{"id":8733,"date":"2012-12-19T09:52:14","date_gmt":"2012-12-19T09:52:14","guid":{"rendered":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=8733"},"modified":"2023-03-10T15:40:30","modified_gmt":"2023-03-10T15:40:30","slug":"non-covalent-interactions-in-the-sharpless-transition-state-for-asymmetric-epoxidation","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=8733","title":{"rendered":"Non covalent interactions in the Sharpless transition state for asymmetric epoxidation."},"content":{"rendered":"
\n

The Sharpless epoxidation of an allylic alcohol had a big impact on synthetic chemistry when it was introduced in the 1980s, and led the way for the discovery (design?) of many new asymmetric catalytic systems. Each achieves its chiral magic by control of the geometry at the transition state for the reaction, and the stabilizations (or destabilizations) that occur at that geometry. These in turn can originate from factors such as stereoelectronic control or simply by the overall sum of many small attractions and repulsions we call dispersion interactions<\/em>. Here I take an initial look at these for the binuclear transition state shown schematically below.<\/p>\n

\"sharpless-binuclear\"<\/p>\n

The NCI method was described recently[1]<\/a><\/span> as a method for probing the non-covalent electron density in a molecule. It does this by cleverly filtering out the covalent density via<\/em> computing a first derivative of the density \u03c1(r) called the reduced density gradient<\/i> and taking the band of values appropriate for non-covalent densities. By inspecting the Laplacian<\/a> of these densities at any point in space, the region can be characterised as attractive, repulsive or neutral. Visually, this information can be transformed into isosurfaces which are colour coded depending on whether the region is attractive (=blue to green) or repulsive (yellow to red). In the previous post<\/a>, it turned out that the attractive contributions to the dispersion energies differed for the two diasteromeric transition states (in the conformations calculated) by about 2.6 kcal\/mol. Shown below are the two NCI surfaces for these which allow one to get some insight into where this overall contribution might come from (together with weak hydrogen bonds and other non-covalent contributions).<\/p>\n\n\n\n
\n
\"(R)-diastereomer.

(R)-diastereomer. Click for NCI surfaces<\/p><\/div>\n<\/td>\n

\n
\"(S)-diastereomer.

(S)-diastereomer. Click for NCI surfaces.<\/p><\/div>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Yes, it is a very complex diagram, and you really do need to study it by obtaining the 3D model and rotating it around to explore the 3D space. I would note that it is possible to integrate the NCI function (see [2]<\/a><\/span> for an example and leading references) and hence try to obtain further insights. I highlight just one here; \u00a0the terminal \u00a0=CH2<\/sub> of the allyl alcohol points into empty space for \u00a0(R), but folds back to interact with the catalyst for \u00a0(S).\u00a0<\/p>\n

Finally, in case you are asking how do I obtain an NCI surface, I have created a little web site<\/a>\u00a0where you can submit a computed (or indeed experimental) electron density cube for processing using Jmol. Give it a go and see how it works (and thanks to \u00a0Julia \u00a0Contreras-Garcia and \u00a0Bob Hanson for putting this together).<\/p>\n

References<\/h2>\n
  1. E.R. Johnson, S. Keinan, P. Mori-S\u00e1nchez, J. Contreras-Garc\u00eda, A.J. Cohen, and W. Yang, \"Revealing Noncovalent Interactions\", Journal of the American Chemical Society<\/i>, vol. 132, pp. 6498-6506, 2010. https:\/\/doi.org\/10.1021\/ja100936w<\/a>\n\n<\/li>\n
  2. J.L. Arbour, H.S. Rzepa, J. Contreras\u2010Garc\u00eda, L.A. Adrio, E.M. Barreiro, and K.K.(. Hii, \"Silver\u2010Catalysed Enantioselective Addition of O\uf8ffH and N\uf8ffH Bonds to Allenes: A New Model for Stereoselectivity Based on Noncovalent Interactions\", Chemistry \u2013 A European Journal<\/i>, vol. 18, pp. 11317-11324, 2012. https:\/\/doi.org\/10.1002\/chem.201200547<\/a>\n\n<\/li>\n<\/ol>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

