Enantioselective alkene hydroalkylation overcoming heteroatom constraints via cobalt catalysis

Golden, D. L., Suh, S.-E. & Stahl, S. S. Radical C(sp3)–H functionalization and cross-coupling reactions. Nat. Rev. Chem. 6, 405–427 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Lovering, F., Bikker, J. & Humblet, C. Escape from flatland: increasing saturation as an approach to improving clinical success. J. Med. Chem. 52, 6752–6756 (2009).Article 
CAS 
PubMed 

Google Scholar 
Talele, T. T. Opportunities for tapping into three-dimensional chemical space through a quaternary carbon. J. Med. Chem. 63, 13291–13315 (2020).Article 
CAS 
PubMed 

Google Scholar 
Chen, C. Designing catalysts for olefin polymerization and copolymerization: beyond electronic and steric tuning. Nat. Rev. Chem. 2, 6–14 (2018).Article 
CAS 

Google Scholar 
Geist, E., Kirschning, A. & Schmidt, T. sp3–sp3 coupling reactions in the synthesis of natural products and biologically active molecules. Nat. Prod. Rep. 31, 441–448 (2014).Article 
CAS 
PubMed 

Google Scholar 
Choi, J. & Fu, G. C. Transition metal-catalyzed alkyl–alkyl bond formation: another dimension in cross-coupling chemistry. Science 356, eaaf7230 (2017).Article 
PubMed 
PubMed Central 

Google Scholar 
Yan, M., Lo, J. C., Edwards, J. T. & Baran, P. S. Radicals: reactive intermediates with translational potential. J. Am. Chem. Soc. 138, 12692–12714 (2016).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Chen, C. & Fu, G. C. Copper-catalysed enantioconvergent alkylation of oxygen nucleophiles. Nature 618, 301–307 (2023).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Chen, J.-J. et al. Enantioconvergent Cu-catalysed N-alkylation of aliphatic amines. Nature 618, 294–300 (2023).Article 
CAS 
PubMed 

Google Scholar 
Giese, B. & Lachhein, S. Steric effects in the addition of alkyl radicals to alkenes. Angew. Chem. Int. Ed. 20, 967 (1981).Article 

Google Scholar 
Giese, B. Formation of CC bonds by addition of free radicals to alkenes. Angew. Chem. Int. Ed. 22, 753–764 (1983).Article 

Google Scholar 
Sibi, M. P. & Porter, N. A. Enantioselective free radical reactions. Acc. Chem. Res. 32, 163–171 (1999).Article 
CAS 

Google Scholar 
Nagib, D. A. Asymmetric catalysis in radical chemistry. Chem. Rev. 122, 15989–15992 (2022).Article 
CAS 
PubMed 

Google Scholar 
Sibi, M. P. et al. Chiral Lewis acid catalysis in radical reactions: enantioselective conjugate radical additions. J. Am. Chem. Soc. 118, 9200–9201 (1996).Article 
CAS 

Google Scholar 
Kern, N., Plesniak, M. P., McDouall, J. J. W. & Procter, D. J. Enantioselective cyclizations and cyclization cascades of samarium ketyl radicals. Nat. Chem. 9, 1198–1204 (2017).Article 
CAS 
PubMed 

Google Scholar 
Zhang, K. et al. Exploration of a chiral cobalt catalyst for visible-light-induced enantioselective radical conjugate addition. Angew. Chem. Int. Ed. 58, 13375–13379 (2019).Article 
CAS 

Google Scholar 
Bauer, A., Westkämper, F., Grimme, S. & Bach, T. Catalytic enantioselective reactions driven by photoinduced electron transfer. Nature 436, 1139–1140 (2005).Article 
CAS 
PubMed 

Google Scholar 
Murphy, J. J. et al. Asymmetric catalytic formation of quaternary carbons by iminium ion trapping of radicals. Nature 532, 218–222 (2016).Article 
CAS 
PubMed 

Google Scholar 
Xu, X. et al. Highly asymmetric intramolecular cyclopropanation of acceptor-substituted diazoacetates by Co(II)-based metalloradical catalysis: iterative approach for development of new-generation catalysts. J. Am. Chem. Soc. 133, 15292–15295 (2011).Article 
CAS 
PubMed 

Google Scholar 
Fu, G. C. Transition-metal catalysis of nucleophilic substitution reactions: a radical alternative to SN1 and SN2 processes. ACS Cent. Sci. 3, 692–700 (2017).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Gu, Q.-S., Li, Z.-L. & Liu, X.-Y. Copper(I)-catalyzed asymmetric reactions involving radicals. Acc. Chem. Res. 53, 170–181 (2020).Article 
CAS 
PubMed 

