Efficient radical addition of tertiary amines to electron-deficient alkenes using semiconductors as photochemical sensitisers

Article abstract of DOI:10.1039/b104387k

Tertiary amines can be added to electron-deficient alkenes with yields up to 98% in a radical chain reaction initiated by a photochemical electron transfer using inorganic semiconductors like TiO₂ as sensitiser.

Full text of DOI:10.1039/b104387k

Efficient radical addition of tertiary amines to electron-deficient
alkenes using semiconductors as photochemical sensitisers
Sinisˆa Marinkovic´ and Norbert Hoffmann*
Laboratoire des Réactions Sélectives et Applications, UMR CNRS et Université de Reims
Champagne-Ardenne, UFR Sciences, B.P. 1039, F-51687 Reims, Cedex 02, France.
E-mail: norbert.hoffmann@univ-reims.fr
Received (in Cambridge, UK) 18th May 2001, Accepted 9th July 2001
First published as an Advance Article on the web 3rd August 2001
Tertiary amines can be added to electron-deficient alkenes
with yields up to 98% in a radical chain reaction initiated by
a photochemical electron transfer using inorganic semi-
conductors like TiO2 as sensitiser.
low. Much faster conversions was observed when the reaction
was carried out in 2a as solvent (Table 1, entries 4–7) and yields
increased under these conditions. The concentration of 1a was
changed and it turned out that 5 3 1022 mol L21 with a
corresponding quantity of TiO2 is the optimal concentration
(Table 1, entries 4, 6 and 7). Under these reaction conditions, N-
tert-butylpyrrolidine 2b was added to 1a with the same
efficiency (entry 8). As mentioned previously, the addition of
the amine took place exclusively from the less-hindered side of
the furanone 1a.3 Unfortunately, little selectivity was observed
for the asymmetric carbon in the a-position of the nitrogen.
Under the optimised conditions,† the reaction of various a,b-
unsaturated lactones with methylpyrrolidine 2a was examined
(Table 2). Generally, high conversion rates and high yields were
observed. However, in the case of lactone 1e possessing two
substituents in the 4-position, the conversion rate was low. A
low reactivity for b-disubstituted enones is also observed when
homogeneous reaction conditions were applied.3
Radical reactions have become a valuable tool in preparative
organic chemistry.1 Among radicals having a nucleophilic
character which can be considered for addition reactions with
electron deficient alkenes, a-aminoalkyl radicals seem very
attractive.2 Recently, we described an efficient procedure
involving a photochemical electron transfer to initiate the
intermolecular radical addition of tertiary amines to electron
deficient alkenes.3 Under the same conditions, radical tandem
reactions could also be carried out efficiently.4
In principle, photochemical excited semiconductors like
TiO2 could initiate the radical addition of tertiary amines.
Photochemical reactions with TiO2 were studied, for instance,
for detoxification of waste water,5 oxidations and reductions,6
solar energy havesting7 or in the context of organic synthesis.8
Metal sulfides like ZnS and CdS have been used for the
formation of dehydrodimers of olefins or enol/allyl ethers and
for the addition of allyl radicals to imines or diazo com-
pounds.9
When TiO2 was used as sensitiser for the addition of N-
methylpiperidine 2c, only a slow reaction was observed and
During photochemical excitation, an electron is transferred
from the valence band into the conduction band.10 The resulting
electron hole h+ of the valence band can be filled by electron
transfer from a reductive species such as a tertiary amine
(Scheme 1) with the formation of a radical cation and of
nucleophilic a-aminoalkyl radicals by deprotonation.
We started our investigations by irradiating a suspension of
SiC, TiO2 (anatase) or ZnS in a solution containing (5R)-
menthyloxy-2[5H]furanone 1a and N-methylpyrrolidine 2a in
acetonitrile (Table 1, entries 1–3). Low conversion rates were
observed for TiO2 and ZnS while no transformation could be
detected for SiC. The yields based on conversion were rather
Scheme 1 Formation of a-aminoalkyl radicals by single electron transfer to
an electronically excited semiconductor particle.
Table 1 Reaction of (5R)-menthyloxy-2[5H]furanone 1a with N-methylpyrrolidine 2a and tert-butylpyrrolidine 2b under different reaction conditions; 0.1
equivalent of the semiconductor (SC) with respect to 1a was added
Entry
Semiconductor
c(1a)/mol L21
c(2a,b)/mol L21
R
Irradiation time/h
Conversion (%) Yielda (%)
Ratio c(3)/c(4)
1
2
3
4
5
6
7
8
SiC
TiO2
ZnS
TiO2
ZnS
TiO2
TiO2
TiO2
1022
4 3 1021
4 3 1021
4 3 1021
Solvent
Solvent
Solvent
Me
Me
Me
Me
Me
Me
Me
But
8
9
9
2.5
2.5
2.5
2.5
3.5
—
59
68
100
100
73
—
25
28
53
59
90
39
88
—
1022
47/53
45/55
45/55
45/55
45/55
45/55
45/55
1022
1022
1022
5 3 1022
1021
Solvent
Solvent
50
83
5 3 1022
a Based on conversion of 1a.
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Chem. Commun., 2001, 1576–1578
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b104387k

