First asymmetric synthesis of both enantiomers of Tropional and their olfactory evaluation

Article abstract of DOI:10.1016/j.tetasy.2004.04.026

The first asymmetric synthesis of both enantiomers of Tropional is accomplished by asymmetric alkylation by employing the SAMP/RAMP-hydrazone method, respectively. The alkylated hydrazones were oxidatively cleaved with magnesium-monoperoxyphthalate (MMPP). Subsequent reduction of the resulting nitriles with diisobutyl aluminium hydride (DIBAL-H) led to the desired aldehydes in good overall yields (52-53%) and enantiomeric excesses (ee=90%). Furthermore, the olfactory evaluation of both enantiomers showed remarkable differences in odour quality and intensity.

Full text of DOI:10.1016/j.tetasy.2004.04.026

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 1813–1817
First asymmetric synthesis of both enantiomers of Tropionalâ
and their olfactory evaluation
Dieter Enders* and Michael Backes
Institut f€ur Organische Chemie, Rheinisch-Westf€alische Technische Hochschule, Professor-Pirlet-Straße 1, 52074 Aachen, Germany
Received 15 April 2004; accepted 22 April 2004
Abstract—The first asymmetric synthesis of both enantiomers of Tropionalâ is accomplished by asymmetric alkylation by
employing the SAMP/RAMP-hydrazone method, respectively. The alkylated hydrazones were oxidatively cleaved with magnesium-
monoperoxyphthalate (MMPP). Subsequent reduction of the resulting nitriles with diisobutyl aluminium hydride (DIBAL-H) led to
the desired aldehydes in good overall yields (52–53%) and enantiomeric excesses (ee ¼ 90%). Furthermore, the olfactory evaluation
of both enantiomers showed remarkable differences in odour quality and intensity.
Ó 2004 Elsevier Ltd. All rights reserved.
1. Introduction
synthesis employing our SAMP/RAMP-hydrazone
methodology.7 The synthesis of hydrazones 2 was
achieved by reaction of freshly distilled propanal 1 with
the corresponding hydrazines in good yields using
standard conditions (Scheme 1).8
Many well-known odourants are chiral compounds with
their enantiomers sometimes exhibiting totally different
scents [e.g., (þ)-carvone: caraway; (ꢀ)-carvone: spear-
mint] and odour thresholds. Brenna et al. recently
published a review about the enantioselective perception
of chiral odourants.1 Tropionalâ is an a-branched
aldehyde, which is used in many perfumes that present a
marine, fresh note.2 In industry it is produced as a
racemate via aldol condensation of piperonal and
propanal and subsequent hydrogenation3 with an an-
nual production of about 300–350 tons.4 To the best of
our knowledge no asymmetric synthesis of Tropionalâ
has been published. Furthermore nothing is known
about the odour of the two enantiomers, although the
human receptor for the recognition of Tropionalâ has
been known for a few years.5 Today this class of a-
branched aldehydes is of considerable interest, as some
promote the directed migration of sperm to the egg, and
so may allow fertilization to be manipulated.6
*
NR2
O
a
N
H3C
85-92%
H3C
H
H
1
2
b
72-76%
NR2
H
N
*
O
O
de = 90%
CH3
3
O
O
*
NR2
Br
=
OCH3
,
OCH3
;
N
N
4
Scheme 1. Synthesis of the alkylated hydrazones 3. Reagents and
conditions: (a) H2NNRꢁ2, molecular sieves; (b) base, THF, 4 (Table 1).
2. Results and discussion
2.1. Asymmetric synthesis of Tropionalâ
In our first attempt, hydrazone 2 was deprotonated with
lithium diisopropylamide (LDA) and reacted with 5-
(bromomethyl)-1,3-benzodioxole 4 in THF at ꢀ78 °C.
