Asymmetrie allylation of methyl ketones by using chiral phenyl carbinols

Article abstract of DOI:10.1002/chem.200900062

Novel chiral auxiliaries for the stereoselective allylation of aliphatic methyl ketones with allyltrimethylsilane and their use in the synthesis of homoallylic ethers are described. In a multicomponent domino process catalyzed by trifluoromethanesulfonic

Full text of DOI:10.1002/chem.200900062

FULL PAPER
DOI: 10.1002/chem.200900062
Asymmetric Allylation of Methyl Ketones by Using Chiral Phenyl ACTHUNRGTNECNUG arbinols
Lutz F. Tietze,* Tom Kinzel, and Thomas Wolfram[a]
Dedicated to Professor Hans-Ulrich Reißig on the occasion of his 60th birthday
Abstract: Novel chiral auxiliaries for
the stereoselective allylation of aliphat-
ic methyl ketones with allyltrimethylsi-
lane and their use in the synthesis of
homoallylic ethers are described. In a
multicomponent domino process cata-
lyzed by trifluoromethanesulfonic acid,
the allyl moiety and the auxiliary are
transferred onto the substrate to yield
tertiary homoallylic ethers. The most
useful auxiliary for a general applica-
tion turned out to be the trimethylsilyl
ether of phenyl benzyl carbinol with an
induced diastereoselectivity of 90:10
using ethyl methyl ketone and 94:6
using isopropyl methyl ketone as sub-
strates. The transferred substituted
benzyl moiety has good protecting
properties in subsequent transforma-
tions and can easily be removed under
reductive conditions to provide the cor-
responding homoallylic alcohol. The
origin of the high selectivity could be
elucidated by identifying the relevant
transition states using quantum-chemi-
cal calculations. An excellent agree-
ment between calculated and experi-
mentally observed selectivities was ob-
tained assuming an oxocarbenium ion
as intermediate.
Keywords: allylation
·
auxiliary
methods density functional
·
calculations · diastereoselectivity ·
domino reactions · ketones
Introduction
Allylations of carbonyl compounds are amongst the most
ꢀ
frequently used C C bond-forming reactions and are widely
Scheme 1. Multicomponent reaction for the synthesis of homoallylic
ethers.
employed in the synthesis of natural products and other bio-
logically active compounds.[1] An excellent allylation method
is the multicomponent domino reaction[2] of a carbonyl com-
pound 1 using a trimethyl silyl ether 2 and allyltrimethylsi-
lane (3) in the presence of a catalytic amount of an acid to
give homoallylic ethers 4 (Scheme 1).[3] Using silyl ethers 2
with one or more stereogenic centers in R3 as auxiliaries,
the reactions can be performed in a stereoselective way.
Moreover, the transferred auxiliary can act as a hydroxy
protecting group in subsequent transformations.[4]
butanone (5) is possible to give the tertiary homoallylic
ether 7 in 95% yield and in a diastereomeric ratio of 90:10
at ꢀ788C (Scheme 2). Interestingly, there is a reversal in the
induced selectivity of the allylation when going from a
ketone to an aldehyde. The origin of the stereoselectivity
could be elucidated for both substance classes.[6]
Since the allylation of butanone (5) in the presence of the
trimethyl silyl ether of 1-phenylethanol (10a) yielded the
two possible diastereomeric products only in a <2:1 ratio,
we initially assumed that the trifluoroacetamide moiety in 6
is essential for high selectivity. While the amide group does
indeed directly take part in the stereoselective step of alde-
hyde allylations via the formation of an intermediate oxazo-
lidinium ion,[6a] our recent theoretical studies on the allyla-
tion of butanone with 7 showed that in the case of ketones
the amide moiety is simply a spectator substituent.[6b]
Based on the natural product norpseudoephedrine
(NPED), we have developed auxiliary 6 (NPED auxiliary)
with which both aliphatic aldehydes and ketones can be ally-
lated in excellent yields and selectivities.[5] Thus, even the
differentiation between a methyl and an ethyl group as in
[a] Prof. Dr. L. F. Tietze, Dr. T. Kinzel, Dipl.-Chem. T. Wolfram
Institut fꢀr Organische und Biomolekulare Chemie
Georg-August-Universitꢁt Gçttingen, Tammannstrasse 2
37077 Gçttingen (Germany)
Though the NPED auxiliary gave a high selectivity a dis-
advantage of the trifluoroacetamide moiety in the product is
its low stability under basic conditions, which limits the ap-
plicability of the transferred NPED group as protecting
Fax : (+49)551-399476
E-mail: ltietze@gwdg.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200900062.
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6199

triethylamine. The diastereo-
meric ratio of the products was
determined
from
their
13C NMR spectra and in some
cases from their GC at achiral
stationary phase; both analytic
procedures gave identical re-
Scheme 2. Auxiliary-mediated stereoselective allylation of butanone. a) 0.2 equiv TfOH, CH2Cl2, ꢀ788C, 2 h,
95%.
group. Thus, in the course of the total synthesis of natural
products there is a need for a removal of the auxiliary in the
product and a reprotection of the formed homoallylic alco-
hol.[7] An additional drawback of the described allylation
using the NPED auxiliary is the necessity for the employ-
ment of two equivalents of the ketone to obtain yields of
>90% (see Table 2, entry 1).
Table 1. Synthesis of racemic auxiliaries 10a–10k. A) NaBH4, MeOH,
0.5–2 h (TLC); B) iPrMgCl, toluene, 0.5 h; C) TMSCl, NEt3, CH2Cl2,
24 h; D) TMSOTf, NEt3, CH2Cl2, 0.5–1 h (TLC).
On the basis of the aforementioned calculations, we have
now developed new auxiliaries of type 10 that give excellent
yields and selectivities as obtained with the NPED auxiliary
but in addition show excellent protecting group qualities
and can be applied using only one equivalent of the ketone.
Here we describe their synthesis and their employment for
the allylation of butanone (5) and methyl ketones 13a–g. In
addition, the origin of stereoselectivity was determined with
quantum-chemical methods.
Alk
8
Reduction
(Yield [%])
9
Silylation
ACHTUNGTRENUN(NG Yield [%])
10
G
Me
Et
iPr
nBu
–
–
–
–
–
–
–
–
9a
9b
9c
9d
9e
9 f
9g
9h
9i
D (76)
C (86)
C (94)
C (96)
D (97)
C (91)
D (44)[a]
D (94)
D (96)
D (93)
D (97)
10a
10b
10c
10d
10e
10 f
10g
10h
10i
tBu
–
–
cHex
adamantyl
CH2Ph
CHPh2
CPh3
CMe2Ph
8 f
8g
8h
–
8j
8k
A (97)
B
A (92)
–
B (76)
9j
9k
10j
10k
B (59)[b]
Results and Discussion
[a] Yield over three steps (1-adamantanecarboxylic acid!8g!9g!10g).
[b] Yield over two steps (8h!8k!9k).
Development of the novel auxiliary: As novel auxiliaries for
the stereoselective allylation of ketones we developed the
phenylcarbinols 10a–10k and tested them in the allylation
of butanone.
The racemic auxiliaries were synthesized by silylation of
the corresponding alcohols 9a–9k using either chlorotrime-
thylsilane (TMSCl) or trimethylsilyl trifluoromethanesulfo-
nate (TMSOTf) as silylating agents in the presence of tri-
sults. The stereochemistry of the obtained products was ex-
emplarily clarified for the enantiomerically pure homoallylic
ethers 11a and 11h that were synthesized using the auxilia-
ries (R)-10a and (R)-10h, respectively. The alcohols that
were formed by deprotection of 11a and 11h were com-
pared by GC at chiral stationary phase with those that were
obtained by cleavage of the NPED residue from the mixture
of 7. The stereochemistry of the remaining homoallylic
ethers was assigned by comparison of their 13C NMR spec-
tra.
The results of the allylation of butanone (5) using the dif-
ferent auxiliaries 10a–10k to give the homoallylic ethers
11a–11k are displayed in Table 2. Selectivity increases with
increasing steric volume of the alkyl group when going from
methyl (10a) to tert-butyl (10e). However, a further increase
in size as in 10 f and 10g leads to a decrease in selectivity.
Both yield and selectivity are improved when there are one
or two phenyl groups in the 1-position of the alkyl chain; on
the other hand, no product was obtained when the trityl-
auxiliary 10j was used. Auxiliary 10k, in which the two hy-
drogen atoms of the benzyl moiety in 10h are replaced by
methyl groups, leads to an even higher selectivity of 94:6,
however at the cost of significantly reduced yield.
ACHTUNGTRENNUNGethylamine (Table 1). In those cases where the alcohol was
not commercially available, it was obtained by reduction of
the corresponding ketone 8 with sodium borohydride or, in
the sterically challenging cases, with isopropyl magnesium
chloride. Alcohol 9i was synthesized by addition of phenyl
magnesium chloride to diphenylacetaldehyde. Ketone 8g
was provided by reaction of 1-adamantanecarboxylic acid
with two equivalents of phenyllithium, and ketone 8k was
obtained by permethylation of deoxybenzoin (8h) with
methyl iodide in the presence of powdered potassium hy-
droxide and catalytic amounts of [18]crown-6.[8]
To examine the achievable level of induced selectivity
with auxiliaries 10a–10k we followed the procedure for the
allylation of ketones with the NPED-auxiliary 6, using two
equivalents of butanone (5), two equivalents of allyltrime-
thylsilane (3) and one equivalent of the racemic silyl ether
10a–10k in dichloromethane at ꢀ788C in the presence of
20 mol% trifluoromethanesulfonic acid (TfOH). The reac-
tions with auxiliaries 10e and 10h were additionally per-
formed in a 1:1:1 stoichiometric ratio of the substrates.
After 15–20 h, the reactions were quenched by addition of
Replacing the phenyl moiety in the phenyl-tert-butyl aux-
iliary 10e by a 2,6-dichlorophenyl group increases the selec-
tivity from 87:13 to 92:8, but with diminished yield. A simi-
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Chem. Eur. J. 2009, 15, 6199 – 6210

Asymmetric Allylation of Methyl Ketones
FULL PAPER
Table 2. Yields and selectivities of the allylation of butanone in the pres-
ence of the auxiliaries 10a–10k. a) Butanone (5), allyltrimethylsilane (3),
0.2 equiv TfOH, CH2Cl2, ꢀ788C, 15–20 h.
moval of the group after having done its duty as protecting
group.
Scope of the allylation with 10h: The large scope of the ally-
lation using the PBn-auxiliary 10h is demonstrated by the
allylation of the methylketones 13a–13e where high yields
and selectivities were obtained (Table 3). Thus, for the reac-
tion of isopropyl methyl ketone (13b) and cyclohexyl
methyl ketone (13c) a selectivity of even 94:6 is found. On
the other hand, the method is not suitable for the facial se-
lective allylation of sterically very demanding ketones as pi-
nacolone 13g and aromatic ketones like acetophenone
(13 f). Though for the latter ketone the highest selectivity
with 97:3 was observed the yields are too low. Thus, our new
procedure complements very well existing methods that
work nicely with aromatic ketones,[10] but fail using aliphatic
ketones. Moreover, the pronounced variation of reactivity of
different ketones offers the possibility of a chemoselective
allylation in substrates with several ketone functionalities.
Entry Alk
Auxiliary Product Yield [%][a] Selectivity
rac-syn-11/
rac-anti-11
1
NPED-Auxiliary
6
7
95 (48)
56
89
88
85
84 (84)
71
90
95 (93)
99
0
90:10
65:35
73:27
80:20
70:30
87:13
78:22
82:18
90:10
91:9
2
Me
10a
10b
10c
10d
10e
10 f
10g
10h
10i
10j
10k
11a
11b
11c
11d
11e
11 f
11g
11h
11i
11j
11k
3
Et
4
iPr
5
nBu
6
tBu
7
8
9
10
11
12
cHex
adamantyl
CH2Ph
CHPh2
CPh3
CMe2Ph
–
94:6
57
[a] Yield for butanone/allylsilane/auxiliary 2:2:1 stoichiometry. Values in
parentheses: yield for 1:1:1 stoichiometry.
lar increase in selectivity from
90:10 to 92:8 was observed
with the 2,6-dichlorophenyl an-
alogue of the auxiliary 10h
which however, led to the cor-
responding homoallylic ether
in 98% yield. Slightly de-
creased selectivities of 85:15
and 84:16 were obtained using
the auxiliaries, where the
Scheme 3. Synthesis of enantiopure alcohol (S)-9h.
phenyl group was replaced by
a 1-naphthyl and a 3,5-dime-
thylphenyl group, respectively.
It is important to note that in contrast to the use of the
NPED auxiliary 6, the allylations in the presence of the aux-
iliaries 10, as shown for 10e and 10h, give nearly the same
yields regardless of whether one or two equivalents of
ketone were employed. From this observation, we conclude
that the necessity of using two equivalents of the ketone is
specific only for the NPED-auxiliary 6. However, so far we
do not have an explanation for this unusual behavior.
Among the synthesized and tested auxiliaries of type 10,
the trimethylsilyl ether of the simple phenylbenzylcarbinol
(10h, PBn auxiliary) is best suited for a general application
in the light of its high induced diastereoselectivity and its
ready availability as well as atom economy. The correspond-
ing alcohol 9h is commercially available in both enantiomer-
ic forms with 98% ee. It can also be synthesized by CBS re-
duction[9] of deoxybenzoin (8h) in 92% ee, and enriched via
Protecting-group properties of the phenylbenzyl moiety:
The usefulness of the PBn moiety as protecting group was
investigated for subsequent transformations of the homoal-
lylic ether 14c. Ozonolysis as well as hydroboration of 14c
gave the aldehyde 15 and the alcohol 16, respectively, in ex-
cellent yields without affecting the PBn group (Scheme 4).
The cleavage of the PBn residue, for example, from 14c
to 17, can be achieved under Birch conditions[11] (Na/liquid
NH3), or by elementary hydrogen over Pd/C, whereas the
latter proceeds under concomitant hydrogenation of the
double bond to give 18 (Scheme 5).
Origin of stereoselectivity: In order to rationalize the ob-
served stereoselectivities, we computationally identified the
transition states (TSs) of the stereogenic step for the allyla-
tions of butanone (5) with auxiliaries (R)-10a (Alk=Me),
(R)-10e (Alk=tBu) and (R)-10h (Alk=Bn). The proposed
reaction mechanism includes the intermediate formation of
oxocarbenium ion 19, which is intercepted by the nucleo-
phile allyltrimethylsilane (3), thereby forming the new ste-
reogenic center at C-4 of 11 (Scheme 6).[12,4b]
recrystallization of the nitrobenzoate 12 to ACTHNUGRTNEUNG>99% ee
(Scheme 3). The following preparation of the auxiliary 10h
from alcohol 9h is a simple one-step procedure with almost
quantitative yield. The easy accessibility of 10h compensates
for the fact that its chiral information is lost in the final re-
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L. F. Tietze et al.
Table 3. Allylation of ketones 5 and 13a–13g with the phenylbenzyl auxiliary (PBn auxiliary) 10h. a) TMSO-
PBn (10h), allyltrimethylsilane (3), 0.2 equiv TfOH, CH2Cl2, ꢀ788C, 15–20 h.
ured
product
(4R,1’R)-11,
while the attack to the Re face
of 19 in B-TSs gives rise to the
anti-isomer (4S,1’R)-11.
In the relevant TS for the re-
action with the PBn auxiliary
10h, oxocarbenium ion 19h
adopts one of the conforma-
tions 19h-1 or 19h-2 that are
displayed in Figure 2.
Table 4 lists the TS energies
and the calculated selectivities.
