Communications
Radical Chemistry
Hot Paper
Carboamination of Unactivated Alkenes through Three-Component
Radical Conjugate Addition
Abstract: Two-component Giese type radical additions are
highly practical and established reactions. Herein, three-
component radical conjugate additions of unactivated alkenes
to Michael acceptors are reported. Amidyl radicals, oxidatively
generated from a-amido oxy acids using redox catalysis, act as
the third reaction component which add to the unactivated
alkenes. The adduct radicals engage in Giese type additions to
Michael acceptors to provide, after reduction, the three-
component products in an overall alkene carboamination
reaction. Transformations which can be conducted under
practical mild conditions feature high functional group toler-
ance and broad substrate scope.
T
he reductive conjugate radical addition of an alkyl halide to
an electron deficient alkene, known as the Giese reaction,
represents a valuable transformation in organic synthesis.[1]
Along with halides,[2] amine,[3] and alcohol,[4] carboxylic acid
derivatives,[5] among other compound classes, have been used
as radical precursors in such additions (Scheme 1a).[6–8]
Notably, the Giese reaction allows for construction of
quaternary carbons under mild and practical conditions.[9] If
alkenes are used as precursors of nucleophilic C-radicals,
Giese reactions allow the reductive coupling of unactivated
alkenes with electron-poor alkenes. Such two-component
alkene couplings have been achieved following two different
strategies: A) A widely reported approach uses radical
cascades comprising an initial cyclization with subsequent
intermolecular conjugate addition (Scheme 1b, left),[10] and
B) Baran realized a hydroalkylation of alkenes through
radical additions, in which the nucleophilic C-radicals are
Scheme 1. Giese reaction and its application to radical alkene/alkene
coupling (EWG=electron withdrawing group).
As part of our program on N-radical chemistry,[13] we
intended to achieve three-component carboamination of
unactivated alkenes providing valuable d-amino ketone/
ester derivatives where the C-radical required for the Giese
reaction is generated through amidyl radical addition to an
unactivated alkene (Scheme 1c).[14] Carboamination of acti-
vated alkenes including styrenes and acrylates has gained
attention recently,[15] but the herein disclosed strategy shout-
able for unactivated alkenes has not been established to
date.[16] As N-radical precursors, we used readily prepared a-
amido-oxy acids[17] where the N-protecting group can be
varied and radical generation is known to be achieved by
single electron oxidation using a redox catalyst.[18]
À
generated by addition of a Fe H species to the alkene
(Scheme 1b, right).[11] However, three-component radical
additions of unactivated alkenes to Michael acceptors where
À
the C-radicals are generated by intermolecular C X bond
formation leading to alkene 1,2-difunctionalization products
have not been reported.[12]
We commenced the study by using the Cbz-protected N-
radical precursor 1a in combination with 2-ethylbutene 2a
and methyl vinyl ketone (3a) applying photoredox catalysis.
Extensive experimentation revealed that the cascade is best
conducted with Ir(dFCF3ppy)2(dtbbpy)PF6 as the photocata-
lyst (PC, 0.5 mol%) in combination with Cs2CO3 (1.5 equiv)
and H2O (2 equiv) as an additive in dichloromethane (DCM)
at room temperature for 24 hours under blue light irradiation.
Targeted 4aa was isolated in 87% yield by using an excess of
both 1a (1.5 equiv) and 2a (2 equiv). A lower yield (61%)
was obtained upon decreasing the amount of PC to 0.2 mol%.
The use of H2O as an additive, which role is not understood, is
essential to get a high yield: the water free reaction delivered
4aa in only 17% yield. Control experiments showed the
[*] Dr. H. Jiang, G. Seidler, Prof. Dr. A. Studer
Organisch-Chemisches Institut, Westfꢀlische Wilhelms-Universitꢀt
Corrensstraß 40, 48149 Mꢁnster (Germany)
E-mail: studer@uni-muenster.de
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
ꢂ 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co.
KGaA. This is an open access article under the terms of the Creative
Commons Attribution Non-Commercial NoDerivs License, which
permits use and distribution in any medium, provided the original
work is properly cited, the use is non-commercial, and no
modifications or adaptations are made.
Angew. Chem. Int. Ed. 2019, 58, 1 – 6
ꢀ 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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