This reaction led only to a moderate diastereomeric
excess of de ¼ 74%. As it was not possible to determine
the diastereomeric excesses of this reaction by NMR or
Herein, we report the asymmetric synthesis of both
enantiomers of Tropionalâ via an efficient four step
* Corresponding author. Tel.: +49-241-8094676; fax: +49-241-80921-
27; e-mail: enders@rwth-aachen.de
0957-4166/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.04.026

1814
D. Enders, M. Backes / Tetrahedron: Asymmetry 15 (2004) 1813–1817
Table 1. Variation of the a-alkylation conditions
24
D
Entry
Hydrazone
Base
Temperature (°C)
Product
Yield
½aꢂ
––
De (%)a
1
2
3
4
(S)-2
(S)-2
(R)-2
(S)-2
LDA
LDA
LDA
LTMP
ꢀ78
ꢀ100
ꢀ100
ꢀ100
(S)-3
(S)-3
(R)-3
(S)-6
65
76
71
37b
74
90
90
89
þ43.7
ꢀ44.7
––
a Determined by chiral stationary phase HPLC of the corresponding alcohols 7.
b Direct conversion of the crude hydrazone (S)-3 to aldehyde (S)-6.
HPLC, the selectivity was proven by HPLC on a chiral
stationary phase of the corresponding alcohols 7. In
order to improve the diastereomeric excess, the tem-
perature was lowered to ꢀ100 °C. This resulted in an
increase of the observed diastereomeric excess to
de ¼ 90% (Table 1, entries 2 and 3). The change of the
lithium base from LDA to lithium tetramethylpiperidide
(LTMP) led to no significant change in the diastereo-
meric excess. A change of the solvent from THF to Et2O
also proved ineffective due to low solubility of bromide
4.
Et2O. At this stage the enantiomeric excess could be
determined by HPLC on a chiral stationary phase to be
ee ¼ 90%. The absolute configuration of 6 was based on
the general stereochemical outcome of the asymmetric-
alkylation employing SAMP/RAMP hydrazones as
chiral auxiliaries.7
2.2. Olfactory evaluation
The enantiomers of Tropionalâ 6 showed different
odour characteristics (Table 2). Regarding the odour
intensity the (S)-enantiomer (S)-6 was about five times
stronger than the (R)-enantiomer (R)-6. With respect to
the odour quality some striking differences were also
detected.
For cleavage of the hydrazones, a great variety of
methods are available.9 As the cleavage with ozone was
not successful, the ‘salt method’ was applied. Similar to
the preparation of Lilialâ, the desired aldehyde was
obtained by refluxing hydrazones 3 in methyl iodide
with subsequent hydrolysis in a two-phase system of 4 M
aqueous HCl and pentane.10 Unfortunately this proce-
dure only gave moderate yields. The direct hydrolysis of
the hydrazones in a two-phase system of 4 M aqueous
HCl and pentane resulted in a significant drop in
enantiomeric excess to ee ¼ 79%. However, cleavage was
successful by utilizing a two step procedure (Scheme
2).11
Table 2. Olfactory evaluation of both enantiomers of Tropionalâ
(S)-Tropionalâ
(R)-Tropionalâ
Yield (%)a
53
90
90
90
Ee (%)b
22
D
½aꢂ
Odour description
ꢀ2.8
þ3.3
ꢃ Green floral
ꢃ Floral (cyclamen/
lily of the valley)
ꢃ Marine, ozone like ꢃ Aldehydic
ꢃ Cumin like
0.64 ng/L
ꢃ Citrus like
3.43 ng/L
*
NR2
N
Odour threshold
value
CN
*
*
O
O
O
O
a
H
a Overall yield.
CH3
CH3
92-93%
b Determined by chiral stationary phase HPLC of the corresponding
alcohols 6.
3
5
86-87%
b
The (S)-enantiomer exhibited a green-floral odour with
a marine and ozone like note reminiscent of saltwater, as
well as a sweet fruity cumin like scent. Thus, the
(S)-enantiomer represented the typical odour of the
industrially used racemate of Tropionalâ. In contrast,
the (R)-enantiomer showed a floral scent reminding on
cyclamen and lily of the valley. Furthermore this enan-
tiomer smelled aldehydic with a sweet fruity citrus like
note.4
O
*
*
O
O
O
c
OH
H
CH3
CH3
93-95%
O
6 (Tropional®
)
7
ee = 90% (S)-7
ee = 90% (R)-7
Scheme 2. Synthesis of Tropionalâ by cleavage of the hydrazones 3.
Reagents and conditions: (a) MMPP, MeOH, pH 7 buffer, 0 °C; (b)
DIBAL-H, THF, 0 °C; (c) BH3ÆEt2O.
It is worth mentioning, that the marine scent––typical
for racemic Tropionalâ––was completely missing.