In each case, the stereochemis-
try of the main product is cor-
rectly predicted and further-
more, the trend of increasing
selectivity in the series 10a,
Entry
Ketone
R
Product
Yield [%][a]
Selectivity
syn-14/anti-14
[a]2D0 [8][b]
1
2
3
4
5
6
7
8
5
Et
nPent
iPr
cHex
CH2Ph
(CH2)2Ph
11h
14a
14b
14c
14d
14e
14 f
14g
93
93
91
89
86
76
9
90:10
88:12
96:4
96:4
91:9
86:14
97:3
72:28
+27.8[c]
ꢀ19.7[d]
13a
13b
13c
13d
13e
13 f
13g
ꢀ15.5[d]
ꢀ17.2[d]
Ph
tBu
8
[a] Yield for ketone/allylsilane/auxiliary ratio 1:1:1. [b] Optical rotation of the mixture of diastereomers.
[c] Reaction with (R)-10h (ee 98%). [d] Reaction with (S)-10h (ee >99%).
Scheme 4. Investigation of the protecting group quality of the PBn group
in ozonolysis and hydroboration reactions of 14c. a) 1) O3, 2) PPh3,
CH2Cl2, ꢀ788C; b) 1) 9-BBN, 2) H2O2, NaOH, THF, RT.
Figure 1. TSs A1, A2, B1 and B2. R=Me, tBu, CH2Ph.
Scheme 5. Cleavage of the PBn protecting group under Birch-conditions
and with elementary hydrogen. a) Na/NH3 (l), ꢀ788C; b) H2, Pd/C,
MeOH, RT.
Figure 2. Conformations of 19h in relevant TSs.
10e and 10h is properly reproduced. In the case of the PBn-
auxiliary 10h, the computationally calculated and experi-
mentally determined selectivities match perfectly.
In all relevant TSs, the phenyl group in 19 is fixed in or-
thogonal position to the C=O+ bond by a stereoelectronic
effect (Figure 1). Since the attack to the Re face of 19 in B-
TSs leads to a steric repulsion between 3 and the phenyl
group, their energies are in general above those for the A-
TSs, and the reaction is predicted to give the syn isomer
preferentially.
Small alkyl substituents such as methyl in the case of 10a
that should lead to better selectivities because of less steric
bulk for the A-TSs do however give lower selectivities. On
the contrary, selectivity increases with the size of the alkyl
moiety up to Alk=tBu in 10e but only then decreases with
further increase in alkyl size. The calculations show that this
Scheme 6. Stereogenic step of the allylation of butanone with phenylalkyl
auxiliaries.
By analyzing all possible TS structures (48 for the allyla-
tion with 10a or 10e, 144 for the allylation with 10h, see
Supporting Information) we found that in each case, the se-
lectivities can be explained solely with TSs A1, A2, B1 and
B2 in which 19 has the E configuration and where the
double bonds of 19 and 3 adopt an antiperiplanar orienta-
tion (Figure 1).[13] TSs A1 and B1 differ from TSs A2 and
B2 in the respective position of the CH2TMS group. In A-
TSs, the Si face of 19 is attacked, leading to the syn-config-
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Asymmetric Allylation of Methyl Ketones
FULL PAPER
Table 4. Relative TS energies DDG for the stereogenic step of the allyla-
tion of butanone with auxiliaries 10a, 10e and 10h, and the therefrom
calculated selectivities.
System
TS[a]
Product DDG
[kJmolꢀ1
Selectivity
syn-11/anti-11
G
]
calcd
exptl
19a + 3 (Alk=Me)
A1
A2
B1
B2
A1
A2
B1
B2
syn-11a
syn-11a
anti-11a 1.5
anti-11a 4.4
syn-11e
syn-11e
anti-11e 4.3
anti-11e 2.5
2.4
0.0
72:28
65:35
19e + 3 (Alk=tBu)
4.5
0.0
79:21
91:9
87:13
90:10
19h + 3 (Alk=CH2Ph) A1-1 syn-11h 1.6
A1-2 syn-11h 1.8
A2-1 syn-11h 3.8
A2-2 syn-11h 0.0
B1-1 anti-11h 6.3
B1-2 anti-11h 6.0
B2-1 anti-11h 4.1
B2-2 anti-11h 5.1
[a] The suffix -1 and -2 for the TSs of the system 19h + 3 denotes the
conformation of 19h according to Figure 2.
observation cannot be traced back to TSs with Z-configured
19 that might potentially be easier accessible with smaller
alkyl groups. We therefore assume that the A-TSs are stabi-
lized by a van der Waals interaction between the alkyl
group and the attacking silane 3 which increases with alkyl
group size. At a certain size, steric repulsion counterbalan-
ces this effect and as a result, selectivity drops. Benzyl-sub-
stituted auxiliaries such as 10h exhibit excellent selectivities
because the van der Waals stabilization with 3 is possible
without leading to unfavorable steric interactions (Figure 3).
Figure 3. TS structures A2-2 and B2-2 for the allylation of 19h. Hydro-
gen atoms are omitted for clarity.
Lambda 2 spectrometer. IR spectra were recorded as KBr pellets or as
films between NaCl plates with a Bruker IFS 25 spectrometer. 1H and
13C NMR spectra were recorded with Mercury-200, VXR-200, Unity-300,
Inova-500, Unity Inova-600 (Varian) or AMX 300 (Bruker) spectrometer.
Chemical shifts are reported in ppm with tetramethylsilane (TMS) as in-
ternal standard. Multiplicities of 13C NMR peaks were determined with
the APT pulse sequence. Mass spectra were measured with a Finnigan
MAT 95, TSQ 7000 or LCQ instrument. High resolution mass spectra
(ESI-HRMS) were recorded with a Apex IV (Bruker Daltronik).
General procedure A for the reduction of ketones with NaBH4: NaBH4
(1.2 equiv) was added carefully to a stirred 0.3m solution of the ketone
(1 equiv) in MeOH at 08C. Stirring was continued for 0.5–2 h, the solvent
removed under reduced pressure and the residue dissolved in Et2O
(0.3m). The solution was washed with a saturated solution of NH4Cl
(3 mLmmolꢀ1 ketone), water (3 mLmmolꢀ1 ketone) and brine
(3 mLmmolꢀ1 ketone), and dried over Na2SO4. After evaporation of the
solvent the crude product was purified by column chromatography on
silica gel.
Conclusion
Based on the results of our previous theoretical studies, we
developed a new simple phenyl benzyl carbinol-based auxili-
ary, which is easily accessible in both enantiomeric forms
and exhibits high selectivity in aliphatic methyl ketone ally-
lations. In addition, the transferred moiety is a good protect-
ing group and is readily cleaved under standard conditions.
The origin of stereoselectivity was elucidated by quantum-
chemical calculations of the relevant transition states. Excel-
lent agreement between experimentally observed and com-
putationally predicted selectivity was found.
General procedure B for the reduction of ketones with iPrMgCl: To a
stirred solution of isopropyl magnesium chloride (2m solution in Et2O,
2 equiv) in toluene (2 mLmmolꢀ1 ketone), was added slowly at room
temperature a 1m solution of the ketone (1 equiv) in toluene. Stirring
was continued for 0.5 h, the reaction mixture then cooled to 08C and
crushed ice added until gas formation ceased. The formed precipitate was
dissolved by adding a 2n aqueous solution of HCl and the aqueous layer
was extracted with CH2Cl2 (2ꢃ2 mLmmmolꢀ1 ketone). The combined or-
ganic layers were dried over Na2SO4. After evaporation of the solvent,
the crude product was purified by column chromatography on silica gel.
Experimental Section
General procedure C for the silylation of alcohols with TMSCl: To a
stirred 0.2m solution of the alcohol (1 equiv) in CH2Cl2 and NEt3
(2.5 equiv), TMSCl (1.2 equiv) was added dropwise at 08C. After stirring
for 24 h at room temperature, a saturated solution of NH4Cl was added,
the layers separated and the aqueous layer extracted with CH2Cl2 (3ꢃ
3 mLmmolꢀ1 ketone). The combined organic layers were washed with
brine and dried over Na2SO4. After evaporation of the solvent the crude
product was purified by column chromatography on silica gel or by distil-
lation.
General methods: All reactions were performed under argon in flame-
dried flasks. Solvents were used from commercial sources and stored
over molecular sieves. All reagents obtained from commercial sources
were used without further purification. Thin-layer chromatography
(TLC) was performed on precoated silica gel SIL G/UV254 plates (Ma-
cherey-Nagel) and silica gel 60 (0.032–0.063 mm, Merck) was used for
column chromatography. Vanillin in methanolic sulfuric acid was used as
staining reagents for TLC. UV spectra were taken with a Perkin-Elmer
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L. F. Tietze et al.
General procedure D for the silylation of alcohols with TMSOTf: To a
stirred 0.2m solution of the alcohol (1 equiv) in CH2Cl2 and NEt3
(5 equiv) was added dropwise TMSOTf (2.5 equiv) at 08C. After stirring
for 0.5–2 h at room temperature, a saturated solution of NH4Cl was
added. The layers were separated and the aqueous layer extracted with
CH2Cl2 (3ꢃ3 mLmmolꢀ1 ketone). The combined organic layers were
washed with brine and dried over Na2SO4. After evaporation of the sol-
vent the crude product was purified by column chromatography on silica
gel or by distillation.
13C NMR (50 MHz, CDCl3): d=ꢀ0.02 (TMS), 26.00 (C-3), 36.02 (C-2),
82.67 (C-1), 126.64, 127.03, 127.91, 142.81 ppm (Ph); HRMS (ESI): m/z:
calcd for C14H24NaOSi: 259.14886; found 259.14902 [M+Na]+.
Cyclohexylphenylmethanol (9 f): According to general procedure A, cy-
clohexyl phenyl ketone (8 f) (3.00 g, 15.9 mmol, 1.00 equiv) was reacted
with sodium borohydride (720 mg, 19.2 mmol, 1.21 equiv) in methanol
(50 mL). Purification by column chromatography afforded the title com-
pound (2.93 g, 15.4 mmol, 97%) as colorless oil. Rf =0.44 (hexanes/ethyl
acetate 4:1); 1H NMR (300 MHz, CDCl3): d=0.80–2.02 (m, 12H, c-Hex,
OH), 4.34 (d, J=7.2 Hz, 1H, 1-H), 7.20–7.37 ppm (m, 5H, Ph); 13C NMR
(75 MHz, CDCl3): d=25.97 (C-3’), 26.06 (C-5’), 26.39 (C-4’), 28.80 (C-6’),
29.26 (C-2’), 44.91 (C-1’), 79.37 (C-1), 126.61, 127.38, 128.16, 143.57 ppm
(Ph).
(R)-Trimethyl-(1-phenylethoxy)silane (10a): According to general proce-
dure D, (R)-1-phenylethanol (9a) (3.00 g, 24.5 mmol, 1.00 equiv) was re-
acted with NEt3 (12.4 g, 17.0 mL, 123 mmol, 5.02 equiv) and TMSOTf
(13.1 g, 10.7 mL, 59.0 mmol, 2.41 equiv) in CH2Cl2 (100 mL). Distillation
of the crude product at reduced pressure afforded the title compound
(Cyclohexylphenylmethoxy)trimethylsilane (10 f): According to general
procedure C, rac-cyclohexylphenylmethanol (9 f) (2.85 g, 14.9 mmol,
1.00 equiv) was reacted with NEt3 (3.94 g, 5.40 mL, 39.0 mmol,
2.62 equiv) and TMSCl (1.97 g, 2.30 mL, 18.1 mmol, 1.21 equiv) in
CH2Cl2 (70 mL). Distillation of the crude product at reduced pressure af-
forded the title compound (3.55 g, 13.5 mmol, 91%) as yellow liquid. B.p.
788C (0.2 mbar); 1H NMR (300 MHz, CDCl3): d=ꢀ0.04 (s, 9H, TMS),
0.80–2.05 (m, 11H, c-Hex), 4.23 (d, J=7.0 Hz, 1H, 1-H), 7.16–7.36 ppm
(m, 5H, Ph); minor conformer (distinguishable signals): d=0.14 (s, 9H,
TMS), 4.35 ppm (d, J=7.3 Hz, 1H, 1-H). (major/minor conformer
80:20); 13C NMR (75 MHz, CDCl3): d=0.07 (TMS), 26.07 (C-3’), 26.18
(C-5’), 26.52 (C-4’), 28.88 (C-6’), 29.26 (C-2’), 45.84 (C-1’), 79.84 (C-1),
126.75, 127.71, 128.18, 144.34 ppm (Ph); minor conformer (distinguisha-
ble signals): d=1.32 (TMS), 25.99 (C-3’), 26.40 (C-5’), 28.81 (C-4’), 29.29
(C-6’), 44.94 (C-1’), 79.39 (C-1), 126.62, 127.41 ppm (Ph); IR (film): n˜ =
(3.71 g, 19.1 mmol, 76%) as colorless liquid. B.p. 448C (2.0 mbar); [a]D20
=
+57.78 (c=1, CHCl3); 1H NMR (300 MHz, CDCl3): d=0.07 (s, 9H,
TMS), 1.43 (d, J=6.4 Hz, 3H, 2-H), 4.85 (q, J=6.4 Hz, 1H, 1-H), 7.18–
7.36 ppm (m, 5H, Ph); 13C NMR (75 MHz, CDCl3): d=0.08 (TMS), 26.85
(C-2), 70.58 (C-1), 125.34, 126.82, 128.12, 146.44 ppm (Ph); IR (film): n˜ =
2959, 1493, 1450, 1370, 1251, 1207, 1098, 1034, 959, 841, 756, 699 cmꢀ1
;
UV (MeOH): lmax (lg e)=204.5 (4.0075), 246.5 (2.9203), 251.5 (2.9309),
257.0 (2.9298), 263.5 (2.8745), 288.5 nm (2.9607); HRMS (ESI): m/z:
calcd for C11H18NaOSi: 217.10191; found 217.10204 [M+Na]+.
Trimethyl-(1-phenylpropoxy)silane (10b): According to general proce-
dure C, rac-1-phenylpropanol (9b) (3.27 g, 24.0 mmol, 1.00 equiv) was re-
acted with NEt3 (6.13 g, 8.40 mL, 60.6 mmol, 2.52 equiv) and TMSCl
(3.17 g, 3.70 mL, 29.1 mmol, 1.21 equiv) in CH2Cl2 (105 mL). Distillation
of the crude product at reduced pressure afforded the title compound
(4.32 g, 20.7 mmol 86%) as colorless liquid. B.p. 49–508C (1.5 mbar);
1H NMR (200 MHz, CDCl3): d=0.00 (s, 9H, TMS), 0.84 (t, J=7.4 Hz,
3H, 3-H), 1.53–1.77 (m, 2H, 2-Ha, 2-Hb), 4.50 (t, J=6.4 Hz, 1H, 1-H),
7.12–7.32 ppm (m, 5H, Ph); 13C NMR (50 MHz, CDCl3): d=0.09 (TMS),
10.34 (C-3), 33.44 (C-2), 76.36 (C-1), 125.88, 126.81, 127.98, 145.40 ppm
(Ph); HRMS (ESI): m/z: calcd for C12H20NaOSi: 231.11756; found
231.11765 [M+Na]+.
3028, 2925, 2853, 1451, 1250, 1058, 1028, 964, 928, 903, 841, 748, 700 cmꢀ1
;
UV (CH3CN): lmax (lg e)=206.5 (3.9129), 209.0 (3.9145), 252.0 (2.2678),
258.0 (2.3347), 264.0 nm (2.2009); HRMS (EI): m/z: calcd for C16H26OSi:
262.1753; found 262.1750 [M]+.
