Diastereoselective radical tandem addition-cyclization reactions of aromatic tertiary amines by semiconductor-sensitized photochemical electron transfer

Article abstract of DOI:10.1002/ejoc.200400102

The diastereoselective radical tandem addition-cyclization reaction of N,N-dimethylaniline (2) with menthyloxyfuranone 1 was initiated by photochemically induced electron transfer using inorganic semiconductors (TiO₂, ZnS, SiC and SnO₂) as sensitizers. The rearomatization step, which also causes the partial reduction of 1, was studied by isotopic labeling experiments using deuterated derivatives of 2. The influence of the semiconductor surface on these processes has been characterized and compared with the results obtained under homogeneous conditions. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200400102

FULL PAPER
Diastereoselective Radical Tandem Addition-Cyclization Reactions of Aromatic
Tertiary Amines by Semiconductor-Sensitized Photochemical Electron Transfer
[a]
[a]
ˇ
´
Sinisa Marinkovic and Norbert Hoffmann*
Keywords: Radical reactions / Electron transfer / Heterogeneous catalysis / Nitrogen heterocycles / Isotopic labeling
The diastereoselective radical tandem addition-cyclization
beling experiments using deuterated derivatives of 2. The
reaction of N,N-dimethylaniline (2) with menthyloxyfur- influence of the semiconductor surface on these processes
anone 1 was initiated by photochemically induced electron has been characterized and compared with the results ob-
transfer using inorganic semiconductors (TiO2, ZnS, SiC and
SnO2) as sensitizers. The rearomatization step, which also
causes the partial reduction of 1, was studied by isotopic la-
tained under homogeneous conditions.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
addition of tertiary amines to alkenes. The photochemical
reactions of TiO2 have been frequently studied: for detox-
ification of waste water,[12] oxidation and reduction reac-
tions,[13,14] solar energy harvesting[15] or in the context of
organic synthesis.[14,16] Metal sulfides like ZnS and CdS
have been used for the formation of dehydrodimers of olef-
ins or enol/allyl ethers and for the addition of allyl radicals
to imines or diazo compounds.[17] Recently, we have shown
that the radical addition of simple tertiary amines to elec-
tron-deficient alkenes can be successfully carried out with
inorganic semiconductors like TiO2 or ZnS.[18,19] The prod-
ucts were isolated with yields of up to 98% and a facial
diastereoselectivity of Ͼ 95%. In this paper we report our
first results of the tandem addition-cyclization reaction of
aromatic tertiary amines with electron-deficient alkenes
using semiconductors as the sensitizers.
Radical reactions have become an important tool in or-
ganic chemistry.[1,2] However, considerable effort is still
needed to improve the selectivity of these reactions.[2,3] In
this context, the radical addition of simple tertiary amines
to alkenes represents an interesting example. Despite the
great variety of products possessing biological activity, for
instance in the field of pharmacology, this reaction has ra-
rely been applied to organic synthesis since the products are
isolated in low or moderate yields.[4] Recently, we reported
an efficient photochemical method for the stereoselective
radical addition of tertiary amines to electron-deficient
double bonds.[5] The radical chain reaction was initiated by
a single-electron transfer followed by a proton transfer from
the tertiary amine to the electronically excited sensitizer.[6]
Nucleophilic α-aminoalkyl radicals and stable ketyl radicals
were formed as intermediates.[7Ϫ9] The best results were ob-
tained when aromatic ketones possessing electron-donating
substituents were used as the sensitizer. These sensitizers
were used in catalytic amounts (5Ϫ10 mol%) of which up to
80% could be recovered after the reaction. More ambitious
reactions like radical tandem addition-cyclization reactions
have been successfully carried out under the same con-
ditions.[10] For a recent review on these reactions see ref.[11]
We looked for a way to perform these reactions by het-
erogeneous catalysis since these methods often simplify the
procedure as the separation of the catalyst is particularly
easy. We wondered whether photochemically excited inor-
ganic semiconductors such as TiO2 could initiate the radical
Results and Discussion
The irradiation at 350 nm of a suspension of a semicon-
ductor like TiO2 (0.1 mol-equiv. with respect to 1) in a solu-
tion of (5R)-menthyloxyfuran-2(5H)-one (1) and N,N-di-
methylaniline (2) in acetonitrile yielded two stereoisomeric
tetrahydroquinoline derivatives 3a and 3b and the lactone 4
(Scheme 1, Table 1). The major isomer of the tetrahydro-
quinolines, 3a, results from radical attack anti to the men-
thyloxy substituent.[20] The side product 4 was formed in
about the same yield as 3a,b by the partial reduction of 1.