Moreover, compared with the similar aldehyde Lilialâ,
also prepared in our group,10 the odour intensity of the
single enantiomers was different. Whereas in the case of
Lilialâ the (R)-enantiomer exhibited a slightly stronger
scent, the (S)-enantiomer of Tropionalâ showed a
remarkably stronger odour and the differences in odour
quality were more considerable, too.
In the first step the N,N-bond was cleaved under oxi-
dative conditions with MMPP to give nitriles 5 in very
good yields. After reduction with DIBAL-H in THF at
0 °C, both enantiomers of Tropionalâ 6 could be
obtained in 80% yield over two steps. To determine the
enantiomeric excess, the aldehydes were reduced to the
corresponding alcohols by employing BH3ÆDMS in

D. Enders, M. Backes / Tetrahedron: Asymmetry 15 (2004) 1813–1817
1815
3. Conclusion
4.2.2. N-[(S)-2-methoxymethylpyrrolidin-1-yl]propan-1-
imine (S)-2. The enantiomeric hydrazone was prepared
in the same way as (R)-2 by reaction of 20.277 g
(155.7 mmol) of SAMP and 14.0 mL (190.2 mmol) of
In summary, we have successfully applied our hydra-
zone-alkylation strategy in the first asymmetric synthesis
of Tropionalâ 6. Both enantiomers were obtained in
good yields and high enantiomeric excesses. The olfac-
tory evaluation showed remarkable differences in odour
intensity as well as in odour quality between both
enantiomers. Obviously, the scent of the industrially
used racemic Tropionalâ is determined mainly by the
(S)-enantiomer.
propanal 1 yielding 24.451 g (143.6 mmol, 92%) of
23
D
hydrazone (S)-2. ½aꢂ ¼ ꢀ143:3 (c 1.11, CHCl3). {Lit.8
25
½aꢂ ¼ ꢀ145:2 (neat)}. The spectroscopic data corre-
D
spond with those of the literature.8
4.2.3. (2R)-3-(1,3-Benzodioxole-6-yl)-N-[(R)-2-methoxy-
methylpyrrolidin-1-yl]-2-methyl-propan-1-imine (R,R)-3.
To a solution of 11.2 mmol of lithium diisopropyl-
amide [LDA, prepared from 1.6 mL (11.3 mmol) diiso-
propyl-amine and 7.0 mL (11.2 mmol) n-butyllithium in
20 mL of anhydrous THF at 0 °C] 1.698 g (10.0 mmol) of
the hydrazone (R)-3 was slowly added and the reaction
stirred for 3.5 h at 0 °C. After cooling to ꢀ100 °C,
2.276 g (10.6 mmol) of 5-(bromomethyl)-1,3-benzodiox-
ole 4 dissolved in 5 mL anhydrous THF was added very
slowly. The reaction was allowed to warm to room
temperature overnight. After addition of satd aq NH4Cl
solution (10 mL) the two layers were separated and the
aqueous layer extracted with Et2O. The combined
organic layers were washed with satd aq NaHCO3
solution, brine and dried over MgSO4. After evapora-
tion of the solvent, the residue was purified by column
chromatography (silica, pentane–Et2O 4:1 þ 5% NEt3)
and the hydrazone (R,R)-3 (2.321 g, 7.6 mmol, 76%)
obtained as a colourless oil. Rf (silica, pentane–Et2O,
4:1): 0.38. De P90% (HPLC of the corresponding
4. Experimental
4.1. General
n-Butyllithium (1.6 M in hexane) was purchased from
Merck, Darmstadt. DIBAL-H (1.0 M in dichlorome-
thane) and BH3ÆDMS (2.0 M in THF) were purchased
from Aldrich. SAMP/RAMP8 and 5-(bromomethyl)-
1,3-benzodioxole12 4 were prepared according to the
literature. All reactions employing organometallic
compounds were carried out under argon using stan-
dard Schlenk techniques. IR spectra were recorded on a
Perkin–Elmer 1760 FT-IR spectrometer. 1H and 13C
NMR spectra were recorded at 300 or 400 MHz and 75
or 100 MHz, respectively, on Varian Mercury 300 or
Varian Inova 400 spectrometers.3 JH;H coupling con-
stants are expressed in Hz. All measurements were per-
formed in CDCl3 and chemical shifts expressed in ppm
(d) with tetramethylsilane as an internal standard. Mass
spectra (MS) were obtained on a Finnigan SSQ 7000.
