A catalytic asymmetric allylation of aldehydes with allyl trichlorosilane activated by a chiral tetradentate bis-sulfoxide

Article abstract of DOI:10.1016/j.tetasy.2009.01.023

Chiral homoallylic alcohols are easily accessible by asymmetric allylation of aldehydes with allyl trichlorosilane in the presence of catalytic amounts of a chiral tetradentate bis-sulfoxide, as organocatalyst, whose synthesis is reported.

Full text of DOI:10.1016/j.tetasy.2009.01.023

Tetrahedron: Asymmetry 20 (2009) 202–204
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A catalytic asymmetric allylation of aldehydes with allyl trichlorosilane
activated by a chiral tetradentate bis-sulfoxide
a
a
b
a,
Antonio Massa a, , Maria Rosaria Acocella , Vincenzo De Sio , Rosaria Villano , Arrigo Scettri
*
*
a Dipartimento di Chimica, Università di Salerno, Via Ponte don Melillo, 84084 Fisciano, Salerno, Italy
b Istituto di Chimica Biomolecolare-CNR, trav. La Crucca 3, Reg. Baldinca, 07040 Li Punti, Sassari, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Chiral homoallylic alcohols are easily accessible by asymmetric allylation of aldehydes with allyl trichlo-
rosilane in the presence of catalytic amounts of a chiral tetradentate bis-sulfoxide, as organocatalyst,
whose synthesis is reported.
Received 12 November 2008
Accepted 27 January 2009
Available online 23 February 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
tioselective metal-free allylation of aldehydes by using allyl
trichlorosilane as the allyl group transfer reagent.
Chiral homoallylic alcohols are among the most valuable build-
ing blocks for the synthesis of complex molecules.1 The typical pre-
parative approach is represented by the allylation of carbonyl
compounds, and recently many stereoselective procedures have
been reported.2 In particular, allyl trichlorosilane has recently pro-
ven to be a very useful allylating agent: in fact, its activation by
strong neutral Lewis bases, such as N,N-dimethyl formamide,3
was found to result in the formation of a hypervalent silicon com-
pound capable of reacting with suitable electrophiles. As regards
the allylation of carbonyl compounds, the allyl group transfer
through a cyclic six-membered transition state has been exploited
in a variety of enantioselective procedures involving the use of chi-
ral phosphoramides,4 N-oxides,5 formamides,6 ureas,7 and phos-
phine oxides.8
Sulfoxides have been widely exploited as chiral auxiliaries in
many fundamental C–C bond-forming reactions.9 Nevertheless,
their use, as Lewis bases, in allylation reactions with allyl trichlo-
rosilane has found rather modest applications. In fact, while the
allylation of N-acylhydrazones proceeded with good yields and
high enantioselectivities,10 less satisfactory results were obtained
in the allylation of aldehydes.11 Furthermore, the main disadvan-
tage of both the above reactions is represented by the use of the
organocatalysts in high excess (3 equiv) to get the best levels of
enantioselectivity. No significant improvement was observed by
using bidentate mono-sulfoxides (1 equiv),12 while the allylation
of benzoyl hydrazones took place with high enantiomeric excesses
in the presence of chiral sulfoxides10 as well as C2 symmetric bis-
sulfoxides13,14 although relevant organo-catalyst loading was again
required (1–3 equiv).
2. Results and discussion
The key-step of the synthesis of bis-sulfoxide 4 is represented
by the enantioselective sulfoxidation of the commercially available
sulfide 1 (Scheme 1), performed through a suitable modification of
Modena’s protocol:15 in fact, by treatment with cumyl hydroperox-
ide (CHP) in the presence of titanium tetraisopropoxide/(R,R)-
diethyl tartrate (DET) complex at À20 °C, 1 was converted into
the corresponding chiral sulfoxide 2 in 81% yield and 80% ee.
O
O
Ti(OiPr)4 / (R,R)-DET
H
H
CHP, CH2Cl2, -20 ºC
S
S
O
2
1
Scheme 1.
Only one crystallization from diethyl ether gave 2 in 71% yield
(calculated on the starting material 1) and 96% ee. The (R)-absolute
configuration was assigned by reducing 2 with NaBH3CN (49%
yield) and comparing the sign of the specific rotation with the
one of the known (R)-alcohol 316 (Scheme 2).