Traces of compound 5 were also formed in a radical-coup-
ling step. Several other inorganic semiconductors were also
tested as sensitizers. ZnS and SiC (Table 1, Entries 2 and 3)
are more reductive than TiO2 while SnO2 (Entry 4) is more
oxidative.[21] The formation of the reduction product 4 was
only marginally reduced when SnO2 was used. In the case
of the less oxidative semiconductors, ZnS and SiC, the yield
[a]
´
´
Laboratoire des Reactions Selectives et Applications,
´
UMR CNRS et Universite de Reims, Champagne-Ardenne,
UFR Sciences,
B. P. 1039, 51687 Reims, Cedex 02, France
Fax: (internat.) ϩ 33-3-26913166
E-mail: norbert.hoffmann@univ-reims.fr
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DOI: 10.1002/ejoc.200400102
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Diastereoselective Radical Tandem Addition-Cyclization Reactions of Aromatic Tertiary Amines
FULL PAPER
Scheme 1
Table 1. Tandem addition-cyclization of N,N-dimethylaniline (2)
with (5R)-menthyloxyfuran-2(5H)-one (1) using different semi-
conductors as sensitizers (Scheme 1)
Entry Semiconductor Conversion[a] de[b] Yield (%)[c]
(%)
(%) 3a 3b
4
5
1
2
3
4
TiO2
ZnS
SiC
96
92
95
90
62
68
50
56
27
29
7
8
31 traces
33 traces
31 9.5 31 traces
27 27 traces
SnO2
8
[a] Conversion of 1. [b] Determined from NMR spectra. [c] Yields of
the isolated products with respect to the conversion of 1.
of the tetrahydroquinoline derivatives 3a,b was slightly
higher. Under the heterogeneous conditions described her-
ein, the diastereoselectivity of 3a,b was lower than that ob-
tained under homogeneous conditions;[10] when the reac-
Scheme 2
tion was carried out in solution, 3a,b were obtained with able of transferring a hydrogen atom to 1.[10] Further steps
92% diastereoselectivity. Furthermore, the facial diastereo- lead to the formation of the reduction products 4 and 5.
selectivity depends on the semiconductor and varied be- We were able to completely suppress this side reaction by
tween 50% in the case of SiC and 68% in the case of ZnS. adding ketones like acetone to the reaction solution; ke-
These values were reproduced several times either by ana- tones act as a mild oxidants replacing the menthyloxyfur-
lyzing the resulting reaction mixtures or by separating and anone 1 in the rearomatization step.
weighing the diastereoisomers. We attribute these differ-
In order to gain an insight into the mechanism of the
ences in diastereoselectivity to orientation phenomena at rearomatization step in the heterogeneous reaction, we have
the surface of the semiconductor. Probably, the confor- also performed the reaction with deuterated aniline deriva-
mational equilibrium is significantly influenced by the tives. In this case, deuterium can be transferred to 1 and
adsorption at the surface. Recently, we studied the effect of subsequently be detected in the side products 4 and 5. This
the conformational orientation of the menthyloxy substitu- study was carried out using ZnS as the sensitizer. The re-
ent on the diastereoselectivity.[22]
sults are shown in Table 2 and are compared with those
We propose the following mechanism for the radical tan- obtained by homogeneous photocatalysis using aromatic
dem addition-cyclization reaction (Scheme 2). After photo- ketones as sensitizers.
