogen-bond-network","tag-immediate-product","tag-reaction-mechanism"],"yoast_head":"\nTransition state models for Baldwin dig(onal) ring closures. - 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=6921\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Transition state models for Baldwin dig(onal) ring closures. - Henry Rzepa's Blog\" \/>\n<meta property=\"og:description\" content=\"This is a continuation of the previous post exploring the transition state geometries of various types of ring closure as predicted by \u00a0Baldwin’s rules. 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