Stereoselective allylation of ketones: Explanation for the unusual inversion of the induced stereochemistry in the auxiliary-mediated crotylation and pentenylation of butanone by DFT calculations

Article abstract of DOI:10.1002/chem.200801889

Auxiliary-mediated domino crotylations and pentenylations of butanone yield homoallylic ethers with two newly formed stereogenic centers. With our norpseudoephedrine-derived auxiliary, we observed the formation of anti isomers exclusively, and the nature

Full text of DOI:10.1002/chem.200801889

DOI: 10.1002/chem.200801889
Stereoselective Allylation of Ketones: Explanation for the Unusual Inversion
of the Induced Stereochemistry in the Auxiliary-Mediated Crotylation and
Pentenylation of Butanone by DFT Calculations
[
a]
[a]
[b]
Lutz F. Tietze,* Tom Kinzel, and Stefan Schmatz
Dedicated to Professor Armin de Meijere on the occasion of his 70th birthday
Abstract: Auxiliary-mediated domino
the energies of which were determined
by using the B3LYP/6-31+G(d) level
of theory in combination with the
PCM/UAKS method to include the ef-
fects exerted by the solvent dichloro-
methane. To quickly narrow down the
number of potentially relevant TSs
from the whole set of 288 and 864 TSs
for the crotylation and pentenylation,
respectively, we employed a screening
crotylations and pentenylations of bu-
tanone yield homoallylic ethers with
two newly formed stereogenic centers.
With our norpseudoephedrine-derived
auxiliary, we observed the formation of
anti isomers exclusively, and the nature
of the major isomer was independent
of the substrate double bond geometry.
Interestingly, there is a switch in in-
duced selectivity when going from cro-
tylation to pentenylation. Here, we
present the computational rationaliza-
tion for this behavior by identification
of the relevant transition states (TSs),
process based on B3LYP//AM1 ener-
gies. The predicted selectivities are in
good agreement with experimentally
determined ones. Furthermore, the ob-
tained results also facilitate an explana-
tion of the selectivities obtained in hex-
enylations and heptenylations. Finally,
activation energies were determined
that account for the significantly longer
reaction times than those for the
domino allylation with unsubstituted
trimethylallylsilane.
Keywords: allylation · chiral auxil-
iaries · density functional calcula-
tions · diastereoselectivity · nor-
AHCTUNGTRENNUGNp seudoephedrine
Introduction
ACHTUNGTRENNUNG
of catalytic amounts of trifluoromethanesulfonic acid
(TfOH) to give homoallylic ethers such as 4a (Scheme 1).
The transferred auxiliary moiety can be cleaved by using,
for example, Birch conditions to afford the desired homo-
allylic alcohol in high optical purity. With this method, even
the differentiation between a methyl and an ethyl group in 1
is possible with a diastereomeric ratio of 90:10 at À788C
(Table 1, entry 1).
[4]
Homoallylic alcohols and ethers are versatile building
blocks in organic synthesis. While many catalytic methods
exist for the asymmetric allylation of aldehydes, the stereo-
selective allylation of ketones is still a very challenging
task. We have developed an auxiliary-based domino
method in which a methyl ketone such as butanone (1)
reacts together with allyltrimethylsilane (2a) and the nor-
[1]
[5]
[2]
[3]
We have expanded the scope of the reaction by employing
both E- and Z-configured g-substituted allyl silanes (2b–e)
[
a] Prof. Dr. Dr. h. c L. F. Tietze, Dr. T. Kinzel
Institut fꢀr Organische und Biomolekulare Chemie
Georg-August-Universitꢁt Gçttingen
Tammannstrasse 2, 37077 Gçttingen (Germany)
Fax : (+49)551-399476
[6]
(
Table 1, entries 2–9). In each case, only two out of the
four possible isomers of 4b–e are formed (in the following,
termed major and minor isomer). Regardless of the double
bond geometry of the silane, the main and minor isomers of
E-mail: ltietze@gwdg.de
4
b–e are always 3,4-anti-configured. This is in line with our
[
b] Prof. Dr. S. Schmatz
study on the crotylation of aldehydes and ketones with E-
and Z-configured crotyl silanes in the presence of
Institut fꢀr Physikalische Chemie
Georg-August-Universitꢁt Gçttingen
Tammannstrasse 6, 37077 Gçttingen (Germany)
[7]
TMSOMe. Moreover, the absolute stereochemistry of the
formed isomers is independent of the silane double bond ge-
ometry as well. Interestingly, there is an unexpected switch
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200801889.