chemical excitation of the semiconductor particle and for-
In the case of semiconductor photocatalysis and in con-
mation of an electron/hole pair, an electron is transferred trast to homogeneous catalysis with Michler’s ketone, no
from the aromatic tertiary amine to the hole in the valence deuterium was transferred from the deuterated aniline de-
band. The resulting radical cation A yields an α-aminoalkyl rivative 2Ј to 1; lactones 4Ј, 4ЈЈ and 5Ј were not formed,
radical B by deprotonation. This nucleophilic radical read- only undeuterated 4 and 5. However, deuterium was trans-
ily adds to the electron-deficient alkene 1. The resulting in- ferred from 2ЈЈ to 1. In contrast to the corresponding reac-
termediate C possesses an electrophilic oxoallyl radical moi- tion under homogeneous conditions, the deuterium was
ety which rapidly adds to the electron-rich aromatic ring found exclusively at the α-position (4Ј). Similar to the
in an intramolecular reaction. In order to obtain the final homogeneous reaction, one deuterium atom was found at
products, oxidative rearomatization must take place.
one of the α-positions of 5Ј. However, the degree of deuter-
By using isotopic labeling, we have previously shown that ation was lower than in the homogeneous case. The reac-
under homogeneous conditions the intermediate D is cap- tions were also performed with TiO2 as the sensitizer. In
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FULL PAPER
Table 2. Isotopic labeling experiments; transfer of deuterium from 2Ј or 2ЈЈ to 1 during the formation of 4 and 5; yields (%) and percentage
of single deuterium transfer (D1); the percentage of deuterium in 3a,b is Ͼ 95% (D2 in the case of 2Ј and D5 in the case of 2")
[a]
[b]
Incorporation of deuterium into 4 was not observed. Conversion of 100% after 8 h of irradiation. [c] Conversion of 100% after 6.5 h
of irradiation.
the case of 2Ј, the reaction was slightly slower but the same
results were obtained as for ZnS as far as the deuterium
transfer was concerned. In the case of 2ЈЈ, however, the re-
action was significantly slower with TiO2 and considerable
degradation occurred during the prolonged irradiation time
of 18 h (94% conversion). The kinetic isotope effect for the
consumption of 1 was estimated to be 3.5.[23] Such effects
were not observed in the homogeneous reaction.
The results clearly show significant differences between
the heterogeneous and the homogeneous catalytic reactions
in the rearomatization step. In order to explain these obser-
vations, we propose different mechanisms for the homo-
geneous and the heterogeneous catalyses (Scheme 3). As
previously discussed, the rearomatization of D proceeds in
two steps.[10,20] The radical anion F is obtained by electron
transfer from D to 1; cation E, which resembles the σ com-
plex of an electrophilic substitution, is also produced. This
step is followed by proton release from E. Two mesomeric
structures of F preponderate depending on whether the in-
termediate is dissolved in the reaction mixture or adsorbed
by the semiconductor via the carbonyl oxygen atom. (For
references on complexation of carbonyl and carboxy func-
tions, see refs.[19,24]) In the first case (FЈ), the negative
charge is localized near the oxygen atom while in the second
case (F"), this charge is displaced towards the β-carbon
atom. The latter structure is favored in the heterogeneous
system because the semiconductor particle is in a reductive
environment (large excess of 2) which makes the potential
of the conduction band more negative. While it is ir-
radiated, the particle acquires a negative charge by electron
Scheme 3
transfer from the tertiary amine to the hole in the valence of the adsorbed radical anion is pushed away from the sur-
band. This charge causes polarization of any adsorbed par- face. Despite the coulombic repulsion FЈЈ remains adsorbed
ticles or molecules at the surface such that negative charge on the semiconductor due to
a
strong specific
is pushed away from the surface. Hence, the negative charge metalϪoxygen interaction.[13,24,25] Therefore, the radical
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Diastereoselective Radical Tandem Addition-Cyclization Reactions of Aromatic Tertiary Amines
FULL PAPER
anion FЈЈ is protonated at the β-position. In the case of
homogeneous catalysis, however, protonation occurs at the
enolate and after tautomerization, the proton or the deu-
terium (when 2Ј is used) is localized at the α-position. Due
to the fact that FЈЈ is adsorbed by the semiconductor, pro-
tonation preferentially takes place with protons that are on
the surface (compare ref.[19,26]). This may explain why no
deuterium is transferred when 2Ј is used under hetero-
geneous reaction conditions. There is less deuterium on the
semiconductor surface when the deuterium originates from
the corresponding intermediate E (aH ϭ 2H, bH ϭ 1H), and
therefore deuteration of FЈЈ is unlikely. The redox potential
of D is sufficiently negative to reduce 1, as is observed un-
der homogeneous reaction conditions. The results presented
here indicate that the rearomatization step is catalyzed by Scheme 4
the semiconductor, but this must only be a surface effect
since the reduction of 1 to 4 or 5 was not observed when
tivity at the chiral center at the α-position to the nitrogen
atom was significantly increased and the isomers 9a and 9b
were formed in a ratio of about 2:1.
