@article{66ed5159408849caa4987bb41c2044a6,
title = "Synthesis of Bridged Bicyclic Amines by Intramolecular Amination of Remote C-H Bonds: Synergistic Activation by Light and Heat",
abstract = "The construction of complex aza-cycles is of interest to drug discovery due to the prevalence of nitrogen-containing heterocycles in pharmaceutical agents. Herein we report an intramolecular C-H amination approach to afford value-added and complexity-enriched bridged bicyclic amines. Guided by density functional theory and nuclear magnetic resonance investigations, we determined the unique roles of light and heat activation in the bicyclization mechanism. We applied both light and heat activation in a synergistic fashion, achieving gram-scale bridged aza-cycle synthesis.",
author = "Lux, {Michaelyn C.} and Justin Jurczyk and Lam, {Yu Hong} and Song, {Zhiguo J.} and Chao Ma and Roque, {Jose B.} and Ham, {Jin Su} and Nunzio Sciammetta and Donovon Adpressa and Richmond Sarpong and Yeung, {Charles S.}",
note = "Funding Information: This Letter is dedicated to the memory of Professor Kilian Mu{\~n}iz. We thank the Disruptive Chemistry Fellowship program of Merck & Co., Inc., Kenilworth, NJ, USA for the generous support of C.S.Y. and the work disclosed in this manuscript. We thank the Postdoctoral Research Program of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. for its generous support of M.C.L. and the work disclosed in this manuscript. We thank core team members Shane W. Krska, Daniel DiRocco, Thomas W. Lyons, Dan Lenherr, Louis-Charles Campeau, Alan Northrup, and Nicholas K. Terrett and sponsors Emma R. Parmee and Michael H. Kress for the support of Disruptive Chemistry (Merck & Co., Inc.). We thank Emma Edelstein, Tony Siu, Ethan Wappes, Shane Krska (Merck & Co., Inc.) and Adam Trotta (Harvard) for the review of this manuscript. We thank Josep Saur{\'i} and Eugene Kwan for the NMR structure elucidation and Yuan Jiang, Taylor Johnson, Rosina Ayore, and Wilfredo Pinto for the HRMS data (Merck & Co., Inc.). We thank Lisa M. Nogle, David A. Smith, Adam Beard, Miroslawa Darlak, and Mark Pietrafitta for reversed-phase purifications (Merck & Co., Inc.). We thank Jiaoyan Zhang and Jun Zhang for experimental assistance (WuXi AppTec). We thank Jingjun Yin for the support of External Discovery Process Chemistry (Merck & Co., Inc.). R.S. is grateful to the NSF under the CCI Center for Selective C–H functionalization (CHE-1700982) for partial support of the work reported herein (Berkeley). J.B.R. is grateful for a BMS graduate fellowship, and J.S.H. is grateful to SKI Innovation for the support of his graduate studies (Berkeley). Publisher Copyright: Copyright {\textcopyright} 2020 American Chemical Society.",
year = "2020",
month = aug,
day = "21",
doi = "10.1021/acs.orglett.0c02345",
language = "English (US)",
volume = "22",
pages = "6578--6583",
journal = "Organic letters",
issn = "1523-7060",
publisher = "American Chemical Society",
number = "16",
}