{"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_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},"jetpack_post_was_ever_published":false},"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. 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) […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=6921\" \/>\n<meta property=\"og:site_name\" content=\"Henry Rzepa's Blog\" \/>\n<meta property=\"article:published_time\" content=\"2012-06-10T17:33:45+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2012-06-11T10:24:06+00:00\" \/>\n<meta property=\"og:image\" content=\"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2012\/06\/baldwin-dig.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":"Transition state models for Baldwin dig(onal) ring closures. - 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=6921","og_locale":"en_GB","og_type":"article","og_title":"Transition state models for Baldwin dig(onal) ring closures. - Henry Rzepa's Blog","og_description":"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) […]","og_url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=6921","og_site_name":"Henry Rzepa's Blog","article_published_time":"2012-06-10T17:33:45+00:00","article_modified_time":"2012-06-11T10:24:06+00:00","og_image":[{"url":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2012\/06\/baldwin-dig.svg","type":"","width":"","height":""}],"author":"Henry Rzepa","twitter_card":"summary_large_image","twitter_misc":{"Written by":"Henry Rzepa","Estimated reading time":"2 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=6921#article","isPartOf":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=6921"},"author":{"name":"Henry Rzepa","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#\/schema\/person\/2b40f7b9c872a4dc1547e040a11b6281"},"headline":"Transition state models for Baldwin dig(onal) ring closures.","datePublished":"2012-06-10T17:33:45+00:00","dateModified":"2012-06-11T10:24:06+00:00","mainEntityOfPage":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=6921"},"wordCount":509,"commentCount":1,"image":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=6921#primaryimage"},"thumbnailUrl":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2012\/06\/baldwin-dig.svg","keywords":["Baldwins rules","free energy","hydrogen bond network","immediate product","Reaction Mechanism"],"inLanguage":"en-GB","potentialAction":[{"@type":"CommentAction","name":"Comment","target":["https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=6921#respond"]}]},{"@type":"WebPage","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=6921","url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=6921","name":"Transition state models for Baldwin dig(onal) ring closures. - 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Both sets of rules fundamentally explore the geometry of\u2026","rel":"","context":"In "General"","block_context":{"text":"General","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=1"},"img":{"alt_text":"","src":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2012\/06\/baldwin.svg","width":350,"height":200},"classes":[]},{"id":7495,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=7495","url_meta":{"origin":6921,"position":1},"title":"Dynamic effects in nucleophilic substitution at trigonal carbon (with Na+) revisited.","author":"Henry Rzepa","date":"August 13, 2012","format":false,"excerpt":"This reaction looks simple but is deceptively complex. To recapitulate: tolyl thiolate (X=Na)\u00a0reacts with the dichlorobutenone to give two substitution products in a 81:19 ratio, a result that Singleton and Bogle argue arises from a\u00a0statistical distribution of dynamic trajectories bifurcating out of a\u00a0single transition state\u00a0favouring 2 over 3. On the\u2026","rel":"","context":"In \"free energy\"","block_context":{"text":"free energy","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?tag=free-energy"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2012\/08\/singleton-a.gif?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":13300,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=13300","url_meta":{"origin":6921,"position":2},"title":"Mechanism of the solvatochromic reaction of a spiropyran.","author":"Henry Rzepa","date":"February 4, 2015","format":false,"excerpt":"The journal of chemical education has many little gems providing inspiration for laboratory experiments. Jonathan Piard reports one based on the reaction below; here I investigate the mechanism of this transformation. There are two things going on here; an electrocyclic ring opening involving breaking the C-O bond, with\u00a0a cis\/trans isomerism\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":"cis-trans","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2015\/02\/cis-trans.gif?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":7027,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=7027","url_meta":{"origin":6921,"position":3},"title":"Joining up the pieces. Peroxidation of ethyne.","author":"Henry Rzepa","date":"July 9, 2012","format":false,"excerpt":"Sometimes, connections between different areas of chemistry just pop out (without the help of semantic web tools, this is called serendipity). So here, I will try to join up some threads which emerge from previous posts. I had noted that antiaromaticity in cyclopropenium anion is lessened by the system adopting\u2026","rel":"","context":"In "Curly arrows"","block_context":{"text":"Curly arrows","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=2327"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":7779,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=7779","url_meta":{"origin":6921,"position":4},"title":"Oxime formation from hydroxylamine and ketone: a (computational) reality check on stage one of the mechanism.","author":"Henry Rzepa","date":"September 23, 2012","format":false,"excerpt":"The mechanism of forming an oxime from nucleophilic addition of a hydroxylamine to a ketone is taught early on in most courses of organic chemistry. Here I subject the first step of this reaction to form a tetrahedral intermediate to quantum mechanical scrutiny. The first decision is to decide which\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.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2012\/09\/hydroxylamine%2Bacetone-O-1H2O-6-ring_small.gif?resize=350%2C200&ssl=1","width":350,"height":200},"classes":[]},{"id":7100,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=7100","url_meta":{"origin":6921,"position":5},"title":"Dynamic effects in nucleophilic substitution at trigonal carbon.","author":"Henry Rzepa","date":"July 16, 2012","format":false,"excerpt":"Singleton and co-workers have produced some wonderful work showing how dynamic effects and not just transition states can control the outcome of reactions. Steve Bachrach's blog contains many examples, including this recent one. This shows that tolyl thiolate (X=Na)\u00a0reacts with the dichlorobutenone to give two substitution products in a 81:19\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":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2012\/07\/singleton.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\/6921","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=6921"}],"version-history":[{"count":42,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/6921\/revisions"}],"predecessor-version":[{"id":6974,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/6921\/revisions\/6974"}],"wp:attachment":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=6921"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=6921"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=6921"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=6921"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}