aliphatic tertiary amines were added to 1 or similar elec-
tron-deficient alkenes under the same heterogeneous
reaction conditions.[18,19] Therefore, it can be assumed that
electron transfer from the conduction band to 1 does not
occur. The isolation of tetrahydroquinoline derivatives 3a,b
in comparable yields to the reduction products 4 and 5
further supports the proposed mechanism.
When 2ЈЈ is used, the transfer of deuterium occurs one
step later in the mechanism, as illustrated in Scheme 3. In
the case of the homogeneous reaction, the hydroxyallyl in-
termediate G is deuterated leading to the menthyloxylac-
tone 4ЈЈ. In the case of the heterogeneous reaction, the
oxaallyl radical H is reduced either by electron transfer
from the semiconductor particle followed by proton trans-
fer leading to 4 or by deuterium transfer from 2ЈЈ leading
to 4Ј.[27] In contrast to the first hydrogen transfer, which
almost only occurs from the semiconductor surface, the
transfer from 2ЈЈ competes with that from the surface be-
cause the aromatic tertiary amine is applied in large excess.
These effects also explain the results obtained for the
deuteration of the second side product 5. FЈЈ and G are
nucleophilic in character and readily add to 1. For the
reasons indicated above, in this case again, deuterium is
only transferred from 2ЈЈ.
When higher N-substituted aniline derivatives like N-phe-
nylpyrrolidine (8) react with 1 under homogeneous catalysis
conditions, secondary α-aminoalkyl radicals were formed as
intermediates. Their addition to 1 occurred with complete
facial diastereoselectivity. However, the configuration at the
α-position to the nitrogen atom could not be controlled and
two diastereoisomers 9a,b were obtained in almost equal
amounts.[10] We wondered whether this selectivity could be
influenced by performing the reaction under heterogeneous
conditions using TiO2 as the sensitizer. Under the reaction
conditions described above 8 was added to 1 (Scheme 4).
The reaction rate was lower. After 8 h of irradiation, the
conversion reached 53%. Once again the side products 4
and 5 were isolated. As was previously observed under the
homogeneous reaction conditions, the products 9a,b were
obtained with complete facial stereoselectivity. However,
Conclusions
We have shown that the diastereoselective tandem ad-
dition-cyclization reaction of N,N-dimethylaniline (2) with
the menthyloxyfuranone 1 can be performed by photo-
chemically induced electron transfer using inorganic semi-
conductors as sensitizers. In this way, the concept of hetero-
geneous catalysis was applied which simplified product iso-
lation. The whole reaction occurred at the surface of the
semiconductor particle. Two types of catalysis can be dis-
tinguished. On the one hand, steps involving electron trans-
fer to the valence band (oxidation of the amine) or from
the conduction band (reduction of the oxaallyl radicals) are
observed. Of course, these steps can only occur with ad-
sorbed molecules. On the other hand, steps involving only
the surface of the semiconductor particles are detected (e.g.
electron transfer from D to 1). Significant differences in the
rearomatization step of the homogeneous and hetero-
geneous reactions have been detected by isotopic labeling
experiments. These differences result from polarization ef-
fects at the surface of the semiconductor. Based on these
mechanistic results, we are currently trying to optimize the
reaction and in particular to reduce the quantity of the re-
duction side products.
