Stereoselective and diversity-oriented synthesis of trisubstituted allylic alcohols and amines

Article abstract of DOI:10.1002/chem.201100844

Stereoselective and diversity-oriented synthesis of trisubstituted olefins was achieved by using ortho-diphenylphosphanyl benzoate (o-DPPB) as a directing group for allylic substitution. The starting point of this methodology was a set of α-methylene alde

Full text of DOI:10.1002/chem.201100844

FULL PAPER
DOI: 10.1002/chem.201100844
Stereoselective and Diversity-Oriented Synthesis of Trisubstituted Allylic
Alcohols and Amines
Yvonne Schmidt and Bernhard Breit*[a]
Abstract: Stereoselective and diversity-
oriented synthesis of trisubstituted ole-
fins was achieved by using ortho-diphe-
nylphosphanyl benzoate (o-DPPB) as a
directing group for allylic substitution.
The starting point of this methodology
was a set of a-methylene aldehydes de-
rived from Baylis–Hillman adducts.
Subsequent addition of different organ-
ometallic reagents led to a variety of
allylic alcohol substrates. After intro-
duction of the reagent-directing o-
DPPB group, copper-mediated allylic
substitution with wide range of
Grignard reagents enabled the stereo-
selective construction of large
number of E-configured trisubstituted
allylic alcohols and amines in excellent
yields and stereoselectivities. Remark-
able is the synthetic flexibility, which
allows a wide range of permutations
starting from an aldehyde followed by
successive introduction of the substitu-
ents R2 and R3 from organometallic
Grignard based reagents. Thus, starting
from only a few precursors, a diversity-
oriented synthesis of stereodefined tri-
substituted allylic alcohols and amines
becomes possible.
a
a
Keywords: allylation · allylic com-
pounds · directed reactions · diver-
sity-oriented synthesis · trisubstitut-
ed olefins
Introduction
newly formed double bond.[14] To date, modern methods
used to prepare trisubstituted allylic alcohols are alkyne hy-
drometalation or carbometalation, mediated by stoichiomet-
ric organometallic reagents.[15–17] In a similar fashion, allylic
amines are accessible by use of imines are used as the elec-
trophile instead of aldehydes.[18] Most of these methods only
warrant regioselectivity in the metalation step for selected
examples and, thus, the product range of trisubstituted allyl-
ic alcohols and amines is limited.
Trisubstituted allylic alcohols are abundant structural mo-
tives in natural products.[1–6] Not only are they recognized as
valuable target molecules, but allylic alcohols also represent
highly valuable intermediates for asymmetric synthesis. Stra-
tegic applications of allylic alcohols include enantioselective
epoxidation,[2,3,7] cyclopropanation,[2,4] hydrogenation,[2,5]
and allylic substitution,[2,6] en route to chiral building blocks.
Allylic amines, on the other hand, are particularly useful
starting materials for the preparation of amino acids, amino
alcohols, and heterocycles.[8] Additionally, they can be ap-
plied as dipeptide isosteres.[9,10] Peptides possess a broad va-
riety of physiological properties and can be applied as
enzyme inhibitors, growth factors, antimicrobiotics, and
many more.[11] A major drawback regarding the use of pep-
tides as pharmaceuticals is their limited bioavailability due
to the instability of the peptide bond.[12] Therefore, the de-
velopment of peptide isosteres plays an important role in
medicinal chemistry.[10,13]
In this work, we present the use of a directed allylic sub-
stitution for the stereoselective synthesis of trisubstituted al-
lylic alcohols and amines 1 (Scheme 1). Additionally, the di-
Scheme 1. Retrosynthetic analysis of trisubstituted allylic alcohols and
amines 1, which leads to a-methylene aldehydes 2 (X=NHR, X=OR).
Despite such high demands, synthesis of trisubstituted ole-
fins in a stereodefined manner is still an unsolved problem
for a wide range of substrates. Many existing methods are
restricted to the necessary presence of adjacent electron-
withdrawing groups for control of the geometry of the
versity-oriented approach gives rise to a wide variety of
alkene products from simple starting materials and uses in-
expensive copper as the transition-metal reagent. The pre-
sented methodology allows for the synthesis of stereode-
fined backbones, which are not currently available with a
broad side-chain scope.[19,20] Especially, substituents with fur-
ther heteroatom substitution, such as oxygen or nitrogen
atoms, are of interest for potential pharmaceutical applica-
tions.[21] In only a few steps, a large number of products with
high levels of complexity and selectivity can be generated,
which can then be tested for their pharmacological ef-
fects.[19,20]
[a] Dr. Y. Schmidt, Prof. Dr. B. Breit
Institut fꢀr Organische Chemie und Biochemie
Freiburg Institute for Advances Studies (FRIAS)
Universitꢁt Freiburg, Albertstr. 21 (Germany)
Fax : (+49)761-203-8715
E-mail: bernhard.breit@chemie.uni-freiburg.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201100844.
Chem. Eur. J. 2011, 17, 11789 – 11796
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
11789

Scheme 3. Synthesis of the protected MBH adducts 7. (DABCO=1,4-
diazabicyclo[2.2.2]octane.)
AHCTUNGTRENNUNG
should deliver the desired a-methylene aldehydes 8. Ac-
cordingly, the esters 7 were reduced with diisobutylalumi-
num hydride (DIBAL) to the corresponding alcohols in
quantitative yields. Unexpectedly, oxidation of the allylic al-
cohols to the corresponding aldehyde turned out to be prob-
lematic (Table 1).
Table 1. Reduction/oxidation sequence for the protected MBH adducts
7.
Scheme 2. Reactive conformations in the o-DPPB-directed allylic substi-
tution.
Entry
R1
Oxidation
method
t
8/9
Yield
[%][a]
In a previous report, we described the development of an
ortho-diphenylphosphanyl benzoate (o-DPPB)-directed al-
lylic substitution for the stereoselective synthesis of trisubsti-
tuted olefins 5 (Scheme 2).[22] In the course of the reaction,
the organocopper reagent, generated in situ, is bound to the
directing group of the substrate and subsequently delivered
intramolecularly via the sterically and stereoelectronically
favored reactive conformation 4b to furnish (E)-5 as the
major product stereoisomer. A prerequisite for the success-
ful substitution reaction is the extent of 1,2-allylic strain
posed by the substituents R1 and R2 in conformation 4a.