[(1’-Adamantyl)phenylmethoxy]trimethylsilane (10g): 1) Phenyllithium
(20.6 mL of a 2m solution in dibutyl ether, 41.2 mmol, 2.00 equiv) was
added to a solution of adamantane 1-carboxylic acid (3.71 g, 20.6 mmol,
1.00 equiv) in Et2O (200 mL) at 08C. After stirring for 1 h at room tem-
perature, the reaction mixture was poured into a saturated solution of
ammonium chloride (200 mL), and the forming precipitate was dissolved
by addition of 2m HCl solution (100 mL). The aqueous layer was extract-
ed with Et2O (2ꢃ100 mL). The combined organic layers were dried over
sodium sulfate and the solvent was evaporated. The obtained yellow oil
(8g) (3.60 g) was used for the next step without further purification.
Trimethyl-(2-methyl-1-phenylpropoxy)silane (10c): According to general
procedure C, rac-1-phenyl-2-methylpropanol (9c) (3.03 g, 20.2 mmol,
1.00 equiv) was reacted with NEt3 (5.11 g, 7.00 mL, 50.5 mmol,
2.50 equiv) and TMSCl (2.61 g, 3.05 mL, 24.0 mmol, 1.19 equiv) in
CH2Cl2 (90 mL). Distillation of the crude product at reduced pressure af-
forded the title compound (4.17 g, 18.7 mmol, 94%) as colorless liquid.
B.p. 54–558C (1.5 mbar); 1H NMR (200 MHz, CDCl3): d=0.00 (s, 9H,
TMS), 0.76 (d, J=6.9 Hz, 3H, 3a-H), 0.91 (d, J=6.6 Hz, 3H, 3b-H), 1.85
(dqq, J=6.6, 6.6, 6.9 Hz, 1H, 2-H), 4.28 (d, J=6.6 Hz, 1H, 1-H), 7.15–
7.35 ppm (m, 5H, Ph); 13C NMR (50 MHz, CDCl3): d=0.06 (TMS), 18.12
(C-3a), 19.21 (C-3b), 36.29 (C-2), 80.37 (C-1), 126.66, 126.74, 127.70,
144.44 ppm (C-Ph); HRMS (ESI): m/z: calcd for C13H22NaOSi:
245.13321; found 245.13331 [M+Na]+.
2) According to general procedure B, crude 8g was reacted with isopro-
pyl magnesium chloride (20.6 mL of a 2m solution in Et2O, 41.2 mmol,
2.0 equiv) in toluene (50 mL), which afforded a yellow solid (9g) (3.88 g)
that was used for the next step without further purification.
3) According to general procedure D, crude 9g was reacted with NEt3
(8.25 g, 11.3 mL, 81.5 mmol, 3.96 equiv) and TMSOTf (8.94 g, 7.30 mL,
40.2 mmol, 1.95 equiv) in CH2Cl2 (70 mL). Purification by column chro-
matography afforded the title compound (2.82 g, 8.97 mmol, 44% over
three steps) as colorless oil. Rf =0.60 (hexanes/ethyl acetate 10:1);
1H NMR (300 MHz, CDCl3): d=ꢀ0.07 (s, 9H, TMS), 1.35–1.67 (m, 12H,
2’-H, 4’-H), 1.90 (m, 3H, 3’-H), 4.05 (s, 1H, 1-H), 7.14–7.30 ppm (m, 5H,
Ph); 13C NMR (75 MHz, CDCl3): d=0.00 (TMS), 28.43 (C-3’), 37.17 (C-
4’), 37.42 (C-1’), 38.23 (C-2’), 83.27 (C-1), 126.58, 126.92, 128.06,
141.82 ppm (Ph); IR (KBr): n˜ =3026, 2847, 1450, 1360, 1249, 1058, 944,
927, 841, 700, 614, 512 cmꢀ1; UV (CH3CN): lmax (lg e)=191.5 (4.6263),
206.0 (3.9328), 209.5 (3.9272), 252.5 (2.2529), 258.0 nm (2.3216); HRMS
(EI): m/z: calcd for C20H30OSi: 314.2066; found 314.2065 [M]+.
Trimethyl-(1-phenylpentoxy)silane (10d): According to general proce-
dure C, rac-1-phenylpentanol (9d) (3.94 g, 24.0 mmol, 1.00 equiv) was re-
acted with NEt3 (6.13 g, 8.40 mL, 60.6 mmol, 2.52 equiv) and TMSCl
(3.17 g, 3.70 mL, 29.1 mmol, 1.21 equiv) in CH2Cl2 (105 mL). Distillation
of the crude product at reduced pressure afforded the title compound
(5.44 g, 23.0 mmol, 96%) as colorless liquid. B.p. 66–678C (1.0 mbar);
1H NMR (200 MHz, CDCl3): d=ꢀ0.02 (s, 9H, TMS), 0.83 (t, J=6.9 Hz,
3H, 5-H), 1.10–1.45 (m, 4H, 3-H, 4-H), 1.45–1.77 (m, 2H, 2-H), 4.55 (dd,
J=7.7, 5.4 Hz, 1H, 1-H), 7.12–7.33 ppm (m, 5H, Ph); 13C NMR (50 MHz,
CDCl3): d=0.10 (TMS), 14.05 (C-5), 22.57 (C-4), 28.11 (C-3), 40.47 (C-
2), 75.02 (C-1), 125.82, 126.80, 128.01, 145.72 ppm (Ph); HRMS (ESI): m/
z: calcd for C14H24NaOSi: 259.14886; found 259.14910 [M+Na]+.
(S)-1,2-Diphenylethanol (9h) (92% ee): To a solution of deoxybenzoin
(8h) (1.0 g, 5.1 mmol, 1.0 equiv) and (R)-MeCBS reagent (1.0 mL of an
1m solution in toluene, 1 mmol, 20 mol%) in CH2Cl2 (5 mL), BH3·SMe2
(3.0 mL of a 2m solution in toluene, 6.0 mmol, 1.2 equiv) was slowly
added dropwise at ꢀ358C over 6 h. The reaction was quenched by addi-
tion of MeOH (3 mL). After warming to room temperature the solution
was washed with a half-saturated solution of NH4Cl and the aqueous
layer was extracted with CH2Cl2 (3ꢃ15 mL). The combined organic
layers were washed with a saturated solution of NH4Cl and dried over
Trimethyl-(2,2-dimethyl-1-phenylpropoxy)silane (10e): According to gen-
eral procedure D, rac-1-phenyl-2,2-dimethylpropanol (9e) (5.12 g,
31.2 mmol, 1.00 equiv) was reacted with NEt3 (15.5 g, 21.2 mL, 153 mmol,
4.90 equiv) and TMSOTf (16.8 g, 13.7 mL, 75.5 mmol, 2.42 equiv) in
CH2Cl2 (150 mL). Distillation of the crude product at reduced pressure
afforded the title compound (7.14 g, 30.2 mmol, 97%) as colorless liquid.
B.p. 52–548C (1.0 mbar); 1H NMR (200 MHz, CDCl3): d=0.00 (s, 9H,
TMS), 0.89 (s, 9H, 3-H), 4.30 (s, 1H, 1-H), 7.20–7.35 ppm (m, 5H, Ph);
6204
www.chemeurj.org
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 6199 – 6210

Asymmetric Allylation of Methyl Ketones
FULL PAPER
Na2SO4. Purification by column chromatography afforded the title com-
pound (600 mg, 4.3 mmol, 84%, 92% ee) as colorless solid. Rf =0.20
(hexanes/ethyl acetate 20:1); 1H NMR (300 MHz, CDCl3): d=1.99 (d,
J=2.7 Hz, 1H, OH), 3.00 (dd, J=13.5, 8.2 Hz, 1H, 2-Ha), 3.07 (dd, J=
13.5, 5.1 Hz, 1H, 2-Hb), 4.92 (m, 1H, 1-H), 7.18–7.40 ppm (m, 10H, 10ꢃ
Ph-H); 13C NMR (75 MHz, CDCl3): d=46.1 (C-2), 75.3 (C-1), 125.9 (2ꢃ
C-Ph), 126.6 (C-Ph), 127.6 (C-Ph), 128.4 (2ꢃC-Ph), 128.5 (2ꢃC-Ph),
129.5 (2ꢃC-Ph), 138.0 (C-Ph), 143.8 ppm (C-Ph); MS (EI, 70 eV): m/z
was evaporated. Purification by column chromatography afforded the
title compound (1.91 g, 6.96 mmol, 68%) as colorless solid. Rf =0.22
(hexanes/Et2O 5:1); 1H NMR (300 MHz, CDCl3): d=2.15 (d, J=2.9 Hz,
1H, OH), 4.25 (d, J=8.8 Hz, 1H, 2-H), 5.40 (dd, J=8.8, 2.9 Hz, 1H, 1-
H), 7.02–7.46 ppm (m, 15H, 3ꢃPh); 13C NMR (125 MHz, CDCl3): d=
60.27 (C-2), 76.78 (C-1), 126.34, 126.85, 126.91, 127.52, 128.00, 128.19,
128.56, 128.72, 128.92, 140.88, 141.52, 142.21 ppm (3ꢃPh); IR (KBr): n˜ =
3425, 2894, 1598, 1492, 1451, 1032, 743, 698, 600 cmꢀ1; UV (CH3CN): lmax
(lg e)=194.5 (4.8923), 523.5 (2.8007), 258.5 nm (2.8527); HRMS (EI):
m/z: calcd for C20H18O: 274.1358; found 274.1358 [M]+.
(%): 77 (24) [Ph]+, 91 (29) [Bn]+, 92 (100) [Bn+H]+, 107 (74) [
G
N
N
N
R
T
N
T
C
A
MꢀBn]+,
180 (23) [MꢀH2O]+, 198 (3) [M]+; HPLC (Chiralpak IA, n-hexane/
iPrOH 99:1, flow: 0.8 mLminꢀ1 load: 1 mgmLꢀ1
, , injection volume:
(1,2,2-Triphenyl-1-ethoxy)trimethylsilane (10i): According to general pro-
cedure D, rac-1,2,2-triphenyl-ethane-1-ol (9i) (1.50 g, 5.47 mmol,
1.00 equiv) was reacted with NEt3 (2.99 g, 4.10 mL, 29.6 mmol,
5.41 equiv) and TMSOTf (3.19 g, 2.60 mL, 14.3 mmol, 2.62 equiv) in
CH2Cl2 (30 mL). Purification by column chromatography afforded the
title compound (1.82 g, 5.25 mmol, 96%) as slightly yellowish oil.
1H NMR (300 MHz, CDCl3): d=ꢀ0.14 (s, 9H, TMS), 4.22 (d, J=7.9 Hz,
1H, 2-H), 5.29 (d, J=7.9 Hz, 1H, 1-H), 6.94–7.45 ppm (m, 15H, 3ꢃPh);
13C NMR (125 MHz, CDCl3): d=ꢀ0.10 (TMS), 60.77 (C-2), 78.37 (C-1),
126.06, 126.10, 126.92, 127.61, 127.85, 127.99, 128.92, 129.41, 141.82,
142.08, 143.48 ppm (3ꢃPh); IR (film): n˜ =3028, 2957, 1494, 1452, 1251,
1069, 922, 893, 841, 748, 698 cmꢀ1; UV (CH3CN): lmax (lg e)=194.5
(4.8449), 253.5 (2.8899), 258.5 nm (2.9355); HRMS (ESI): m/z: calcd for
C23H26NaOSi: 369.16451; found 369.16450 [M+Na]+.
10 mL, l=210): tR =33 min (R enantiomer), 37 min (S enantiomer);
HRMS (EI): m/z: calcd for C14H14O: 198.1045; found 198.1040 [M]+.
(S)-1’,2’-Diphenylethyl-3,5-dinitrobenzoate (12): To a stirred suspension
of (S)-1,2-diphenylethanol (9h, 92% ee) (570 mg, 2.87 mmol, 1.0 equiv),
3,5-dinitrobenzoyl chloride (820 mg, 3.56 mmol, 1.2 equiv) and DMAP
(35 mg, 0.29 mmol, 10 mol%) in CH2Cl2 (15 mL) was added dropwise at
08C triethylamine (0.65 mL, 4.6 mmol, 1.6 equiv). After stirring for 2 h
CH2Cl2 (200 mL) was added. The obtained solution was washed with 1m
HCl (50 mL) and the aqueous layer was extracted with CH2Cl2 (3ꢃ
80 mL). The combined organic layers were washed with a saturated solu-
tion of NH4Cl and dried over Na2SO4. After purification of the crude
product by column chromatography (pentane/CH2Cl2 2:1!CH2Cl2), the
obtained 3,5-dinitrobenzoate (966 mg, 2.46 mmol, 85%) was recrystal-
lized from ethyl acetate/heptane. The racemate was first obtained first as
colorless, rectangular crystals. The following recrystallizations yielded the
title compound (680 mg, 1.73 mmol, 60% from 9h) as thick, colorless
needles. Rf =0.38 (n-pentane/CH2Cl2 1:2); [a]2D0 =ꢀ21.08 (c=0.1, CHCl3);
1H NMR (300 MHz, CDCl3): d=3.27 (dd, J=14.0, 5.7 Hz, 1H, 2’-Ha),
3.40 (dd, J=14.0, 8.4 Hz, 1H, 2’-Hb), 6.22 (dd, J=8.4, 5.7 Hz, 1H, 1’-H),
7.15–7.42 ppm (m, 10H, 10ꢃPh-H), 9.07 (d, J=2.1 Hz, 2H, 2-H, 6-H),
9.18 ppm (t, J=2.1 Hz, 1H, 4-H); 13C NMR (125 MHz, CDCl3): d=42.8
(C-2’), 79.6 (C-1’), 122.3 (C-Ph), 126.7 (2ꢃC-Ph), 127.0 (C-Ph), 128.5 (2ꢃ
C-Ph), 128.7 (2ꢃC-Ph), 129.3 (2ꢃC-Ph), 129.3 (C-2, C-6), 129.4 (C-3, C-
5), 134.0 (C-Ph), 136.3 (C-1), 138.7 (C-Ph), 148.6 (C-4), 161.6 ppm (C=
1,2,2,2-Tetraphenylethanol (9j): According to general procedure B, tri-
phenylacetophenone (8j) (2.00 g, 5.74 mmol, 1.00 equiv) was reacted with
isopropyl magnesium chloride (5.70 mL of
a 2m solution in Et2O,
11.4 mmol, 1.99 equiv) in toluene (15 mL). Purification by column chro-
matography afforded the title compound (1.52 g, 4.34 mmol, 76%) as col-
orless oil. Rf =0.13 (hexanes/ethyl acetate 20:1); 1H NMR (300 MHz,
CDCl3): d=2.18 (brs, 1H, OH), 6.32 (s, 1H, 1-H), 6.75–7.40 ppm (m,
20H, 4ꢃPh); 13C NMR (75 MHz, CDCl3): d=64.49 (C-2), 76.73 (C-1),
126.32, 127.04, 127.37, 127.49, 129.03, 130.81, 140.81, 143.78 ppm (4ꢃPh).
(1,2,2,2-Tetraphenylethoxy)trimethylsilane (10j): According to general
procedure D, 1,2,2,2-tetraphenylethanol (1.20 g, 3.42 mmol, 1.00 equiv)
was reacted with NEt3 (1.75 g, 2.40 mL, 17.3 mmol, 5.06 equiv) and
TMSOTf (1.90 g, 1.55 mL, 8.54 mmol, 2.50 equiv) in CH2Cl2 (15 mL). Pu-
rification by column chromatography afforded the title compound
(1.34 g, 3.17 mmol, 93%) as colorless solid. Rf =0.67 (hexane/ethyl ace-
tate 10:1); 1H NMR (300 MHz, CDCl3): d=ꢀ0.14 (s, 9H, TMS), 6.04 (s,
1H, 1-H), 6.67–7.23 ppm (m, 20H, 4ꢃPh); 13C NMR (75 MHz, CDCl3):
d=0.30 (TMS), 64.27 (C-2), 79.27 (C-1), 125.85, 126.77, 126.89, 127.27,
130.14, 131.20, 141.45, 144.71 ppm (4ꢃPh); HRMS (EI): m/z: calcd for
C29H30OSi: 422.2066; found 422.2066 [M]+.