Optical rotations were measured on a Perkin–Elmer P
241 polarimeter. Elemental analyses were carried out on
Elementar Vario EL. Determination of the enantiomeric
excesses was accomplished by analytical HPLC on a
chiral stationary phase using a Hewlett Packard 1050
with UV-detector (DAD) utilizing a Chiracel OD
(250 mm ꢄ 4.6 mm), as eluent a mixture of n-heptane/
i-propanol 95/5 was employed.
24
1
alcohol (R)-6). ½aꢂ ¼ þ43:7 (c 1.17, CHCl3). H NMR
D
(400 MHz): d 1.01 (d, 3H, J ¼ 6), 1.78 (m, 1H), 1.89 (m,
3H), 2.47 (dd, 1H, J ¼ 8:1=13:4), 2.55 (m, 1H), 2.66 (q,
1H, J ¼ 8:2), 2.77 (dd, 1H, J ¼ 6:2=13:4), 3.35 (m, 3H),
3.37 (s, 3H), 3.55 (dd, 1H, J ¼ 3:9=9:1), 5.89 (s, 2H),
6.52–6.71 (m, 4H). 13C NMR (100 MHz): d 18.28, 22.06,
26.51, 38.76, 41.37, 50.21, 59.06, 63.31, 74.62, 100.51,
107.71, 109.44, 121.87, 133.99, 142.31, 145.37, 147.15.
MS (EI): m=z (%) 304 (22, Mþ), 260 (17), 259 (100), 170
(9), 169 (95), 160 (27), 135 (15), 70 (11). IR (film):
m ¼ 2964, 2881, 1490, 1443, 1341, 1247, 1194, 1120,
1040, 930, 809. Anal. Calcd for C17H24O3N2: C, 67.08;
H, 7.95; N, 9.20. Found: C, 66.95; H, 7.68; N, 9.59.
4.2. Asymmetric synthesis of Tropionalâ
4.2.4. (2S)-3-(1,3-Benzodioxole-6-yl)-N-[(S)-2-methoxy-
methylpyrrolidin-1-yl]-2-methyl-propan-1-imine (S,S)-3.
The enantiomeric hydrazone was prepared in the same
way as (R,R)-3 by reaction of 11.2 mmol of lithium di-
isopropylamide, 1.669 g (10.0 mmol) of hydrazone (S)-3
and 2.195 g (10.2 mmol) of 5-(bromomethyl)-1,3-benzo-
4.2.1. N-[(R)-2-methoxymethylpyrrolidin-1-yl]propan-1-
imine (R)-2. To a mixture of 10.221 g (78.5 mmol) of
ꢀ
RAMP and molecular sieves (4 A) 7.5 mL (101.9 mmol)
of freshly distilled propanal 1 were added slowly at 0 °C.
The reaction was stirred overnight at room temperature
and diluted with Et2O. After filtration, the solvent was
evaporated under reduced pressure and the hydrazone
(R)-2 (11.332 g, 66.6 mmol, 85%) obtained as a colour-
less oil by distillation in vacuo bp ¼ 54–56 °C (1 mbar).
dioxole
4 to obtain hydrazone (S,S)-3 (2.171 g,
7.1 mmol, 71%). De P90% (HPLC of the corresponding
24
alcohol (S)-6). ½aꢂ ¼ ꢀ44:7 (c 1.27, CHCl3). The spec-
D
troscopic data correspond with those of the enantio-
meric hydrazone (R,R)-3.