Therefore, we envisioned the use of a stereogenic center as
the controlling factor in the o-DPPB-directed allylic substi-
tution, as shown for the heteroatom branching of 1 in
Scheme 1.
[h]
[b]
1
2
3
4
5
6
7
8
9
Et
Et
Et
Ph
Ph
Ph
MnO2
24
2
5:1
<10
64
70
35
23
65
34
61
23
PCC[c]
Swern[d]
Swern[e]
PCC
>98:2
>98:2
2:1
0.083
1.5
2
1
n.d.
PCC
PCC
Swern
PCC
>98:2
>98:2
>98:2
>98:2
PhCH2CH2
PhCH2CH2
3-pyridyl
2
0.083
1
[a] Isolated yields. [b] c=1m in CH2Cl2, MnO2 (6 equiv), RT. [c] PCC
(2.0 equiv), AloxN (1 gmmolÀ1), PCC, NaOAc (0.2 equiv), RT.
[d] DMSO (2.4 equiv), oxalyl chloride (1.2 equiv); then À788C, alcohol
(1 equiv), 5 min, NEt3 (5 equiv). [e] DMSO (2.4 equiv), oxalyl chloride
(1.2 equiv); then À788C, alcohol (1 equiv),1 h, NEt3 (5 equiv).
Initial attempts with manganese dioxide gave low yield
and concomitant decomposition of the starting material was
observed (Table 1, entry 1). Furthermore, the reaction fur-
nished a mixture of the desired aldehyde 8 and the isomeric
ketone 9. Presumably, this side product is formed by silyl
group migration prior to oxidation.[28] Classical Swern oxida-
tion conditions with a reaction time of 90 min at À788C also
led to a mixture of 8 and 9 (Table 1, entry 4). Improved
yields could be obtained upon addition of triethylamine
after 5 min. This procedure suppressed the undesired iso-
merization (Table 1, entries 3 and 8). A pyridinium chloro-
chromate (PCC) oxidation protocol was also tested for the
allylic oxidation and good yields were obtained upon careful
monitoring of the conversion by TLC (Table 1, entries 2 and
6). Again, prolonged reaction times led to inferior results
(Table 1, entry 5 versus 6).
Results and Discussion
Substrate synthesis: The atom economic,[23] organocata-
lyzed[24] the Morita–Baylis–Hillman (MBH) reaction repre-
sents an ideal method for the preparation of a-methylene al-
dehydes 2 (Scheme 1).[25] Thus, starting from Michael ac-
ceptors and aldehyde or imine electrophiles, in the presence
of a nucleophilic organocatalyst, the corresponding geminal-
ly substituted allylic alcohols or amines are potentially avail-
able.[26] However, the desired reaction with acrolein itself as
the Michael acceptor was not possible due to polymerization
under the reaction conditions.[27] Therefore, we employed a
standard protocol for the MBH reaction of aldehydes with
ethyl acrylate, furnishing the desired products 6 in very
good yields (Scheme 3). In the following step, the adducts 6
were protected as the corresponding tert-butyldimethylsilyl
(TBS) ethers 7 and, finally, oxidation state adjustment
Furthermore, the enantiomerically enriched b-aminoalde-
hyde (S)-12 was prepared from the tosyl imine 10 and acro-
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Chem. Eur. J. 2011, 17, 11789 – 11796

Synthesis of Trisubstituted Allylic Alcohols
FULL PAPER
Table 3. Addition of organometallic reagents to a-methylene aldehydes.[a]
Entry
Product
[M]
t
T
Yield
[%][b]
d.r.
AHCTUNGTRENN[GUN min] [8C]
1
2
3
4
14a Mg
14b Li
15a Mg
15b Li
3
3
3
3
À20
À20
À20
À20
79
71
69
70
83:17
80:20
70:30
60:40
Scheme 4. Preparation of the enantiomerically enriched a-methylene al-
dehyde (S)-12.
lein by using the known asymmetric Baylis–Hillman proto-
col (Scheme 4). In this reaction, the axially chiral, bifunc-
tional organocatalyst 11 delivers the aldehyde (S)-12 with an
enantiomeric excess (ee) of 78%.[29]
Next, 1,2-addition of an organometallic reagent to alde-
hydes 8 or 12 to furnish the corresponding gem-disubstituted
allylic alcohols 13–17 was explored (Tables 2 and 3). Howev-
5
16
17
Mg 720
Mg 720
0–RT 36
80:20
6
7
8
À20–RT 53
77:23
56:44
Table 2. Optimization of the reaction conditions for the addition of or-
ganometallic reagents to a-methylene aldehydes.[a]
13c Mg
15c Mg
3
3
À20
À20
51
44 (80)[c] 66:34
Entry
R2[M]
t
T
[8C]
Yield
[%][b]
[a] Conditions: c=0.5m in diethyl ether, organometallic reagent (1.1–1.3
equiv). [b] Isolated yield. [c] Yield in brackets refers to the yield based on re-
covered aldehyde due to incomplete conversion of the bromide reagent into
the Grignard reagent.
[h]
1
2
3
4
5
6
7
nBuMgBr
nBuMgBr
nBuMgBr
BnMgBr
BnMgBr
BnMgBr
BnLi
12
0–RT
0
51[c]
0.25
0.05
12
16[c]
À20
64 (d.r.[d] =52:48)
0–RT
30[c]
4
0.05
0.05
0
À20
À20
37[c]
44
Next, the optimized reaction conditions were applied to
prepare a broad range of differently substituted allylic alco-
hols (Table 3). Simple alkyl- and aryl-substituted aldehydes
gave the corresponding products in good yields under the
optimized conditions (Table 3, entries 1–4, 7 and 8). For ni-
trogen-functionalized substrates, such as the pyridine or
tosyl amine derivatives, prolonged reaction times were nec-
essary to obtain full conversion (Table 3, entries 5 and 6).
The enantiomerically enriched aldehyde (S)-12 furnished
(1’S)-17 in good yield as a mixture of syn- and anti-diaste-
reomers (Table 3, entry 6). As noted earlier, the configura-
tion of the stereocenter formed after Grignard addition is ir-
relevant to the stereochemical course of the alkene-forming
allylic substitution reaction.
