biostudies-literatureNguyen THCenter for Selective C-H Functionalization, National Science FoundationLilly Research Award Program28098-28106https://www.ebi.ac.uk/biostudies/studies/S-EPMC12333343biostudies-literatureUnknown147(31)Dirhodium tetracarboxylate-catalyzed reaction of aryldiazoacetates with <i>N</i>-Boc-2,5-dihydro-1<i>H</i>-pyrrole results in a highly enantio- and diastereoselective C-H functionalization exclusively at the α-<i>N</i> C2 position. This result is a sharp contrast to the reaction with ethyl diazoacetate, which results in cyclopropanation of the olefinic site. Rh₂(<i>S</i>- or <i>R</i>-PTAD)₄ is the optimal chiral catalyst and is capable of generating the C-H functionalization products in up to 87% yield with high levels of diastereoselectivity (>20:1 d.r.) and enantioselectivity (97% ee) with a low catalyst loading (0.05 mol %). Computational studies were conducted to rationalize the reactivity difference between donor/acceptor carbenes and acceptor carbenes. The utiliJournal of the American Chemical SocietyAsymmetric C-H Functionalization of &lt;i&gt;N&lt;/i&gt;-Boc-2,5-dihydro-1&lt;i&gt;H&lt;/i&gt;-pyrrole and Its Application as a Key Step in the Synthesis of (-)-Dragocin D.PMC12333343CHE-1700982Shimabukuro KDavies HMLNguyen THBacsa JMusaev DGNavarro AfalseAsymmetric C-H Functionalization of &lt;i&gt;N&lt;/i&gt;-Boc-2,5-dihydro-1&lt;i&gt;H&lt;/i&gt;-pyrrole and Its Application as a Key Step in the Synthesis of (-)-Dragocin D.Dirhodium tetracarboxylate-catalyzed reaction of aryldiazoacetates with <i>N</i>-Boc-2,5-dihydro-1<i>H</i>-pyrrole results in a highly enantio- and diastereoselective C-H functionalization exclusively at the α-<i>N</i> C2 position. This result is a sharp contrast to the reaction with ethyl diazoacetate, which results in cyclopropanation of the olefinic site. Rh₂(<i>S</i>- or <i>R</i>-PTAD)₄ is the optimal chiral catalyst and is capable of generating the C-H functionalization products in up to 87% yield with high levels of diastereoselectivity (>20:1 d.r.) and enantioselectivity (97% ee) with a low catalyst loading (0.05 mol %). Computational studies were conducted to rationalize the reactivity difference between donor/acceptor carbenes and acceptor carbenes. The utili2025-01-01T00:00:00Z2025 Aug2026-04-15T19:11:15.521Z2026-04-07T14:01:01.906ZS-EPMC123333434072190310.1021/jacs.5c08080