{"id":5763,"date":"2011-12-06T13:28:19","date_gmt":"2011-12-06T13:28:19","guid":{"rendered":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=5763"},"modified":"2020-12-08T20:31:18","modified_gmt":"2020-12-08T20:31:18","slug":"so-near-and-yet-so-far-the-story-of-the-pericyclic-electrocyclic-ring-opening-of-hexatriene","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=5763","title":{"rendered":"So near and yet so far. The story of the electrocyclic ring opening of a cyclohexadiene."},"content":{"rendered":"
\n

My previous<\/a> three posts set out my take on three principle categories of pericyclic reaction. Here I tell a prequel to the understanding of these reactions. In 1965, Woodward and Hoffmann[1]<\/a><\/span> in their theoretical analysis (submitted Nov 30, 1964) for which the Nobel prize (to Hoffmann only of the pair, Woodward having died) was later awarded. But in the same year, Elias Corey[2]<\/a><\/span> reported the conclusion of a project\u00a0started several years earlier (first reported (DOI: 10.1021\/ja00907a030<\/a>, Nov 1, 1963) to synthesize the sesquiterpene dihydrocostunolide.<\/p>\n

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

The key element of this synthesis is described as the photochemical ring-opening of 10<\/strong> to give a thermally unstable ten-membered ring compound 13<\/strong>, which at room temperature recyclizes to 16<\/strong>. These two reactions constitute perfect examples of the Woodward-Hoffmann rules, a modern statement of which is that a 4n+2 electron photochemical pericyclic reaction (for the above example, n=1) normally proceeds with one\u00a0antarafacial <\/em><\/strong>component\u00a0whilst a thermal one proceeds with only\u00a0supra facial <\/em><\/strong>components (a more recent extension of this statement would be the rule for\u00a0two<\/em><\/strong> antarafacial components).\u00a0To illustrate this, shown below is the thermal cyclisation<\/a> of dimethylhexatriene as a model for 13<\/strong>. The IRC shows one interesting conformational feature at ~+8, which is the rotation of the two methyl groups to replace the eclipsed by a gauche orientation. Clearly visible is the suprafacial<\/em><\/strong> component (the new bond forms on the bottom face of both termini of the triene) and in the example of 13<\/strong> \u2192 16<\/strong> resulting in the observed stereochemistry.<\/p>\n\n\n\n\n
\"\"<\/a><\/td>\n\"\"<\/a><\/td>\n<\/tr>\n
\n
\"\"

Thermal electrocyclic reaction of a dimethyl-hexatriene. Click for 3D.<\/p><\/div>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

The photochemical reaction of 10<\/strong> can be illustrated by the nature of the conical intersection<\/a> where the singlet (S0<\/sub>\/S1<\/sub>) surfaces touch<\/a>. The antarafacial<\/em><\/strong> component is clearly seen (bottom face of lhs of the triene, top face of the rhs of the other end of the triene), leading to the observed stereochemistry of the photochemical product 13<\/strong>.<\/p>\n

\"\"

Geometry of a conical intersection for photochemical electrocyclisation of hexatriene. Click for 3D.<\/p><\/div>\n

So Corey had in his hands in 1963 an unambiguous and clear cut example of stereoselection operating in a pericyclic reaction, and an opportunity in 1965 (if not earlier) to infer and declare a general guiding principle from that reaction. In fact that opportunity was not taken by Corey, and he was (DOI: 10.1021\/jo049925d<\/a>) left to rue\u00a0decades later on what might have been!<\/p>\n

References<\/h2>\n
  1. R.B. Woodward, and R. Hoffmann, \"Stereochemistry of Electrocyclic Reactions\", Journal of the American Chemical Society<\/i>, vol. 87, pp. 395-397, 1965. https:\/\/doi.org\/10.1021\/ja01080a054<\/a>\n\n<\/li>\n
  2. E.J. Corey, and A.G. Hortmann, \"The Total Synthesis of Dihydrocostunolide\", Journal of the American Chemical Society<\/i>, vol. 87, pp. 5736-5742, 1965. https:\/\/doi.org\/10.1021\/ja00952a037<\/a>\n\n<\/li>\n<\/ol>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