59 (d.r.=79:21)
[a] Conditions: c=0.5m in diethyl ether, R2[M] (1.1–1.3 equiv). [b] Isolat-
ed yield. [c] Yields refer to inseparable mixtures of isomers due to silyl
group migration. [d] Diastereomeric ratio.
er, initial experiments that employed n-butylmagnesium bro-
mide proved cumbersome. Under the basic conditions, prod-
uct mixtures due to silyl group migration were obtained
(Table 2, entries 1 and 2). Fortunately, lowering the addition
temperature to À208C, together with a shortened reaction
time, furnished 13a in good yield without concomitant silyl
group migration (Table 2, entry 3). However, for the re-
ACHTUNGTRENNUNGaction with the benzyl Grignard reagent these optimized
conditions only gave modest yields, presumably due to com-
petitive 1,4-addition (Table 2, entry 6). To improve the selec-
tivity for 1,2-addition, we used benzyl lithium as a harder
nucleophile and obtained the desired product 13b in 59%
yield (Table 2, entry 7). Notably, the monoprotected diols
were obtained as diastereomeric mixtures in all cases, and
they can be used as such. We have previously shown that
the absolute and relative configurations of such stereocen-
ters do not affect the E/Z selectivity of the directed allylic
substitution reaction.[22]
To activate the thus obtained gem-disubstituted allylic al-
cohols for the directed allylic substitution they were trans-
formed into the corresponding o-DPPB esters 18
(Scheme 5). Standard Steglich esterification conditions fur-
nished the desired products in moderate to very good
yields.[30] Additionally, the enantiomerically enriched o-
DPPB ester (1’S)-19 was obtained by using the same proce-
dure (Scheme 6). Following this route, we were able to
access eleven different o-DPPB esters as starting materials
for the directed allylic substitution. All of these examples
Chem. Eur. J. 2011, 17, 11789 – 11796
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11791

B. Breit and Y. Schmidt
95:5 and >98:2 were obtained for the reactions with both
the n-butyl- and isopropyl Grignard reagents. In most cases,
only the E isomer could be detected. The observed high ste-
reoselectivity is presumably a consequence of the high steric
demand of the OTBS group, thus reactive conformation 4b
is favored due to the minimization of A1,2 strain (see
Scheme 2). Compared to our previous results with methyl
substituents in this position,[22] the OTBS group yielded su-
perior selectivities. Even the less sterically demanding
methyl Grignard reagent gave rise to a high E selectivity of
95:5 (Table 4, entry 3).
Scheme 5. Esterification of monoprotected allylic alcohols with o-
DPPBA under Steglich conditions. (o-DPPBA=ortho-diphenylphosphan-
yl benzoic acid, DCC=N,N-dicyclohexylcarbodiimide, DMAP=4-dime-
thylaminopyridine)
Furthermore, several side-chain functionalized o-DPPB
esters 26 were tested as substrates for the directed allylic
substitution (Table 5). Both the olefin- and oxygen-function-
alized esters (Table 5, entries 1 and 2) showed no significant
Scheme 6. Esterification of the enantiomerically enriched amine (1’S)-17.
Table 5. Directed allylic substitution with functionalized o-DPPB
esters.[a]
were accessible in just three steps from only four different
a-methylene aldehydes.
Next, o-DPPB esters 18 were examined in the directed al-
lylic substitution with different alkyl Grignard reagents
(Table 4). With all of the alkyl- and phenyl-substituted
esters good yields were observed under standard conditions.
Additionally, excellent E/Z selectivities ranging between
Entry
Product
E/Z
SN2’/SN2 Yield
[%][b]
1
2
3
4
5
27
96:4
>98:2
>98:2
97:3
82
Table 4. Directed allylic substitution with functionalized o-DPPB
esters.[a]
28 >98:2
29 >98:2
91
86[c]
Entry
Product
R3
E/Z[b]
Yield
[%][c]
100
(83% ee)[d]
(R)-29 >98:2
98:2
ACHTUNGTRENNUNG
1
2
3
20a
20b
20c
nBu
iPr
Me
>98:2
>98:2
95:5
72
83
91
30
60:40
84:16
68
4
5
21a
21b
nBu
iPr
>98:2
>98:2
52
66
[a] Conditions: c=0.05m in diethyl ether, Grignard reagent (1.1–1.3
equiv), RT. [b] Isolated yield. [c] The reaction was performed with
Grignard reagent (2 equiv). [d] Determined by chiral HPLC.
6
7
22a
22b
nBu
iPr
97:3
95:5
91
85
8
9
23a
23b
nBu
iPr
>98:2
>98:2
81
71
difference in reactivity and selectivity compared to the re-
sults shown in Table 4. Accordingly, the corresponding prod-
ucts 27 and 28 were isolated in high yields and with excel-
lent E selectivity. Initially, in the case of the tosyl amine, an
additional equivalent of Grignard reagent was used to de-
protonate the amine. Directed allylic substitution then yield-
ed the allylic amine 29 with high diastereoselectivity
(Table 5, entry 3). However, further experiments showed
that the substitution reaction is faster than deprotonation of
the amine. Thus, the enantiomerically enriched product (R)-
29 (Table 5, entry 4) was isolated in excellent yield and se-
lectivity by using only a slight excess of Grignard reagent.
HPLC analysis proved the preservation of the stereochemi-
10
11
24a
24b
nBu
iPr
>98:2
97:3
66
89
12
13
25a
25b
nBu
iPr
>98:2
>98:2
88
97
[a] Conditions: c=0.05m in diethyl ether, Grignard reagent (1.1–1.3
equiv), RT. [b] The E/Z ratio was determined from the 500 MHz
1H NMR spectra, the assignment of the E- or Z-isomer was determined
by measurement of NOE contacts. [c] Isolated yields. The SN2’/SN2 selec-
tivity was >98:2 in all cases.
