{"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":"2012-06-10T18:33:45","modified_gmt":"2012-06-10T17:33:45","slug":"transition-state-models-for-baldwin-digonal-ring-closures","status":"publish","type":"post","link":"https:\/\/rzepa.net\/blog\/2012\/06\/10\/transition-state-models-for-baldwin-digonal-ring-closures\/","title":{"rendered":"Transition state models for Baldwin dig(onal) ring closures."},"content":{"rendered":"

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.<\/figcaption><\/figure><\/td>\n
\n
\"\"
6-endo-dig transition state. Click for 4D.<\/figcaption><\/figure><\/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<\/figcaption><\/figure><\/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","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":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[256,1038,1220,1248,2076],"class_list":["post-6921","post","type-post","status-publish","format-standard","hentry","category-uncategorized","tag-baldwins-rules","tag-free-energy","tag-hydrogen-bond-network","tag-immediate-product","tag-reaction-mechanism"],"_links":{"self":[{"href":"https:\/\/rzepa.net\/blog\/wp-json\/wp\/v2\/posts\/6921","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/rzepa.net\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/rzepa.net\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/rzepa.net\/blog\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/rzepa.net\/blog\/wp-json\/wp\/v2\/comments?post=6921"}],"version-history":[{"count":0,"href":"https:\/\/rzepa.net\/blog\/wp-json\/wp\/v2\/posts\/6921\/revisions"}],"wp:attachment":[{"href":"https:\/\/rzepa.net\/blog\/wp-json\/wp\/v2\/media?parent=6921"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/rzepa.net\/blog\/wp-json\/wp\/v2\/categories?post=6921"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/rzepa.net\/blog\/wp-json\/wp\/v2\/tags?post=6921"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}