{"id":7444,"date":"2012-08-07T06:23:59","date_gmt":"2012-08-07T05:23:59","guid":{"rendered":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=7444"},"modified":"2012-08-10T09:17:10","modified_gmt":"2012-08-10T08:17:10","slug":"the-stereochemical-origins-of-the-wittig-reaction","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=7444","title":{"rendered":"The stereochemical origins of the Wittig reaction."},"content":{"rendered":"
\n

This is another of those textbook reactions, involving reaction of a carbonyl compound with a phosphonium ylid to form an alkene and a phosphine oxide. The reaction continues to be frequently used, in part because it can be highly stereospecific.\u00a0<\/p>\n

\"\"<\/p>\n

Thus the standard version<\/a> tends to give Z<\/em>-alkenes with good specificity, and is thought to proceed via<\/em> an oxaphosphatane 4-ring intermediate. The reaction and its stereochemistry is sensitive to the reagent (including the nature of the R group), and so one model cannot capture all the aspects of this transform. Here I am starting with the very simple model shown above, where R=H (\u03c9B97XD\/6-311G(d,p)\/SCRF=tetrahydrofuran). There are four transition states to consider; whether the \u00a0rate-determining (stereochemical determining) step is TS1 or TS2, and whether the relative orientation of the two (in this example methyl) groups are syn<\/em> or anti<\/em>, resulting in E<\/em>– or Z<\/em>– alkenes. The most interesting issue would be whether the mechanism can account for why the apparently more sterically hindered route leading to the Z<\/em>-alkene is often the actual outcome.\u00a0<\/p>\n\n\n\n\n\n\n\n\n
Leading to E-alkene<\/th>\n<\/tr>\n
TS1 0.0<\/a> kcal\/mol<\/td>\nTS2 -3.9<\/a><\/td>\n<\/tr>\n
\"\"<\/td>\n\"\"<\/td>\n<\/tr>\n
Leading to Z-alkene<\/th>\n<\/tr>\n
TS1 0.0<\/a> kcal\/mol<\/td>\nTS2 -2.6<\/a><\/td>\n<\/tr>\n
\"\"<\/td>\n\"\"<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Key comments about these results:<\/p>\n

    \n
  1. TS1 is higher than TS2 in both cases, and so (for these substituents) is rate determining.<\/li>\n
  2. At this transition state, the two methyl groups are moving apart for the E<\/em>-isomer but together for the Z<\/em>-isomer. But at the transition states themselves, the steric interaction of these two groups is fairly similar, and the Z<\/em>-transition state has much better antiperiplanar bond alignments compensating for the methyl clash. To put it in a nutshell, the increased steric clash for formation of the Z<\/em>-isomer comes only AFTER the transition state is passed.
    \n\n\n\n\n
    E-alkene forming<\/th>\nZ-alkene forming<\/th>\n<\/tr>\n
    \"\"<\/td>\n\"\"<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/li>\n
  3. The gradients of the IRC profile for this step of the Wittig reveal that much of the action occurs after the transition state is passed, at IRC=3 for the E<\/em> and IRC=4 for Z<\/em>, this comprising rotation around the first formed C-C bond in order to create the P-O bond. This is where the steric clash of methyls for the Z<\/em>-isomer really kicks in, but it has no impact upon the energy of the transition state, coming too late for that.
    \n\n\n\n\n
    E-alkene forming<\/th>\nZ-alkene forming<\/th>\n<\/tr>\n
    \"\"<\/td>\n\"\"<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/li>\n
  4. The model we have built is sterically incomplete; we have used PH3<\/sub> rather than eg PPh3<\/sub> (done so as to allow an IRC to be computed in a reasonable time). If we look at the models above (click on the images to get a 3D model), then it is clear that the E<\/em>-transition state will suffer the greater steric clash of a methyl with one of the phenyl groups on the phosphorus than the Z<\/em>-isomer will. This probably accounts for why this latter isomer is the normal stereochemical outcome.<\/li>\n<\/ol>\n

    Much more could be done here, but even a fairly simple model of the Wittig reaction can bring a lot of insight into its unique characteristics.<\/p>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

    This is another of those textbook reactions, involving reaction of a carbonyl compound with a phosphonium ylid to form an alkene and a phosphine oxide. The reaction continues to be frequently used, in part because it can be highly stereospecific.\u00a0 Thus the standard version tends to give Z-alkenes with good specificity, and is thought to […]<\/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":[],"tags":[843,373,903],"ppma_author":[2661],"class_list":["post-7444","post","type-post","status-publish","format-standard","hentry","tag-reaction-mechanism","tag-tutorial-material","tag-wittig-reaction"],"yoast_head":"\nThe stereochemical origins of the Wittig reaction. - 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=7444\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"The stereochemical origins of the Wittig reaction. - Henry Rzepa's Blog\" \/>\n<meta property=\"og:description\" content=\"This is another of those textbook reactions, involving reaction of a carbonyl compound with a phosphonium ylid to form an alkene and a phosphine oxide. 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It is always neat to conjure up a simple switch\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":12810,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=12810","url_meta":{"origin":7444,"position":3},"title":"Using a polar bond to flip: a follow up project.","author":"Henry Rzepa","date":"August 6, 2014","format":false,"excerpt":"In my earlier post on the topic, I discussed how inverting the polarity of the C-X bond from X=O to X=Be could flip the stereochemical course of the electrocyclic pericyclic reaction of a divinyl system. An obvious question would be: what happens at the half way stage, ie X=CH2? Well,\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":23319,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=23319","url_meta":{"origin":7444,"position":4},"title":"The thermal reactions \u2026 took precisely the opposite stereochemical course to that which we had predicted. A non-covalent-interaction view of the model.","author":"Henry Rzepa","date":"February 3, 2021","format":false,"excerpt":"Another foray into one of the more famous anecdotal chemistry \"models\", the analysis of which led directly to the formulation of the WoodWard-Hoffmann (stereochemical) rules for pericyclic reactions. Previously, I tried to produce a modern computer model of what Woodward might have had to hand when discovering that the stereochemical\u2026","rel":"","context":"In "Historical"","block_context":{"text":"Historical","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=565"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/02\/yes.jpg?resize=350%2C200&ssl=1","width":350,"height":200},"classes":[]},{"id":5716,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=5716","url_meta":{"origin":7444,"position":5},"title":"A modern take on pericyclic sigmatropic migrations.","author":"Henry Rzepa","date":"November 29, 2011","format":false,"excerpt":"Another common type of pericyclic reaction is the migration of hydrogen or carbon along a conjugated chain, as in the [1,3] migration of a carbon as shown below. As before, I explore the stereochemistry of the thermal and photochemical reactions. 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