{"id":8588,"date":"2012-12-09T08:56:23","date_gmt":"2012-12-09T08:56:23","guid":{"rendered":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=8588"},"modified":"2012-12-09T08:56:23","modified_gmt":"2012-12-09T08:56:23","slug":"why-is-the-sharpless-epoxidation-enantioselective-part-1-a-simple-model","status":"publish","type":"post","link":"https:\/\/www.rzepa.net\/blog\/?p=8588","title":{"rendered":"Why is the Sharpless epoxidation enantioselective? Part 1: a simple model."},"content":{"rendered":"
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Sharpless epoxidation converts a prochiral allylic alcohol into the corresponding chiral epoxide with > 90% enantiomeric excess[1]<\/a><\/span>,[2]<\/a><\/span>. Here is the first step in trying to explain how this magic is achieved.<\/p>\n

\"\"<\/p>\n

The scheme above shows how (achiral) prop-2-enol is converted using the asymmetric catalyst\u00a0(R,R)-diethyl tartrate \u00a0and t<\/em>-butyl hydroperoxide as oxidant into the (S)-chiral epoxide. The first step is to try to construct a simple model for the reaction, and in this post I will start by using one titanium as the core of the stage on which these actors will perform. This is the\u00a0mononuclear model<\/strong><\/em>\u2020<\/sup>. One can simply envisage that a molecule of tartrate displaces two i<\/sup>PrOH molecules from Ti(Oi<\/sup>Pr)4<\/sub> in an ester exchange to form a Ti(Oi<\/sup>Pr)2<\/sub>(tartrate) complex. The remaining two iso-propanols\u00a0are then replaced by one molecule each of prop-2-enol and\u00a0t<\/sup>Bu-OOH. Now we have the species Ti(OOt<\/sup>Bu)(O-CH2<\/sub>CH=CH2<\/sub>)(tartrate) as the starting point from which a transition state for oxygen transfer to the alkene to form the (S) epoxide (for R,R tartrate) can be constructed\u00a0(\u03c9B97XD\/6-311G(d,p)\/SCRF=dichloromethane model).<\/p>\n\n\n\n\n\n
\n
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Mononuclear TS for S-epoxide. Click for 3D.<\/p><\/div>\n<\/td>\n

\n
\"\"

Mononuclear TS for R-epoxide. Click for 3D.<\/p><\/div>\n<\/td>\n<\/tr>\n

IRC for mononuclear model showing oxygen atom transfer<\/span><\/th>\n<\/tr>\n
\"\"<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

The transition state leading to (S)<\/a> epoxide emerges as 0.86 kcal\/mol higher in \u0394G\u2021<\/sup> than the (R)<\/a>, contrary to the experimental result where (S) is formed with high specificity[1]<\/a><\/span>. Inspecting the model, it is clear that the allylic alcohol substrate sits in a very open pocket un-encumbered by any nearby groups (bottom right in the animation above) and so the lack of \u03c0-facial selectivity is perhaps not surprising.<\/p>\n

To elaborate the model, I will turn to a crystal structure determined for a Ti complex bearing a t<\/em>-butyl peroxy group[3]<\/a><\/span>, showing it to be a binuclear complex\u00b6<\/sup> (magenta arrows indicate the peroxy groups)\u00a0with bridging oxygen atoms.\u2021<\/sup><\/p>\n

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ZUKJIY. Click for 3D<\/p><\/div>\n

In the follow-up post, \u00a0we will see whether these binuclear models can do better at explaining the enantioselectivity of the Sharpless reaction.<\/p>\n

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\u2020<\/sup> See this post<\/a> for an example of such “single-site” catalysis using Mg or this article for an example using silver[4]<\/a><\/span>.<\/p>\n

\u00b6<\/sup>A binuclear Zn catalyst with similar oxy-bridges is used to co-polymerise epoxides themselves with carbon dioxide[5]<\/a><\/span>. Many such binuclear complexes are known.<\/p>\n

\u2021<\/sup> The other element for which a number of examples of such t<\/em>-butyl peroxy bonding are known is oddly enough, lithium.[6]<\/a><\/span><\/p>\n

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MUKVAQ. Click for 3D.<\/p><\/div>\n

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Postscript:<\/strong> Two lower energy conformations for the S<\/a> and R<\/a> transition states have been found, the latter being 1.6 kcal\/mol lower in free energy.\u00a0<\/p>\n\n\n\n\n
S<\/th>\nR<\/th>\n<\/tr>\n
\"S-new\"<\/td>\n\"R-new\"<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

References<\/h2>\n
  1. J.M. Klunder, S.Y. Ko, and K.B. Sharpless, \"Asymmetric epoxidation of allyl alcohol: efficient routes to homochiral .beta.-adrenergic blocking agents\", The Journal of Organic Chemistry<\/i>, vol. 51, pp. 3710-3712, 1986. https:\/\/doi.org\/10.1021\/jo00369a032<\/a>\n\n<\/li>\n
  2. R.M. Hanson, and K.B. Sharpless, \"Procedure for the catalytic asymmetric epoxidation of allylic alcohols in the presence of molecular sieves\", The Journal of Organic Chemistry<\/i>, vol. 51, pp. 1922-1925, 1986. https:\/\/doi.org\/10.1021\/jo00360a058<\/a>\n\n<\/li>\n
  3. G. Boche, K. M\u00f6bus, K. Harms, and M. Marsch, \"[((\u03b7<sup>2<\/sup>-<i>tert<\/i>-Butylperoxo)titanatrane)<sub>2<\/sub>\u00b7 3 Dichloromethane]:\u2009 X-ray Crystal Structure and Oxidation Reactions\", Journal of the American Chemical Society<\/i>, vol. 118, pp. 2770-2771, 1996. https:\/\/doi.org\/10.1021\/ja954308f<\/a>\n\n<\/li>\n
  4. 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
  5. A. Buchard, F. Jutz, M.R. Kember, A.J.P. White, H.S. Rzepa, and C.K. Williams, \"Experimental and Computational Investigation of the Mechanism of Carbon Dioxide\/Cyclohexene Oxide Copolymerization Using a Dizinc Catalyst\", Macromolecules<\/i>, vol. 45, pp. 6781-6795, 2012. https:\/\/doi.org\/10.1021\/ma300803b<\/a>\n\n<\/li>\n
  6. W. Uhl, M. Reza\u2005Halvagar, and M. Claesener, \"Reducing Ga\uf8ffH and Ga\uf8ffC Bonds in Close Proximity to Oxidizing Peroxo Groups: Conflicting Properties in Single Molecules\", Chemistry \u2013 A European Journal<\/i>, vol. 15, pp. 11298-11306, 2009. https:\/\/doi.org\/10.1002\/chem.200900746<\/a>\n\n<\/li>\n<\/ol>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

    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 into the (S)-chiral epoxide. The […]<\/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":[6],"tags":[32,950,1139,957,164,973,1530,1527],"class_list":["post-8588","post","type-post","status-publish","format-standard","hentry","category-interesting-chemistry","tag-animation","tag-asymmetric-epoxidation","tag-catalysis","tag-enantioselective","tag-free-energy","tag-lower-energy-conformations","tag-reaction-mechanism","tag-tutorial-material"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p1gPyz-2ew","jetpack_likes_enabled":true,"_links":{"self":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts\/8588","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=8588"}],"version-history":[{"count":0,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts\/8588\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=8588"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=8588"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=8588"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}