Finally, bis-sulfoxide 4 was obtained through a modification of a
known procedure17 by reacting 2 with ethylenediamine in reflux-
ing methanol (95% yield), Scheme 3. 1H NMR analysis (400 MHz)
of the purified product did not exhibit the typical signals of
meso-4,17 confirming that no significant change of the absolute
configuration of the stereogenic centers had been caused by the
above treatment.
Herein, we report a very simple approach to a chiral tetraden-
tate bis-sulfoxide of type 4 and its application in a catalytic enan-
* Corresponding authors. Tel.: +39 089 969583; fax: +39 089 969603 (A.S.).
E-mail address: scettri@unisa.it (A. Scettri).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.01.023

A. Massa et al. / Tetrahedron: Asymmetry 20 (2009) 202–204
203
enantioselective oxidation of 2-(methylthio)benzaldehyde in the
key-step. Furthermore, the achievement of a new asymmetric
procedure for the allylation of aldehydes with allyl trichlorosi-
lane, involving catalytic amounts of a chiral bis-sulfoxide, can
be considered a notable improvement with respect to the known
procedures, which required strong excesses of mono-sulfoxides
as activators.
O
OH
H
NaBH3CN, CH3CO2H
CH3CN
S
S
O
O
2
3
Scheme 2.
4. Experimental
Preliminary experiments were devoted to verify the possibility
of employment of bis-sulfoxide 4 as an organocatalyst in an allyla-
tion reaction. Benzaldehyde 5a and 5-nitro-2-formyl-furan 5b
were chosen as representative substrates and were reacted with al-
lyl trichlorosilane in the presence of catalytic amounts (0.2 equiv)
of the compound 4.
Under the conditions reported in Scheme 4 and Table 1, the for-
mation of the corresponding chiral homoallylic alcohols 6a and 6b
was found to occur albeit in moderate yields and enantiomeric ex-
cesses (Table 1, entries 1 and 2). Nevertheless, the enhancement of
the organocatalyst loading up to 0.3 equiv resulted in an apprecia-
ble increase in efficiency and enantioselectivity (entries 3 and 4).
The extension of the procedure with results comparable to other
aromatic (entry 6), heteroaromatic (entry 5) and, more interest-
ingly, aliphatic aldehydes (entry 7) foresees a wide field of
applicability.
All reactions were performed in oven-dried (140 °C) or flame-
dried glassware under an atmosphere of dry nitrogen. All the sol-
vents for the reactions were of reagent grade and were dried and
distilled immediately before use (dichloromethane from calcium
hydride, diethyl ether from lithium aluminium hydride). Column
chromatographic purification of products was carried out using Sil-
ica Gel 60 (70–230 mesh, Merck). The reagents (Aldrich and Fluka)
were used without further purification. The NMR spectra were re-
corded on a Bruker DRX 400 (400 MHz, 1H; 100 MHz, 13C). Spectra
were referenced to residual chloroform (7.26 ppm, 1H, 77.23 ppm,
13C). Chemical shifts are reported in ppm, multiplicities are indi-
cated by s (singlet), d (doublet), t (triplet), q (quartet), quint (quint-
ept), m (multiplet) and by br (broad). Coupling constants, J, are
reported in Hertz. Yields are given for isolated products showing
one spot on a TLC plate and no impurities detectable in the NMR
spectrum. IR spectra were recorded on a Bruker Vector 22 (fre-
quencies 400–4000 cmÀ1, resolution 2 cmÀ1). Mass spectrometry
analysis was carried out using an electrospray spectrometer
Waters 4 micro quadrupole. HPLC analyses were performed with
Waters Associates equipment (Waters 2487 Dual l absorbance
Detector) and using a CHIRALPAK AD. CHIRALCEL OD, CHIRALCEL
OB, CHIRALCEL AS column with hexane/isopropyl alcohol mixtures
and flow rates as indicated. Chiral GC (Supelco b-DEX 120 analyses
were performed with FOCUS GC/FID Thermo Scientific. The HPLC
and GC methods were calibrated with the corresponding racemic
mixtures. Optical rotations were measured with a JASCO DIP-
1000 polarimeter.