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Chem. Eur. J. 2011, 17, 11789 – 11796

Synthesis of Trisubstituted Allylic Alcohols
FULL PAPER
cal information of the allylic amine during the course of the
directed allylic substitution reaction. A 3-pyridyl substituent
turned out to be inferior in terms of selectivity and reactivi-
ty in the directed allylic substitution. Thus, not only was the
E/Z selectivity lower for this example, but the SN2 side re-
substituted vinyl Grignard reagent was unsuccessful, even
under optimized reaction conditions; only 1,2-addition of
the organometallic reagent to the ester carbonyl was ob-
served (Table 6, entry 7). In general, when applying sp2
Grignard reagents the yields were normally lower. Further-
more, as observed previously, the reaction with phenyl
Grignard occurred with inverted Z selectivity, presumably
due to a change in mechanism toward a carbometalation
pathway.[22]
ACHTUNGTRENNUNGaction was also observed (Table 5, entry 5). To rationalize
this result, a competing coordination of the copper reagent
with the pyridyl substituent may be envisioned. As such, the
directing function of the o-DPPB group is disturbed by this
interaction with an alternative ligand. The use of directing
pyridine groups in copper-mediated reactions has been de-
scribed previously by Itami and Yoshida.[17,31]
Conclusion
Finally, the reactions with functionalized Grignard re-
agents were examined (Table 6). As previously found, the
Grignard reagents with remote oxygen and olefin function-
We have developed a stereoselective and flexible synthetic
methodology for the divergent construction of stereodefined
trisubstituted allylic alcohols and amines. A key component
of the methodology is the o-DPPB-directed allylic substitu-
tion with Grignard-derived organocopper reagents to furnish
the corresponding E alkenes in excellent yield and selectivi-
ty. The starting point of this diversity-oriented methodology
is a-methylene aldehydes derived from Baylis–Hillman ad-
ducts. The successive addition of organometallic reagents
(mostly inexpensive and readily available Grignard re-
agents) allows highly flexible access to a wide range of tri-
substituted allylic alcohols and amines. The latter have
found use as peptide isosteres, therefore, this approach
might be ideally suited to generate a library of such com-
pounds for evaluation in medicinal chemistry.
Table 6. Directed allylic substitution with functionalized o-DPPB
esters.[a]
Entry
Product
E/Z
97:3
97:3
94:6
Addition
Yield
[%][b]
normal
30 min
1
2
21c
21d
60
99
normal
30 min
Experimental Section
normal
30 min
3
5
6
7
23c
20d
22c
21e
100
36[c]
24[d]
0[e]
General remarks: All reactions were carried out under an atmosphere of
argon 5.0 (Sꢀdwest-Gas) in dried glassware. Air- and moisture-sensitive
liquids and solutions were transferred by syringe. All solvents were dried
and distilled by standard procedures. Solutions were concentrated under
reduced pressure by rotary evaporation. Chromatographic purification of
products was accomplished on Merck silica gel 60 ꢃ (200–400 mesh). 1H
and 13C NMR spectra were acquired on a Varian Mercury spectrometer
(300 MHz and 75 MHz, respectively) or a Bruker AMX 400 spectrometer
(400 MHz and 101 MHz, respectively) and are referenced to an internal
TMS standard or solvent signals (CDCl3: d=7.26 ppm; C6D6: d=
7.16 ppm). Data for 1H NMR spectra are reported as follows: chemical
shift (d, in ppm), multiplicity (s, singlet; brs, broad singlet; d, doublet; t,
triplet; q, quartet; sept, septet; mc, centered multiplet; m, multiplet; app,
apparent signal), coupling constant (Hz), integration. Data for 13C NMR
spectra are reported in terms of chemical shift (d, in ppm). E/Z ratios
inverse
90 min
2:98
inverse
90 min
21:79
–
inverse
30 min
[a] Conditions: c=0.05m in diethyl ether, Grignard reagent (1.1–1.3
equiv), RT. [b] Isolated yields. The SN2’/SN2-selectivity was >98:2 in all
cases. [c] [Grignard]=0.10m, [ester/Cu]=0.056m. [d] [Grignard]=0.15m,
[ester/Cu]=0.21m. [e] Only 1,2-addition of organometallic reagent to the
ester was observed.
1
were determined from the H NMR spectra. Assignment of the 1H NMR
spectra were accomplished by H,H-COSY experiments and the 13C NMR
spectra by C,H-COSY experiments. The shift values, given in square
brackets, refer to the differing values for the second isomer. Stereogenic
centers are represented by an asterisk (*). 2D-NOESY or 2D-ROESY
experiments confirmed the assignment of E and Z configurations, respec-
tively. HRMS were obtained on a Finnigan MAT 8200 instrument. Ele-
mental analysis was performed on an Elementar vario instrument (Fa. El-
ementar Analysensysteme GmbH).
ality gave excellent results in the directed allylic substitution
(Table 6, entries 1 and 2).[22] Additionally, we were able to
apply a benzyl Grignard reagent which yielded alkene 23c
with excellent E/Z selectivity and in quantitative yield
(Table 6, entry 3). With sp2-hybridized Grignard reagents it
was found that both the inverse addition method and a high
dilution of the Grignard reagent were crucial to obtain high
Typical procedure for the preparation of MBH adducts 6, in particular
for; ethyl-2-(hydroxyACTHNUTRGNE(NUG phenyl)methyl)acrylate (6b): A mixture of ethyl ac-
rylate (8.3 mL, 7.6 g, 76 mmol, 1.5 equiv), benzaldehyde (5.2 mL, 5.5 g,
51 mmol), and DABCO (841 mg, 7.5 mmol, 15 mol%) was stirred at RT
until complete conversion of the aldehyde was observed (NMR control,
10 d). The reaction mixture was quenched with water, extracted with
E/Z selectivity (Table 6, entry 5 versus
6 for phenyl
Grignard reagent). However, the reaction with a simple, un-
Chem. Eur. J. 2011, 17, 11789 – 11796
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11793

B. Breit and Y. Schmidt
À
À
À
ethyl acetate, and dried under high vacuum (to remove excess ethyl acry-
late). Compound 6b (9.0 g, 85%) was obtained as a colorless liquid. Rf =
0.08 (petroleum ether/tert-butyl methyl ether (TBME) 10:1). The product
was used without further purification. An analytical sample was purified
by flash chromatography on silica (petroleum ether/TBME 5:1). Rf =0.08
(petroleum ether/TBME 10:1); 1H NMR (400.130 MHz, CDCl3): d=1.24
(t, 3J=7.4 Hz, 3H; 2’-H), 3.05 (d, 3J=5.7 Hz, 1H; OH), 4.18, (q, 3J=
7.1 Hz, 2H; 1’-H), 5.56 (d, 3J=5.7 Hz, 1H; 2-CHOH), 5.81 (dd, 2J=
1.2 Hz, J=1.2 Hz, 1H; 3-HAHB), 6.34 (dd, J=1.2 Hz, J=0.7 Hz, 1H; 3-
HAHB) 7.27–7.31 (m, 1H; Ar-H), 7.32–7.40 ppm (m, 4H; Ar-H);
13C NMR (100.613 MHz, CDCl3): d=14.1 (C-2’), 61.0 (C-1’), 73.5 (2-
CHOH), 126.0, 126.7 (2C), 127.9, 128.5 (2C), 141.4, 142.2, 166.4 ppm (C-
1). The analytical data match those reported previously.[32]
À4.9 (Si CH3), À4.8 (Si CH3), 9.0 (C-5), 18.2 (Si Cq), 25.7 (3C, tBu),
30.1 (C-4), 69.2 (C-3), 134.5 (2-CH2), 153.4 (C-2), 193.7 ppm (C-1); MS
(EI, 70 eV): m/z (%): 230 (19) [M+2H]+, 229 (100) [M+H]+, 171 (38);
HRMS: m/z: calcd for C12H25O2Si: 229.16238 [M+H]+; found: 229.16200
(+1.7 ppm).
