The reaction discovery was serendipitous, says University at Buffalo\u2019s Patricia Z. Musacchio<\/a>, who led the research effort with Binghamton University\u2019s Jennifer S. Hirschi<\/a>. The origins of the discovery came when Mrinmoy Das, a postdoctoral researcher in Musacchio\u2019s lab, found an unexpected difunctionalized product while running a photoredox-triggered hydrogen-atom transfer reaction.<\/p>\n \u201cAt first I wasn\u2019t very excited about it,\u201d Musacchio says. She thought it was just a riff on some chemistry they\u2019d already published. But Das went back to the lab and proved to her that the disubstituted product was coming from one central mechanistic intermediate, instead of being produced by two distinct reactions occurring back-to-back in the reaction vial. This piqued Musacchio\u2019s interest, and she reached out to Hirschi to help figure out the mechanism.<\/p>\n The simplest explanation was that the reaction was a substitution reaction going through a halonium intermediate. \u201cBut none of those were working on a computational surface,\u201d Hirschi says.<\/p>\n Instead, computational studies from Hirschi\u2019s group indicate that a concerted reaction takes place. When the hydrogen-atom transfer occurs, the homobenzylic halide undergoes heterolytic cleavage to generate a styrene radical cation, in what\u2019s called a spin-center shift process. A nucleophile can then attack the cation portion, leaving behind a benzylic radical that gets oxidized to a benzylic carbocation, which then reacts with another nucleophile.<\/p>\n “I think this is just a really cool way to redefine how people are using alkyl halides in synthesis.”<\/p>\n Patricia Z. Musacchio, Assistant professor, University at Buffalo<\/p>\n Share The cosolvent 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) plays a key role in pulling the halide off. Organic chemists talk about HFIP having a sort of magical quality, Musacchio says. \u201cYou just throw it in, and you get something very different from the standard sweep of solvents.\u201d<\/p>\n If the chemists use certain reaction partners, they can isolate benzylic bromide and chloride compounds where the halide has shuttled from the homobenzylic position to the benzylic position.<\/p>\n Zachary K. Wickens<\/a>, a synthetic organic chemist at the University of Wisconsin\u2013Madison, says in an email, \u201cIt\u2019s rare that we find a way to take a classic reaction like substitution of an alkyl halide and totally reinvent it. But that\u2019s exactly what the authors report here.\u201d<\/p>\n Wickens points out that substitution of an alkyl halide is typically a straightforward functional group interconversion. But Musacchio and Hirschi\u2019s work shows a way to shuttle the halide over by a carbon rather than displacing it from the molecule. \u201cThis gives us super versatile building blocks since the halide product can then be substituted by a distinct second nucleophile,\u201d he says.<\/p>\n\n
\n <\/a><\/p>\n<\/blockquote>\n
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<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"\u00a0 Harken back to your early days in organic chemistry class and you\u2019ll recall learning how SN1 and…\n","protected":false},"author":2,"featured_media":578940,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":"","_share_on_mastodon":"0"},"categories":[77],"tags":[246305,18,246307,246304,19,17,133,246306,74313],"class_list":["post-578939","post","type-post","status-publish","format-standard","has-post-thumbnail","category-science","tag-alkene-radical-cation","tag-eire","tag-electrophilic-shuttling","tag-hydrogen-atom-transfer","tag-ie","tag-ireland","tag-science","tag-spin-center-shift","tag-synthesis"],"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@ie\/116896712441745244","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/578939","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/comments?post=578939"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/578939\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media\/578940"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media?parent=578939"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/categories?post=578939"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/tags?post=578939"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}