O); MS (DCI, 200 eV): m/z (%): 198 (100), 216 (55), 410 (16) [NGUNETRGUNTCHA
M+NH4]+.
(S)-1,2-Diphenylethanol (9h) (>99% ee): To a solution of the 3,5-dini-
trobenzoate (12; 290 mg, 0.74 mmol, 1.0 equiv) in CH2Cl2 (2 mL) was
added a solution of LiOH·H2O (47 mg, 1.1 mmol, 1.5 equiv) in MeOH
(10 mL) and H2O (0.5 mL) at 08C. After stirring at room temperature
for 0.5 h, saturated NH4Cl solution (3 mL) was added and the aqueous
layer was extracted with CH2Cl2 (3ꢃ20 mL). The combined organic
layers were washed with brine and dried over Na2SO4. Purification by
column chromatography afforded the title compound (144 mg,
0.73 mmol, 98%, >99% ee) as colorless solid. [a]2D0 =+50.38 (c=1,
EtOH).
1,2-Diphenyl-2-methylpropane-1-ol (9k) 1) In
a round-bottom flask
equipped with a reflux condenser, a suspension of 2-phenylacetophenone
(8h) (4.00 g, 20.4 mmol, 1.00 equiv), powdered KOH (techn. 85%, 5.40 g,
82.5 mmol, 4.04 equiv) and [18]crown-6 (10 mg, 37.8 mmol, 0.002 equiv) in
toluene (8 mL) was heated to 708C. Methyl iodide (8.80 g, 62.0 mmol,
3.03 equiv) was added and the reaction was stirred at 708C for 3 h.
Again, methyl iodide was added (8.80 g, 62.0 mmol, 3.03 equiv) and the
reaction was stirred at 708C for 15 h. After cooling to room temperature,
water was added (30 mL), the layers were separated and the aqueous
layer was extracted with Et2O (2ꢃ30 mL). The combined organic phases
were evaporated in vacuo to afford a yellow oil (8k) (4.40 g), which was
used for the next step without further purification.
(S)-(1,2-Diphenylethoxy)trimethylsilane (10h) (>99% ee): According to
general procedure D, (S)-1,2-diphenylethanol (9h) (590 mg, 3.0 mmol,
1.0 equiv) was reacted with NEt3 (2.1 mL, 15 mmol, 5.0 equiv) and
TMSOTf (1.4 mL, 7.5 mmol, 2.5 equiv) in CH2Cl2 (20 mL). Purification
by column chromatography afforded the title compound (756 mg,
2.8 mmol, 93%) as colorless oil. Rf =0.70 (hexanes/ethyl acetate 15:1);
[a]2D0 =ꢀ27.08 (c=1, CHCl3); 1H NMR (300 MHz, CDCl3): d=0.00 (s,
9H, TMS), 3.07 (d, J=6.5 Hz, 2H, 2-H), 4.92 (t, J=6.5 Hz, 1H, 1-H),
7.28–7.49 ppm (m, 10H, 2ꢃPh); 13C NMR (75 MHz, CDCl3): d=ꢀ0.28
(TMS), 47.52 (C-2), 76.40 (C-1), 125.82, 126.08, 126.99, 127.95, 128.03,
129.79, 139.04, 144.91 ppm (2ꢃPh); IR (film): n˜ =3029, 2956, 1495, 1454,
1251, 1092, 943, 841, 758, 698 cmꢀ1; UV (CH3CN): lmax (lg e)=194.0
(4.8064), 252.5 (2.5678), 258.0 (2.645), 264.0 nm (2.5313); HRMS (ESI):
m/z: calcd for C17H22NaOSi: 293.13321; found 293.13343 [M+Na]+.
2) According to general procedure B, crude 8k was reacted with isopro-
pyl magnesium chloride (19.6 mL of a 2m solution in Et2O, 39.2 mmol,
1.92 equiv) in toluene (60 mL). Purification by column chromatography
afforded the title compound (2.74 g, 12.1 mmol, 59% over two steps) as
colorless solid. Rf =0.29 (hexanes/ethyl acetate 10:1); 1H NMR
(300 MHz, CDCl3): d=1.28 (s, 3H, 3a-H), 1.32 (s, 3H, 3b-H), 1.77 (brs,
1H, OH), 4.76 (s, 1H, 1-H), 7.10–7.43 ppm (m, 10H, 2ꢃPh); 13C NMR
(125 MHz, CDCl3): d=22.40 (C-3a), 25.72 (C-3b), 43.15 (C-2), 82.01 (C-
1), 126.28, 126.95, 127.30, 127.76, 128.09, 140.79, 146.28 ppm (2ꢃPh); IR
(film): n˜ =3454, 2971, 1601, 1452, 1387, 1042, 771, 723, 700 cmꢀ1; UV
(CH3CN): lmax (lg e)=192.5 (4.7093), 194.5 (4.7124), 252.0 (2.5737), 257.5
(2.6452), 264.0 nm (3.5178). MS (EI, 70 eV): m/z (%): 226.3 (1) [M]+,
1,2,2-Triphenylethane-1-ol (9i): A solution of phenyl magnesium chloride
(7.60 mL of a 2m solution in THF, 15.2 mmol, 1.49 equiv) was diluted
with dry THF (20 mL) and cooled to 08C. Diphenylacetaldehyde (2.00 g,
10.2 mmol, 1.00 equiv) was added and the reaction mixture was stirred at
room temperature for 1 h. The reaction was stopped by the addition of
saturated ammonium chloride solution (10 mL). Water was added
(60 mL), and the mixture was extracted with CH2Cl2 (3ꢃ30 mL). The
combined organic layers were dried over sodium sulfate and the solvent
Chem. Eur. J. 2009, 15, 6199 – 6210
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6205

L. F. Tietze et al.
209.2 (1) [MꢀOH]+, 149.2 (5) [MꢀPh]+, 120.2 (100) [Mꢀ2MeꢀPh]+,
H), 0.96 (s, 3H, 4-CH3), 1.49–1.56 (m, 1H, 2’-Ha), 1.56–1.62 (m, 1H, 2’-
Hb), 4.35 (dd, J=6.5, 6.5 Hz, 1H, 1’-H), 5.72 ppm (dddd, J=17.0, 10.3,
7.3, 7.3 Hz, 1H, 2-H); 13C NMR (75 MHz, CDCl3):
ACTHNUTRGNEUNG(4,1’)-syn-11b: d=
119.2 (55) [PhCMe2]+, 107.1 (50) [PhCHOH]+.
(1,2-Diphenyl-2-methyl-1-propoxy)trimethylsilane (10k): According to
general procedure D, rac-1,2-diphenyl-2-methylpropane-1-ol (9k) (2.23 g,
9.85 mmol, 1.00 equiv) was reacted with NEt3 (5.33 g, 7.30 mL,
52.7 mmol, 5.35 equiv) and TMSOTf (5.76 g, 4.70 mL, 25.9 mmol,
2.63 equiv) in CH2Cl2 (65 mL). Purification by column chromatography
afforded the title compound (2.85 g, 9.54 mmol, 97%) as slightly yellow-
ish liquid. Rf =0.71 (hexanes/Et2O 10:1); 1H NMR (300 MHz, CDCl3):
d=ꢀ0.19 (s, 9H, TMS), 1.22 (s, 3H, 3a-H), 1.30 (s, 3H, 3b-H), 4.59 (s,
1H, 1-H), 6.92–7.31 ppm (m, 10H, 2ꢃPh); 13C NMR (75 MHz, CDCl3):
d=ꢀ0.32 (TMS), 23.74 (C-3a), 24.49 (C-3b), 43.36 (C-2), 82.73 (C-1),
125.65, 126.69, 126.73, 126.81, 127.32, 127.40, 127.89, 142.05, 147.22 ppm
(2ꢃPh); IR (film): n˜ =2959, 1699, 1603, 1497, 1452, 1384, 1363, 1251,
1068, 1031, 884, 842, 771, 699 cmꢀ1; UV (CH3CN): lmax (lg e)=194.0
(4.7434), 252.0 (2.5429), 258.0 (2.6196), 264.0 nm (2.4921); HRMS (ESI):
m/z: calcd for C19H26NaOSi: 321.16451; found 321.16464 [M+Na]+.
8.16 (C-6), 10.32 (C-3’), 23.27 (4-CH3), 31.93 (C-5), 32.88 (C-2’), 43.43 (C-
3), 75.02 (C-1’), 78.00 (C-4), 116.82 (C-1), 126.41, 126.50, 127.86, 146.32
(Ph), 135.14 ppm (C-2); (4,1’)-anti-11b (distinguishable signals): d=8.12
(C-6), 10.29 (C-3’), 23.49 (4-CH3), 31.35 (C-5), 43.67 (C-3), 74.96 (C-1’),
77.96 (C-4), 116.74 (C-1), 127.75, 127.88, 128.16, 146.28 ppm (Ph); IR
(film): n˜ =3076, 2969, 1639, 1493, 1453, 1377, 1052, 912, 755, 701 cmꢀ1
;
UV (CH3CN): lmax (lg e)=192.0 (4.5631), 252.5 (2.2807), 258.0 (2.3445),
264.0 nm (2.2306); HRMS (ESI): m/z: calcd for C16H24NaO: 255.17194;
found 255.17204 [M+Na]+.
4-Methyl-4-(2’-methyl-1’-phenyl-1’-propoxy)hex-1-ene (11c): According
to general procedure D, rac-trimethyl-(2-methyl-1-phenylpropoxy)silane
10c (1.11 g, 5.00 mmol, 1.00 equiv) was reacted with butanone (5)
(720 mg, 10.0 mmol, 2.00 equiv), allyltrimethylsilane (3) (1.14 g,
10.0 mmol, 2.00 equiv) and TfOH (151 mg, 88.0 mL, 1.00 mmol,
0.20 equiv) in CH2Cl2 (25 mL). Aqueous workup and evaporation of the
solvent afforded 1.32 g of the crude product. 781 mg of the crude product
were reacted with TBAF·3H2O (1.1 g) in Et2O (12 mL). Purification by
column chromatography afforded the title compound (640 mg,
2.60 mmol, corresponds to 88%) as colorless oil. Rf =0.65 (hexanes/Et2O
General procedure E for the allylation of methyl ketones: To a stirred
0.2m solution of the auxiliary (1 equiv) and the ketone (1 or 2 equiv) in
CH2Cl2 was added at ꢀ788C allyltrimethylsilane (1 or 2 equiv) and tri-
fluoromethanesulfonic acid (TfOH) (20 mol%) and stirring was contin-
ued for 12 h at the same temperature. The reaction was quenched by
adding NEt3 (1.5 equiv) and the solvent was evaporated in vacuo. The
residue was taken up in THF to give a 0.2m solution, which was treated
with TBAF·3H2O (1.2 equiv) to deprotect unreacted auxiliary. The solu-
tion was stirred at room temperature for 2 h, filtered through Celite,
which was washed with Et2O (3ꢃ3 mLmmolꢀ1 ketone). After evapora-
tion of the solvent, the crude product was purified by column chromatog-
raphy on silica gel.
1
50:1); H NMR (300 MHz, CDCl3): (4,1’)-syn-11c: d=0.71 (d, J=6.8 Hz,
3H, 3’a-H), 0.74 (t, J=7.5 Hz, 3H, 6-H), 0.90 (d, J=6.8 Hz, 3H, 3’b-H),
0.91 (s, 3H, 4-CH3), 1.33 (dq, J=3.5, 7.5 Hz, 2H, 5-H), 1.79 (dqq, J=6.5,
6.8, 6.8 Hz, 1H, 2’-H), 2.25 (d, J=7.4 Hz, 2H, 3-H), 4.14 (d, J=6.5 Hz,
1H, 1’-H), 4.96–5.09 (m, 2H, 1-H), 5.84 (dddd, J=17.7, 9.4, 7.4, 7.4 Hz,
1H, 2-H), 7.15–7.29 ppm (m, 5H, Ph); (4,1’)-anti-11c (distinguishable sig-
nals): d=0.86 (t, J=7.4 Hz, 3H, 6-H), 0.94 (s, 3H, 4-CH3), 1.49 (dq, J=
3.5, 7.4 Hz, 2H, 5-H), 2.04 (d, J=7.4 Hz, 2H, 3-H), 4.83–4.96 (m, 2H, 1-
H), 5.71 ppm (dddd, J=16.4, 10.4, 7.5, 7.5 Hz, 1H, 2-H); 13C NMR
(75 MHz, CDCl3): (4,1’)-syn-11c: d=8.21 (C-6), 18.93 (C-3’b), 19.14 (C-
3’a), 23.20 (4-CH3), 32.23 (C-5), 35.84 (C-2’), 43.36 (C-3), 77.83 (C-4),
78.73 (C-1’), 116.77 (C-1), 126.42, 127.27, 127.49, 145.07 (Ph), 135.29 ppm
(C-2); (4,1’)-anti-11c (distinguishable signals): d=8.26 (C-6), 19.12 (C-
3’a), 31.52 (C-5), 43.96 (C-3), 77.79 (C-4), 78.67 (C-1’), 116.60 (C-1),
126.44, 127.52, 145.00 ppm (Ph); IR (film): n˜ =3076, 2969, 1639, 1492,
1376, 1052, 912, 746, 702 cmꢀ1; UV (CH3CN): lmax (lg e)=191.5 (4.6181),
248.0 (2.1612), 252.5 (2.2506), 258.5 (2.2983), 264.5 nm (2.1421); HRMS
(ESI): m/z: calcd for C17H26NaO: 269.18759; found 269.18772 [M+Na]+.
4-Methyl-4-(1’-phenyl-1’-ethoxy)hex-1-ene (11a): According to general
procedure E, (R)-trimethyl-(1-phenylethoxy)silane (10a) (3.11 g,
16.0 mmol, 1.00 equiv) was reacted with butanone (5) (1.15 g, 16.0 mmol,
1.00 equiv), allyltrimethylsilane (3) (1.83 g, 16.0 mmol, 1.00 equiv) and
TfOH (496 mg, 290mL, 3.30 mmol, 0.21 equiv) in CH2Cl2 (80 mL). Purifi-
cation by column chromatography afforded the title compound (1.96 g,
8.98 mmol, 56%) as colorless oil. [a]2D0 =+39.58 (c=1, CHCl3); 1H NMR
(300 MHz, CDCl3): (4R,1’R)-11a: d=0.84 (t, J=7.4 Hz, 3H, 6-H), 1.02
(s, 3H, 4-CH3), 1.39 (d, J=6.5 Hz, 3H, 2’-H), 1.42–1.67 (m, 2H, 5-H),
2.22 (dd, J=14.2, 7.3 Hz, 1H, 3-Ha), 2.35 (dd, J=14.2, 7.3 Hz, 1H, 3-Hb),
4.69 (q, J=6.4 Hz, 1H, 1’-H), 4.95–5.15 (m, 2H, 1-H), 5.70–5.95 (m, 1H,
2-H), 7.18–7.40 ppm (m, 5H, Ph); (4S,1’R)-11a (distinguishable signals):
d=0.89 (t, J=7.4 Hz, 3H, 6-H), 1.03 (s, 3H, 4-CH3), 1.47 (d, J=6.8 Hz,
3H, 2’-H), 2.15–2.31 ppm (m, 2H, 3-Ha, 3-Hb); 13C NMR (125 MHz,
CDCl3): (4R,1’R)-11a: d=8.15 (C-6), 23.18 (4-CH3), 26.69 (C-2’), 31.60
(C-5), 43.33 (C-3), 69.46 (C-1’), 78.12 (C-4), 116.90 (C-1), 125.60, 126.47,
128.05, 147.59 (Ph), 134.94 ppm (C-2); (4S,1’R)-11a (distinguishable sig-
nals): d=8.07 (C-6), 23.57 (4-CH3), 26.89 (C-2’), 31.07 (C-5), 43.34 (C-3),
69.39 (C-1’), 78.08 (C-4), 126.17, 128.19, 128.41, 147.58 (Ph), 134.97 ppm
(C-2); IR (film): n˜ =1639, 1451, 1375, 1084, 1030, 912, 760, 700 cmꢀ1; UV
(CH3CN): lmax (lg e)=247.5 (2.2569), 252.0 (2.3391), 257.5 (2.3852),
263.0 nm (2.2477); HRMS (ESI): m/z: calcd for C15H22NaO: 241.15629;
found 241.15639 [M+Na]+.