23
25
½aꢂ ¼ þ144:5 (c 1.59, CHCl3). {Lit.8 ½aꢂ ¼ þ148:3
D
D
1
(neat)}. H NMR (300 MHz): d 1.05 (t, 3H, J ¼ 7:6),
1.75–1.97 (m, 4H), 2.23 (dq, 2H, J ¼ 5:4=7:6), 2.71 (m,
1H), 3.39 (m, 3H), 3.38 (s, 3H), 3.57 (m, 1H), 6.65 (t,
1H, J ¼ 5:4). 13C NMR (75 MHz): d 12.13, 22.17, 26.43,
26.62, 50.44, 59.19, 63.52, 74.89, 140.40. The spectro-
scopic data correspond with those of the literature.8
4.2.5. (2R)-2-Amino-3-(1,3-benzodioxole-5-yl)propannit-
rile (R)-5. A solution of 1.669 g (5.5 mmol) of hydra-
zone (R,R)-3 in methanol (33 mL) was added dropwise
to a suspension of pH 7 buffer (44 mL) and 6.826 g

1816
D. Enders, M. Backes / Tetrahedron: Asymmetry 15 (2004) 1813–1817
(13.8 mmol) of MMPP at 0 °C. After the addition was
complete, the reaction was stirred for 2 h at 0 °C and
then finally diluted with 110 mL of Et2O. The two layers
were separated and the aqueous layer extracted with
Et2O. The combined organic layers were dried over
MgSO4 and after filtration and evaporation of the sol-
vent, the residue was purified by column chromatogra-
phy (silica, pentane–Et2O 4:1). Nitrile (R)-5 (0.971 g,
5.5 mmol, 93%) was obtained as a colourless liquid. Rf
(6.0 mmol) of nitrile (S)-5 and 9.0 mL (9.0 mmol) of
DIBAL-H in dichloromethane to obtain aldehyde (S)-6
(0.944 g, 5.2 mmol, 87%). Ee P90% [HPLC of the cor-
24
responding alcohol (S)-7]. ½aꢂ ¼ ꢀ2:8 (c 1.07, CHCl3).
D
The spectroscopic data correspond with those of the
enantiomeric aldehyde (R)-6.
4.2.9. (2R)-3-(1,3-Benzodioxole-5-yl)-2-methylpropan-1-
ol (R)-7. To a solution of 0.217 g (1.13 mmol) of alde-
hyde (R)-6 in anhydrous THF (11 mL), 2.80 mL
(5.60 mmol) of a solution of BH3ÆDMS in THF were
added slowly at 0 °C. After stirring for 45 min at 0 °C
4 M HCl (11 mL) was slowly added, the cooling bath
removed and the reaction was stirred for another 2 h at
room temperature. The organic layer was separated and
the aqueous layer extracted with Et2O. The combined
organic layers were washed with satd aq sodium thio-
sulfate solution and dried over MgSO4. After evapora-
tion of the solvent the residue was purified by column
chromatography (silica, pentane–Et2O 1:1) and alcohol
(R)-7 (0.208 g, 1.07 mmol, 95%) obtained as a colourless
(silica, pentane–Et2O, 4:1): 0.46. Ee P90% (HPLC of
24
the corresponding alcohol (R)-7). ½aꢂ ¼ ꢀ34:8 (c 1.32,
D
1
CHCl3). H NMR (300 MHz): d 1.31 (d, 3H, J ¼ 6:9),
2.79 (m, 3H), 5.95 (s, 2H), 6.23–6.78 (m, 3H). 13C NMR
(75 MHz): d 17.52, 27.79, 39.74, 101.07, 108.42, 109.31,
122.24, 122.49, 130.55, 146.80, 147.86. MS (EI): m=z (%)
189 (22, Mþ), 136 (10), 135 (100), 77 (12), 51 (7). IR
(film): m ¼ 2934, 2899, 1493, 1445, 1250, 1194, 1103,
1040, 931, 815. Anal. Calcd for C11H11O2N: C, 69.83; H,
5.86; N, 7.40. Found: C, 69.81; H, 5.86; N, 7.84.
4.2.6. (2S)-2-Amino-3-(1,3-benzodioxole-5-yl)propannit-
rile (S)-5. The enantiomeric nitrile was prepared in the
same way as (R)-5 by reaction of 8.063 g (16.3 mmol) of
MMPP in pH 7 buffer (52 mL) and 1.979 g (6.5 mmol) of
the hydrazone (S,S)-3 in methanol (33 mL) to obtain
liquid. Rf (silica, pentane–Et2O, 1:1): 0.35. Ee P90%
22
(HPLC, tR ¼ 22:9 min). ½aꢂ ¼ þ11:1 (c 0.98, CHCl3).
