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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.

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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

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