Google Scholar 
Sibi, M. P., Manyem, S. & Zimmerman, J. Enantioselective radical processes. Chem. Rev. 103, 3263–3296 (2003).Article 
CAS 
PubMed 

Google Scholar 
Xiong, T. & Zhang, Q. Recent advances in the direct construction of enantioenriched stereocenters through addition of radicals to internal alkenes. Chem. Soc. Rev. 50, 8857–8873 (2021).Article 
CAS 
PubMed 

Google Scholar 
Biegasiewicz, K. F. et al. Photoexcitation of flavoenzymes enables a stereoselective radical cyclization. Science 364, 1166–1169 (2019).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Ye, Y. et al. Using enzymes to tame nitrogen-centred radicals for enantioselective hydroamination. Nat. Chem. 15, 206–212 (2023).Article 
CAS 
PubMed 

Google Scholar 
Zhang, Z. et al. Photoenzymatic enantioselective intermolecular radical hydroamination. Nat. Catal. 6, 687–694 (2023).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Zhao, B. et al. Direct visible-light-excited flavoproteins for redox-neutral asymmetric radical hydroarylation. Nat. Catal. 6, 996–1004 (2023).Article 
CAS 

Google Scholar 
Xu, Y. et al. A light-driven enzymatic enantioselective radical acylation. Nature 625, 74–78 (2024).Article 
CAS 
PubMed 

Google Scholar 
Shi, Q. et al. Single-electron oxidation-initiated enantioselective hydrosulfonylation of olefins enabled by photoenzymatic catalysis. J. Am. Chem. Soc. 146, 2748–2756 (2024).Article 
CAS 
PubMed 

Google Scholar 
Huang, X. et al. Photoenzymatic enantioselective intermolecular radical hydroalkylation. Nature 584, 69–74 (2020).Article 
CAS 
PubMed 

Google Scholar 
Huang, X. et al. Photoinduced chemomimetic biocatalysis for enantioselective intermolecular radical conjugate addition. Nat. Catal. 5, 586–593 (2022).Article 
CAS 

Google Scholar 
Sun, S.-Z. et al. Enantioselective decarboxylative alkylation using synergistic photoenzymatic catalysis. Nat. Catal. 7, 35–42 (2024).Article 
CAS 

Google Scholar 
Li, Y. et al. Cobalt-catalysed enantioselective C(sp3)–C(sp3) coupling. Nat. Catal. 4, 901–911 (2021).Article 
CAS 

Google Scholar 
Zhang, Z.-L. et al. Cobalt-catalyzed facial-selective hydroalkylation of cyclopropenes. Angew. Chem. Int. Ed. 62, e202306381 (2023).Article 
CAS 

Google Scholar 
Li, Z. et al. Ligand-controlled cobalt-catalyzed regio-, enantio-, and diastereoselective oxyheterocyclic alkene hydroalkylation. J. Am. Chem. Soc. 146, 3405–3415 (2024).Article 
CAS 
PubMed 

Google Scholar 
Wang, Z., Yin, H. & Fu, G. C. Catalytic enantioconvergent coupling of secondary and tertiary electrophiles with olefins. Nature 563, 379–383 (2018).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Bera, S., Mao, R. & Hu, X. Enantioselective C(sp3)–C(sp3) cross-coupling of non-activated alkyl electrophiles via nickel hydride catalysis. Nat. Chem. 13, 270–277 (2021).Article 
CAS 
PubMed 

Google Scholar 
Wang, J.-W. et al. Catalytic asymmetric reductive hydroalkylation of enamides and enecarbamates to chiral aliphatic amines. Nat. Commun. 12, 1313 (2021).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Wang, J.-W. et al. Nickel-catalyzed remote asymmetric hydroalkylation of alkenyl ethers to access ethers of chiral dialkyl carbinols. J. Am. Chem. Soc. 145, 10411–10421 (2023).Article 
CAS 
PubMed 

Google Scholar 
Wang, Y.-M. et al. Enantioselective synthesis of carbo- and heterocycles through a cuh-catalyzed hydroalkylation approach. J. Am. Chem. Soc. 137, 10524–10527 (2015).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Dong, Y. et al. Copper hydride-catalyzed enantioselective olefin hydromethylation. J. Am. Chem. Soc. 144, 16303–16309 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Liu, B. et al. Ligand-controlled stereoselective synthesis of 2-deoxy-β-C-glycosides by cobalt catalysis. Angew. Chem. Int. Ed. 62, e202218544 (2023).Article 
CAS 