4-Methyl-4-(1’-phenyl-1’-pentoxy)hex-1-ene (11d): According to general
procedure E, rac-trimethyl-(1-phenylpentoxy)silane (10d) (1.18 g,
5.00 mmol, 1.00 equiv) was reacted with butanone (5) (720 mg,
10.0 mmol, 2.00 equiv), allyltrimethylsilane (3) (1.14 g, 10.0 mmol,
2.00 equiv) and TfOH (151 mg, 88.0 mL, 1.00 mmol, 0.20 equiv) in CH2Cl2
(25 mL). Aqueous workup and evaporation of the solvent afforded the
crude product (1.35 g). The crude product (1.01 g) was reacted with
TBAF·3H2O (0.5 g) in CH2Cl2 (3 mL). Purification by column chroma-
tography afforded the title compound (826 mg, 3.17 mmol, corresponds
to 89%) as colorless oil. Rf =0.49 (hexanes/Et2O 50:1); 1H NMR
(600 MHz, CDCl3): (4,1’)-syn-11d: d=0.75 (t, J=7.3 Hz, 3H, 6-H), 0.83
(t, J=7.3 Hz, 3H, 5’-H), 0.93 (s, 3H, 4-CH3), 1.06–1.76 (m, 8H, 4’-H, 3’-
H, 2’-H, 5-H), 2.05–2.39 (m, 2H, 3-H), 4.41 (t, J=6.4 Hz, 1H, 1’-H),
4.83–5.08 (m, 2H, 1-H), 5.81 (dddd, J=17.8, 9.5, 7.3, 7.3 Hz, 1H, 2-H),
7.10–7.37 ppm (m, 5H, Ph); (4,1’)-anti-11d (distinguishable signals): d=
0.81 (t, J=7.6 Hz, 3H, 6-H), 0.84 (t, J=7.4 Hz, 3H, 5’-H), 0.96 (s, 3H, 4-
CH3), 4.40 (t, J=6.4 Hz, 1H, 1’-H), 5.71 ppm (dddd, J=17.1, 10.2, 7.3,
7.3 Hz, 1H, 2-H); 13C NMR (75 MHz, CDCl3): (4,1’)-syn-11d: d=8.15
(C-6), 14.02 (C-5’), 22.72 (C-4’), 23.30 (4-CH3), 28.03 (C-3’), 31.93 (C-5),
39.92 (C-2’), 43.44 (C-3), 73.86 (C-1’), 78.05 (C-4), 116.83 (C-1), 126.35,
126.49, 127.90, 146.66 (Ph), 135.12 ppm (C-2); (4,1’)-anti-11d (distinguish-
able signals): d=23.53 (4-CH3), 28.01 (C-3’), 31.35 (C-5), 39.94 (C-2’),
43.68 (C-3), 73.79 (C-1’), 78.01 (C-4), 116.74 (C-1), 127.67, 12.91, 128.17,
146.63 ppm (Ph); IR (film): n˜ =3075, 2934, 1639, 1454, 1376, 1053, 913,
758, 701 cmꢀ1; UV (CH3CN): lmax (lg e)=191.5 (4.6481), 252.5 (2.6051),
258.0 nm (2.5905); HRMS (ESI): m/z: calcd for C18H28NaO: 283.20324;
found 283.20331 [M+Na]+.
4-Methyl-4-(1’-phenyl-1’-propoxy)hex-1-ene (11b): According to general
procedure E, rac-trimethyl-(1-phenylpropoxy)silane (10b) (1.04 g,
5.00 mmol, 1.00 equiv) was reacted with butanone (5) (720 mg,
10.0 mmol, 2.00 equiv), allyltrimethylsilane (3) (1.14 g, 10.0 mmol,
2.00 equiv) and TfOH (151 mg, 88.0 mL, 1.00 mmol, 0.20 equiv) in CH2Cl2
(25 mL). Aqueous workup and evaporation of the solvent afforded 1.45 g
crude product. 1.04 g of the crude product was reacted with TBAF·3H2O
(0.5 g) in CH2Cl2 (3 mL). Purification by column chromatography afford-
ed the title compound (737 mg, 3.17 mmol, corresponds to 89%) as color-
less oil. Rf =0.70 (hexanes/Et2O 50:1); 1H NMR (600 MHz, CDCl3):
(4,1’)-syn-11b: d=0.74 (t, J=7.2 Hz, 3H, 6-H), 0.80 (t, J=7.2 Hz, 3H, 3’-
H), 0.94 (s, 4-CH3), 1.27–1.49 (s, 2H, 5-H), 1.54–1.60 (m, 1H, 2’-Ha),
1.65–1.72 (m, 1H, 2’-Hb), 2.07–2.38 (m, 2H, 3-H), 4.34 (dd, J=6.5,
6.5 Hz, 1H, 1’-H), 4.86–5.06 (m, 2H, 1-H), 5.82 (dddd, J=18.0, 9.1, 7.4,
7.4 Hz, 1H, 2-H), 7.10–7.33 ppm (m, 5H, Ph); (4,1’)-anti-11b (distinguish-
able signals): d=0.75 (t, J=7.3 Hz, 3H, 6-H), 0.84 (t, J=7.4 Hz, 3H, 3’-
6206
www.chemeurj.org
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 6199 – 6210

Asymmetric Allylation of Methyl Ketones
FULL PAPER
4-Methyl-4-(2’,2’-dimethyl-1’-phenyl-1’-propoxy)hex-1-ene (11e): Accord-
ing to general procedure E, rac-trimethyl-(2,2-dimethyl-1-phenylprop-
ACHTUNGTRENNUNGoxy)silane (10e) (500 mg, 2.11 mmol, 1.00 equiv) was reacted with buta-
1.92–1.98 (m, 2H, 3-H), 4.82–4.95 (m, 2H, 1-H), 5.73 ppm (dddd, J=16.6,
10.4, 7.4, 7.4 Hz, 1H, 2-H); 13C NMR (75 MHz, CDCl3): (4,1’)-syn-11g:
d=8.42 (C-6), 22.99 (4-CH3), 28.51 (C-3’’), 32.72 (C-5), 37.18 (C-4’’),
37.28 (C-1’’), 38.82 (C-2’’), 43.21 (C-3), 77.61 (C-1’), 81.69 (C-4), 116.72
(C-1), 126.28, 127.03, 128.62, 142.91 ppm (Ph); (4,1’)-anti-11g (distin-
guishable signals): d=135.50 (C-2), 8.48 (C-6), 22.79 (4-CH3), 31.69 (C-
5), 44.35 (C-3), 81.63 (C-4), 116.48 (C-1), 126.32, 126.61, 128.42 ppm
(Ph). IR (film): n˜ =2904, 2848, 1639, 1451, 1375, 1086, 1053, 911,
704 cmꢀ1; UV (CH3CN): lmax (lg e)=191.5 (4.7137), 247.5 (2.5908), 253.0
(2.6033), 258.5 (2.6124), 265.0 nm (2.5071); HRMS (ESI): m/z: calcd for
C24H34NaO: 361.25019; found 361.25012 [M+Na]+.
none (5) (152 mg, 2.11 mmol, 1.00 equiv), allyltrimethylsilane (3)
(241 mg, 2.11 mmol, 1.00 equiv) and TfOH (65.0 mg, 38.0 mL, 0.43 mmol,
0.20 equiv) in CH2Cl2 (10 mL). The crude product was reacted with
TBAF·3H2O (333 mg, 1.10 mmol) in CH2Cl2 (3 mL). Purification by
column chromatography afforded the title compound (458 mg,
1.76 mmol, 84%) as colorless oil. Rf =0.40 (hexanes 100%); 1H NMR
(600 MHz, CDCl3): (4,1’)-syn-11e: d=0.77 (t, J=7.5 Hz, 3H, 6-H), 0.84
(s, 9H, 3’-H), 0.85 (s, 3H, 4-CH3), 1.21–1.33 (m, 2H, 5-H), 2.24 (dd, J=
13.6, 7.4 Hz, 1H, 3-Ha), 2.30 (dd, J=13.6, 7.4 Hz, 1H, 3-Hb), 4.11 (s, 1H,
1’-H), 4.98–5.05 (m, 2H, 1-H), 5.85 (dddd, J=16.7, 10.4, 7.4, 7.4 Hz, 1H,
2-H), 7.14–7.31 ppm (m, 5H, Ph); (4,1’)-anti-11e (distinguishable signals):
d=0.88 (t, J=7.5 Hz, 3H, 6-H), 0.90 (s, 3H, 4-CH3), 1.45–1.53 (m, 2H, 5-
H), 1.96 (d, J=7.3 Hz, 2H, 3-H), 4.85–4.94 (m, 2H, 1-H), 5.70 ppm
(dddd, J=17.2, 10.2, 7.3, 7.3 Hz, 1H, 2-H); 13C NMR (75 MHz, CDCl3):
(4,1’)-syn-11e: d=8.41 (C-6), 22.96 (4-CH3), 26.69 (C-3’), 32.72 (C-5),
35.81 (C-2’), 43.18 (C-3), 77.76 (C-4), 80.93 (C-1’), 116.74 (C-1), 126.32,
126.35, 128.35, 143.92 (Ph), 135.46 ppm (C-2); (4,1’)-anti-11e (distinguish-
able signals): d=8.43 (C-6), 22.77 (4-CH3), 31.65 (C-5), 43.35 (C-3), 77.73
(C-4), 80.87 (C-1’), 116.52 (C-1), 135.50 ppm (C-2); IR (film): n˜ =3076,
2973, 1639, 1481, 1453, 1375, 1199, 1144, 1088, 1058, 1030, 912, 733,
704 cmꢀ1; UV (CH3CN): lmax (lg e)=191.5 (4.6489), 253.0 (2.1985), 258.5
(2.2787), 264.5 nm (2.1355); HRMS (ESI): m/z: calcd for C18H28NaO:
283.20324; found 283.20347 [M+Na]+.
4-Methyl-4-(1,2-diphenylethoxy)hex-1-ene (11h): According to general
procedure E, rac-(1,2-diphenylethoxy)-trimethylsilane (10h) (270 mg,
1.00 mmol, 1.00 equiv) was reacted with butanone (5) (72.2 mg,
1.00 mmol, 1.00 equiv), allyltrimethylsilane (3) (114 mg, 1.00 mmol,
1.00 equiv) and TfOH (30.1 mg, 18.0 mL, 0.21 mmol, 0.21 equiv) in
CH2Cl2 (4 mL). Aqueous workup and evaporation of the solvent afforded
the crude product (309 mg). The crude product (260 mg) was reacted
with TBAF·3H2O (0.3 g) in CH2Cl2 (4 mL). Purification by column chro-
matography afforded the title compound (231 mg, 0.78 mmol, corre-
sponds to 93%) as colorless oil. Rf =0.64 (hexanes/Et2O 5:1); [a]D20
=
1
+27.88 (c=1, CHCl3, when using (R)-10h); H NMR (300 MHz, CDCl3):
(4,1’)-syn-11g: d=0.72 (t, J=7.4 Hz, 3H, 6-H), 0.79 (s, 3H, 4-CH3), 1.34
(q, J=7.3 Hz, 1H, 5-Ha), 1.35 (q, J=7.6 Hz, 1H, 5-Hb), 2.01 (d, J=
7.2 Hz, 2H, 3-H), 2.82 (dd, J=13.1, 5.8 Hz, 1H, 2’-Ha), 2.96 (dd, J=13.1,
7.5 Hz, 1H, 2’-Hb), 4.62 (dd, J=7.5, 5.8 Hz, 1H, 1’-H), 4.90–5.00 (m, 2H,
1-H), 5.67 (dddd, J=16.2, 11.2, 7.2, 7.2 Hz, 1H, 2-H), 6.97–7.36 ppm (m,
10H, 2ꢃPh); (4,1’)-anti-11g (distinguishable signals): d=0.73 (t, J=
7.4 Hz, 3H, 6-H), 5.66 ppm (dddd, J=17.3, 10.2, 7.2, 7.2 Hz, 1H, 2-H);
13C NMR (125 MHz, CDCl3): (4,1’)-syn-11g: d=8.11 (C-6), 23.02 (4-
CH3), 31.90 (C-5), 43.05 (C-3), 47.03 (C-2’), 75.44 (C-1’), 78.30 (C-4),
116.68 (C-1), 125.98, 126.38, 126.67, 127.80, 127.86, 130.01, 138.89, 145.79
(2ꢃPh), 135.07 ppm (C-2); (4,1’)-anti-11g (distinguishable signals): 7.97
(C-6), 23.14 (4-CH3), 31.20 (C-5), 43.58 (C-3), 47.07 (C-2’), 75.40 (C-1’),
78.26 (C-4), 116.68 (C-1), 135.04 (C-2), 127.88, 145.76 ppm (Ph); IR
4-Methyl-4-(1’-cyclohexyl-1’-phenylmethoxy)hex-1-ene (11 f): According
to general procedure E, rac-(cyclohexylphenylmethoxy)trimethylsilane
(10 f) (393 mg, 1.50 mmol, 1.00 equiv) was reacted with butanone (5)
(216 mg, 3.00 mmol, 2.00 equiv), allyltrimethylsilane (3) (343 mg,
3.00 mmol, 2.00 equiv) and TfOH (44.5 mg, 26.0 mL, 0.30 mmol,
0.20 equiv) in CH2Cl2 (8 mL). Aqueous workup and evaporation of the
solvent afforded the crude product (395 mg). The crude product (164 mg)
was reacted with TBAF·3H2O (0.2 g) in CH2Cl2 (3 mL). Purification by
column chromatography afforded the title compound (127 mg,
0.44 mmol, corresponds to 71%) as colorless oil. Rf =0.66 (hexanes/Et2O
50:1); 1H NMR (600 MHz, CDCl3): (4,1’)-syn-11 f: d=0.80 (t, J=7.5 Hz,
3H, 6-H), 0.96 (s, 3H, 4-CH3), 1.06–2.08 (m, 11H, c-Hex), 2.30 (d, J=
7.3 Hz, 2H, 3-H), 4.20 (d, J=7.1 Hz, 1’ H), 5.05–5.12 (m, 2H, 1-H), 5.89
(dddd, J=16.7, 10.8, 7.3, 7.3 Hz, 1H, 2-H), 7.04–7.47 ppm (m, 5H, Ph);
(4,1’)-anti-11 f (distinguishable signals): d=0.92 (t, J=7.4 Hz, 3H, 6-H),
1.00 (s, 3H, 4-CH3), 2.10 (d, J=7.4 Hz, 2H, 3-H), 4.95–5.00 (m, 2H, 1-
H), 5.76 ppm (dddd, J=16.7, 10.3, 7.4, 7.4 Hz, 1H, 2-H); 13C NMR
(75 MHz, CDCl3): (4,1’)-syn-11 f: d=8.20 (C-6), 23.25 (4-CH3), 26.32 (C-
3’’), 26.60 (C-5’’), 29.49 (C-4’’), 29.69 (C-2’’), 29.71 (C-6’’), 32.24 (C-5),
43.43 (C-3), 45.50 (C-1’’), 77.88 (C-4), 78.38 (C-1’), 116.77 (C-1), 126.40,
127.30, 127.52, 145.29 ppm (Ph); (4,1’)-anti-11 f (distinguishable signals):
d=26.49 (C-5’’), 26.53 (C-3’’), 29.46 (C-4’’), 31.57 (C-5), 43.98 (C-3),
45.53 (C-1’’), 77.85 (C-4), 78.32 (C-1’), 116.58 (C-1), 125.78, 126.43,
127.55, 145.23 ppm (Ph); IR (film): n˜ =3075, 2925, 2852, 1639, 1451, 1375,
1147, 1052, 912, 759, 702 cmꢀ1; UV (CH3CN): lmax (lg e)=192.0 (4.6359),
248.0 (2.3179), 253.0 (2.4011), 258.5 (2.4392), 264.5 nm (2.3274); HRMS
(ESI): m/z: calcd for C20H30NaO: 309.21889; found 309.21900 [M+Na]+.