Typical procedure for DIBAL reduction/PCC oxidation, in particular for
2-[(tert-butyldimethylsilyloxy)ACTHNUTRGNE(NUG phenyl)methyl]acrylaldehyde (8b): A so-
lution of the ester 7b (1.60 g, 5.00 mmol) in CH2Cl2 (16 mL) was cooled
to À78 C and a solution of DIBAL in CH2Cl2 (12 mL, 12 mmol 1.0m,
2.4 equiv) was added. The reaction mixture was stirred at À78 C until
complete conversion of the ester was observed (TLC). The reaction mix-
ture was quenched at-788C by addition of a saturated aqueous solution
of sodium acetate (8 mLmmolÀ1), a saturated aqueous solution of NH4Cl
(1.5 mLmmolÀ1), and EtOAc (8 mLmmolÀ1) and the mixture was stirred
at room temperature for 1 h. The resulting gel was filtered over Celite
and rinsed with EtOAc. If no gelation occurred, the phases were separat-
ed and the aqueous phase was extracted with EtOAc. The combined or-
ganic phases were dried over Na2SO4 and the solvent was evaporated
under reduced pressure. The obtained alcohol was used directly in the
next step. Sodium acetate (324 mg, 3.94 mmol, 0.340 equiv) was added to
a suspension of PCC (8.51 g, 39.5 mmol, 3.4 equiv) and AloxN (40 g) in
4
2
4
Typical procedure for the protection with TBS Cl; in particular ethyl 2-
[(tert-butyldimethylsilyloxy)ACTHUNRTGNEUNG(phenyl)methyl]acrylate (7b): A solution of
the Baylis–Hillman adduct 6b (4.60 g, 22.3 mmol) in CH2Cl2 (135 mL)
was stirred over 4 ꢃ molecular sieves for 30 min at RT. Imidazole (1.82 g,
26.7 mmol, 1.2 equiv) was added and the mixture was cooled to 08C,
then TBSCl (3.91 g, 24.5 mmol, 1.1 equiv) was added. After stirring for
24 h at RT, the molecular sieves was filtered off and the reaction mixture
was diluted with water and extracted with CH2Cl2. The combined organic
phases were washed with brine and dried over anhydrous Na2SO4. Purifi-
cation by flash chromatography (silica, petroleum ether/TBME 20:1) fur-
CH2Cl2 (80 mL) at RT. Then,
a solution of the alcohol (3.24 g,
11.6 mmol) in CH2Cl2 was added slowly. After the reaction time indicated
(see Table 1), the reaction mixture was filtered over Celite, rinsed with
CH2Cl2, and the solvent was evaporated under reduced pressure. Com-
pound 8b (2.1 g, 65%) was obtained as a colorless oil. An analytical
sample was purified by flash chromatography (silica, petroleum ether/
TBME 20:1). Rf =0.56 (petroleum ether/TBME 15:1); 1H NMR
nished 7b (5.67 g, 79%) as a colorless oil. Rf =0.51 (petroleum ether/
1
À
TBME 15:1); H NMR (400.130 MHz, CDCl3): d=À0.12 (s, 3H; Si
3
À
CH3), 0.05 (s, 3H; Si CH3), 0.87 (s, 9H; tBu), 1.22 (t, J=7.1 Hz, 3H; 2’’-
H), 4.08 (dq, 2J=10.8 Hz, 3J=7.1 Hz, 1H; 1’’-HA), 4.16 (dq, 2J=10.8 Hz,
3J=7.1 Hz, 1H; 1’’-HB), 5.60 (pseudos, 1H; 1’-H), 6.05 (dd, 2J=1.7 Hz,
4J=1.7 Hz, 1H, 3-HA), 6.25 (dd, J=1.8 Hz, J=1.2 Hz, 1H; 3-HB), 7.19–
2
4
7.24 (m, 1H), 7.25–7.30 (m, 2H), 7.33–7.37 ppm (m, 2H); 13C NMR
À
À
(400.130 MHz, CDCl3): d=0.10 (s, 3H; Si CH3), 0.04 (s, 3H; Si CH3),
0.88 (s, 9H; tBu), 5.63 (s, 1H; 1’-H), 6.07 (dd, 2J=1.0 Hz, 4J=1.0 Hz,
1H; 3-HA), 6.66 (dd, 2J=1.3 Hz, 4J=1.3 Hz, 1H; 3-HB), 7.19–7.24 (m,
À
À
(100.613 MHz, CDCl3): d=À4.9 (Si CH3), À4.8 (Si CH3), 14.2 (C-2’’),
À
18.3 (Si Cq), 25.9 (3C; tBu), 60.6, 72.9, 123.7, 127.2 (2C), 127.4, 128.1
1H), 7.25–7.30 (m, 2H), 7.35–7.38 (m, 2H), 9.53 ppm (s, 1H; 1-H);
(2C), 142.8, 144.3, 166.1 (C-1); MS (CI, NH3, 130 eV): m/z (%): 275 (20),
274 (71), 273 (100), 243 (13), 215 (68), 187 (14), 169 (12); MS (EI,
70 eV): m/z (%): 243 (31), 216 (15), 215 (100), 187 (39), 169 (59), 75 (20),
73 (17); HRMS: m/z calcd for C18H29O3Si: 321.18860 [M+H]+; found:
321.18930 (À2.2 ppm); elemental analysis (%) calcd for C18H28O3Si
(320.50): C 67.46, H 8.81; found: C 67.36, H 8.99.
