.
Angewandte
Communications
DOI: 10.1002/anie.201403776
Single-Electron-Transfer Catalysis
Oxidative Catalysis Using the Stoichiometric Oxidant as a Reagent: An
Efficient Strategy for Single-Electron-Transfer-Induced Tandem
Anion–Radical Reactions**
ˇ
ˇ
Frantisek Kafka, Martin Holan, Denisa Hidasovꢀ, Radek Pohl, Ivana Cꢁsarovꢀ,
ˇ
Blanka Klepetꢀrovꢀ, and Ullrich Jahn*
Abstract: Oxidative single-electron transfer-catalyzed tandem
reactions consisting of a conjugate addition and a radical
cyclization are reported, which incorporate the mandatory
terminal oxidant as a functionality into the product.
(III)-catalyzed reactions,[1,7] photoredox-catalytic transforma-
tions,[1,8] and some Minisci-type reactions.[1] However, even
though they are catalytic in the SET-active species, they
always require sacrificial reductants or oxidants to achieve
turnover, such as metals, tBuOOH, and amines, which end as
waste after completion of the reaction (Figure 1).[9]
S
ingle-electron-transfer(SET)-mediated
transformations
are a very convenient strategy for the synthesis of complex
molecules. In such processes radical ions are generated from
neutral precursors, whereas organometallic or carbocationic
intermediates lead to radicals. SET-mediated reactions can be
classified according to the overall change of the oxidation
state as redox-neutral, oxidative, or reductive. Redox-neutral
processes are often transition-metal-catalyzed cross-coupling
reactions involving alkyl halides or sulfur electrophiles,[1,2]
transition-metal-catalyzed atom-transfer radical reactions,[1,3]
the more recently rediscovered homolytic aromatic substitu-
tions,[1,4] tetrathiafulvalene-promoted radical reactions[5a] and
cycloaddition reactions,[1] in which the catalytic SET oxidant
or reductant is regenerated at the end of the catalytic cycle by
the reverse electron transfer. The majority of the known SET-
induced reactions are, however, overall reductive[1,5] or
oxidative,[1,6] which means that at least two equal SET steps
occur sequentially in the process. They require stoichiometric
amounts of SET oxidants or reducing agents to proceed.
Catalytic versions are rare; notable are reductive titanium-
Figure 1. Conventional oxidative transformation, in which the stoichio-
metric reduced species is wasted; in contrast, in oxidative catalysis it
serves as a reagent.
We hypothesized that it would be more environmentally
sustainable to use the sacrificial reduced or oxidized species
resulting from promotion of the SET steps productively to
introduce useful functionality into the target molecules. This
gives the redox reagent a double function and renders the
overall transformation redox-economic and complexity gen-
erating. Such a strategy can be considered complementary to
recently introduced “borrowing-hydrogen” and related two-
electron-transfer processes.[10]
[*] Ing. F. Kafka,[+] Ing. M. Holan,[+] M.Sc. D. Hidasovꢀ, Dr. R. Pohl,
ˇ
Dr. B. Klepetꢀrovꢀ, Dr. U. Jahn
Institute of Organic Chemistry and Biochemistry
Academy of Sciences of the Czech Republic
ˇ
Flemingovo nꢀmestꢁ 2, 16610 Prague (Czech Republic)
E-mail: jahn@uochb.cas.cz
We report here that catalytic oxidative SET is indeed
possible and can be applied to tandem processes consisting of
asymmetric organometallic conjugate addition, radical cycli-
zation, and oxygenation steps. The reactions proceed with
catalytic amounts of cheap ferrocene and 2,2,6,6-tetramethyl-
N-oxopiperidinium hexafluorophosphate as the stoichiomet-
ric oxidant. The resulting reduced species TEMPO serves
subsequently as an oxygenating agent introducing a useful
protected alcohol functionality.
ˇ
Dr. I. Cꢁsarovꢀ
Department of Inorganic Chemistry, Faculty of Science
Charles University in Prague
Hlavova 2030/8, 12843 Prague (Czech Republic)
[+] These authors contributed equally to this work.
[**] Generous financial support by the Grant Agency of the Czech
Republic (13-40188S), the Institute of Organic Chemistry and
Biochemistry, Academy of Sciences of the Czech Republic (RVO:
61388963), the COST action CM1201 “Biomimetic Radical
Chemistry”, and the Gilead Sciences & IOCB Research Center is
gratefully acknowledged. I.C. thanks the Ministry of Education,
Youth and Sports of the Czech Republic (MSM0021620857) for
financial support. We thank Prof. Dr. Klaus Dietrich (BASF SE) for
a gift of the 1-phenylethylamine enantiomers.
It is known that ferrocenium hexafluorophosphate (1+)
does not oxidize TEMPO (2) and thus the equilibrium is on
the left (Scheme 1).[11] Therefore the opposite process should
proceed spontaneously and allow the catalytic SEToxidation.
Indeed, an instantaneous and quantitative reaction to 1+ and 2
occurred when ferrocene (1) and the N-oxopiperidinium
hexafluorophosphate 2+ were mixed.
Supporting information for this article is available on the WWW
9944
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 9944 –9948