{"id":16361,"date":"2016-05-11T13:00:50","date_gmt":"2016-05-11T12:00:50","guid":{"rendered":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=16361"},"modified":"2016-05-11T13:00:50","modified_gmt":"2016-05-11T12:00:50","slug":"what-is-the-approach-trajectory-of-enhanced-super-nucleophiles-towards-a-carbonyl-group","status":"publish","type":"post","link":"https:\/\/www.rzepa.net\/blog\/?p=16361","title":{"rendered":"What is the approach trajectory of enhanced (super?) nucleophiles towards a carbonyl group?"},"content":{"rendered":"
\n

\n\tI have previously commented<\/a> on the Bürgi–Dunitz angle, this being the preferred approach trajectory of a nucleophile towards the electrophilic carbon of a carbonyl group. Some special types of nucleophile such as hydrazines (R2<\/sub>N-NR2<\/sub>) are supposed to have enhanced reactivity[1]<\/a><\/span> due to what might be described as buttressing of adjacent lone pairs. Here I focus in on how this might manifest by performing searches of the Cambridge structural database for intermolecular (non-bonded) interactions between X-Y nucleophiles (X,Y= N,O,S) and carbonyl compounds OC(NM)2<\/sub>.\n<\/p>\n

\n\t\"\"\n<\/p>\n

\n\tThe search query[2]<\/a><\/span> is shown above and involves plotting the distance from the nucleophilic atom (N above) to the carbon of the carbonyl group. The carbon is defined as having 3-coordination, one of which is O=C and two non-metal attachments. The torsion is constrained to values of |70-110|° to ensure that the approach of the nucleophile is approximately perpendicular to the plane of the carbonyl in order to overlap with the π*-orbital as electrophile. The pairwise sums of van der Waals radii are NC, 3.25; OC, 3.22 and SC, 3.5Å and the plots show all contacts shorter than these. The results of the searches are shown below.\n<\/p>\n

\n\t\"\"\n<\/p>\n

\n\t\"\"\n<\/p>\n

\n\t\"\"\n<\/p>\n

\n\tThe general observation is that the red hotspots do tend to come at trajectory angles of <100° and many are <90° such as the X=Y=N or X=Y=S examples. Given that the original Bürgi–Dunitz hypothesis (actually based on a small number of molecules synthesized for the purpose) proposed rather larger angles (105±5°) corresponding to optimum alignment of the nucleophile with the carbonyl π*-orbital, we might speculate whether the use of enhanced nucleophiles is the reason for the apparent decrease in the angle. And if so, what the underlying reasons would be.\n<\/p>\n

\n\tI also cannot help but observe that the term supernucleophile<\/strong><\/span> is quite rare in the literature; SciFinder gives only 45 hits, but most are about neither hydrazines nor peroxides. There are also some unusual nucleophile varieties such as Cob(I)alamin[3]<\/a><\/span>, of which there are probably insufficient examples to reflect in the crystal structure statistics shown above. Given the interest in superbases<\/a>, the relative lack of examples of unusual supernucleophiles seems surprising.<\/p>\n

References<\/h2>\n
  1. G. Klopman, K. Tsuda, J. Louis, and R. Davis, \"Supernucleophiles\u2014I\", Tetrahedron<\/i>, vol. 26, pp. 4549-4554, 1970. https:\/\/doi.org\/10.1016\/s0040-4020(01)93101-1<\/a>\n\n<\/li>\n
  2. H. Rzepa, \"Crystal structure search using enhanced nucleophiles\", 2016. https:\/\/doi.org\/10.14469\/hpc\/487<\/a>\n\n<\/li>\n
  3. K.P. Jensen, \"Electronic Structure of Cob(I)alamin:\u2009 The Story of an Unusual Nucleophile\", The Journal of Physical Chemistry B<\/i>, vol. 109, pp. 10505-10512, 2005. https:\/\/doi.org\/10.1021\/jp050802m<\/a>\n\n<\/li>\n<\/ol>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

    I have previously commented on the Bürgi–Dunitz angle, this being the preferred approach trajectory of a nucleophile towards the electrophilic carbon of a carbonyl group. Some special types of nucleophile such as hydrazines (R2N-NR2) are supposed to have enhanced reactivity due to what might be described as buttressing of adjacent lone pairs. Here I focus in on […]<\/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":[3,1754],"tags":[1622,1404,1413,1441,1788,1790,1453,194,1812,1813,1497,733,1841],"class_list":["post-16361","post","type-post","status-publish","format-standard","hentry","category-chemical-it","category-crystal_structure_mining","tag-bases","tag-burgi-dunitz-angle","tag-carbonyl","tag-electrophile","tag-ester","tag-flippin-lodge-angle","tag-functional-groups","tag-hydrazine","tag-non-metal-attachments","tag-nucleophile","tag-physical-organic-chemistry","tag-search-query","tag-superbase"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p1gPyz-4fT","jetpack_likes_enabled":true,"_links":{"self":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts\/16361","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=16361"}],"version-history":[{"count":0,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts\/16361\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=16361"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=16361"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=16361"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}