Communications
How to cite:
Hypervalent Iodine
An a-Cyclopropanation of Carbonyl Derivatives by Oxidative
Umpolung
In memory of Kilian MuÇiz
Abstract: The reactivity of iodine(III) reagents towards
nucleophiles is often associated with umpolung and cationic
mechanisms. Herein, we report a general process converting
a range of ketone derivatives into a-cyclopropanated ketones
by oxidative umpolung. Mechanistic investigation and careful
characterization of side products revealed that the reaction
follows an unexpected pathway and suggests the intermediacy
of non-classical carbocations.
The a-functionalization of certain ketones through oxi-
dative umpolung with iodine(III) was pioneered already in
the 1960s,[30,31] has been extensively investigated in the
1980s,[32–36] and gained further attention in more recent
years.[37–41] It is believed that the reaction involves an
enolonium species (compound 8, Scheme 1a).[42,43] This
highly electrophilic intermediate can react with a variety of
different nucleophiles. Such oxidations are often promoted by
acids[32] or less frequently by bases,[44] with enol ethers[32,41] or
active methylene compounds[37,38] being commonly employed.
In many cases however, the enolonium species does not
directly react with an external nucleophile. Instead, skeletal
rearrangements are observed leading to stabilized carbocat-
ionic intermediates. Net 1,2-phenyl migrations for instance
which proceed via a phenonium intermediate[45,46] are fre-
quently witnessed (Scheme 1b).[47–49] This illustrates that a-
umpolung chemistry of carbonyl compounds can be leveraged
to a new avenue for carbocationic rearrangements which no
T
he importance of the carbonyl functionality has been
identified already at the dawn of modern organic chemistry in
the 19th century and remains at a cardinal point of chemical
synthesis. With the advent of the umpolung approach,
developed by Seebach and Corey, an important paradigm
shift was provided, delivering a systematic perspective to
overcome the limitations of the natural polarity of the
carbonyls (Scheme 1a–I).[1,2] The inversion of the polarity
through derivatization was showcased first by dithiane
chemistry, where a thioketal could be effectively used as C1
nucleophile (Scheme 1a–II).[1,3] Some umpolung reagents
such as the cyanide anion[4,5] or thiazolium based NHCs[6]
(both react as C1 nucleophiles and derive formally from
formic acid) can transfer this umpolung-reactivity through
catalysis (Scheme 1a–III).[7] A third approach to reverse the
polarity of a given functional group consist in its oxidation or
reduction by an external or internal reagent (Scheme 1a–
IV).[8] Ketones and their derivatives for instance are com-
monly employed in oxidative umpolung reactions. Classically
promoted by toxic elements such as Hg(II),[9,10] Tl(III),[9,11]
Pb(IV),[9,12,13] or Se(IV)[14] more modern variants rely on
Bi(V),[15] N-oxides,[16–19] Mn(III),[20,21] halosuccinimides,[22]
sulfoxides,[23] and on iodine(III).[24–29]
[*] A. Bauer, G. Di Mauro,[+] N. Maulide
Institute of Organic Chemistry, University of Vienna
Wꢀhringer Strasse 38, 1090 Vienna (Austria)
E-mail: Nuno.Maulide@univie.ac.at
J. Li[+]
Department of Chemistry, Tohoku University
Aoba-ku, 980-8578 Sendai (Japan)
[+] These authors contributed equally to this work.
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
ꢁ 2020 The Authors. Published by Wiley-VCH GmbH. This is an
open access article under the terms of the Creative Commons
Attribution License, which permits use, distribution and reproduc-
tion in any medium, provided the original work is properly cited.
Scheme 1. a) Natural polarity and types of umpolung. b) a-Arylation by
À
C C bond activation. c) This work: oxidative a-cyclopropanation.
Angew. Chem. Int. Ed. 2020, 59, 1 – 6
ꢀ 2020 The Authors. Published by Wiley-VCH GmbH
1
These are not the final page numbers!