13
À
À
C NMR (100.613 MHz, CDCl3): d=À5.1 (Si CH3), À4.9 (Si CH3), 18.2
À
(Si Cq), 25.7 (3C; tBu), 70.5 (C-1’), 126.6 (2C), 127.4, 128.1 (2C), 133.0,
142.5, 153.3, 192.8 ppm (C-1); MS (CI, NH3, 130 eV): m/z (%): 278 (14),
277 (82), 220 (18), 219 (100), 162 (82), 145 (56); MS (EI, 70 eV): m/z
(%): 220 (13), 219 (100), 189 (10), 115 (35), 113 (47), 75 (64), 73 (17), 59
(16); HRMS calcd for C16H25O2Si: 277.16238 [M+H]+; found: 277.16210
(+1.0 ppm).
Typical procedure for DIBAL reduction/Swern oxidation, in particular
for 3-(tert-butyldimethylsilyloxy)-2-methylenepentanal (8a): A solution
of ester 7a (6.96 g, 25.6 mmol) in CH2Cl2 (80 mL) was cooled to À788C
and a solution of DIBAL in CH2Cl2 (44 mL, 62 mmol, 2.4 equiv) was
added. The reaction mixture was stirred at À788C until complete conver-
sion of the ester was observed (TLC). The reaction mixture was
quenched at À788C by addition of a saturated aqueous solution of
sodium acetate (8 mLmmolÀ1), a saturated aqueous solution of NH4Cl
(1.5 mLmmolÀ1), and EtOAc (8 mLmmolÀ1). The mixture was stirred at
RT for 1 h. The resulting gel was filtered over Celite and rinsed with
EtOAc. If no gelation occurred, the phases were separated and the aque-
ous phase was extracted with EtOAc. The combined organic phases were
dried over anhydrous Na2SO4 and the solvent was evaporated under re-
duced pressure. The obtained alcohol was used directly in the next step.
A solution of oxalyl chloride (0.52 mL, 0.77 g, 6.1 mmol) in CH2Cl2
(8 mL) was cooled to À508C and DMSO (0.85 mL, 0.94 g, 12 mmol) in
CH2Cl2 (8 mL) was added. After stirring for 15 min at À508C a solution
of the alcohol (1.16 g, 5.02 mmol) in CH2Cl2 (8 mL) was added. Immedi-
ately after the addition, triethylamine (3.5 mL, 2.5 g, 25 mmol) was added
and the mixture was stirred for 5 min at À508C. The reaction mixture
was warmed to RT, diluted with water, and extracted with CH2Cl2. The
combined organic phases were washed with brine, dried over anhydrous
MgSO4, and the solvent was evaporated under reduced pressure. Purifica-
tion by flash chromatography (silica, petroleum ether/TBME 50:1) fur-
Typical procedure for the addition of alkyl Grignard reagent to TBS-pro-
tected aldehydes, in particular 3-(tert-butyldimethylsilyloxy)-4-methyl-
AHCTUNGERTGeNNUN nenonan-5-ol (14a): A solution of aldehyde 8a (200 mg, 0.88 mmol) in
diethyl ether (2 mL) was cooled to À208C and the Grignard reagent
(0.55 m in diethyl ether, 2.0 mL, 1.1 mmol) was added dropwise. After
complete addition, the reaction was immediately quenched with a satu-
rated aqueous solution of NH4Cl and the phases were separated. The
aqueous phase was extracted with CH2Cl2, the combined organic phases
were dried over anhydrous Na2SO4, and the solvent was evaporated
under reduced pressure. Purification by flash chromatography (silica, pe-
troleum ether/TBME 30:1) furnished 14a (200 mg, 79%, d.r.=83:17) as
a
colorless oil. Rf =0.22 (petroleum ether/TBME 15:1); 1H NMR
À
(400.130 MHz, CDCl3): d=0.03
[0.05] (s, 3H; Si CH3), 0.07
N
[0.83] (t, 3J=7.4 Hz, 3H; 9-H), 0.89–0.94 (m, 3H; 1-H),
À
Si CH3), 0.87
0.90 (s, 9H; tBu), 1.27–1.40[1.42–1.50] (m, 4H; 7-H, 8-H), 1.58–1.70[1.98–
2.09] (m, 4H; 2-H, 6-H), 4.16
(t, J=7.4 Hz, 1H; 5-H)*, 5.02
5.05 ppm [5.09] (dd, 4J=1.2, 1.2 Hz, 1H; 4-CHAHB); 13C NMR
N
ACHTUNGTRENNUNG[4.11]
3
N
À À
[À4.77] (Si CH3), À4.5 (Si CH3), 10.2-
(100.613 MHz, CDCl3): d=À4.80
[10.1] (C-9), 14.2 (C-1), 18.22[18.18] (Si Cq), 22.8
28.4[28.1], 30.3[29.5], 36.8[35.4], 72.5[70.3], 77.3[78.7], 111.3ACHTUNGTRENNUNG
G
À
R
G
ACHTUNGTRENNUNG
R
G
N
E
U
CH2), 153.4 ppm [152.0] (C-4); MS (CI, NH3, 130 eV): m/z (%): 287 (34)
[M+H]+, 229 (25), 138 (11), 137 (100); MS (EI, 70 eV): m/z (%): 257
(23), 229 (28), 211 (24), 201 (11), 173 (12), 147 (12), 143 (21), 137 (26),
133 (30), 115 (14), 95 (81), 81 (58), 75 (100), 73 (41), 69 (14), 67 (14), 52
(19), 55 (15), 41 (17); HRMS: m/z: calcd for C16H35O2Si: 287.24063
[M+H]+; found: 287.24030 (+1.2 ppm); elemental analysis (%) calcd for
C16H34O2Si (286.52): C 67.07, H 11.96; found: C 67.21, H 12.00.