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Chem. Eur. J. 2009, 15, 1706 – 1712

FULL PAPER
formation 53 (in all relevant
TSs in the gas phase, 5 exclu-
sively adopts this conforma-
tion), whereas the more com-
pact TSs with conformations 51
and 5 become relevant in solu-
2
Scheme 1. Allylation of butanone for the stereoselective formation of homoallylic ethers.
Table 1. Selectivities and configuration of the main isomer for the allyla-
tion, because the surface acces-
sible for the solvent molecules
is only small. A simple 2-TS
model cannot sufficiently explain the stereoinduction for
this process.
tion of butanone with unsubstituted and g-substituted allyl silanes.
Entry
Allyl
silane
R
E/Z
Product
Selectivity
Main isomer
of 4 (X-ray)
1
3
In the present work, we adapted the computational ap-
proach to identify the relevant TSs for the allylation of buta-
none with g-substituted allyl silanes to explain a) why the
same isomer is formed when either E- or Z-configured si-
lanes are employed, and b) why there is an inversion in ste-
reoselectivity when going from crotylation to pentenylation.
We selected three systems for a detailed study: The attack
of the butanone-derived oxocarbenium ion 5 with E- and Z-
configured crotyl silane ((E)-2b and (Z)-2b) (Table 1, en-
tries 2 and 3), and the pentenylation of 5 with (Z)-pentenyl
silane ((Z)-2c) (Table 1, entry 5). The agreement of the
computationally predicted with the experimentally observed
selectivites represents a strong validation of the assumed
mechanism and the relevance of the calculated TS struc-
tures.
A( C NMR)
H
U
G
R
N
N
1
2
3
4
5
6
7
8
9
2a
H
–
4a
4b
4b
4c
4c
4d
4d
4e
4e
90:10
90:10
75:25
70:30
86:14
82:18
93:7
4R
(E)-2b
(Z)-2b
(E)-2c
(Z)-2c
(E)-2d
(Z)-2d
(E)-2e
(Z)-2e
Me
Me
Et
E
Z
E
Z
E
Z
E
Z
3S,4R
3S,4R
3R,4S
3R,4S
3R,4S
3R,4S
3R,4S
3R,4S
Et
nPr
nPr
nBu
nBu
85:15
95:5
in the induced selectivity when going from crotyl silanes
(
2b) to longer chained silanes (2c–e).
Recently, we were able to elucidate the origin of the high
stereoselectivity of the allylation
with 2a by a systematic compu-
tational study of all possible
For simplification, only the descriptors of the stereogenic
centers at C-3 and C-4 of 4b and 4c are given in the follow-
ing; for example, (RS)-4b corresponds to (3R,4S,1’S,2’S)-4b.
transition state (TS) geome-
[8]
tries. We assumed the stereo-
genic step to be the nucleophilic
attack of allyl silane on an inter-
Results and Discussion
mediate oxocarbenium ion
5
Scheme 2. Proposed stereogen-
ic step for the auxiliary-medi-
ated allylation of butanone.
(
Scheme 2). This mechanism is
Identification of relevant TSs: As in the allylation reaction
with 2a, there are 288 possible TS conformations for the
crotylations with (E)-2b or (Z)-2b. This number is a result
from attack of the Re- or Si-face of 2b at the Re- or Si-face
of the E- or Z-configured oxocarbenium ion 5 in one of
three relative orientations of the double bonds in 2b and 5
(antiperiplanar or one of two synclinal possibilities), in com-
bination with several conformational degrees of freedom
within 5. This number increases by a factor of 3 to a total of
864 structures for the pentenylation with 2c, since the ethyl
group in the g-position of the allyl silane may adopt one of
substantiated by the results of a
number of experimental and
computational studies.
[9]
The systematic consideration of the conformational de-
grees of freedom for the system 2a+5 leads to 288 possible
TS conformations. To deal with this large number, we have
developed a procedure based on B3LYP//AM1 energies to
quickly select potentially relevant TSs before performing
time-consuming calculations at the final DFT level. Thus,
we were able to narrow down the size of the final set of TSs
to 61, from which 14 relevant
TSs were identified. These TSs
can be grouped by Re- or Si-
face attack to the oxocarbeni-
um ion 5 in conformations 51,
52
, or 5 (Scheme 3). The pre-
3
dicted selectivity of 85:15 is in
excellent agreement with the
experimental value of 90:10.
The order of the TS energies
is a result of two competing ef-
fects: Intra-TS steric interac-
tions are minimized with con-
Scheme 3. Contribution of relevant TSs to the product formation of 4a grouped by conformations 5
1 2
, 5 , and
5
3
. In all relevant TSs, 5 has E-configuration.
