{"id":2120,"date":"2010-07-01T18:19:52","date_gmt":"2010-07-01T17:19:52","guid":{"rendered":"http:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=2120"},"modified":"2011-07-07T06:05:08","modified_gmt":"2011-07-07T06:05:08","slug":"the-mysteries-of-stereoinduction","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=2120","title":{"rendered":"The mysteries of stereoinduction."},"content":{"rendered":"<div class=\"kcite-section\" kcite-section-id=\"2120\">\n<p>Stereo-induction is, lets face it, a <a href=\"http:\/\/www.ch.ic.ac.uk\/rzepa\/talks\/hofmann\/\" target=\"_blank\">subtle phenomenon<\/a>. The ratio of two stereoisomers formed in a reaction can be detected very accurately by experiment, and when converted to a free energy difference using \u0394G = -RT Ln K, this can amount to quite a small value (between 0.5 &#8211; 1.5 kcal\/mol). Can modelling reproduce effects originating from such small energy differences? Well one system that has been argued about now for several decades is shown below as <strong>1<\/strong>.<\/p>\n<div id=\"attachment_2121\" style=\"width: 411px\" class=\"wp-caption aligncenter\"><a href=\"http:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2010\/07\/norbornene.jpg\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-2121\" class=\"size-full wp-image-2121\" title=\"Stereoinduction: syn or anti?\" src=\"http:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2010\/07\/norbornene.jpg\" alt=\"\" width=\"401\" height=\"148\" \/><\/a><p id=\"caption-attachment-2121\" class=\"wp-caption-text\">Norbornene systems<\/p><\/div>\n<p><a href=\"http:\/\/dx.doi.org\/10.1039\/C39920000998\" target=\"_blank\">Way back in 1992<\/a>, we thought that the explanation for attack by an electrophile on the alkene from the <em>syn<\/em> face was electrostatic (although it did depend on the nature of the electropile; thus we concluded that attack by Hg(OH)<sub>2<\/sub> was electrostatic, but by BH<sub>3<\/sub> was orbital controlled). Recently, a different explanation has emerged, relating to how the fundamental normal vibrational modes of the molecule interact with the transition normal mode for the reaction. A <a href=\"http:\/\/dx.doi.org\/10.1038\/nchem.577\" target=\"_blank\">new example of this<\/a>, relating to reaction of the isomeric <strong>2<\/strong> with a peracid has recently been discussed on <a href=\"http:\/\/comporgchem.com\/blog\/?p=977\" target=\"_blank\">Steve Bachrach&#8217;s blog<\/a>. Here, the peroxide of the peracid is thought to act as an electrophile (although one must bear in mind that it does bear two electron lone pairs!). The conclusion was pretty clear cut; the experimental preference for <em>syn<\/em> (92%) over the <em>anti<\/em> isomer (8%, \u0394\u0394G = 1.4 kcal\/mol) was NOT due to electrostatic effects, but due to distorsional asymmetry in the vibrational mode that couples\/forms the transition state mode.<\/p>\n<p>I could not resist revisiting this system. As in 1992, a molecular electrostatic potential was calculated for <strong>2<\/strong>. The method used was wB97XD\/aug-cc-pvdz, and if you want the archive of this calculation to evaluate it yourself, <a href=\"http:\/\/hdl.handle.net\/10042\/to-4996\" target=\"_blank\">see here<\/a>).<\/p>\n<p><div id=\"attachment_2122\" style=\"width: 273px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-2122\" class=\"size-full wp-image-2122\" title=\"Electrostatic potential\" onclick=\"jmolInitialize('..\/Jmol\/');jmolSetAppletColor('white');jmolApplet([450,450],'load wp-content\/uploads\/2010\/07\/norbornene_0.029.jvxl;isosurface &quot;&quot; translucent;zoom 60;spin 3;');\" src=\"http:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2010\/07\/norbornene-0.031.jpg\" alt=\"\" width=\"263\" height=\"263\" \/><p id=\"caption-attachment-2122\" class=\"wp-caption-text\">MEP for 2. Click on diagram for 3D.<\/p><\/div>A very clear electrostatic bias for <em>syn<\/em> attack emerges (orange = attractive to a proton=electrophile). This electrostatic picture is not directly related to any distortional asymmetry, although of course both could arise from the same electronic factors. They may indeed be different manifestations of the same underlying nature of the wavefunction. But I would claim here that to make the clear statement that electrostatic effects are <strong>NOT<\/strong> responsible for the discrimination in this reaction is perhaps too simplistic (electrostatic potentials were not reported in the original article). The control experiment is <strong>3<\/strong>, which is known to be far less selective. The calculated electrostatic potential likewise shows much less discrimination.<\/p>\n<p><div id=\"attachment_2136\" style=\"width: 231px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-2136\" class=\"size-full wp-image-2136\" title=\"The norbornene with a four-membered ring\" onclick=\"jmolInitialize('..