nished 8a (796 mg, 70%) as a colorless oil. Rf =0.74 (petroleum ether/
1
À
TBME 10:1); H NMR (400.130 MHz, CDCl3): d=À0.03 (s, 3H; Si
CH3), 0.05 (s, 3H; Si CH3), 0.84 (t, 3J=7.4 Hz, 3H; 5-H), 0.91 (s, 9H;
À
tBu), 1.47 (ddq, 2J=13.8 Hz, 3J=7.4, 6.4 Hz, 1H; 3-HA), 1.64 (ddq, 2J=
14.3 Hz, 3J=7.2, 4.1 Hz, 1H; 3-HB), 4.59 (mc, 1H; 3-H), 6.08 (dd, 2J=
1.0 Hz, 4J=0.9 Hz, 1H; 2-CHAHB), 6.52 (dd, 2J=1.4 Hz, 4J=1.4 Hz, 1H;
2-CHAHB), 9.57 ppm (s, 1H; 1-H); 13C NMR (100.613 MHz, CDCl3): d=
11794
www.chemeurj.org
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 11789 – 11796

Synthesis of Trisubstituted Allylic Alcohols
FULL PAPER
Typical procedure for the addition of benzyllithium to TBS-protected al-
dehydes, in particular for 4-(tert-butyldimethylsilyloxy)-3-methylene
(14b): nBuLi (0.48 mL, 1.1 mmol, 1.2 equiv) was added to a solution of
TMEDA (0.16 mL, 0.12 g, 1.1 mmol, 1.2 equiv) in toluene (1.1 mL,
11 mmol, 12 equiv) at RT. After stirring for 30 min, the reaction mixture
was cooled to À208C and a solution of aldehyde 8a (200 mg, 0.88 mmol)
in THF (1 mL) was added. The reaction was quenched immediately with
a saturated aqueous solution of NH4Cl and the phases were separated.
The aqueous phase was extracted with CH2Cl2, the combined organic
phases were dried over anhydrous Na2SO4, and the solvent was evaporat-
ed under reduced pressure. Purification by flash chromatography (silica,
petroleum ether/TBME 15:1) furnished 14b (200 mg, 71%, d.r.=80:20)
as a colorless oil. Rf =0.47 (petroleum ether/TBME 15:1); 1H NMR
termined by TLC and the reaction mixture was directly applied onto a
silica gel column. Purification by flash chromatography (silica, petroleum
ether/TBME 100:1) furnished 20a (14 mg, 72%, E/Z>98:2) as a color-
less oil. Rf =0.87 (petroleum ether/TBME 100:1); 1H NMR
À
À
(400.132 MHz, CDCl3): d=À0.02 (s, 3H; Si CH3), 0.02 (s, 3H; Si CH3),
0.81 (t, 3J=7.4 Hz, 3H; 1-H), 0.87–0.92 (m, 6H; 9-H, 5’-H), 0.89 (s, 9H;
tBu), 1.21–1.41 (m, 10H; 2’-H, 3’-H, 4’-H, 7-H, 8-H), 1.47 (mc, 2H; 2-H),
1.86–2.04 (m, 4H; 6-H, 1’-H), 3.87 (t, 3J=6.2 Hz, 1H; 3-H), 5.28 ppm (t,
3J=6.9 Hz, 1H; 5-H); C NMR (100.613 MHz, CDCl3): d=À4.9 (Si
13
À
À
À
CH3), À4.4 (Si CH3), 10.4 (C-1), 14.1 (C-9/5’), 14.2 (C-5’/9), 18.4 (Si Cq),
22.55, 22.62, 26.0 (3C; tBu), 27.28 (C-6/1’), 27.32 (C-1’/6), 29.7, 29.9 (C-
2), 32.2, 32.7, 79.1 (C-3), 126.3 (C-5), 141.4 ppm (C-4); MS (CI, NH3,
130 eV): m/z (%): 297 (15), 269 (23), 212 (11), 196 (14), 195 (100); MS
(EI, 70 eV): m/z (%): 298 (26), 297 (88), 270 (28), 269 (100), 75 (32), 73
(11); elemental analysis (%) calcd for calcd for C20H42OSi (326.63): C
73.54, H 12.96; found: C 73.14, H 13.08.
À
À
(400.130 MHz, CDCl3): d=0.05 (s, 3H; Si CH3), 0.07CAHTUNGTRENNNUG
3
CH3), 0.80
ACHTUNGTRENNUNG[0.87] (t, J=7.4 Hz, 3H; 6-H), 0.905ACHTUNGTRENNUNG
1.71 (m, 2H; 5-H), 2.63
N
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
Typical procedure for allylic substitution with o-DPPB esters 18, inverse
addition method, in particular for (Z)-(4-benzylnon-4-ene-3-yloxy)-(tert-
butyl)dimethylsilane (20d): The Grignard reagent (0.72 m, in diethyl
ether, 0.072 mmol, 1.3 equiv) was diluted with diethyl ether (0.62 mL) to
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
13
À
5H; Ar-H); C NMR (100.613 MHz, CDCl3): d=À4.8 (Si CH3), À4.55-
0.1m concentration.
A solution of 19c (32 mg, 0.056 mmol) and
À
À
A
R
ACHTUNGTRENNUNG
CuBr·SMe2 (5.8 mg, 0.028 mmol, 0.50 equiv) in diethyl ether (1.0 mL)
was added by syringe pump at RT over 30 min. After stirring overnight,
the conversion was determined by TLC and the reaction mixture was ap-
plied onto a silica gel column. Purification by flash chromatography
(silica, petroleum ether) furnished 20d (10.8 mg, contained biphenyl,
36%, E/Z 98:2) as a colorless oil. Rf =0.44 (petroleum ether); 1H NMR
G
G
E
ACHTUNGTRENNUNG
N
G
E
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
(%): 312 (14), 311 (20), 310 (100), 245 (14); MS (EI, 70 eV): m/z (%):
273 (27), 263 (19), 229 (31), 172 (14), 171 (100), 143 (44), 133 (21), 129
(66), 115 (18), 97 (10), 91 (34), 75 (41), 73 (23); elemental analysis (%)
calcd for C19H32O2Si (320.54): C 71.19, H 10.06; found: C 71.17, H 10.29.