Experimental Section
General Methods: NMR spectra were recorded with a Bruker AC
250 (250 MHz for 1H and 62 MHz for 13C) or Bruker DRX 500
spectrometer (500 MHz for 1H and 126 MHz for 13C). Chemical
shifts are given in ppm relative to tetramethylsilane as an internal
standard. MS spectra were recorded with a JEOL D-300 spec-
trometer. [α] values were recorded with a PerkinϪElmer 241 polar-
imeter. Preparative chromatography was carried out with Merck
art 9385 Kieselgel 60. Commercial TiO2 (99% anatase, from
AGROS), SnO2 (from AGROS), ZnS (Prolabo) and SiC (Aldrich)
compared with the homogeneous reaction, the stereoselec- were used as sensitizers.
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S. Marinkovic, N. Hoffmann
FULL PAPER
Radical Tandem Reaction of Menthyloxyfuranone 1 with N,N-Di-
methylaniline (2): After being degassed with argon, a well-stirred
suspension of the semiconductor (0.1 mol-equiv. with respect to
1) in a solution of (5R)-menthyloxyfuran-2(5H)-one (1) (500 mg,
2.1 mmol) and N,N-dimethylaniline (2) (6 mL) in acetonitrile (40
mL) was irradiated in a pyrex tube (diameter: 2 cm) at 350 nm
(Rayonet reactor) for 5 h. The reaction mixture was filtered
through Celite before evaporation of 2 and the solvent. The residue
was purified and separated by flash chromatography on silica gel
(eluent: ethyl acetate/petroleum ether).
(46), 216 (100), 139 (84). C28H46O6 (478.66): calcd. C 70.54, H 9.31;
found C 70.30, H 9.19. For further characterizations see ref.[10]
Radical Tandem Reaction of Menthyloxyfuranone 1 with N-Phenyl-
pyrrolidine (8): After being degassed with argon, a well-stirred sus-
pension of TiO2 (12 mg, 0.15 mmol, 0.1 mol-equiv. with respect to
1) in a solution of (5R)-menthyloxyfuran-2(5H)-one (1) (375 mg,
1.6 mmol) and N-phenylpyrrolidine (8) (5.5 g) in acetonitrile (30
mL) was irradiated in a pyrex tube (diameter: 2 cm) at 350 nm
(Rayonet reactor) for 8 h. The reaction mixture was filtered
through Celite before evaporation of 8 and the solvent. The residue
was purified and separated by flash chromatography on silica gel
(eluent: ethyl acetate/petroleum ether). After 8 h of irradiation the
conversion was 53%.
Tetrahydroquinoline 3a: M.p. 116 °C. [α]2D1 ϭ Ϫ206.9 (c ϭ 0.98,
1
CH2Cl2). H NMR (CDCl3): δ ϭ 0.82 (d, J ϭ 6.9 Hz, 3 H), 0.92