Chem. Eur. J. 2009, 15, 1706 – 1712
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1707

L. F. Tietze et al.
three conformations relative to the position of the silyl
group.
and EC-B are shown in Figure 1. On the other hand, the
2
TS EC-C with synclinal orientation of the double bonds is
3
The aforementioned screening method allowed us to
select 22, 24, and 33 potentially relevant TSs for the attack
of (E)-2b, (Z)-2b, and (Z)-2c, respectively, by selecting all
calculated to be energetically accessible although its product
(RR)-4b is not observed in experiments.
À1
TSs with relative energies of less than 15 kJmol as deter-
mined by B3LYP/6-31+G(d)/PCM/UAKS single-point cal-
culations on AM1-optimized geometries (see Computational
Details). Relevant TSs are defined as having a relative free
À1
energy of less than 6 kJmol in relation to the lowest-
energy TS; only relevant TSs may contribute significantly to
product formation.
The sets of TSs were subjected to geometry optimization
and frequency calculation at the B3LYP/6-31+G(d)/PCM/
UAKS level of theory. In our previous studies on related
systems, we found the inclusion of solvent effects in the opti-
mization step to be essential.
Figure 1. TSs EC-A
3 2
and EC-B for the crotylation of butanone with (E)-
2
b. Hydrogen atoms are omitted for clarity.
Crotylation with (E)-2b: For the crotylation with (E)-2b,
the six TSs displayed in Table 2 were found to be relevant.
From their energies, an isomer ratio of anti-4b:syn-4b of
Crotylation with (Z)-2b: Five TSs were found to be relevant
for the crotylation with (Z)-2b, the energies of which trans-
late to a predicted ratio of anti-4b:syn-4b of 98:2. The anti
isomers (SR)-4b:(RS)-4b are predicted to be formed in a
Table 2. Relevant TSs for the crotylation of butanone with (E)-crotylsi-
lane (EC, (E)-2b). R=(S,S)-CH CAHTUNGTRENNGU(N CH )-NHCOCF .
3 3
59:41 ratio, which reproduces the experimental value of
75:25 well. Moreover, the trend of the crotylation with (Z)-
2b being less selective than with (E)-2b is correctly repro-
duced.
Table 3 displays the TSs and their energies. As in the cro-
tylation with (E)-2b, the formation of the anti isomers is
predicted to proceed via TSs in which 5 adopts conforma-
tions 5 , 5 , or 5 , and where the double bonds of 5 and (Z)-
[
a]
[b]
1
2
3
Stereoisomer Trajectory TS
G
rel
c
TS
Isomer ratio [%]
À1
[c]
2b adopt an antiperiplanar orientation. The most relevant
TSs ZC-A and ZC-B are displayed in Figure 2.
A
H
U
G
R
N
U
G
]
[%] calcd
exptl
3
3
(
(
SR)-4b
RS)-4b
A
B
EC-A
EC-A
EC-B
EC-B
EC-B
EC-C
3
2
0.0
4.6
3.2
3.4
5.7
0.7
50.0 53 (78)
2.9
6.9
6.1
1.5
90
2
15 (22)
10
-
Table 3. Relevant TSs for the crotylation of butanone with Z-crotylsilane
1
(
ZC, (Z)-2b). R=(S,S)-CH
A
H
U
G
R
N
N
(CH
3
)-NHCOCF
3
.
3
3
(
RR)-4b
C
32.4 32
[
a] Subscripts 1, 2, and 3 denote the oxocarbenium ion geometry accord-
ing to Scheme 3. [b] cTS =TS contribution to product formation.
c] Values in parentheses correspond to the ratio of the anti isomers.
[
6
8:32 is calculated. While the amount of the syn isomer is
[
a]
[b]
overestimated, the calculation correctly predicts the anti
isomer to be the main product. The ratio of the anti isomers
Stereoisomer Trajectory TS
G
rel
c
TS
Isomer ratio [%]
À1
A
H
U
G
R
N
U
G
]
[%] calcd
exptl
(
(
SR)-4b
RS)-4b
A
B
ZC-A
3
0.0
0.8
5.0
5.9
58.3 58
35.6 40
2.7
1.5
1.8
75
25
(
SR)-4b:(RS)-4b is predicted to be 78:22, which is very
ZC-B
ZC-B
ZC-B
3
close to the experimental value of 90:10.