\/Jmol\/');jmolSetAppletColor('white');jmolApplet([450,450],'load wp-content\/uploads\/2010\/07\/norbornene4_0.029.jvxl;isosurface &quot;&quot; translucent;zoom 60;spin 3;');\" src=\"http:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2010\/07\/norbornene4-0.029.jpg\" alt=\"\" width=\"221\" height=\"239\" \/><p id=\"caption-attachment-2136\" class=\"wp-caption-text\">The norbornene with a four-membered ring<\/p><\/div>Is there another take on <strong>2<\/strong>? Well, how about an NBO (natural bond order) analysis? The interaction energy between the filled C1-C2 orbital and the antibonding\u00a0C15-C16 \u03c0* bond is 3.24. This could be regarded as pushing electrons into the anti-periplanar <em>syn<\/em> face of the alkene. The corresponding\u00a0C2-C9\/C15-C16 interaction resulting in an <em>anti<\/em>-preference is less at 2.55 kcal\/mol. This effect arises because the C1-C2 bond (localised as an NBO) is a better donor (E=-17.8eV) than C2-C9 (E=-18.1eV). Because C2 is common to both, it must be the difference between C1 and C9 (i.e. the hybridization of each). Perhaps it&#8217;s an orbital effect after all?<\/p>\n<div id=\"attachment_2124\" style=\"width: 304px\" class=\"wp-caption aligncenter\"><a href=\"http:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2010\/07\/norbornene-0.029.jpg\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-2124\" class=\"size-full wp-image-2124\" title=\"Norbornene electrostatic potential\" src=\"http:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2010\/07\/norbornene-0.029.jpg\" alt=\"\" width=\"294\" height=\"294\" \/><\/a><p id=\"caption-attachment-2124\" class=\"wp-caption-text\">Norbornene electrostatic potential<\/p><\/div>\n<p>I would conclude by saying that it can be ferociously difficult to identify the fundamental origins of stereo-induction. But I leave the argument in the hands of the reader now. What do you think?<\/p>\n<!-- kcite active, but no citations found -->\n<\/div> <!-- kcite-section 2120 -->","protected":false},"excerpt":{"rendered":"<p>Stereo-induction is, lets face it, a subtle phenomenon. The ratio of two stereoisomers formed in a reaction can be detected very accurately by experiment, and when converted to a free energy difference using \u0394G = -RT Ln K, this can amount to quite a small value (between 0.5 &#8211; 1.5 kcal\/mol). Can modelling reproduce effects [&hellip;]<\/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":[4],"tags":[575,239,240,238,41,2648,20],"ppma_author":[2661],"class_list":["post-2120","post","type-post","status-publish","format-standard","hentry","category-interesting-chemistry","tag-chiroptical","tag-energy-differences","tag-free-energy-difference","tag-hybridization","tag-interaction-energy","tag-interesting-chemistry","tag-steve-bachrach"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>The mysteries of stereoinduction. - Henry Rzepa&#039;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=2120\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"The mysteries of stereoinduction. - Henry Rzepa&#039;s Blog\" \/>\n<meta property=\"og:description\" content=\"Stereo-induction is, lets face it, a subtle phenomenon. The ratio of two stereoisomers formed in a reaction can be detected very accurately by experiment, and when converted to a free energy difference using \u0394G = -RT Ln K, this can amount to quite a small value (between 0.5 &#8211; 1.5 kcal\/mol). 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The ratio of two stereoisomers formed in a reaction can be detected very accurately by experiment, and when converted to a free energy difference using \u0394G = -RT Ln K, this can amount to quite a small value (between 0.5 &#8211; 1.5 kcal\/mol). Can modelling reproduce effects [&hellip;]","og_url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=2120","og_site_name":"Henry Rzepa&#039;s Blog","article_published_time":"2010-07-01T17:19:52+00:00","article_modified_time":"2011-07-07T06:05:08+00:00","og_image":[{"url":"http:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2010\/07\/norbornene.jpg","type":"","width":"","height":""}],"author":"Henry Rzepa","twitter_card":"summary_large_image","twitter_misc":{"Written by":"Henry Rzepa","Estimated reading time":"3 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=2120#article","isPartOf":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=2120"},"author":{"name":"Henry Rzepa","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#\/schema\/person\/2b40f7b9c872a4dc1547e040a11b6281"},"headline":"The mysteries of stereoinduction.","datePublished":"2010-07-01T17:19:52+00:00","dateModified":"2011-07-07T06:05:08+00:00","mainEntityOfPage":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=2120"},"wordCount":588,"commentCount":1,"image":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=2120#primaryimage"},"thumbnailUrl":"http:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2010\/07\/norbornene.jpg","keywords":["chiroptical","energy differences","free energy difference","hybridization","interaction energy","Interesting chemistry","Steve Bachrach"],"articleSection":["Interesting chemistry"],"inLanguage":"en-GB","potentialAction":[{"@type":"CommentAction","name":"Comment","target":["https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=2120#respond"]}]},{"@type":"WebPage","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=2120","url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=2120","name":"The mysteries of stereoinduction. - 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