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Review
. 2014 Aug 25;53(35):9142-50.
doi: 10.1002/anie.201403873. Epub 2014 Jul 23.

Catalytic enantioselective C-H functionalization of alcohols by redox-triggered carbonyl addition: borrowing hydrogen, returning carbon

John M Ketcham  1 , Inji Shin, T Patrick Montgomery, Michael J Krische
Affiliations
Review

Catalytic enantioselective C-H functionalization of alcohols by redox-triggered carbonyl addition: borrowing hydrogen, returning carbon

John M Ketcham et al. Angew Chem Int Ed Engl. .

Abstract

The use of alcohols and unsaturated reactants for the redox-triggered generation of nucleophile-electrophile pairs represents a broad, new approach to carbonyl addition chemistry. Discrete redox manipulations that are often required for the generation of carbonyl electrophiles and premetalated carbon-centered nucleophiles are thus avoided. Based on this concept, a broad, new family of enantioselective C-C coupling reactions that are catalyzed by iridium or ruthenium complexes have been developed, which are summarized in this Minireview.

Keywords: enantioselective catalysis; iridium; polyketide natural products; ruthenium; transfer hydrogenation.

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Figures

Figure 1
Figure 1
Redox-economy in carbonyl addition: three general mechanistic pathways identified for redox-triggered alcohol C-H functionalization.
Figure 2
Figure 2
General catalytic mechanism and selected bond lengths obtained via single crystal X-ray diffraction analysis of a series of π-allyliridium C,O-benzoate complexes.
Figure 3
Figure 3
Catalytic alcohol C-C coupling streamlines organic synthesis, enabling a step-function change in efficiency (ref. 28).
scheme 1
scheme 1
Ruthenium catalyzed diene hydrohydroxyalkylation: diastereo- and enantioselective carbonyl crotylation from the alcohol oxidation level.a aYields are of material isolated by silica gel chromatography. (R)-DM-SEGPHOS = [R)-(+)-5,5’-bis(di[3,5–xylyl]phosphino)-4,4’-bi-1,3-benzodioxole]; DPPF = 1,1’-bis(diphenylphosphino)ferrocene; (S)-SEGPHOS = (S)-(−)-5,5’-bis-(diphenylphosphino)-4,4’-bi-1,3-benzodioxole.
scheme 2
scheme 2
Iridium catalyzed 1,3-enyne and allene hydrohydroxyalkylation: enantioselective carbonyl propargylation and tert-prenylation from the alcohol oxidation levela aAs described in Scheme 1.b(R)-SEGPHOS was used as ligand and PhCF3 was used as solvent.c50°C.
scheme 3
scheme 3
Iridium catalyzed C-C coupling of primary alcohols with allyl acetate: enantioselective carbonyl allylation from the alcohol oxidation level.a aAs described in Scheme 1
scheme 4
scheme 4
Iridium catalyzed C-C coupling of primary alcohols with α-methyl allyl acetate: enantioselective carbonyl crotylation from the alcohol oxidation level.a aAs described in Scheme 1.
scheme 5
scheme 5
Iridium catalyzed C-C coupling of primary alcohols with α-substituted allyl donors.a aAs described in Scheme 1.
scheme 6
scheme 6
Iridium catalyzed C-C coupling of primary alcohols with allyl donors possessing olefinic substitution.a aAs described in Scheme 1.
scheme 7
scheme 7
Iridium catalyzed C-C coupling of primary alcohols with vinylcyclopropanes and vinylepoxides.a aAs described in Scheme 1.
scheme 8
scheme 8
Ruthenium(0) catalyzed C-C coupling of secondary alcohols.a aAs described in Scheme 1.
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References

    1. “The ideal synthesis creates a complex skeleton… in a sequence only of successive construction reactions involving no intermediary refunctionalizations, and leading directly to the structure of the target, not only its skeleton but also its correctly placed functionality” Hendrickson JB. J. Am. Chem. Soc. 1975;97:5784–5800.

    1. For a review of redox-economy, see: Burns NZ, Baran PS, Hoffmann RW. Angew. Chem. 2009;121:2896–2910. Angew. Chem. Int. Ed.2009, 48, 2854–2867.

    1. For selected reviews on selectivity and efficiency in chemical synthesis, see: Trost BM. Science. 1983;219:245–250. Newhouse T, Baran PS, Hoffmann RW. Chem. Soc. Rev. 2009;38:3010–3021.

    1. For selected reviews on protecting group-free organic synthesis, see: Hoffmann RW. Synthesis. 2006:3531–3541. Young IS, Baran PS. Nature Chem. 2009;1:193–205. Roulland E. Angew. Chem. 2011;123:1260–1262. Angew. Chem. Int. Ed.2011, 50, 1226–1227.

    1. Preactivation in organic synthesis, see: Han SB, Kim IS, Krische MJ. Chem. Commun. 2009:7278–7287.

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