2
As in the allylation reaction with 2a, in relevant TSs 5 is
always E-configured and the side chain adopts one of the
conformations 51–3 that are shown in Scheme 3. Concerning
the relative orientation of (E)-2b and 5, there are three
attack trajectories A, B, and C shown in Table 2. In trajecto-
ries A and B, the double bonds adopt an antiperiplanar ori-
entation with the methyl group in the g-position pointing
away from the auxiliary side chain. Apart from the chiral
residue, A and B represent mirror images and lead to the
anti isomers (SR)-4b and (RS)-4b, respectively. TSs EC-A3
1
(SS)-4b
D
ZC-D2 5.6
2
–
[a] Subscripts 1, 2, and 3 denote the oxocarbenium ion geometry accord-
ing to Scheme 3. [b] cTS =TS contribution to product formation.
Trajectories A and B for the crotylation with (E)-2b and
(Z)-2b differ only in the position of the CH TMS group. In
comparison to the TSs with (E)-2b, this introduces a subtle
additional steric interaction with the ethyl group in 5 that
2
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Chem. Eur. J. 2009, 15, 1706 – 1712

Stereoselective Allylation of Ketones
FULL PAPER
is now favored, leading to a ratio of 29:71 which correctly
reproduces the inversion of selectivity.
Rationalization of TS energies: For a rationalization of the
calculated relative free energies in solution, G , steric and
rel
electronic effects within the TS must be separated from the
free energy of solvation DGsolv. Our previous study has
shown that differences in DGsolv have a pronounced impact
[8]
on the energetic accessibility of certain groups of TSs.
Thus, we performed single-point calculations without the in-
clusion of solvent (gas phase) on the structures that were
optimized in solution. Table 5 displays the resulting relative
Figure 2. TSs ZC-A
3
and ZC-B
3
for the crotylation of butanone with (Z)-
GP
energy differences, Grel , and the relative energies of solva-
2
b. Hydrogen atoms are omitted for clarity.
tion, DGsolv,rel, for all TSs with attack trajectories A and B.
Additionally, the geometric parameters d (distance between
the bond-forming carbons), a (Bꢀrgi–Dunitz angle), g (rela-
tive orientation of the double bonds in 5 and 2), and d (tilt-
ing of the auxiliary phenyl group in relation to the double
bond in 5), as defined in Figure 4, were measured for these
TSs.
however applies uniformly to all relevant TSs, thus not
changing the order of the TS energies. Consequently, the
same main isomer is formed independent of the double
bond geometry of 2b.
Pentenylation with (Z)-2c: Of the 864 possible TSs for the
pentenylation with (Z)-2c, only two were found to be of
relevance, each leading to one of the experimentally ob-
served anti isomers of 4c (Table 4, Figure 3). In contrast to
the crotylations, the attack at the Re-face of 5 via TS ZP-B3
Table 4. Relevant TSs for the pentenylation of butanone with Z-pente-
nylsilane (ZP, (Z)-2c). R=(S,S)-CH ACHTUNGTRENN(NUG CH )-NHCOCF .
3 3
Figure 4. Selected geometric parameters for the description of TS confor-
mations. R=(S,S)-CH ACHTUNGERTNN(NUG CH )-NHCOCF ; R’=Me, Et.
3 3
Inspection of Table 5 reveals that in the gas phase, only
[
a]
[b]
Stereoisomer Trajectory TS
G
rel
c
TS
Isomer ratio [%]
TSs in which 5 adopts conformation 5 are energetically ac-
3
À1
A
H
U
G
R
N
U
G
]
[%] calcd
exptl
cessible. This is simply explained by 5 being the conforma-
3
(
(
SR)-4c
RS)-4c
A
B
ZP-A
ZP-B
3
1.4
0.0
29.2 29
70.8 71
14
86
tion in which the distance between the auxiliary side chain
and the approaching silane is maximized, thus leading to
minimum steric interaction. Furthermore, Si-face attack of 5
via TSs A is favored over Re-face attack via TSs B which
3
[
a] Subscript 3 denotes the oxocarbenium ion geometry according to
Scheme 3. [b] cTS =TS contribution to product formation.
3
3
can be traced back to the loss of stereoelectronic stabiliza-
tion of 5 by the phenyl group which needs to tilt away from
about 948 in TSs A to about 1258 in TSs B . The energy dif-
3
3
ference becomes less pronounced when going from (E)-2b
to (Z)-2b or (Z)-2c, which might be due to the fact that the
CH TMS group is further away from the auxiliary side chain
2
in TSs with Z-configured silanes.