(film): n˜ =3028, 2969, 1639, 1495, 1454, 1377, 1060, 912, 758, 699 cmꢀ1
;
UV (CH3CN): lmax (lg e)=253.0 (2.551), 258.5 (2.6297), 264.0 nm
(2.5119); HRMS (ESI): m/z: calcd for C21H26NaO: 317.18759; found
317.18789 [M+Na]+.
4-Methyl-4-(1,2,2-triphenylethoxy)hex-1-ene (11i): According to general
procedure E, rac-(1,2,2-triphenyl-1-ethoxy)trimethylsilane (10i) (693 mg,
2.00 mmol, 1.00 equiv) was reacted with butanone (5) (288 mg,
4.00 mmol, 2.00 equiv), allyltrimethylsilane (3) (456 mg, 4.00 mmol,
2.00 equiv) and TfOH (61.6 mg, 36.0 mL, 0.41 mmol, 0.20 equiv) in
CH2Cl2 (8 mL). Aqueous workup and evaporation of the solvent afforded
the crude product (797 mg). The crude product (722 mg) was reacted
with TBAF·3H2O (0.5 g) in CH2Cl2 (3 mL). Purification by column chro-
matography afforded the title compound (671 mg, 1.81 mmol, corre-
sponds to 99%) as colorless oil. Rf =0.63 (hexanes/Et2O 5:1); 1H NMR
(300 MHz, CDCl3): (4,1’)-syn-11i: d=0.75 (t, J=7.3 Hz, 3H, 6-H), 0.87
(s, 3H, 4-CH3), 1.27–1.47 (m, 2H, 5-H), 2.03 (dd, J=13.9, 7.2 Hz, 1H, 3-
Ha), 2.18 (dd, J=13.9, 7.4 Hz, 1H, 3-Hb), 4.31 (d, J=7.8 Hz, 1H, 2’-H),
4.93–5.08 (m, 2H, 1-H), 5.26 (d, J=7.8 Hz, 1H, 1’-H), 5.60 (dddd, J=
18.0, 9.3, 7.4, 7.2 Hz, 1H, 2-H), 7.17–7.79 ppm (m, 15H, 3ꢃPh); (4,1’)-
anti-11i (distinguishable signals): d=4.36 (d, J=8.0 Hz, 1H, 2’-H), 5.27
(d, J=8.0 Hz, 1H, 1’-H), 5.49 ppm (dddd, J=16.6, 10.4, 7.4, 7.4 Hz, 1H,
2-H); 13C NMR (125 MHz, CDCl3): (4,1’)-syn-11i: d=8.08 (C-6), 22.93
(4-CH3), 32.29 (C-5), 42.91 (C-3), 61.15 (C-2’), 77.89 (C-1’), 78.61 (C-4),
116.42 (C-1), 126.01, 126.15, 126.58, 127.43, 127.46, 127.82, 127.90, 129.16,
129.74, 141.82, 141.98, 144.48 (3ꢃPh), 135.19 ppm (C-2); (4,1’)-anti-11i
(distinguishable signals): d=7.87 (C-6), 22.77 (4-CH3), 31.36 (C-5), 44.06
(C-3), 60.77 (C-2’), 77.86 (C-1’), 78.55 (C-4), 116.49 (C-1), 126.06, 126.10,
126.61, 126.92, 127.61, 127.85, 127.98, 128.91, 129.41, 141.84, 144.44 (3ꢃ
Ph), 135.14 ppm (C-2); IR (film): n˜ =3028, 2971, 2935, 1600, 1494, 1452,
1376, 913, 754, 699 cmꢀ1; UV (CH3CN): lmax (lg e)=194.5 (4.901), 220.5
(4.2386), 254.5 (2.7928), 259.5 nm (2.8514); HRMS (ESI): m/z: calcd for
C27H30NaO: 393.21889; found 393.21907 [M+Na]+.
4-Methyl-4-[1’-(1’’-adamantyl)-1’-phenylmethoxy]hex-1-ene (11g): Ac-
cording to general procedure E, rac-[(1’-adamantyl)phenylmethoxy]tri-
methylsilane (10g) (472 mg, 1.50 mmol, 1.00 equiv) was reacted with bu-
tanone (5) (216 mg, 3.00 mmol, 2.00 equiv), allyltrimethylsilane (3)
(343 mg, 3.00 mmol, 2.00 equiv) and TfOH (44.5 mg, 26.0 mL, 0.30 mmol,
0.20 equiv) in CH2Cl2 (8 mL). Aqueous workup and evaporation of the
solvent afforded 559 mg crude product. 299 mg of the crude product was
reacted with TBAF·3H2O (0.3 g) in CH2Cl2 (3 mL). Purification by
column chromatography afforded the title compound (245 mg,
0.72 mmol, corresponds to 90%) as colorless oil. Rf =0.70 (hexanes/Et2O
50:1); 1H NMR (300 MHz, CDCl3): (4,1’)-syn-11g: d=0.76 (t, J=7.5 Hz,
3H, 6-H), 0.82 (s, 3H, 4-CH3), 1.25 (q, J=7.5 Hz, 1H, 5-Ha), 1.26 (q, J=
7.5 Hz, 1H, 5-Hb), 1.33–1.68 (m, 12H, 2’’-H, 4’’-H), 2.18–2.34 (m, 2H, 3-
H), 3.92 (s, 1H, 1’-H), 4.97–5.08 (m, 2H, 1-H), 5.85 (dddd, J=16.1, 10.6,
7.6, 7.6 Hz, 1H, 2-H), 6.80–7.60 ppm (m, 5H, Ph); (4,1’)-anti-11g (distin-
guishable signals): d=0.86 (t, J=7.5 Hz, 3H, 6-H), 0.88 (s, 3H, 4-CH3),
Chem. Eur. J. 2009, 15, 6199 – 6210
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6207

L. F. Tietze et al.
4-Methyl-4-(1,2-diphenyl-2-methyl-1-propoxy)hex-1-ene (11k): Accord-
ing to general procedure E, rac-(1,2-diphenyl-2-methyl-1-propoxy)trime-
thylsilane (10k) (299 mg, 1.00 mmol, 1.00 equiv) was reacted with buta-
none (5) (144 mg, 2.00 mmol, 2.00 equiv), allyltrimethylsilane (3)
(228 mg, 2.00 mmol, 2.00 equiv) and TfOH (30.8 mg, 18.0 mL, 0.21 mmol,
0.21 equiv) in CH2Cl2 (4 mL). Aqueous workup and evaporation of the
solvent afforded the crude product (331 mg). The crude product (231 mg)
was reacted with TBAF·3H2O (0.3 g) in CH2Cl2 (3 mL). Purification by
column chromatography afforded the title compound (127 mg,
0.39 mmol, corresponds to 57%) as colorless oil. Rf =0.72 (hexanes/Et2O
CDCl3): syn-14b: d=17.18 (1ꢃCH
ACHTUNTGRENGU(N CH3)2), 17.25 (1ꢃCHACHUTNGTRNE(NUGN CH3)2), 20.89
(4-CH3), 35.07 (CH(CH3)2), 40.49 (C-3), 47.00 (C-2’), 75.44 (C-1’), 80.09
AHCTUNGTRENNUNG
(C-4), 116.51 (C-1), 125.98 (C-Ph), 126.49 (2ꢃC-Ph), 126.64 (C-Ph),
127.80 (2ꢃC-Ph), 127.81 (2ꢃC-Ph), 130.04 (2ꢃC-Ph), 135.00 (C-2),
138.75 (Cquart-Ph), 145.83 ppm (Cquart-Ph); anti-14b (distinguishable sig-
nals): d=17.21 (2ꢃCHACHTNUGTRENN(GU CH3)2), 20.29 (4-CH3), 34.97 (CHCAHTUNGTREN(NUGN CH3)2), 41.90
(C-3), 47.13 (C-2’), 79.97 (C-4), 126.69 (C-Ph), 127.87 ppm (2ꢃC-Ph); IR
(film): n˜ =3064, 3028, 2974, 1638, 1603, 1495, 1453, 1375, 1146, 1059, 912,
758, 700 cmꢀ1; UV (CH3CN): lmax (lg e)=248.0 (2.4154), 253.0 (2.5463),
258.5 (2.6275), 264.0 nm (2.5123); MS (DCI, 200 eV): m/z (%): 111 (42),
128 (100), 145 (27), 198 (27), 216 (18), 308 (14), 326 (35) [M+NH4]+.
1
5:1); H NMR (300 MHz, CDCl3): (4,1’)-syn-11k: d=0.66 (s, 3H, 4-CH3),
0.70 (t, J=7.4 Hz, 3H, 6-H), 1.18 (q, J=7.4 Hz, 2H, 5-H), 1.21 (s, 3H,
3a’-H), 1.32 (s, 3H, 3b’-H), 1.93 (dd, J=13.6, 7.0 Hz, 1H, 3-Ha), 2.10 (dd,
J=13.6, 7.6 Hz, 1H, 3-Hb), 4.43 (s, 1H, 1’-H), 4.89–5.00 (m, 2H, 1-H),
5.70 (dddd, J=16.0, 11.2, 7.6, 7.0 Hz, H, 2-H), 6.88–7.40 ppm (m, 10H,
2ꢃPh); (4,1’)-anti-11k (distinguishable signals): d=0.68 (s, 3H, 4-CH3),
0.77 (t, J=7.4 Hz, 3H, 6-H), 1.25 (s, 3H, 3a’-H), 1.34 (s, 3H, 3b’-H),
4.78–4.89 (m, 2H, 1-H), 5.64 ppm (dddd, J=16.9, 10.3, 7.3, 7.3 Hz, 1H, 2-
H); 13C NMR (125 MHz, CDCl3): (4,1’)-syn-11k: d=8.38 (C-6), 22.93 (4-
CH3), 24.28 (C-3a’), 25.42 (C-3b’), 32.52 (C-5), 42.91 (C-3), 43.17 (C-2’),
78.12 (C-4), 81.40 (C-1’), 116.60 (C-1), 125.64, 126.40, 126.68, 127.28,
127.57, 128.42, 143.07, 147.49 (2ꢃPh), 135.35 ppm (C-2); (4,1’)-anti-11k
(distinguishable signals): d=8.30 (C-6), 22.77 (4-CH3), 24.35 (C-3a’),
26.91 (C-3b’), 31.47 (C-5), 44.09 (C-3), 78.09 (C-4), 81.33 (C-1’), 116.53
(C-1), 126.44, 127.37 ppm (C-Ph); IR (film): n˜ =2971, 1639, 1453, 1382,
1056, 912, 772, 700 cmꢀ1; UV (CH3CN): lmax (lg e)=194.0 (4.7922), 253.0
(2.5924), 258.5 (2.6501), 264.0 nm (2.5191); HRMS (ESI): m/z: calcd for
C23H30NaO: 345.21889; found 345.21885 [M+Na]+.
4-(1,2-Diphenylethoxy)-4-cyclohexylpent-1-ene (14c): According to gen-
eral procedure E, rac-(1,2-diphenylethoxy)trimethylsilane (10h) (1.35 g,
5.0 mmol, 1.0 equiv), cyclohexyl methyl ketone (13c) (0.69 mL, 5.0 mmol
1.0 equiv) and allyltrimethylsilane (3) (0.8 mL, 5.0 mmol, 1.0 equiv) was
reacted with TfOH (90 mL, 1.0 mmol, 20 mol%) in CH2Cl2 (20 mL). Pu-
rification by column chromatography afforded the title compound
(1.56 g, 4.45 mmol, 89%) as colorless oil. Rf =0.39 (hexanes/ethyl acetate
100:1); [a]2D0 =ꢀ 15.58 (c=1, CHCl3, when (S)-10h was used); 1H NMR
(300 MHz, CDCl3): d=0.75 (s, 3H, 5-H3), 0.92–1.41 (m, 6H, 6ꢃCy-H),
1.54–1.92 (m, 5H, 5ꢃCy-H), 2.09 (brdd, J=14.2, 7.0 Hz, 1H, 3-Ha), 2.13
(brdd, J=14.2, 7.0 Hz, 1H, 3-Hb), 2.84 (dd, J=13.2, 6.0 Hz, 1H, 2’-Ha),
3.01 (dd, J=13.2, 7.2 Hz, 1H, 2’-Hb), 4.64 (t, J=6.6 Hz, 1H, 1’-H), 4.91–
5.01 (m, 2H, 1-H2), 5.55–5.72 (m, 1H, 2-H), 7.05 (dd, J=7.8, 1.8 Hz, 2H,
2ꢃPh-H), 7.16–7.27 ppm (m, 8H, 8ꢃPh-H); 13C NMR (125 MHz,
CDCl3): syn-14c: d=21.51 (C-5), 26.68 (1ꢃC-Cy), 26.72 (1ꢃC-Cy), 26.92
(1ꢃC-Cy), 27.02 (1ꢃC-Cy), 27.19 (1ꢃC-Cy), 40.45 (C-3), 45.51 (1ꢃC-
Cy), 46.94 (C-2’), 75.42 (C-1’), 79.92 (C-4), 116.42 (C-1), 125.94 (C-Ph),
126.51 (2ꢃC-Ph), 126.60 (C-Ph), 127.78 (4ꢃC-Ph), 130.00 (2ꢃC-Ph),
135.05 (C-2), 138.76 (Cquart-Ph), 145.79 ppm (Cquart-Ph); anti-14c (distin-
guishable signals): d=20.74 (C-5), 26.97 (1ꢃC-Cy), 27.08 (1ꢃC-Cy),
45.44 (1ꢃC-Cy), 47.12 (C-2’), 79.86 (C-4), 126.47 (2ꢃC-Ph), 127.84 ppm
(4ꢃC-Ph); IR (film): n˜ =3064, 3028, 2926, 2852, 1638, 1603, 1495, 1453,
1377, 1150, 1059, 911, 758, 699 cmꢀ1; UV (CH3CN): lmax (lg e)=253.0
(2.5624), 258.5 (2.6376), 264.5 nm (2.5246); MS (DCI, 200 eV): m/z (%):
151 (55), 168 (100), 198 (13), 216 (24), 348 (20), 366 (100) [M+NH4]+.
