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Review
. 2019 Oct 1;58(40):14055-14064.
doi: 10.1002/anie.201905532. Epub 2019 Jul 26.

Feedstock Reagents in Metal-Catalyzed Carbonyl Reductive Coupling: Minimizing Preactivation for Efficiency in Target-Oriented Synthesis

Rosalie S Doerksen  1 , Cole C Meyer  1 , Michael J Krische  1
Affiliations
Review

Feedstock Reagents in Metal-Catalyzed Carbonyl Reductive Coupling: Minimizing Preactivation for Efficiency in Target-Oriented Synthesis

Rosalie S Doerksen et al. Angew Chem Int Ed Engl. .

Abstract

Use of abundant feedstock pronucleophiles in catalytic carbonyl reductive coupling enhances efficiency in target-oriented synthesis. For such reactions, equally inexpensive reductants are desired or, ideally, corresponding hydrogen autotransfer processes may be enacted wherein alcohols serve dually as reductant and carbonyl proelectrophile. As described in this Minireview, these concepts allow reactions that traditionally require preformed organometallic reagents to be conducted catalytically in a byproduct-free manner from inexpensive π-unsaturated precursors.

Keywords: atom efficiency; carbonyl addition; enantioselectivity; hydrogenation; total synthesis.

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Figures

Figure 1.
Figure 1.
Propionate synthons for polyketide construction.
Scheme 1.
Scheme 1.
An inverse relationship between complexity and efficiency highlights the need for redox- and site-selective catalytic C-C bond formation.
Scheme 2
Scheme 2
Catalytic reductive coupling of π-unsaturated feedstocks: beyond stoichiometric organometallic reagents. Production statistics shown here and elsewhere in this review are taken from the Kirk-Other Encyclopedia of Chemical Technologyor Ullmann’s Encyclopedia of Industrial Chemistry.
Scheme 3.
Scheme 3.
Removing degrees of separation between reagent and feedstock in asymmetric carbonyl crotylation.
Scheme 4.
Scheme 4.
Direct butadiene-mediated carbonyl crotylation with chiral counterion-dependent stereoselectivity.
Scheme 5.
Scheme 5.
Hydrogen-mediated aldol reductive coupling for the total synthesis of swinholide A.
Scheme 6.
Scheme 6.
Stereo- and site-selective alcohol-mediated carbonyl allylation for the total synthesis of swinholide A.
Scheme 7.
Scheme 7.
Polyketide construction via two-directional allylation of feedstock glycols using allyl acetate.
Scheme 8.
Scheme 8.
Hydrogen-mediated reductive coupling of acetylene with imines or aldehydes.
Scheme 9.
Scheme 9.
Synthesis of terpenoid natural products using a byproduct-free hydrogen auto-transfer addition.
Scheme 10.
Scheme 10.
Ethylene and higher feedstock olefins as non-stabilized carbanion equivalents.
See this image and copyright information in PMC

References

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