OH
O
4
, DIPEA, TBAI
SiCl3
+
R
R
H
CH2Cl2, -78 ºC
6
5
Scheme 4.
Table 1
Asymmetric allylation of aldehydes 5
Entry
Cat. 4 (equiv)
R
6
Yielda (%)
ee (%)
1
2
3
4
5
6
7
0.2
0.2
0.3
0.3
0.3
0.3
0.3
Ph
6a
43
61
57
69
65
60
60
47
63
53
66
70
61
62
4.1. (R)-(+)-2-(Methylsulfinyl)benzaldehyde 2
5-NO2-2-Furyl
Ph
5-NO2-2-Furyl
5-NO2-2-Thienyl
p-CNC6H4
6b
6a
6b
6c
6d
6e
In a flame-dried, two-necked, round-bottomed flask, a solution
of cumene hydroperoxide (1.2 mL, 6.0 mmol) in dichloromethane
dry (11.1 mL) was added to a solution of (R,R)-diethyl tartrate
C6H5CH2CH2
(346
l
L, 4.0 mmol), Ti(OiPr)4 (257
lL, 0.99 mmol), and 2-(methyl-
a
All the yields refer to isolated, chromatographically pure compounds whose
structures were confirmed by analytical and spectroscopic data. Enantiomeric
excesses were determined by chiral HPLC analysis. Absolute configurations were
assigned to compounds 6a (S),4k 6d (S),4k and 6e (R)5e by comparison of the specific
rotations with the literature data. (S)-Absolute configuration was assigned to 6b
thio)benzaldehyde (390
lL, 3.0 mmol) in dry dichloromethane
(11.1 mL) under nitrogen at À18 °C. At the end of the reaction, the
reaction was quenched with saturated aqueous Na2SO3 1 M
(22.0 mL), extracted with (25 Â 3 mL) of CH2Cl2, and dried over
anhydrous Na2SO4. After removing the solvent under reduced pres-
sure, the crude oil was purified by silica gel chromatography with
ethyl acetate. 1H NMR d 2.76 (s, 3H), 7.67 (dt, 1H, J = 7.2 Hz,
J = 1.2 Hz), 7.83 (dt, 1H, J = 7.7 Hz, J = 1.5 Hz), 7.94 (dd, 1H,
J = 7.3 Hz, J = 1.4 Hz), 8.25 (dd, 1H, J = 7.1 Hz, J = 1.5 Hz), 9.98 (s,
1H). 13C NMR d 42.3, 123.4, 129.6, 133.6, 134.2, 191.0. ESI-MS m/z
and 6c by 1H NMR analysis of the corresponding (R)-(À)- and (S)-(+)-
a-methoxy-a-
(trifluoromethyl)phenylacetic acid derivatives.
3. Conclusion
In conclusion, the chiral tetradentate imino-sulfoxide
4
169 [MH]+. [
a]D = +145.8 (c 1.0, CHCl3). Ee 96% (after crystallization
proved to be available through a rapid sequence involving the
O
H
N
N
CH3OH, reflux
NH2CH2CH2NH2
+
2
S
S
S
O
O
O
4
2
Scheme 3.

