Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Mar 27;146(12):7905-7914.
doi: 10.1021/jacs.4c01857. Epub 2024 Mar 13.

Leveraging the Stereochemical Complexity of Octahedral Diastereomeric-at-Metal Catalysts to Unlock Regio-, Diastereo-, and Enantioselectivity in Alcohol-Mediated C-C Couplings via Hydrogen Transfer

Jonathan Z Shezaf  1 , Catherine G Santana  1 , Eliezer Ortiz  1 , Cole C Meyer  1 , Peng Liu  2 , Ken Sakata  3 , Kuo-Wei Huang  4 , Michael J Krische  1
Affiliations
Review

Leveraging the Stereochemical Complexity of Octahedral Diastereomeric-at-Metal Catalysts to Unlock Regio-, Diastereo-, and Enantioselectivity in Alcohol-Mediated C-C Couplings via Hydrogen Transfer

Jonathan Z Shezaf et al. J Am Chem Soc. .

Abstract

Experimental and computational studies illuminating the factors that guide metal-centered stereogenicity and, therefrom, selectivity in transfer hydrogenative carbonyl additions of alcohol proelectrophiles catalyzed by chiral-at-metal-and-ligand octahedral d6 metal ions, iridium(III) and ruthenium(II), are described. To augment or invert regio-, diastereo-, and enantioselectivity, predominantly one from among as many as 15 diastereomeric-at-metal complexes is required. For iridium(III) catalysts, cyclometalation assists in defining the metal stereocenter, and for ruthenium(II) catalysts, iodide counterions play a key role. Whereas classical strategies to promote selectivity in metal catalysis aim for high-symmetry transition states, well-defined low-symmetry transition states can unlock selectivities that are otherwise difficult to achieve or inaccessible.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Carbonyl addition beyond stoichiometric organometallic nucleophiles.
Figure 2:
Figure 2:
The unique reactivity and stereochemical complexity of octahedral d6-metal ions (an idealized octahedral splitting diagram is shown).
Figure 3.
Figure 3.
Metal-centered stereogenicity in enantioselective π-allyliridium-C,O-benzoate-catalyzed carbonyl allylations of alcohol proelectrophiles.
Figure 4:
Figure 4:
Inversion of enantioselectivity in carbonyl allylations catalyzed by diastereomeric-at-iridium complexes.
Figure 5.
Figure 5.
Metal-centered stereogenicity in enantioselective ortho-cyclometallated π-allyliridium-PhanePhos-catalyzed carbonyl allylations.
Figure 6.
Figure 6.
Metal-centered stereogenicity in enantioselective π-allylruthenium-JOSIPHOS-catalyzed carbonyl allylations.
Figure 7.
Figure 7.
Structures of RuX(CO)(JOSIPHOS)(?3-C3H5), where X = Cl, Br, I, determined by X-ray diffraction.
Figure 8.
Figure 8.
The control of metal-centered stereogenicity unlocks diverse enantioselective ruthenium-JOSIPHOS-catalyzed carbonyl additions.
Figure 9.
Figure 9.
Divergent regioselectivity guided by metal-centered stereogenicity in enantioselective π-allylruthenium-SEGPHOS-catalyzed C-C couplings of primary alcohols with isoprene.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. For reviews, see: (a) Trost BM The Atom Economy—A Search for Synthetic Efficiency. Science 1991, 254, 1471–1477. - PubMed
    2. (b) Doerksen RS; Meyer CC; Krische MJ Feedstock Reagents in Metal-Catalyzed Carbonyl Reductive Coupling: Minimizing Preactivation for Efficiency in Target-Oriented Synthesis. Angew. Chem. Int. Ed 2019, 58, 14055–14064 and references cited therein. - PMC - PubMed
    1. For selected reviews on enantioselective hydrogenation and transfer hydrogenation in the synthesis of pharmaceutical ingredients, see: (a) Hawkins JM; Watson TJN Asymmetric Catalysis in the Pharmaceutical Industry. Angew. Chem. Int. Ed 2004, 43, 3224–3228. - PubMed
    2. (b) Thommen M Homogeneous Asymmetric Hydrogenation: Mature and Fit for Early Stage Drug Development. Spec. Chem. Mag 2005, 25, 26–28.
    3. (c) Thayer AM Chiral Catalysis. Chem. Eng. News 2005, 83, 40–58.
    4. (d) Farina V; Reeves JT; Senanayake CH; Song JJ Asymmetric Synthesis of Active Pharmaceutical Ingredients. Chem. Rev 2006, 106, 2734–2793. - PubMed
    5. (e) Carey JS; Laffan D; Thomson C; Williams MT Analysis of The Reactions Used for The Preparation of Drug Candidate Molecules. Org. Biomol. Chem 2006, 4, 2337–2347. - PubMed
    6. (f) Ager DJ; de Vries AHM; de Vries JG Asymmetric Homogeneous Hydrogenations at Scale. Chem. Soc. Rev 2012, 41, 3340–3380. - PubMed
    7. (g) Etayo P; Vidal-Ferran A Rhodium-Catalyzed Asymmetric Hydrogenation as a Valuable Synthetic Tool for The Preparation of Chiral Drugs. Chem. Soc. Rev 2013, 42, 728–754. - PubMed
    8. (h) Hayler JD; Leahy DK; Simmons EM A Pharmaceutical Industry Perspective on Sustainable Metal Catalysis. Organometallics 2019, 38, 36–46.
    1. Stoffels MA; Klauck FJR; Hamadi T; Glorius F; Leker J Technology Trends of Catalysts in Hydrogenation Reactions: A Patent Landscape Analysis. Adv. Synth. Catal 2020, 362, 1258–1274. - PMC - PubMed
    1. For a review on the Haber-Bosch process, see: Smil V Enriching the Earth: Fritz Haber, Carl Bosch, and the Transformation of World Food Production, MIT Press: Cambridge, MA, 2004; pp 68–107.
    1. For a review on methane-steam reforming, see: Hook van J. P. Methane-Steam Reforming. Catal. Rev 1980, 21, 1–51.

LinkOut - more resources