Table 2 Reaction of different a,b-unsaturated lactones with methylpyrroli-
dine 2a under different reaction conditions; 0.1 equivalent of the
semiconductor with respect to 1a was added
the ring of 2a,c and never at the methyl group. Therefore, we
propose a tautomeric equilibrium of the iminium ions 7 and 8.11
As described previously, only one diastereomer was isolated.3
Such a bimolecular reaction between two reactive intermediates
appears more realistic if the overall reaction takes place near the
surface of the semiconductor.
Oxidation of an a-aminoalkyl radical by excited TiO2 is also
possible. Therefore, we searched to diminish the two-electron
oxidation by changing the semiconductor (Table 3, entry 4).
When ZnS was used as sensitiser, only product 4g could be
isolated. Despite the more rapid conversion, the yield of the
desired product 4g remained low. Probably, this semiconductor
is less oxidative due to the higher energy level of its valence
band edge12 and its surface properties.
The most apparent difference between the reaction conditions
of the homogeneous and the heterogeneous catalysis is the
concentration of the tertiary amine. In the case of homogeneous
catalysis, acetonitrile must be used as solvent to obtain the best
results3 and the reaction is slower and less chemoselective when
the tertiary amine is used as solvent. These results might be
explained by the higher polarity of acetonitrile solutions which
stabilise the radical ion pairs formed by electron transfer and
decrease the rate of the back electron transfer. In the case of
heterogeneous catalysis, the electron transfer from the amine to
the sensitiser takes place at the surface of the semiconductor.
Molecules at interfaces are less mobile than the same molecules
in solution. Therefore, the back electron transfer can be slowed
down only by enhancement of the subsequent deprotonation
step. This acid–base reaction is facilitated by the presence of a
large excess of tertiary amine. A higher concentration of the
tertiary amine favours also the hydrogen abstraction of the
oxoallyl radical 6 in the chain propagation.
Irradiation
time/h
Conversion Yielda Ratio
1
(%)
(%)
c(3)/c(4)
1b
1c
2
90
100
100
64
98
90
45/55
43/57
44/56
2
1db
3.5
1e
13
20
76
44/56
a Based on conversion of 1. b The starting concentration was
1022 mol L21
.
Table 3 Reaction of (5R)-menthyloxy-2[5H]furanone 1a with N-methylpi-
peridine 2c under different reaction conditions; 0.1 equivalent of the
semiconductor (SC) with respect to 1a was added
We thank Professor J. P. Pete for his support and for helpful
discussions. S. M. thanks the Ministère de la Recherche for a
doctoral fellowship.
Yielda
Notes and references
† Experimental: a Rayonet photochemical chamber reactor equipped with
lamps emitting at l = 350 nm was used as the light source.
Entry Semiconductor c(1a)/mol L21 Conversion (%) 4g
5
A suspension of the substrate (7.5 mmol) and the semiconductor (0.15
mmol) in 150 ml of the tertiary amine was irradiated in Pyrex-tubes (outside
diameter: 4 cm) under vigorous stirring with a magnetic stir bar. The
mixture was filtered through Celite and the solvent was recycled by
distillation under reduced pressure. The residue was purified by flash
chromatography (silica gel, eluent: light petroleum–ethyl acetate: 2+1)
1
2
3
4
TiO2
TiO2
TiO2
ZnS
5 3 1022
5 3 1022
1022
72
15
34
94
—
74
b
Trace 90
28
23
62
Trace
1022
a Based on conversion of 1a. b The amine was distilled over CaH2 under
argon and the semiconductor was kept at 100 °C for 48 h.
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product 5 resulting from a Michael addition of piperidine to 1a
was isolated (Table 3, entry 1). Due to their lower reactivity of
a-aminoalkyl radicals derived from N-methylpiperidine, the
oxidation of these radicals became competitive and demethyla-
tion occurred.11 Even under strictly anhydrous conditions, this
side reaction took place (entry 2). However, when the
concentration of compound 1a was reduced, the radical addition
could be observed and product 4g was isolated with moderate
yield (entry 3). This result indicates that 1 or, more likely, the
oxoallyl radical 6 might participate in the demethylation process
via an electron transfer from the radical cation to 7 (Scheme 2).
It should be noted that the radical addition always takes place on
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Scheme 2 Possible mechanism of the oxidation of an a-aminoalkyl radical
by an oxoallyl radical introducing the demethylation of 2c.
Chem. Commun., 2001, 1576–1578
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