Schreiber, S. L. Target-oriented and diversity-oriented organic synthesis in drug discovery. Science 287, 1964–1969 (2000).

Article  CAS  PubMed  Google Scholar 

Campos, K. R. et al. The importance of synthetic chemistry in the pharmaceutical industry. Science 363, eaat0805 (2019).

Article  CAS  PubMed  Google Scholar 

Blakemore, D. C. et al. Organic synthesis provides opportunities to transform drug discovery. Nat. Chem. 10, 383–394 (2018).

Article  CAS  PubMed  Google Scholar 

Cernak, T., Dykstra, K. D., Tyagarajan, S., Vachal, P. & Krska, S. W. The medicinal chemist’s toolbox for late stage functionalization of drug-like molecules. Chem. Soc. Rev. 45, 546–576 (2016).

Article  CAS  PubMed  Google Scholar 

Jurczyk, J. et al. Single-atom logic for heterocycle editing. Nat. Synth. 1, 352–364 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Szpilman, A. M. & Carreira, E. M. Probing the biology of natural products: molecular editing by diverted total synthesis. Angew. Chem. Int. Ed. 49, 9592–9628 (2010).

Article  CAS  Google Scholar 

Vitaku, E., Smith, D. T. & Njardarson, J. T. Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among US FDA approved pharmaceuticals. J. Med. Chem. 57, 10257–10274 (2014).

Article  CAS  PubMed  Google Scholar 

Campos, K. R. Direct sp3 C–H bond activation adjacent to nitrogen in heterocycles. Chem. Soc. Rev. 36, 1069–1084 (2007).

Article  CAS  PubMed  Google Scholar 

Feng, K. et al. Late-stage oxidative C(sp3)–H methylation. Nature 580, 621–627 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jain, P., Verma, P., Xia, G. & Yu, J.-Q. Enantioselective amine α-functionalization via palladium-catalysed C–H arylation of thioamides. Nat. Chem. 9, 140–144 (2017).

Article  CAS  PubMed  Google Scholar 

Topczewski, J. T., Cabrera, P. J., Saper, N. I. & Sanford, M. S. Palladium-catalysed transannular C–H functionalization of alicyclic amines. Nature 531, 220–224 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lin, W., Zhang, K.-F. & Baudoin, O. Regiodivergent enantioselective C–H functionalization of Boc-1,3-oxazinanes for the synthesis of β2- and β3-amino acids. Nat. Catal. 2, 882–888 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen, W., Paul, A., Abboud, K. A. & Seidel, D. Rapid functionalization of multiple C–H bonds in unprotected alicyclic amines. Nat. Chem. 12, 545–550 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sarver, P. J. et al. The merger of decatungstate and copper catalysis to enable aliphatic C(sp3)–H trifluoromethylation. Nat. Chem. 12, 459–467 (2020).

Article  CAS  PubMed  Google Scholar 

Oeschger, R. et al. Diverse functionalization of strong alkyl C–H bonds by undirected borylation. Science 368, 736–741 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fan, Z. et al. Molecular editing of aza-arene C–H bonds by distance, geometry and chirality. Nature 610, 87–93 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Roque, J. B., Kuroda, Y., Göttemann, L. T. & Sarpong, R. Deconstructive fluorination of cyclic amines by carbon–carbon cleavage. Science 361, 171–174 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Roque, J. B., Kuroda, Y., Göttemann, L. T. & Sarpong, R. Deconstructive diversification of cyclic amines. Nature 564, 244–248 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kennedy, S. H., Dherange, B. D., Berger, K. J. & Levin, M. D. Skeletal editing through direct nitrogen deletion of secondary amines. Nature 593, 223–227 (2021).

Article  CAS  PubMed  Google Scholar 

Jurczyk, J. et al. Photomediated ring contraction of saturated heterocycles. Science 373, 1004–1012 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wright, B. A. et al. Skeletal editing approach to bridge-functionalized bicyclo[1.1.1]pentanes from azabicyclo[2.1.1]hexanes. J. Am. Chem. Soc. 145, 10960–10966 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Woo, J. et al. Scaffold hopping by net photochemical carbon deletion of azaarenes. Science 376, 527–532 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dherange, B. D., Kelly, P. Q., Liles, J. P., Sigman, M. S. & Levin, M. D. Carbon atom insertion into pyrroles and indoles promoted by chlorodiazirines. J. Am. Chem. Soc. 143, 11337–11344 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hyland, E. E., Kelly, P. Q., McKillop, A. M., Dherange, B. D. & Levin, M. D. Unified access to pyrimidines and quinazolines enabled by N–N cleaving carbon atom insertion. J. Am. Chem. Soc. 144, 19258–19264 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Reisenbauer, J. C., Green, O., Franchino, A., Finkelstein, P. & Morandi, B. Late-stage diversification of indole skeletons through nitrogen atom insertion. Science 377, 1104–1109 (2022).

Article  CAS  PubMed  Google Scholar 

Lyu, H., Kevlishvili, I., Yu, X., Liu, P. & Dong, G. Boron insertion into alkyl ether bonds via zinc/nickel tandem catalysis. Science 372, 175–182 (2021).

Article  CAS  PubMed  Google Scholar 

Feng, Q., Wang, Q. & Zhu, J. Oxidative rearrangement of 1,1-disubstituted alkenes to ketones. Science 379, 1363–1368 (2023).

Article  CAS  PubMed  Google Scholar 

Wang, H. et al. Dearomative ring expansion of thiophenes by bicyclobutane insertion. Science 381, 75–81 (2023).

Article  CAS  PubMed  Google Scholar 

Ouyang, K., Hao, W., Zhang, W.-X. & Xi, Z. Transition-metal-catalyzed cleavage of C–N single bonds. Chem. Rev. 115, 12045–12090 (2015).

Article  CAS  PubMed  Google Scholar 

Huang, C.-Y. & Doyle, A. G. The chemistry of transition metals with three-membered ring heterocycles. Chem. Rev. 114, 8153–8198 (2014).

Article  CAS  PubMed  Google Scholar 

Donald, J. R. & Unsworth, W. P. Ring-expansion reactions in the synthesis of macrocycles and medium-sized rings. Chemistry 23, 8780–8799 (2017).