4-(1,2-Diphenylethoxy)-4-methylnon-1-ene (14a): According to general
procedure E, (S)-(1,2-diphenyl-ethoxy)trimethylsilane (10h) (76 mg,
0.29 mmol, 1.0 equiv), 2-heptanone (13a) (42 mL, 0.29 mmol 1.0 equiv)
and allyltrimethylsilane (3) (50 mL, 0.29 mmol, 1.0 equiv) was reacted
with TfOH (6 mL, 0.06 mmol, 20 mol%) in CH2Cl2 (2 mL). Purification
by column chromatography afforded the title compound (82 mg,
0.24 mmol, 85% [with 1.0 mmol rac-10h: 93%]) as colorless oil. Rf =0.32
(pentane/Et2O 100:1); [a]D20 =ꢀ19.78 (c=1, CHCl3); 1H NMR (300 MHz,
CDCl3): d=0.82 (s, 3H, 4-CH3), 0.85 (t, J=7.0 Hz, 3H, 9-H3), 0.94–1.36
(m, 8H, 5-H2, 6-H2, 7-H2, 8-H2), 2.09 (d, J=7.2 Hz, 2H, 3-H2), 2.85 (dd,
J=13.3, 5.8 Hz, 1H, 2’-Ha), 3.01 (dd, J=13.3, 7.6 Hz, 1H, 2’-Hb), 4.63
(dd, J=7.6, 5.8 Hz, 1H, 1’-H), 4.97 (brd, J=16 Hz, 1H, 1-Ha), 4.98 (brd,
J=11 Hz, 1H, 1-Hb), 5.68 (ddt, J=16, 11, 7.2 Hz, 1H, 2-H), 7.10 (dd, J=
7.8, 1.8 Hz, 2H, 2ꢃPh-H), 7.16–7.31 ppm (m, 8H, 8ꢃPh-H); 13C NMR
(125 MHz, CDCl3): (4,1’)-syn-14a: d=14.02 (C-9), 22.58 (C-8), 23.20 (C-
7), 23.66 (4-CH3), 32.29 (C-6), 39.31 (C-5), 43.49 (C-3), 47.01 (C-2’), 75.51
(C-1’), 78.11 (C-4), 116.69 (C-1), 125.97 (C-Ph), 126.43 (2ꢃC-Ph), 126.68
(C-Ph), 127.80 (2ꢃC-Ph), 127.85 (2ꢃC-Ph), 130.00 (2ꢃC-Ph), 135.10 (C-
2), 138.91 (Cquart-Ph), 145.71 ppm (Cquart-Ph); (4,1’)-anti-14a (distinguisha-
ble signals): d=14.07 (C-9), 23.13 (C-7), 23.61 (4-CH3), 32.40 (C-6), 38.67
(C-5), 44.21 (C-3), 47.09 (C-2’), 75.47 (C-1’), 78.09 (C-4), 126.39 (2ꢃC-
Ph), 127.88 (2ꢃC-Ph), 138.95 (Cquart-Ph), 145.76 ppm (Cquart-Ph); IR
(film): n˜ =3064, 3028, 2933, 2860, 1639, 1603, 1495, 1454, 1376, 1315,
1146, 1057, 998, 912, 757, 699 cmꢀ1; UV (CH3CN): lmax (lg e)=253.0
(2.4705), 258.5 (2.5577), 264.0 nm (2.4238); MS (DCI, 200 eV): m/z (%):
139 (27), 156 (100), 173 (19), 198 (13), 216 (7), 336 (16), 354 (65)
[M+NH4]+.
4-(1,2-Diphenylethoxy)-4-methyl-5-phenylpent-1-ene (14d): According to
general procedure E, rac-(1,2-diphenyl-ethoxy)-trimethylsilane (10h)
(270 mg, 1.0 mmol, 1.0 equiv), phenyl acetone (13d) (130 mL, 1.0 mmol
1.0 equiv) and allyltrimethylsilane (3; 160 mL, 1.0 mmol, 1.0 equiv) was
reacted with TfOH 18 mL, 0.2 mmol, 20 mol%) in CH2Cl2 (4 mL). Purifi-
cation by column chromatography afforded the title compound (317 mg,
0.89 mmol, 89%) as colorless oil. Rf =0.36 (pentane/Et2O 100:1);
1H NMR (300 MHz, CDCl3): d=0.88 (s, 3H, 4-CH3), 2.14 (dd, J=14.2,
6.9 Hz, 1H, 3-Ha), 2.23 (dd, J=14.2, 7.4 Hz, 1H, 3-Hb), 2.74 (d, J=
13.1 Hz, 1H, 5-Ha), 2.84 (d, J=13.1 Hz, 1H, 5-Hb), 2.97 (dd, J=13.1,
5.4 Hz, 1H, 2’-Ha), 3.09 (dd, J=13.1, 7.8 Hz, 1H, 2’-Hb), 4.83 (dd, J=7.8,
5.4 Hz, 1H, 1’-H), 5.10 (brd, J=17 Hz, 1H, 1-Ha), 5.16 (brd, J=10 Hz,
1H, 1-Hb), 5.88 (ddt, J=17, 10, 7.2 Hz, 1H, 2-H), 7.18 (brdd, J=7.8,
2.0 Hz, 2H, 2ꢃPh-H), 7.22–7.43 ppm (m, 13H, 13ꢃPh-H); 13C NMR
(125 MHz, CDCl3): syn-14d: d=23.31 (4-CH3), 42.83 (C-3), 46.51 (C-5),
46.97 (C-2’), 75.65 (C-1’), 78.23 (C-4), 117.22 (C-1), 125.90 (C-Ph), 125.99
(C-Ph), 126.19 (2ꢃC-Ph), 126.62 (C-Ph), 127.54 (2ꢃC-Ph), 127.77 (2ꢃC-
Ph), 127.83 (2ꢃC-Ph), 130.04 (2ꢃC-Ph), 130.98 (2ꢃC-Ph), 134.90 (C-2),
138.21 (Cquart-Ph), 138.72 (Cquart-Ph), 145.63 ppm (Cquart-Ph); anti-14d (dis-
tinguishable signals): d=22.47 (4-CH3), 44.11 (C-3), 45.92 (C-5), 47.03
(C-2’), 75.75 (C-1’), 78.29 (C-4), 117.27 (C-1), 125.92 (C-Ph), 126.06 (C-
Ph), 126.25 (2ꢃC-Ph), 126.72 (C-Ph), 127.62 (2ꢃC-Ph), 127.93 (2ꢃC-
Ph), 128.02 (2ꢃC-Ph), 129.99 (2ꢃC-Ph), 130.95 (2ꢃC-Ph), 134.85 (C-2),
138.30 (Cquart-Ph), 138.75 (Cquart-Ph), 145.58 ppm (Cquart-Ph); IR (film):
n˜ =3062, 3028, 2975, 2919, 1638, 1603, 1494, 1453, 1377, 1265, 1150, 1060,
913, 757, 699 cmꢀ1; UV (CH3CN): lmax (lg e)=252.5 (2.8026), 258.5
(2.8601), 264.0 nm (2.7500); MS (DCI, 200 eV): m/z (%): 176 (18), 194
(16), 198 (11), 339 (13), 356 (20), 374 (100) [M+NH4]+.
4-(1,2-Diphenylethoxy)-4,5-dimethylhex-1-ene (14b): According to gener-
al procedure E, rac-(1,2-diphenyl-ethoxy)-trimethylsilane (10h) (270 mg,
1.0 mmol, 1.0 equiv), 3-methyl-2-butanone (13b) (110 mL, 1.0 mmol
1.0 equiv) and allyltrimethylsilane (3) (160 mL, 1.0 mmol, 1.0 equiv) was
reacted with TfOH (18 mL, 0.2 mmol, 20 mol%) in CH2Cl2 (4 mL). Purifi-
cation by column chromatography afforded the title compound (265 mg,
0.91 mmol, 91%) as colorless oil. Rf =0.35 (hexanes/ethyl acetate 100:1);
1H NMR (300 MHz, CDCl3): d=0.77 (s, 3H, 4-CH3), 0.84 (d, J=6.8 Hz,
3H, 1ꢃCH
N
ACHTUGNTRENUN(NG CH3)2), 1.75 (sep, J=
6.8 Hz, 1H, CHACHTUNGTRENNUNG
4-(1,2-Diphenylethoxy)-4-methyl-6-phenylhex-1-ene (14e): According to
general procedure E, (S)-(1,2-diphenyl-ethoxy)-trimethylsilane (10h)
(118 mg, 0.43 mmol, 1.0 equiv), benzyl acetone (13e) (66 mL, 0.43 mmol
1.0 equiv) and allyltrimethylsilane (3; 75 mL, 0.43 mmol, 1.0 equiv) was
1H, 2’-Ha), 3.03 (dd, J=13.1, 7.3 Hz, 1H, 2’-Hb), 4.68 (dd, J=7.3, 6.0 Hz,
1H, 1’-H), 4.99 (brd, J=11 Hz, 1H, 1-Ha), 5.00 (brd, J=16 Hz, 1H, 1-
Hb), 5.66 (ddt, J=16, 11, 7.2 Hz, 1H, 2-H), 7.08 (dd, J=7.8, 1.8 Hz, 2H,
2ꢃPh-H), 7.16–7.33 ppm (m, 8H, 8ꢃPh-H); 13C NMR (125 MHz,
6208
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ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 6199 – 6210

Asymmetric Allylation of Methyl Ketones
FULL PAPER
reacted with TfOH (8 mL, 0.09 mmol, 20 mol%) in CH2Cl2 (3 mL). Purifi-
cation by column chromatography afforded the title compound (116 mg,
0.31 mmol, 72% [with 1.0 mmol rac-10h: 76%]) as colorless oil. Rf =0.30
(pentane/Et2O 100:1); [a]D20 =ꢀ17.28 (c=1, CHCl3); 1H NMR (300 MHz,
CDCl3): d=0.88 (s, 3H, 4-CH3), 1.56–1.67 (m, 2H, 5-H2), 2.13 (dd, J=
13.7, 7.4 Hz, 1H, 3-Ha), 2.18 (dd, J=13.7, 7.4 Hz, 1H, 3-Hb), 2.39–2.69
(m, 2H, 6-H2), 2.88 (dd, J=13.2, 5.6 Hz, 1H, 2’-Ha), 3.01 (dd, J=13.2,
7.8 Hz, 1H, 2’-Hb), 4.68 (dd, J=7.8, 5.6 Hz, 1H, 1’-H), 4.97–5.06 (m, 2H,
1-H2), 5.69 (ddt, J=17.6, 9.5, 7.4 Hz, 1H, 2-H), 6.96 (brd, J=7.8 Hz, 2H,
2ꢃPh-H), 7.10–7.35 ppm (m, 13H, 13ꢃPh-H); 13C NMR (125 MHz,
CDCl3): (4,1’)-syn-14e: d=23.74 (4-CH3), 29.93 (C-6), 41.58 (C-5), 43.48
(C-3), 47.07 (C-2’), 75.61 (C-1’), 77.75 (C-4), 117.17 (C-1), 125.45 (C-Ph),
126.06 (C-Ph), 126.47 (2ꢃC-Ph), 126.87 (C-Ph), 127.85 (2ꢃC-Ph), 128.03
(2ꢃC-Ph), 128.15 (2ꢃC-Ph), 128.25 (2ꢃC-Ph), 130.03 (2ꢃC-Ph), 134.70
1454, 1376, 1362, 1150, 1104, 1063, 912, 758, 699 cmꢀ1; UV (CH3CN): lmax
(lg e)=252.5 (2.8771), 258.5 (2.9180), 264.0 (2.8588), 268.0 nm (2.8095);
MS (DCI, 200 eV): m/z (%): 125 (20), 142 (100), 159 (19), 198 (3), 216
(5), 322 (1), 340 (5) [M+NH4]+.
3-Cyclohexyl-3-(1,2-diphenylethoxy)butanal (15): In a 100 mL-flask, a so-
lution of rac-14c (520 mg, 1.5 mmol, 1.0 equiv) in CH2Cl2 (50 mL) was
purged with nitrogen, and then ozone was bubbled through the solution
at ꢀ788C until the mixture remained pale blue (ꢁ5 min). To remove
excess ozone, the solution was purged with nitrogen. After complete dis-
coloring, triphenylphosphine (547 mg, 2.1 mmol, 1.4 equiv) was added to
the solution at ꢀ788C and then the solution was stirred at ꢀ788C to
room temperature for 8 h. After evaporation of the solvent, the crude
product was purified by column chromatography on silica gel (pentane/
Et2O 20:1). The title compound (470 mg, 1.3 mmol, 90%) was obtained
as a colorless oil. Rf =0.20 (pentane/Et2O 20:1); 1H NMR (300 MHz,
CDCl3): d=0.87 (s, 3H, 4-H3), 0.77–1.38 (m, 6H, 6ꢃCy-H), 1.56 (brd,
J=8.5, 3 Hz, 2H, 2ꢃCy-H), 1.75 (brt, J=10 Hz, 1H, Cy-H), 2.87 (dd,
J=13.3, 5.2 Hz, 1H, 2-Ha), 2.96 (dd, J=13.3, 8.4 Hz, 1H, 2-Hb), 4.66 (dd,
J=8.4, 5.2 Hz, 1H, 1’-H), 7.13 ppm (brdd, J=7.8, 1.8 Hz, 2H, 2ꢃPh-H),
7.17–7.33 (m, 8H, 8ꢃPh-H), 9.30 (t, J=3.0 Hz, 1H, 1-H); 13C NMR
(125 MHz, CDCl3): d=22.0 (C-4), 26.3 (C-Cy), 26.4 (C-Cy), 26.7 (C-Cy),
27.3 (C-Cy), 27.5 (C-Cy), 46.6 (C-2), 46.7 (C-Cy), 2’ (C-2’), 76.3 (C-1’),
80.0 (C-3), 126.3 (C-Ph), 126.4 (2ꢃC-Ph), 127.0 (C-Ph), 128.1 (2ꢃC-Ph),
128.1 (2ꢃC-Ph), 129.8 (2ꢃC-Ph), 138.6 (Cquart-Ph), 145.1 (Cquart-Ph),
203.6 ppm (C-1); MS (ESI): m/z=373.4 [M+Na]+.
(C-2), 138.81 (Cquart-Ph), 142.96 (Cquart-Ph), 145.54 ppm (Cquart-Ph); ACTHNUTRGENUG(N 4,1’)-
anti-14e (distinguishable signals): d=23.54 (4-CH3), 29.83 (C-6), 40.87
(C-5), 44.26 (C-3), 47.14 (C-2’), 77.78 (C-4), 125.50 (C-Ph), 126.39 (C-
Ph), 126.84 (C-Ph), 128.00 (2ꢃC-Ph), 128.20 (2ꢃC-Ph), 138.86 (Cquart
-
Ph), 142.99 (Cquart-Ph), 145.59 ppm (Cquart-Ph); IR (film): n˜ =3063, 3027,
2933, 1639, 1603, 1495, 1454, 1377, 1152, 1060, 914, 758, 699 cmꢀ1; UV
(CH3CN): lmax (lg e)=253.0 (2.7377), 258.5 (2.8189), 263.5 (2.7129),
267.5 nm (2.6378); MS (DCI, 200 eV): m/z (%): 190 (100), 198 (26), 353
(21), 370 (25), 388 (72) [M+NH4]+.