    The Sharpless epoxidation of an allylic alcohol had a big impact on synthetic chemistry when it was introduced in the 1980s, and led the way for the discovery (design?) of many new asymmetric catalytic systems. Each achieves its chiral magic by control of the geometry at the transition state for the reaction, and the stabilizations […]<\/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":true,"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":[965,839,1138,249,964,958,959,843,966],"ppma_author":[2661],"class_list":["post-8733","post","type-post","status-publish","format-standard","hentry","category-interesting-chemistry","tag-asymmetric-catalytic-systems","tag-bob-hanson","tag-catalysis","tag-julia-contreras-garcia","tag-little-web-site","tag-nci","tag-non-covalent-analysis","tag-reaction-mechanism","tag-terminal-ch"],"yoast_head":"\nNon covalent interactions in the Sharpless transition state for asymmetric epoxidation. - 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=8733\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Non covalent interactions in the Sharpless transition state for asymmetric epoxidation. - Henry Rzepa's Blog\" \/>\n<meta property=\"og:description\" content=\"The Sharpless epoxidation of an allylic alcohol had a big impact on synthetic chemistry when it was introduced in the 1980s, and led the way for the discovery (design?) of many new asymmetric catalytic systems. Each achieves its chiral magic by control of the geometry at the transition state for the reaction, and the stabilizations […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=8733\" \/>\n<meta property=\"og:site_name\" content=\"Henry Rzepa's Blog\" \/>\n<meta property=\"article:published_time\" content=\"2012-12-19T09:52:14+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2023-03-10T15:40:30+00:00\" \/>\n<meta property=\"og:image\" content=\"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2012\/12\/sharpless-binuclear.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":"Non covalent interactions in the Sharpless transition state for asymmetric epoxidation. - 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=8733","og_locale":"en_GB","og_type":"article","og_title":"Non covalent interactions in the Sharpless transition state for asymmetric epoxidation. - Henry Rzepa's Blog","og_description":"The Sharpless epoxidation of an allylic alcohol had a big impact on synthetic chemistry when it was introduced in the 1980s, and led the way for the discovery (design?) of many new asymmetric catalytic systems. 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Here in part 2, I investigate whether a binuclear model might have more success.\u00a0The new model is constructed using two units of\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":"WAWBUR. Click for 3D","src":"https:\/\/i0.wp.com\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2012\/12\/WAWBUR.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":8588,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=8588","url_meta":{"origin":8733,"position":1},"title":"Why is the Sharpless epoxidation enantioselective? Part 1: a simple model.","author":"Henry Rzepa","date":"December 9, 2012","format":false,"excerpt":"Sharpless epoxidation converts a prochiral allylic alcohol into the corresponding chiral epoxide with > 90% enantiomeric excess,. Here is the first step in trying to explain how this magic is achieved. The scheme above shows how (achiral) prop-2-enol is converted using the asymmetric catalyst\u00a0(R,R)-diethyl tartrate \u00a0and t-butyl hydroperoxide as oxidant\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\/12\/sharpless.gif?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":12308,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=12308","url_meta":{"origin":8733,"position":2},"title":"Enantioselective epoxidation of alkenes using the Shi Fructose-based catalyst. An undergraduate experiment.","author":"Henry Rzepa","date":"April 15, 2014","format":false,"excerpt":"The journal of chemical education can be a fertile source of ideas for undergraduate student experiments. Take this procedure for asymmetric epoxidation of an alkene. When I first spotted it, I thought not only would it be interesting to do in the lab, but could be extended by incorporating some\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":8850,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=8850","url_meta":{"origin":8733,"position":3},"title":"Sharpless epoxidation, enantioselectivity and conformational analysis.","author":"Henry Rzepa","date":"January 3, 2013","format":false,"excerpt":"I return to this reaction one more time. Trying to explain why it is enantioselective for the epoxide product poses peculiar difficulties. Most of the substituents can adopt one of several conformations, and some exploration of this conformational space is needed. Amongst the conformational possibilities are the two rotations shown\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":1466,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=1466","url_meta":{"origin":8733,"position":4},"title":"Chemical intimacy: Ion pairs in carbocations","author":"Henry Rzepa","date":"January 11, 2010","format":false,"excerpt":"The scheme below illustrates one of the iconic reactions in organic chemistry. It is a modern representation of Meerwein's famous experiment from which he inferred a carbocation intermediate, deduced from studying the rate of enantiomerization of isobornyl chloride when treated with the Lewis acid SnCl4. Meerwein himself suggested (in effect,\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.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2010\/01\/h-shift.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":8761,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=8761","url_meta":{"origin":8733,"position":5},"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":[]}],"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\/8733","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=8733"}],"version-history":[{"count":28,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/8733\/revisions"}],"predecessor-version":[{"id":25964,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/8733\/revisions\/25964"}],"wp:attachment":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=8733"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=8733"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=8733"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=8733"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}