(d, J ϭ 7.6 Hz, 3 H), 0.94 (d, J ϭ 6.9 Hz, 3 H), 0.79Ϫ1.07 (m, 3
H), 1.21Ϫ1.47 (m, 2 H), 1.58Ϫ1.72 (m, 2 H), 2.07Ϫ2.17 (m, 2 H),
2.76Ϫ2.91 (m, 2 H), 2.85 (s, 3 H), 3.21 (m, 1 H), 3.57 (td, J ϭ 10.7,
4.2 Hz, 1 H), 3.84 (d, J ϭ 6.9 Hz, 1 H), 5.49 (d, J ϭ 1.5 Hz, 1 H),
6.68 (d, J ϭ 8.4 Hz, 1 H), 6.82 (td, J ϭ 7.2, 1.1 Hz, 1 H), 7.17 (td,
J ϭ 8.4, 1.1 Hz, 1 H), 7.46 (d, J ϭ 7.2 Hz, 1 H) ppm. 13C NMR
(CDCl3): δ ϭ 15.7, 20.8, 22.2, 23.2, 25.5, 31.3, 34.3, 39.4, 39.9,
40.4, 41.1, 47.7, 49.9, 77.2, 101.5, 112.0, 116.9, 118.4, 128.3, 130.5,
146.8, 175.5 ppm. C22H31NO3 (357.23): calcd. C 73.90, H 8.99, N
3.92; found C 73.62, H 8.99, N 3.80. For further characterizations
see ref.[10]
Benzoindolizidine Derivative 9a: M.p. 130 °C. [α]2D1 ϭ Ϫ115.2 (c ϭ
1
1.00, CH2Cl2). H NMR (CDCl3): δ ϭ 0.74 (d, J ϭ 6.9 Hz, 3 H),
0.84 (d, J ϭ 6.9 Hz, 3 H), 0.88 (d, J ϭ 7.6 Hz, 3 H), 0.70Ϫ1.00 (m,
3 H), 1.03Ϫ1.38 (m, 2 H), 1.53Ϫ1.72 (m, 4 H), 1.83Ϫ2.14 (m, 3
H), 2.22 (dsept, J ϭ 6.9, 2.7 Hz, 1 H), 2.30 (dd, J ϭ 11.0, 7.2 Hz,
1 H), 2.68 (ddd, J ϭ 11.0, 10.0, 5.7 Hz, 1 H), 3.05 (ddd, J ϭ 14.8,
9.1, 4.6 Hz, 1 H), 3.36 (dd, J ϭ 14.8, 8.8 Hz, 1 H), 3.51 (td, J ϭ
10.7, 4.2 Hz, 1 H), 3.80 (d, J ϭ 7.2 Hz, 1 H), 5.47 (s, 1 H), 6.45 (d,
J ϭ 8.0 Hz, 1 H), 6.69 (dd, J ϭ 7.6, 7.2 Hz, 1 H), 7.08 (dd, J ϭ
7.6, 7.2 Hz, 1 H), 7.39 (d, J ϭ 7.2 Hz, 1 H) ppm. 13C NMR
(CDCl3): δ ϭ 15.7, 20.9, 22.2, 22.7, 23.2, 25.7, 30.8, 31.4, 34.3,
39.7, 40.0, 45.6, 46.6, 47.7, 55.9, 77.5, 100.3, 111.7, 115.5, 117.3,
128.3, 130.7, 144.3, 176.1 ppm. C24H33NO3 (383.26): calcd. C
75.14, H 9.20, N 3.65; found C 74.99, H 8.96, N 3.56. For further
characterizations see ref.[10]
Tetrahydroquinoline 3b: [α]2D1 ϭ Ϫ52.4 (c ϭ 0.42, CH2Cl2). 1H
NMR (CDCl3): δ ϭ 0.71 (d, J ϭ 6.9 Hz, 3 H), 0.82 (d, J ϭ 7.6 Hz,
3 H), 0.89 (d, J ϭ 6.9 Hz, 3 H), 0.79Ϫ1.07 (m, 3 H), 1.18Ϫ1.39
(m, 2 H), 1.52Ϫ1.65 (m, 2 H), 2.01Ϫ2.14 (m, 2 H), 2.81Ϫ2.94 (m,
2 H), 2.83 (s, 3 H), 3.21 (dd, J ϭ 12.0, 4.7 Hz, 1 H), 3.56 (td, J ϭ
10.7, 4.2 Hz, 1 H), 3.64 (d, J ϭ 7.1 Hz, 1 H), 5.80 (d, J ϭ 4.4 Hz,
1 H), 6.61 (d, J ϭ 8.0 Hz, 1 H), 6.73 (td, J ϭ 7.4, 1.0 Hz, 1 H),
7.11 (td, J ϭ 8.5, 1.4 Hz, 1 H), 7.33 (d, J ϭ 7.2 Hz, 1 H) ppm. 13C
NMR (CDCl3): δ ϭ 15.9, 20.9, 22.2, 23.2, 25.6, 31.4, 34.3, 38.0,
39.6, 39.8, 43.1, 47.4, 47.8, 78.6, 100.2, 111.8, 116.3, 117.8, 128.5,
130.7, 146.9, 173.9 ppm. C22H31NO3 (357.23): calcd. C 73.90, H