    My previous three posts set out my take on three principle categories of pericyclic reaction. Here I tell a prequel to the understanding of these reactions. In 1965, Woodward and Hoffmann in their theoretical analysis (submitted Nov 30, 1964) for which the Nobel prize (to Hoffmann only of the pair, Woodward having died) was later […]<\/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":[4],"tags":[774,781,2651,2650,776,780,373],"ppma_author":[2661],"class_list":["post-5763","post","type-post","status-publish","format-standard","hentry","category-interesting-chemistry","tag-electrocyclic","tag-elias-corey","tag-historical","tag-pericyclic","tag-photochemical","tag-photochemical-product","tag-tutorial-material"],"yoast_head":"\nSo near and yet so far. The story of the electrocyclic ring opening of a cyclohexadiene. - 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=5763\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"So near and yet so far. The story of the electrocyclic ring opening of a cyclohexadiene. - Henry Rzepa's Blog\" \/>\n<meta property=\"og:description\" content=\"My previous three posts set out my take on three principle categories of pericyclic reaction. Here I tell a prequel to the understanding of these reactions. In 1965, Woodward and Hoffmann in their theoretical analysis (submitted Nov 30, 1964) for which the Nobel prize (to Hoffmann only of the pair, Woodward having died) was later […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=5763\" \/>\n<meta property=\"og:site_name\" content=\"Henry Rzepa's Blog\" \/>\n<meta property=\"article:published_time\" content=\"2011-12-06T13:28:19+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2020-12-08T20:31:18+00:00\" \/>\n<meta property=\"og:image\" content=\"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2011\/12\/p34a.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":"So near and yet so far. The story of the electrocyclic ring opening of a cyclohexadiene. - 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=5763","og_locale":"en_GB","og_type":"article","og_title":"So near and yet so far. The story of the electrocyclic ring opening of a cyclohexadiene. - Henry Rzepa's Blog","og_description":"My previous three posts set out my take on three principle categories of pericyclic reaction. Here I tell a prequel to the understanding of these reactions. In 1965, Woodward and Hoffmann in their theoretical analysis (submitted Nov 30, 1964) for which the Nobel prize (to Hoffmann only of the pair, Woodward having died) was later […]","og_url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=5763","og_site_name":"Henry Rzepa's Blog","article_published_time":"2011-12-06T13:28:19+00:00","article_modified_time":"2020-12-08T20:31:18+00:00","og_image":[{"url":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2011\/12\/p34a.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=5763#article","isPartOf":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=5763"},"author":{"name":"Henry Rzepa","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#\/schema\/person\/2b40f7b9c872a4dc1547e040a11b6281"},"headline":"So near and yet so far. 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Niels Bohr was one such and four decades later Robert Woodward wrote \"The conservation of orbital symmetry\" (Chem. Soc. Special Publications (Aromaticity), 1967, 21, 217-249; it is not online and so no doi\u2026","rel":"","context":"In "pericyclic"","block_context":{"text":"pericyclic","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=559"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":5632,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=5632","url_meta":{"origin":5763,"position":1},"title":"A modern take on the pericyclic electrocyclic ring opening of cyclobutene.","author":"Henry Rzepa","date":"November 26, 2011","format":false,"excerpt":"Woodward and Hoffmann published their\u00a0milestone article\u00a0 \"Stereochemistry of Electrocyclic Reactions\" in 1965. This brought maturity to the electronic theory of organic chemistry, arguably started by the proto-theory of Armstrong some 75 years earlier. Here, I take a modern look at the archetypal carrier of this insight, the ring opening of\u2026","rel":"","context":"In \"Adam\"","block_context":{"text":"Adam","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?tag=adam"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2011\/11\/con-open.gif?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":10611,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=10611","url_meta":{"origin":5763,"position":2},"title":"Another Woodward pericyclic example dissected: all is not what it seems.","author":"Henry Rzepa","date":"May 22, 2013","format":false,"excerpt":"Here is another example gleaned from that Woodward essay of 1967 (Chem. Soc. Special Publications (Aromaticity), 1967, 21, 217-249), where all might not be what it seems. Woodward notes that the reaction between the (highly reactive) 1 does not occur. This is attributed to it being a disallowed \u03c06 +\u2026","rel":"","context":"In \"free energy barrier\"","block_context":{"text":"free energy barrier","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?tag=free-energy-barrier"},"img":{"alt_text":"w2+2+2","src":"https:\/\/i0.wp.com\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2013\/05\/w2%2B2%2B2.gif?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":8761,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=8761","url_meta":{"origin":5763,"position":3},"title":"Vitamin B12 and the genesis of a new theory of chemistry.","author":"Henry Rzepa","date":"December 20, 2012","format":false,"excerpt":"I have written earlier about dihydrocostunolide, and how in 1963 Corey missed spotting the electronic origins of a key step in its synthesis.. A nice juxtaposition to this failed opportunity relates to Woodward's project at around the same time to synthesize vitamin B12. The step in the synthesis that caused\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":"","width":0,"height":0},"classes":[]},{"id":25633,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25633","url_meta":{"origin":5763,"position":4},"title":"A new type of bispericyclic reaction: Cyclopropanone + butadiene.","author":"Henry Rzepa","date":"September 30, 2022","format":false,"excerpt":"The term bispericyclic reaction was famously coined by Caramella et al in 2002 to describe the unusual features of the apparently innocuous dimerisation of cyclopentadiene. It shows features of two paths for different pericyclic reactions, comprising a 2+4 cycloaddition in the early stages, but evolving into a (degenerate) pair of\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":"","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2022\/09\/anomalous.gif?resize=350%2C200&ssl=1","width":350,"height":200},"classes":[]},{"id":9,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=9","url_meta":{"origin":5763,"position":5},"title":"A Disrotatory 4n+2 electron anti-aromatic M\u00f6bius transition state for a thermal electrocyclic reaction.","author":"Henry Rzepa","date":"April 2, 2009","format":false,"excerpt":"Mauksch and Tsogoeva have recently published an article illustrating how a thermal electrocyclic reaction can proceed with distoratory ring closure, whilst simultaneously also exhibiting 4n electron M\u00f6bius-aromatic character. Why is this remarkable? Because the simple Woodward-Hoffmann rules state that a disrotatory thermal electrocyclic reaction should proceed via a H\u00fcckel-aromatic 4n+2\u2026","rel":"","context":"In "pericyclic"","block_context":{"text":"pericyclic","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=559"},"img":{"alt_text":"Electrocylization of [14] annulene","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2009\/04\/p322.jpg?resize=350%2C200","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\/5763","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=5763"}],"version-history":[{"count":42,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/5763\/revisions"}],"predecessor-version":[{"id":23099,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/5763\/revisions\/23099"}],"wp:attachment":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=5763"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=5763"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=5763"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=5763"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}