204
A. Massa et al. / Tetrahedron: Asymmetry 20 (2009) 202–204
from Et2O at 0 °C). The enantiomeric excess was determined by
chiral HPLC (Chiralcel OB, hexane/2-propanol 1:1, 0.6 mL/min,
254 nm, tS = 10.53 min for minor enantiomer, tR = 14.62 min for
major enantiomer). Anal. Calcd for C8H8O2S: C, 57.12; H, 4.79; S,
19.06. Found: C, 57.35; H, 4.68; S, 19.27. Mp 67–69 °C.
4.6. (S)-(À)-1-[(5-Nitro)-2-thienyl]but-3-ene-1-ol 6c
This product was purified by silica gel flash chromatography
with petroleum ether to petroleum ether/Et2O 60:40 mixture as
eluant. 1H NMR d 2.51–2.68 (m, 2H), 2.82 (br s, 1H), 4.97–5.02
(dd, 1H, J = 5.1, 7.3 Hz), 5.19–5.30 (m, 2H), 5.72–5.89 (m, 1H),
6.89–6.91 (dd, 1H, J = 0.9, 4.2 Hz), 7.80 (d, 1H, J = 4.2). 13C NMR d
43.1, 68.8, 119.9, 122.0, 128.3, 131.8, 145.9, 156.8. ESI-MS m/z
4.2. (R,R)-(+)-N1,N2-Bis-(2-(Methylsulfinyl)-benzylidene)-
ethane-1,2-diamine 4
200 [MH]+. [
a]
D = À6 (c 3.0, CHCl3). Ee 70%. The enantiomeric ex-
To
(150.0 mg, 0.89 mmol) in MeOH (7.3 mL) was added ethylenedia-
mine (30.1 L, 0.45 mmol) at room temperature. Then the mixture
a
solution of (R)-(+)-2-(methylsulfinyl)benzaldehyde
cess was determined by chiral HPLC (Chiralcel AD, hexane/2-pro-
panol 95:5, 0.8 mL/min, 254 nm, tS = 18.38 min for minor
enantiomer, tR = 20.29 min for major enantiomer). Anal. Calcd for
C8H9NO3S: C, 48.23; H, 4.55; N, 7.03; S, 16.09. Found: C, 48.42;
H, 4.64; N, 7.23; S, 16.29.
l
was heated at reflux for 22 h. After removing the solvent under re-
duced pressure, the crude oil was purified by silica gel flash chro-
matography with THF/Et2O 2:1. 1H NMR d 2.69 (s, 6H), 3.87–3.90
(m, 2H), 4.02–4.06 (m, 2H), 7.46–7.61 (m, 6H), 8.20 (d, 2H,
J = 8.32 Hz), 8.32 (s, 2H). 13C NMR d 42.9, 60.6, 122.9, 129.2,
130.2, 130.4, 131.5, 146.3, 159.6. ESI-MS m/z 361 [MH]+.
Acknowledgments
We are grateful to Università di Salerno and MIUR for the finan-
cial support.
[a]D = +329.0 (c 0.4, CHCl3). Ee 96%. Anal. Calcd for C18H20N2O2S2:
C, 59.97; H, 5.59; N, 7.77; S, 17.79. Found: C, 59.79; H, 5.77; N,
7.62; S, 17.96. Mp 71–73 °C.
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In a flame-dried, two-necked, round-bottomed flask, allyltri-
chlorosilane (19 L, 0.13 mmol) was added to a solution of sulf-
oxide (0.03 mmol), diisopropylethylamine (20 L, 0.13 mmol),
l
l
and N(Bu)4I (44.3 mg, 0.12 mmol) in dry dichloromethane
(0.6 mL) under nitrogen at À78 °C. After 5 min of stirring at that
temperature, aldehyde was added (0.10 mmol). At the end of the
reaction, the reaction was quenched with saturated aqueous
NaHCO3 (1.0 mL), extracted with 10 Â 3 mL of CH2Cl2, and dried
over anhydrous Na2SO4. After removing the solvent under re-
duced pressure, the crude oil was purified by silica gel flash
chromatography.
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This product was purified by silica gel flash chromatography
with petroleum ether to petroleum ether/Et2O 60:40 mixture as
eluant. 1H NMR d 2.56 (br s, 1H), 2.58–2.74 (m, 2H), 4.83 (t, 1H,
J = 5.5 Hz), 5.19–5.24 (m, 2H), 5.75–5.81 (m, 1H), 6.52 (d, 1H,
J = 3.6 Hz), 7.27 (d, 1H, J = 3.6 Hz). 13C NMR d 39.9, 66.7, 109.4,
112.4, 119.9, 132.0, 150.6, 159.7. ESI-MS m/z 184 [MH]+. [
a]
D
À62 (c 1.0, CHCl3). Ee 66%. The enantiomeric excess was deter-
mined by chiral HPLC (Chiralcel AD, hexane/2-propanol 95:5,
0.8 mL/min, 254 nm, tS = 18.04 min for major enantiomer,
tR = 20.97 min for minor enantiomer). Anal. Calcd for C8H9NO4: C,
52.46; H, 4.95; N, 7.65. Found: C, 52.25; H, 4.77; N, 7.81.