À
À
(499.630 MHz, CDCl3): d=À0.09 (s, 3H; Si CH3), À0.05 (s, 3H; Si
3
3
CH3), 0.77 (t, J=7.4 Hz, 3H; 9-H), 0.87 (s, 9H; tBu), 0.89 (t, J=7.1 Hz,
3H; 1-H), 1.29–1.40 (m, 6H; 2-H, 7-H, 8-H), 2.09 (td, 3J=7.2, 7.2 Hz,
Typical procedure for the preparation of o-DPPB esters 19 from allylic
alcohols 13–16, in particular 3-(tert-butyldimethylsilyloxy)-4-methylene-
nonan-5-yl 2-(diphenylphosphanyl) benzoate (19c): A solution of allylic
alcohol 14a (150 mg, 0.66 mmol) in CH2Cl2 was added to a suspension of
o-DPPBA (244 mg, 0.80 mmol, 1.2 equiv), DCC (165 mg, 0.80 mmol,
1.2 equiv), and DMAP (99 mg, 0.81 mmol, 1.2 equiv) in CH2Cl2 (3.5 mL)
at RT. The reaction mixture was stirred until complete conversion of the
allylic alcohol was observed (TLC). The mixture was filtered over Celite,
rinsed with CH2Cl2, and the filtrate was evaporated under reduced pres-
sure. Purification by flash chromatography (silica, petroleum ether/
TBME 20:1) furnished 18c (271 mg, 72%, d.r=43:57) as yellow oil. Rf =
0. 76 (petroleum ether/TBME 15:1); 1H NMR (400.130 MHz, CDCl3):
3
2
1H; 6-HA), 2.10 (td, J=7.1, 7.1 Hz, 1H; 6-HB), 3.28 (d, J=15.4 Hz, 1H;
1’-HA), 3.52 (d, 2J=15.4 Hz, 1H; 1’-HB), 3.90 (dd, 3J=6.1, 5.3 Hz, 1H; 3-
H), 5.59 (dd, 3J=7.3, 7.3 Hz, 1H; 5-H), 7.13–7.19 (m, 3H; Ar-H), 7.22–
13
À
7.25 ppm (m, 2H; Ar-H); C NMR (125.312 MHz, CDCl3): d=À5.0 (Si
À
À
CH3), À4.6 (Si CH3), 10.1 (C-1), 14.1 (C-9), 18.3 (Si Cq), 22.6, 26.0 (3C;
tBu), 27.8 (C-6), 29.8, 32.0, 33.1 (C-1’), 77.9 (C-3), 125.7, 127.8 (C-5),
128.2 (2C), 128.6 (2C), 139.3, 140.7 ppm; MS (EI, 70 eV): m/z (%): 317
(22), 290 (24), 289 (100) [MÀC4H9]+, 75 (16), 44 (27); HRMS: m/z: calcd
+
for C22H38OSiÀC4H9
:
289.19877 [MÀC4H9]+, found: 289.19900 (+
0.8 ppm).
À
À
d=À0.05
(t, 3J=7.3 Hz, 3H; 1/9-H), 0.81–0.92 (m, 3H; 9/1-H), 0.88
tBu), 1.09–1.33 (m, 6H) [1.37–1.48 (m, 2H)], 1.53–1.69 (m, 2H) [1.72–
1.88 (m, 2H)], 4.08 [5.11] (mc,
[4.01] (dd, 3J=6.0, 6.0 Hz, 1H; 3-H), 5.12
1H; 4-CHAHB), 5.16
[5.13] (dd, 2J=1.5 Hz, 4J=1.5 Hz, 1H; 4-CHAHB),
5.37
[5.30] (dd, 3J=8.0, 5.0 Hz, 1H; 5-H), 6.89–6.96 (m, 1H; Ar-H), 7.20–
G
E
ACHTUNGTRNE[NUNG 0.73]
AHCTUNGTRENNUNG
Acknowledgements
ACHTUNGTRENNUNG
This work was supported by the DFG, the International Research Train-
ing Group “Catalysts and Catalytic Reactions for Organic Synthesis”
(IRTG 1038) and the Fonds der Chemischen Industrie (fellowship to
Y.S.). We thank Dr. M. Keller for NOE measurements and J. Weipert for
technical assistance.
ACHTUNGTRENNUNG
7.33 (m, 10H; Ar-H), 7.35–7.44 (m, 2H; Ar-H), 8.08–8.12[8.03–8.07] ppm
(m, 1H; Ar-H); 13C NMR (100.613 MHz, CDCl3): d=À4.91
[À4.52] (Si
À
G
À
À
CH3), À4.52
25.95
[75.5], 110.9
7.2 Hz, 2C), 128.6, 130.62
133.9 (d, J=20.6 Hz, 4C), 134.19
[134.5], 150.4
[150.2], 165.8 ppm (d, J=2.9 Hz); 31P NMR (161.976 MHz,
CDCl3): d=À4.7[À5.0] ppm; MS (CI, NH3, 130 eV): m/z (%): 592 (20)
[M+NH4]+, 591 (49) [M+NH3]+, 576 (31) [M+H]+A[M+H]+, 575 (80)
N
G
ACHTUNGTRENNUNG
E
G
E
G
ACHTUNGTRENNUNG
G
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
[1] D. M. Hodgson, P. G. Humphreys in Science of synthesis: Houben-
Weyl: Methods of Molecular Transformations, Vol. 36 (Eds.: M. J.
Bingham, J. Clayden, D. Bellus, J. Houben, T. Weyl), Thieme, Stutt-
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E
CTHUNGTRENNUNG
[M]+, 533 (10), 379 (14), 323 (22), 306 (20), 305 (100); MS (EI, 70 eV):
m/z (%): 306 (21), 305 (100), 213 (20); HRMS: m/z: calcd for
C35H48O3PSi: 575.31104 [M+H]+; found: 575.31100; elemental analysis
(%) calcd for C35H47O3PSi (574.80): C 73.13, H 8.24; found: C 73.00, H
8.39.
Typical procedure for allylic substitution with o-DPPB esters 18, normal
addition method, in particular for (E)-tert-butyldimethyl(4-pentylnon-4-
ene-3-yloxy)silane (20a): CuBr·SMe2 (6.2 mg, 0.030 mmol, 0.51 equiv)
was added to a solution of 19c (34 mg, 0.059 mmol) in diethyl ether
(1.2 mL) at RT. The Grignard reagent (0.55 m in diethyl ether,
0.082 mmol, 1.4 equiv) was added to this intensely yellow solution over
30 min by syringe pump. After stirring overnight, the conversion was de-
Chem. Eur. J. 2011, 17, 11789 – 11796
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
11795

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Received: March 18, 2011
Published online: September 6, 2011
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