8.99, N 3.92; found C 73.66, H 8.96, N 3.78. For further charac-
terizations see ref.[10]
Benzoindolizidine Derivative 9b: M.p. 124 °C. [α]2D1 ϭ Ϫ109.9 (c ϭ
1
1.00, CH2Cl2). H NMR (CDCl3): δ ϭ 0.74 (d, J ϭ 6.9 Hz, 3 H),
0.83 (d, J ϭ 6.9 Hz, 3 H), 0.93 (d, J ϭ 7.6 Hz, 3 H), 0.69Ϫ0.97 (m,
3 H), 1.10Ϫ1.34 (m, 2 H), 1.51Ϫ1.67 (m, 4 H), 1.81Ϫ2.09 (m, 3
H), 2.16 (dsept, J ϭ 6.9, 2.7 Hz, 1 H), 2.83Ϫ2.99 (m, 2 H), 3.18
(ddd, J ϭ 11.8, 6.9, 3.4 Hz, 1 H), 3.40Ϫ3.55 (m, 2 H), 3.89 (d, J ϭ
9.5 Hz, 1 H), 5.63 (d, J ϭ 6.5 Hz, 1 H), 6.48 (dd, J ϭ 8.4, 0.8 Hz,
1 H), 6.68 (dt, J ϭ 7.2, 0.8 Hz, 1 H), 7.07 (dt, J ϭ 8.4, 0.8 Hz, 1
H), 7.42 (dd, J ϭ 7.2, 0.8 Hz, 1 H) ppm. 13C NMR (CDCl3): δ ϭ
15.9, 21.0, 22.3, 22.7, 23.1, 25.3, 27.3, 31.4, 34.3, 40.0, 43.7, 45.6,
47.1, 48.0, 55.8, 78.2, 101.0, 112.3, 116.8, 118.0, 128.4, 129.2, 146.1,
174.4 ppm. C24H33NO3 (383.26): calcd. C 75.14, H 9.20, N 3.65;
found C 74.93, H 8.91, N 3.59. For further characterizations see
ref.[10]
Lactone 4: M.p. 58 °C. [α]2D1 ϭ Ϫ141.3 (c ϭ 0.86, CH2Cl2). 1H
NMR (CDCl3): δ ϭ 0.78 (d, J ϭ 6.9 Hz, 3 H), 0.88 (d, J ϭ 7.1 Hz,
3 H), 0.93 (d, J ϭ 6.6 Hz, 3 H), 0.65Ϫ1.07 (m, 3 H), 1.15Ϫ1.28
(m, 1 H), 1.30Ϫ1.45 (m, 1 H), 1.60Ϫ1.71 (m, 2 H), 2.03Ϫ2.15 (m,
3 H), 2.33 (m, 1 H), 2.43 (ddd, J ϭ 18.1, 9.5, 3.4 Hz, 1 H), 2.67
(td, J ϭ 17.6, 9.5 Hz, 1 H), 3.52 (td, J ϭ 10.7, 4.2 Hz, 1 H), 5.72
(dd, J ϭ 5.3, 1.9 Hz, 1 H) ppm. 13C NMR (CDCl3): δ ϭ 15.5,
20.8, 22.2, 23.0, 25.4, 27.0, 29.1, 31.3, 34.2, 39.7, 47.7, 76.5, 100.3,
176.7 ppm. C14H24O3 (240.17): calcd. C 69.95, H 10.07; found C
69.71, H 9.79. For further characterizations see ref.[10]
Acknowledgments
`
S. M. thanks the Ministere de la Recherge for a doctoral fellowship.
The reaction of 1 with deuterated aniline derivatives 2Ј and 2ЈЈ
was carried out with ZnS and TiO2 under the same conditions as
described above. The irradiation times are indicated in Table 2. For
the synthesis of 2Ј see refs.[10,28] and for the synthesis of 2ЈЈ see
refs.[10,23e,29] The position and the amount of deuterium
incorporated into 4Ј, 4ЈЈ and 5Ј was determined by 1H and 13C
NMR spectroscopy.
The work was funded by the CNRS and the Deutsche Forschungs-
gemeinschaft in the context of a French-German bilateral re-
search project.
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