D
1H NMR (400 MHz): d 0.90 (d, 3H, J ¼ 6:6), 1.51 (s,
1H), 1.88 (m, 1H), 2.34 (dd, 1H, J ¼ 8:0=13:7), 2.67 (dd,
1H, J ¼ 6:3=13:5), 3.48 (m, 2H), 5.91 (s, 2H), 6.60–6.73
(m, 3H). 13C NMR (100 MHz): d 16.38, 37.84, 39.33,
67.42, 100.59, 107.87, 109.29, 121.71, 134.21, 145.43,
147.28. MS (EI): m=z (%) 194 (28, Mþ), 136 (29), 135
(100), 105 (5), 77 (9), 51 (5). IR (film): m ¼ 3367, 2956,
2918, 1491, 1442, 1361, 1247, 1191, 1125, 1101, 1039,
935, 865, 808, 771. Anal. Calcd for C11H14O3: C, 68.02;
H, 7.26. Found: C, 68.16; H, 7.55.
nitrile (S)-5 (1.139 g, 6.0 mmol, 92%). Ee P90% [HPLC
24
of the corresponding alcohol (S)-7]. ½aꢂ ¼ þ35:2 (c
D
0.88, CHCl3). The spectroscopic data correspond with
those of the enantiomeric nitrile (R)-5.
4.2.7. (2R)-3-(1,3-Benzodioxole-5-yl)-2-methylpropanal
(R)-6 [(R)-Tropionalâ]. To
a solution of 0.971 g
(5.1 mmol) of nitrile (R)-5 in anhydrous THF (10 mL),
7.7 mL (7.7 mmol) of DIBAL-H in dichloromethane
were added via a syringe pump over 30 min at 0 °C. The
cooling bath was removed and the reaction stirred for
another 2 h at room temperature. It was then poured
into a mixture of 25 mL of a solution of tartaric acid
(25 mL, 1 M) and 10 mL Et2O (10 mL). The organic
layer was separated and the aqueous layer extracted
with Et2O. The combined organic layers were dried over
MgSO4 and after evaporation of the solvent the residue
was purified by column chromatography (silica, pen-
tane–Et2O 4:1). Aldehyde (R)-6 (0.857 g, 4.4 mmol, 86%)
was obtained as a pale yellow liquid. Rf (silica, pentane–
Et2O, 4:1): 0.51. Ee P90% (HPLC of the corresponding
4.2.10. (2S)-3-(1,3-Benzodioxole-5-yl)-2-methylpropan-1-
ol (S)-7. The enantiomeric alcohol was prepared in the
same way as (R)-7 by reaction of 0.213 g (1.11 mmol) of
aldehyde (S)-6 and 2.80 mL (5.60 mmol) of BH3ÆDMS in
THF to obtain alcohol (S)-7 (0.201 g, 1.03 mmol, 93%).
22
Ee P90% (HPLC, tR ¼ 25:0 min). ½aꢂ ¼ ꢀ11:0 (c 1.07,
D
CHCl3). The spectroscopic data correspond with those
of the enantiomeric alcohol (R)-7.
Acknowledgements
24
1
alcohol (R)-7). ½aꢂ ¼ þ3:3 (c 0.98, CHCl3). H NMR
D
(300 MHz): d 1.07 (d, 3H, J ¼ 6:9), 2.59 (m, 2H), 2.99
(dd, 1H, J ¼ 5:6=13:3), 5.91 (s, 2H), 6.59–6.74 (m, 3H),
9.69 (d, 1H, J ¼ 1:5). 13C NMR (75 MHz): d 13.17,
36.39, 48.19, 100.91, 108.24, 109.30, 121.94, 132.52,
146.11, 147.75, 204.34. MS (EI): m=z (%) 192 (34, Mþ),
136 (9), 135 (100), 122 (6), 105 (5), 77 (10), 51 (6). IR
(film): m ¼ 2971, 2895, 1725, 1492, 1444, 1364, 1248,
1193, 1124, 1101, 1039, 932, 813. Anal. Calcd for
C11H12O3: C, 68.74; H, 6.29. Found: C, 68.58; H, 6.27.
This work was supported by the Deutsche Forschungs-
gemeinschaft (Sonderforschungsbereich 380) and the
Fonds der Chemischen Industrie. We thank the com-
panies BASF AG, Bayer AG and Degussa AG for the
donation of chemicals. We owe special thanks to Dr. P.
Kraft (Givaudan Schweiz AG) for carrying out the
olfactory evaluation.
References and notes
4.2.8. (2S)-3-(1,3-Benzodioxole-5-yl)-2-methylpropanal
(S)-6 [(S)-Tropionalâ]. The enantiomeric aldehyde was
prepared in the same way as (R)-6 by reaction of 1.139 g
1. Brenna, E.; Fuganti, C.; Serra, S. Tetrahedron: Asymmetry
2003, 14, 1–42.

D. Enders, M. Backes / Tetrahedron: Asymmetry 15 (2004) 1813–1817
1817
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