Dual Intermolecular Allylic C–H Functionalization of the
Tetrasubstituted Alkene Scaffold
and Kilian Muñiz*
Dedicated to the memory of Professor Ricardo Llavona.
Abstract: Activation of chloramine-T (TsNNaCl) with a Brønsted
acid generates an active reagent for the double allylic C–H func-
tionalization of tetrasubstituted alkenes in an intermolecular
manner. The reaction generates a carbon–nitrogen and a
carbon–chlorine bond, and proceeds with complete regio- and
Intermolecular carbon–heteroatom bond formation through di-
rect oxidative C–H functionalization at the allylic position repre-
sents a versatile strategy for the derivatization of unsaturated
Such reactions are widely sought after, and
some well-designed, innovative metal-based C–H oxidation re-
have emerged over recent years. Despite these broad
advances, reactions that can be carried out without the require-
ment of a metal promoter represent a conceptually important
for both economical and ecological rea-
sons. Examples of such practical transformations include selen-
ium-mediated allylic oxygenation
and related radical-based
In this context, N-haloamines represent powerful
alternative oxidants for metal-free oxidation,
by the versatile Wohl–Ziegler reaction for allylic halogen-
and the prominent Hofmann–Löffler reaction.
latter is a particularly instructive reaction, since the N-haloge-
nated amines involved usually promote highly selective C–H
In the broader N-haloamine area, commer-
cially available chloramine-T (1)
has attracted significant in-
terest in the field of alkene oxidation.
Despite the mature
state of this area of expertise, it appears that the exploration of
innovative and practical reactivity based on 1 may still be possi-
ble. In this paper, we report such a case of an unprecedented
double allylic C–H functionalization in a metal-free reaction. We
recently reported conditions for a metal-free aminochlorination
reaction of alkenes through an operationally convenient Brøn-
[a] Institute of Chemical Research of Catalonia (ICIQ),
Av. Països Catalans 16, 43007 Tarragona, Spain
Pg. Lluís Companys 23, 08010 Barcelona, Spain
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201701624.
Eur. J. Org. Chem. 2018, 1248–1254
© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
chemoselectivity. A total of 14 examples demonstrate the appli-
cability of the dual C–H functionalization process. The mecha-
nism involves the intermediacy of a 1,3-butadiene derivative;
1,3-butadienes can also be used directly as substrates.
sted-acid activation of chloramine-T (1).
This reaction is char-
acterized by an unusually broad substrate scope, as it tolerates
all the different alkene classes. For cyclic tetrasubstituted alk-
enes, clean vicinal aminochlorination was observed (Scheme 1).
However, the outcome was found to change completely for
acyclic tetrasubstituted alkenes. In this paper, we report condi-
tions for a dual allylic amination/chlorination reaction through
selective oxidation under metal-free conditions.
Scheme 1. Oxidation of tetrasubstituted alkenes with the TsNHCl reagent.
Results and Discussion
The reaction was discovered and optimized for 2-phenyl-3-
methyl but-2-ene (2a). Treatment of this tetrasubstituted alkene
with 1 (1.2 equiv.) and pivalic acid (1.2 equiv.) in dichloroethane
did not provide the expected corresponding vicinal amino-
chlorination product, but gave rise to the unexpected forma-
tion of 3a, which appeared to be the product of a regioselec-
tive aminochlorination at two of the allylic positions (Table 1,
entry 1). The formation of product 3a requires two formal allylic
oxidation events, and the yield increased when the amount of
the chloramine reagent was increased to 2.4 equiv. (Table 1,