Angewandte
Chemie
Photochemistry
Three-Component Azidation of Styrene-Type Double Bonds: Light-
Switchable Behavior of a Copper Photoredox Catalyst**
Gabriele Fumagalli, Pauline T. G. Rabet, Scott Boyd, and Michael F. Greaney*
Abstract: [Cu(dap) ]Cl effectively catalyzes azide addition
2
from the Zhdankin reagent to styrene-type double bonds, and
subsequent addition of a third component to the benzylic
position. In the presence of light, a photoredox cycle is
implicated with polar components such as methanol or
bromide adding to a benzylic cation. In the absence of light,
by contrast, double azidation takes place to give diazides.
Therefore, regioselective double functionalization can be
achieved in good to excellent yields, with a switch between
light and dark controlling the degree of azidation.
N
ew azidation methods continue to stimulate reaction
invention, and are driven by the exceptional versatility of the
[1,2]
azide group in chemistry and biology.
Most methods for
the installation of this fundamental building block use either
highly toxic and/or explosive reagents, which are usually
nucleophilic sources of azide. As an alternative, an electro-
philic source of azide was reported in 1994 by Zhdankin and
co-workers, in the form of the hypervalent iodine reagent 1-
Scheme 1. Application of the Zhdankin reagent 1 in alkene functional-
ization. acac=acetylacetonate, TEMPO=2,2,6,6-tetramethylpiperidin-
1-oxyl.
3
[3]
azido-1l -benzo[d][1,2]iodaoxol-3(1H)-one (1). In contrast
to other iodine(I) and iodine(III) azides, 1 is a crystalline solid
and thermally stable up to 1308C, features which have been
exploited in a range of pioneering azidation methods in recent
require 3 equivalents of TEMPONa, a reactive reagent which
must be freshly prepared using sodium metal, and it is also
specific for introducing the tetramethylpiperidine oxide
group. We reasoned that the power of PRC to enable new
[
4]
literature.
We were interested in employing 1 in a new way, using
photoredox catalysis (PRC) to activate the reagent for alkene
azidation. Application of the Zhdankin reagent to alkene
functionalization is limited to two literature reports (Scheme
[
5]
reactions under mild reaction conditions, particularly in the
[
6]
area of alkene functionalization,
could substantially
[
4c,g]
1
):
the group of Jiao reported an oxy azidation of indoles
enhance the scope of this transformation. In addition, PRC
[
7]
with 1 using copper catalysis, and the group of Studer
described a more general alkene azidation using 1 in the
presence of TEMPONa. This latter procedure does, however,
for azidyl radical addition has yet to be investigated, and
would represent a versatile and mild approach to valuable
organic azides. PRC applications of azides to date have
[
8]
involved nitrene generation from vinyl or aryl azides.
A
[
9]
single report from Masson, Magnier, and co-workers
[
*] M. Sc. G. Fumagalli, M. Sc. P. T. G. Rabet, Prof. Dr. M. F. Greaney
School of Chemistry, The University of Manchester
Oxford Road, Manchester, M13 9PL (UK)
describes the trifluoromethyl azidation of double bonds
using an azide anion introduced from TMSN3.
E-mail: michael.greaney@manchester.ac.uk
Our plan was to investigate one-electron reduction of
1
using a suitable photoredox catalyst (Scheme 1), thus
B. Sc. S. Boyd
Department of Oncology, AstraZeneca
Alderley Park, Macclesfield, SK10 4TG (UK)
generating azidyl radicals, which we planned to capture in
[10]
a three-component coupling based on our previous expe-
[11]
[
**] We thank the EPSRC, University of Manchester, and AstraZeneca for
funding (CASE Award studentships to G. F. and P.T.G.R.). Dr. Paul
Lusby (University of Edinburgh) is acknowledged for helpful
scientific discussions.
rience with alkoxy and amino arylations of styrenes.
We began our investigation using 5 equivalents of styrene
(2a) and 1 as the limiting reagent, and 1 mol% of a photo-
redox catalyst in methanol as the solvent of choice (Table 1).
Interestingly, the commonly used [Ir(ppy)3] and [Ru-
(
bpy) Cl ] photoredox catalysts failed to deliver any product
3 2
ꢀ
2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co.
in appreciable yields (entries 1 and 2). We were delighted to
KGaA. This is an open access article under the terms of the Creative
Commons Attribution License, which permits use, distribution and
reproduction in any medium, provided the original work is properly
cited.
find, however, that the copper salt [Cu(dap) ]Cl [dap = 2,9-
2
bis(p-anisyl)-1,10-phenanthroline], successfully gave the azi-
domethoxylated 3a in 60% yield (entry 3). First-row tran-
Angew. Chem. Int. Ed. 2015, 54, 11481 –11484
ꢀ 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
11481