4-(1,2-Diphenylethoxy)-4-phenyl-pent-1-ene (14 f): According to general
procedure E, rac-(1,2-diphenyl-ethoxy)-trimethylsilane (10h) (270 mg,
1.0 mmol, 1.0 equiv), acetophenone (13 f) (120 mL, 1.0 mmol 1.0 equiv)
and allyltrimethylsilane (3) (160 mL, 1.0 mmol, 1.0 equiv) was reacted
with TfOH (18 mL, 0.2 mmol, 20 mol%) in CH2Cl2 (4 mL). Purification
by column chromatography afforded the title compound (32 mg,
4-Cyclohexyl-4-(1,2-diphenylethoxy)pentan-1-ol (16): To a stirred solu-
tion of rac-14c (350 mg, 1.0 mmol, 1 equiv) in THF (5 mL), 9-BBN
(5 mL of a 0.5m solution in THF, 3.0 mmol, 3 equiv) was added dropwise
at 08C. After stirring for 10 h at room temperature, H2O2 (1.5 mL of a
30% solution, 15 mmol, 15 equiv) and NaOH (1.5 mL of a 3n solution,
4.5 mmol, 4.5 equiv) were added at 08C. The solution was stirred for an-
other 12 h and then half of solvent was removed under reduced pressure.
CH2Cl2 (10 mL) and a saturated solution of NH4Cl (10 mL) were added
and the aqueous layer was extracted with CH2Cl2 (3ꢃ15 mL). The com-
bined organic layers were washed with brine and dried over Na2SO4. Pu-
rification by column chromatography afforded the title compound
(312 mg, 0.85 mmol, 85%) as colorless oil. Rf =0.12 (CH2Cl2); 1H NMR
(300 MHz, CDCl3): d=0.71 (s, 3H, 5-H3), 0.80–1.35 and 1.38–1.87 (2ꢃm,
15H, 15ꢃCy-H, 2-H2, 3-H2), 2.80 (dd, J=13.2, 5.7 Hz, 1H, 2’-Ha), 2.94
(dd, J=13.2, 7.7 Hz, 1H, 2’-Hb), 3.33 (dd, J=11.5, 6 Hz, 1H, 1-Ha), 3.38
(dd, J=11.5, 6 Hz, 1H, 1-Hb), 4.57 (dd, J=7.7, 5.7 Hz, 1H, 1’-H), 7.07
(brdd, J=7.8, 1.8 Hz, 2H, 2ꢃPh-H), 7.14–7.25 ppm (m, 8H, 8ꢃPh-H);
13C NMR (125 MHz, CDCl3): d=21.5 (C-5), 26.3 (C-Cy), 26.7 (C-Cy),
27.0 (C-Cy), 27.2 (C-Cy), 27.5 (C-Cy), 31.6 (C-3), 34.7 (C-2), 45.1 (C-Cy),
47.0 (C-2’), 63.4 (C-1), 75.6 (C-1’), 80.4 (C-4), 125.9 (C-Ph), 126.5 (2ꢃC-
Ph), 126.7 (C-Ph), 127.9 (2ꢃC-Ph), 127.9 (2ꢃC-Ph), 130.1 (2ꢃC-Ph),
139.3 (Cquart-Ph), 145.9 ppm (Cquart-Ph); MS (DCI, 200 eV): m/z (%): 367
(7) [M+H]+, 384 (26) [M+NH4]+.
1
0.09 mmol, 9%) as colorless oil. Rf =0.19 (pentane/Et2O 100:1); H NMR
(300 MHz, CDCl3): d=1.50 (s, 3H, 5-H3), 2.65 (d, J=7.2 Hz,2H, 3-H2),
3.03 (dd, J=13.2, 6.7 Hz, 1H, 2’-Ha), 3.11 (dd, J=13.2, 6.6 Hz, 1H, 2’-
Hb), 4.58 (t, J=6.6 Hz, 1H, 1’-H), 5.04 (brd, J=10.4 Hz, 1H, 1-Ha), 5.05
(brd, J=17.0 Hz, 1H, 1-Hb), 5.61 (ddt, J=17.0, 10.4, 7.2 Hz, 1H, 2-H),
7.08 (brdd, J=7.5, 1.8 Hz, 2H, 2ꢃPh-H), 7.16 (brdd, J=7.5, 1.8 Hz, 2H,
2ꢃPh-H), 7.24–7.44 ppm (2ꢃm, 11H, 11ꢃPh-H); 13C NMR (125 MHz,
CDCl3): syn-14 f: d=24.75 (C-5), 46.38 (C-2’), 46.41 (C-3), 76.87 (C-1’),
79.64 (C-4), 117.15 (C-1), 125.98 (C-Ph), 126.61 (C-Ph), 126.65 (2ꢃC-Ph),
126.68 (2ꢃC-Ph), 126.70 (C-Ph), 127.51 (2ꢃC-Ph), 127.64 (2ꢃC-Ph),
127.80 (2ꢃC-Ph), 129.95 (2ꢃC-Ph), 134.57 (C-2), 138.41 (Cquart-Ph),
144.41 (Cquart-Ph), 144.71 ppm (Cquart-Ph); anti-14 f (distinguishable sig-
nals): d=46.60 (C-3/C-2’), 117.34 (C-1), 125.92 (2ꢃC-Ph), 126.40 (C-Ph),
126.54 (2ꢃC-Ph), 126.80 (C-Ph), 127.44 (2ꢃC-Ph), 127.86 (2ꢃC-Ph),
130.03 (2ꢃC-Ph), 134.42 ppm (C-2); IR (film): n˜ =3062, 3028, 2978, 2926,
1639, 1603, 1495, 1453, 1375, 1288, 1152, 1071, 914, 759, 699 cmꢀ1; UV
(CH3CN): lmax (lg e)=252.5 (2.7523), 258.0 (2.8252), 264.0 nm (2.7265);
MS (DCI, 200 eV): m/z (%): 145 (100), 162 (19), 360 (59) [M+NH4]+.
4-(1,2-Diphenylethoxy)-4,5,5-trimethyl-hex-1-ene (14g): According to
general procedure E, rac-(1,2-diphenyl-ethoxy)-trimethylsilane (10h)
(270 mg, 1.0 mmol, 1.0 equiv), 3,3-dimethyl-2-butanone (13g) (130 mL,
1.0 mmol 1.0 equiv) and allyltrimethylsilane (3) (160 mL, 1.0 mmol,
1.0 equiv) was reacted with TfOH (18 mL, 0.2 mmol, 20 mol%) in CH2Cl2
(4 mL). Purification by column chromatography afforded the title com-
pound (25 mg, 0.08 mmol, 8%) as colorless oil. Rf =0.50 (pentane/Et2O
100:1); 1H NMR (300 MHz, CDCl3): syn-14g: d=0.80 (s, 3H, 4-CH3),
(R)-2-Cyclohexyl-pent-4-en-2-ol (17): A solution of (4R,1’S)-14c (80 mg,
0.23 mmol, 1.0 equiv) in dry Et2O (1 mL) was added to liquid ammonia
(30 mL) at ꢀ788C. Sodium (ꢁ24 mg, 1.0 mmol, 4.3 equiv) was added in
small portions until the mixture remained deep blue. After stirring for
1 h, the reaction was quenched by addition of MeOH (2 mL). The solu-
tion was allowed to warm to room temperature over 2–3 h. To the solu-
tion Et2O (50 mL) and a half saturated solution of NH4Cl (25 mL) was
added and the aqueous layer was extracted with CH2Cl2 (3ꢃ50 mL). The
combined organic layers were washed with brine and dried over Na2SO4.
After purification by column chromatography on silica gel (pentane/Et2O
20:1) the title compound (28 mg, 0.17 mmol, 75%) [using 0.29 mmol rac-
14c as substrate: 80% yield]) was obtained as a colorless oil. Rf =0.10
(pentane/Et2O 20:1); [a]D20 =ꢀ1.88 (c=1, CHCl3); 1H NMR (300 MHz,
CDCl3): d=0.80–1.47 (m, 6H, 6ꢃCy-H), 1.10 (s, 3H, 1-H3), 1.57–1.93 (m,
5H, 5ꢃCy-H), 2.20 (brdd, J=13.8, 7.5 Hz, 1H, 3-Ha), 2.27 (brdd, J=
13.8, 7.5 Hz, 1H, 3-Hb), 5.07–5.19 (m, 2H, 5-H2), 5.89 ppm (ddt, J=17,
10, 7.5 Hz, 1H, 4-H); 13C NMR (75 MHz, CDCl3): d=23.7 (C-1), 26.5 (C-
Cy), 26.7 (C-Cy), 26.7 (C-Cy), 26.8 (C-Cy), 27.6 (C-Cy), 44.2 (C-3), 47.4
(C-Cy), 73.9 (C-2), 118.6 (C-5), 134.1 ppm (C-4); MS (DCI, 200 eV): m/z
0.93 (s, 9H, CACHTUNGTRENNUNG(CH3)3), 2.10 (brdd, J=15.0, 7.5 Hz, 1H, 3-Ha), 2.17 (brdd,
J=15.0, 7.3 Hz, 1H, 3-Hb), 2.81 (dd, J=13.2, 5.8 Hz, 1H, 2’-Ha), 2.98 (dd,
J=13.2, 7.3 Hz, 1H, 2’-Hb), 4.74 (dd, J=7.3, 5.8 Hz, 1H, 1’-H), 4.89–5.02
(m, 2H, 1-H2), 5.80 (ddt, J=16.8, 10.5, 7.4 Hz, 1H, 2-H), 7.00–7.31 ppm
(m, 10H, 10ꢃPh-H); anti-14g (distinguishable signals): d=2.43 (m, 2H,
3-H2), 5.67 ppm (ddt, J=17.2, 10.0, 7.2 Hz, 1H, 2-H); 13C NMR (75 MHz,
CDCl3): syn-14g: d=18.90 (4-CH3), 26.10 (CACHTUNTRGENNGU(CH3)3), 39.19 (CACHTUNGTRENN(UNG CH3)3),
40.56 (C-3), 47.08 (C-2’), 76.10 (C-1’), 81.85 (C-4), 115.98 (C-1), 125.97
(C-Ph), 126.48 (2ꢃC-Ph), 126.52 (C-Ph), 127.75 (2ꢃC-Ph), 127.77 (2ꢃC-
Ph), 130.11 (2ꢃC-Ph), 137.11 (C-2), 138.82 (Cquart-Ph), 146.10 ppm (Cquart
-
Ph); anti-14g (distinguishable signals): d=39.82 (C(CH3)3), 42.77 (C-3),
AHCTUNGTRENNUNG
47.69 (C-2’), 116.19 (C-1), 125.79 (C-Ph), 126.09 (2ꢃC-Ph), 128.03 (2ꢃC-
Ph), 128.15 (2ꢃC-Ph), 129.17 (2ꢃC-Ph), 136.77 (C-2), 140.42 (Cquart-Ph),
144.40 ppm (Cquart-Ph); IR (film): n˜ =3063, 3028, 2957, 1637, 1603, 1495,
Chem. Eur. J. 2009, 15, 6199 – 6210
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6209

L. F. Tietze et al.
(%): 168 (18) [MꢀH2O+NH4]+, 186 (100) [M+NH4]+, 203 (18) [M+
NH3 +NH4]+, 336 (23) [2ꢃMꢀH2O+NH4]+, 354 (19) [2ꢃM+NH4]+.
Wulff, B. Weigand, C. Bittner, P. McGrath, K. Johnson, M. Schꢁfer,
Chem. Eur. J. 2001, 7, 1304–1308; g) L. F. Tietze, S. Hçlsken, J.
Adrio, T. Kinzel, C. Wegner, Synthesis 2004, 2236–2239.
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Kinzel, S. Schmatz, J. Am. Chem. Soc. 2008, 130, 4386–4395.
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2-Cyclohexyl-pentan-2-ol (18): A solution of rac-14c (351 mg, 1.01 mmol,
1.0 equiv) in MeOH (5 mL) was hydrogenated using 10% palladium on
charcoal (11 mg, 10 mmol, 1 mol%) as catalyst under a hydrogen atmos-
phere (balloon) at room temperature. After stirring the solution for 18 h,
the mixture was filtered and the residue was washed with CH2Cl2 (3ꢃ
20 mL). The combined organic layers were evaporated under reduced
pressure (600 mbar, 408C). The crude product was purified by column
chromatography on silica gel (pentane/Et2O 20:1) to obtain the title com-
pound (165 mg, 0.99 mmol, 98%) as colorless oil. Rf =0.21 (pentane/Et2O
1
20:1); H NMR (300 MHz, CDCl3): d=0.89 (t, J=6.8 Hz, 3H, 5-H3), 1.05
(s, 3H, 1-H3), 1.15 (s, 1H, OH), 0.92–1.44 and 1.58–1.84 ppm (2ꢃm, 15H,
11ꢃCy-H, 2-H2, 3-H2); 13C NMR (75 MHz, CDCl3): d=15.0 (C-5), 16.7
(C-4), 24.2 (C-1), 26.8 (C-Cy), 27.0 (C-Cy), 27.1 (C-Cy), 27.1 (C-Cy), 27.8
(C-Cy), 42.3 (C-3), 47.5 (C-Cy), 74.7 ppm (C-2); MS (DCI, 200 eV): m/z
(%): 170 (100) [MꢀH2O+NH4]+, 188 (9) [M+NH4]+.
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11483–11495.
[13] This limitation neglects TSs that contribute to 25% of product for-
mation in the case of 8a and to 5% product formation in the case
of 8h. The calculated selectivities change only slightly: For 8a, con-
sidering all relevant TSs leads to a predicted selectivity of 70:30 (in
contrast to 72:28 when considering only TSs A1, A2, B1 and B2). In
the case of 8h, a selectivity of 90:10 is predicted (instead of 91:9)
when all relevant TSs are included. For details, see Supporting Infor-
mation.
Computational details: All calculations were performed with the Gaussi-
an 03 program package.[14] TS geometries and energies for the stereogen-
ic step were calculated at the B3LYP/6-31+G(d)/PCM/UAKS level of
theory[15] with CH2Cl2 as solvent at T=195 K. Our previous theoretical
studies on related systems showed that the effect of the solvent need to
be included already for the geometry optimization. The nature of the TSs
was validated by inspection of the eigenvalues of the Hessian matrices
obtained by frequency calculation at the same level of theory. Employing
transition-state theory, we calculated the relative rate constants krel for
every TS. Addition of the rate constants krel of all TSs leading to each of
the possible stereoisomers gave overall rate constants the ratio of which
corresponds to the predicted ratio of product isomers. In this respect,
only TSs with a relative energy to the lowest-energy TS (DDG) of not
more than 6 kJmolꢀ1 (in the following, termed “relevant TSs”) will con-
tribute to product formation with more than 2% in the limiting case of
only one lower-energy TS. In each of the three studied systems, there are
more than only one lower-energy TSs; consequently, higher-energy TSs
can be neglected without any loss of accuracy.
[14] Gaussian 03, Revision B.04, M. J. Frisch, G. W. Trucks, H. B. Schle-
gel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Montgom-
Acknowledgements
AHCTUNGTREGeNNUN ry, Jr., T. Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S.
Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani,
N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K.
Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda,
O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian,
J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E.
Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W.
Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J.
Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C.
Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari,
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slowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaro-
mi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng,
A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W.
Chen, M. W. Wong, C. Gonzalez, J. A. Pople, Gaussian, Inc., Wall-
ingford CT, 2004.
This work has been supported by the Fonds der Chemischen Industrie.
We thank the Gesellschaft fꢀr wissenschaftliche Datenverarbeitung Gçt-
tingen (GWDG) for providing access to their computing resources. T.K.
acknowledges the Studienstiftung des Deutschen Volkes for a PhD schol-
arship.
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Received: February 8, 2009
Published online: May 14, 2009
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