{"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":"2012-08-07T06:23:59","modified_gmt":"2012-08-07T05:23:59","slug":"the-stereochemical-origins-of-the-wittig-reaction","status":"publish","type":"post","link":"https:\/\/www.rzepa.net\/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,"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}},"categories":[1],"tags":[1530,1527,902],"class_list":["post-7444","post","type-post","status-publish","format-standard","hentry","category-uncategorized","tag-reaction-mechanism","tag-tutorial-material","tag-wittig-reaction"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p1gPyz-1W4","jetpack_likes_enabled":true,"_links":{"self":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts\/7444","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=7444"}],"version-history":[{"count":0,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts\/7444\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=7444"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=7444"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=7444"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}