Google Scholar 
Lu, X. et al. Practical carbon–carbon bond formation from olefins through nickel-catalyzed reductive olefin hydrocarbonation. Nat. Commun. 7, 11129 (2016).Article 
PubMed 
PubMed Central 

Google Scholar 
Wang, X.-X. et al. Recent advances in nickel-catalyzed reductive hydroalkylation and hydroarylation of electronically unbiased alkenes. Sci. China Chem. 63, 1586–1600 (2020).Article 
CAS 

Google Scholar 
Li, Y., Lu, X. & Fu, Y. Recent advances in cobalt-catalyzed regio- or stereoselective hydrofunctionalization of alkenes and alkynes. CCS Chem. 6, 1130–1156 (2024).Article 
CAS 

Google Scholar 
Zhang, Z., Bera, S., Fan, C. & Hu, X. Streamlined alkylation via nickel-hydride-catalyzed hydrocarbonation of alkenes. J. Am. Chem. Soc. 144, 7015–7029 (2022).Article 
CAS 
PubMed 

Google Scholar 
Wang, Y., He, Y. & Zhu, S. NiH-catalyzed functionalization of remote and proximal olefins: new reactions and innovative strategies. Acc. Chem. Res. 55, 3519–3536 (2022).Article 
CAS 
PubMed 

Google Scholar 
Yang, P.-F. & Shu, W. Asymmetric alkyl–alkyl cross-coupling enabled by earth-abundant metal-catalyzed hydroalkylations of olefins. Chem Catal. 3, 100508 (2023).Article 
CAS 

Google Scholar 
Yang, J.-S. et al. NiH-catalyzed regio- and enantioselective hydroalkylation for the synthesis of β- or γ-branched chiral aromatic N-heterocycles. J. Am. Chem. Soc. 145, 22122–22134 (2023).Article 
CAS 
PubMed 

Google Scholar 
Puleo, T. R., Strong, A. J. & Bandar, J. S. Catalytic α-selective deuteration of styrene derivatives. J. Am. Chem. Soc. 141, 1467–1472 (2019).Article 
CAS 
PubMed 

Google Scholar 
Di Martino, R. M. C., Maxwell, B. D. & Pirali, T. Deuterium in drug discovery: progress, opportunities and challenges. Nat. Rev. Drug Discov. 22, 562–584 (2023).Article 
PubMed 

Google Scholar 
Griller, D. & Ingold, K. U. Free-radical clocks. Acc. Chem. Res. 13, 317–323 (1980).Article 
CAS 

Google Scholar 
Gottschling, S. E. et al. Cyclopropyl alkynes as mechanistic probes to distinguish between vinyl radical and ionic intermediates. J. Org. Chem. 70, 2686–2695 (2005).Article 
CAS 
PubMed 

Google Scholar 
Huang, M., Zhang, L., Pan, T. & Luo, S. Deracemization through photochemical E/Z isomerization of enamines. Science 375, 869–874 (2022).Article 
CAS 
PubMed 

Google Scholar 
Wang, W., Ding, C. & Yin, G. Catalyst-controlled enantioselective 1,1-arylboration of unactivated olefins. Nat. Catal. 3, 951–958 (2020).Article 
CAS 

Google Scholar 
Li, Y. et al. Ligand-controlled cobalt-catalyzed regiodivergent alkyne hydroalkylation. J. Am. Chem. Soc. 144, 13961–13972 (2022).Article 
CAS 
PubMed 

Google Scholar 
Reed, A. E., Weinstock, R. B. & Weinhold, F. Natural population analysis. J. Chem. Phys. 83, 735–746 (1985).Article 
CAS 

Google Scholar 
Lu, T. & Chen, Q. Independent gradient model based on Hirshfeld partition: a new method for visual study of interactions in chemical systems. J. Comput. Chem. 43, 539–555 (2022).Article 
CAS 
PubMed 

Google Scholar 
Smith DGA et al. PSI4 1.4: open-source software for high-throughput quantum chemistry. J. Chem. Phys. 152, 184108 (2020).Article 
PubMed 

Google Scholar 
Lu, T. & Chen, Q. Simple, efficient, and universal energy decomposition analysis method based on dispersion-corrected density functional theory. J. Phys. Chem. A 127, 7023–7035 (2023).Article 
CAS 
PubMed 

Google Scholar 
Enantioselective alkene hydroalkylation overcoming heteroatom constraints via cobalt catalysis. Zenodo https://zenodo.org/records/10997417 (2024).