Upon solvation, all shown TSs gain relevance with respect
to TSs A . On the one hand, TSs with conformations 5 and
3
1
52
become accessible for the crotylation systems; however,
this stabilization is not sufficient to replace TSs with 5 as
3
the most relevant TSs, therefore leading to an increased
number of relevant TSs. This can be traced back to the com-
pact nature of these TSs, resulting in a smaller solvent acces-
sible surface and thus (relative) stabilization in the non-co-
ordinating solvent dichloromethane. Furthermore, the TSs
Figure 3. TSs ZP-A
3 3
and ZP-B for the pentenylation of butanone with
(
Z)-2c. Hydrogen atoms are omitted for clarity.
Chem. Eur. J. 2009, 15, 1706 – 1712
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1709

L. F. Tietze et al.
Table 5. Energies and selected geometric parameters for TSs with attack trajectories A and B.
TSs A3 (in absolute terms),
leading to higher selectivity for
the crotylation and lower selec-
tivities in pentenylations, hexe-
nylations, and heptenylations.
GP
[a]
System
TS
G
rel
G
rel
DGSolv,rel
d
[ꢃ]
a
g
d
À1
À1
À1
A[ kJmol
H
U
G
R
N
N
]
A
H
U
G
R
N
U
G
]
A[ kJmol
H
U
G
R
N
U
G
]
[8]
[8]
[8]
5
+ (E)-2b
EC-A
EC-A
3
2
0.0
4.6
3.2
3.4
5.7
0.0
0.0
2.088
2.053
2.063
2.085
2.090
99.1
À174.4
À173.3
178.2
177.2
177.0
95.3
82.3
87.5
78.4
128.4
12.3
14.9
18.0
9.4
À7.7
À11.7
À14.6
À3.7
100.1
100.9
100.3
99.5
EC-B
EC-B
EC-B
2
1
Activation energies: Activation
energies were determined as
the free energy difference be-
tween the sum of the ground
states of 5 and 2, and the
lowest-energy TS. The thermo-
dynamic correction term from
the B3LYP/6-31+G(d)/PCM/
UAKS calculation was added to
3
5
5
+ (Z)-2b
+ (Z)-2c
ZC-A
3
0.0
0.8
5.0
5.9
0.0
4.1
12.6
16.6
0.0
2.047
2.071
2.039
2.056
100.3
100.3
101.8
101.6
À173.5
174.0
172.7
173.0
93.8
123.7
88.9
81.5
ZC-B
ZC-B
ZC-B
3
À3.3
À7.6
À10.7
2
1
ZP-A
ZP-B
3
0.0
À1.4
0.0
3.5
0.0
À4.9
1.989
1.998
101.2
101.3
À173.9
93.4
121.1
3
173.4
À1
GP
[
a] Relative free energy of solvation with DGSolv for A
3
-TSs arbitrarily set to 0 kJmol (Grel =Grel
+
DGSolv,rel).
the B3LYP/6–311++G
ACHTUNGTRENNUNG( 2d,p)/
PCM/UAKS single-point
B are additionally stabilized in solution because of their
energy on the geometries obtained with the smaller basis
set. We found activation energies of 159.9, 156.2, and
165.8 kJmol for the reaction with (E)-2b, (Z)-2b, and (Z)-
1
large dipole moment (ꢀ15 D) in comparison to TSs with 5
2
À1
or 5 (ꢀ9 to 10 D).
3
On the other hand, TSs B are better stabilized than TSs
2c, respectively. These values are significantly higher than
3
À1
À1 [8]
A by 3.3–4.9 kJmol , which in the case of (Z)-2c is suffi-
those for the allylation with 2a (139.1 kJmol ) and might
3
cient to replace ZP-A3 as the lowest-energy TS. Conse-
quently, (RS)-4c is formed as main product, whereas in the
case of crotylation, (SR)-4b is mainly formed. The change in
relative energy is illustrated in Figure 5: A trend can be
seen that helps to understand the selectivities with g-substi-
tuted silanes: With some confidence, we may assume that
explain why the reaction times need to be increased from
2 h with 2a to several days with g-substituted allyl silanes.
On the other hand, the stereoselective step is not neccessari-
ly also the rate-determining step of the homoallylic ether
formation.
Experimental elucidation of the minor isomer stereochemis-
try: To assess the validity of the computational results, the
predicted and observed ratios of both the main and minor
isomer must be compared. In the original publication, only
the major isomer stereochemistry was determined by X-ray
crystallography, while the minor isomer was argued to be
[6]
the second anti isomer by analogy reasoning. Computa-
tional results for the crotylation with (E)-2b however pre-
dict the minor isomer to be (RR)-4b and not the originally
published (RS)-4b, while the main isomer is correctly pre-
dicted to have (SR)-configuration.
To resolve the uncertainty concerning the minor isomer,
we unambigously determined its absolute configuration:
Under the assumption that the minor isomer is the predicted
3 3
Figure 5. Relative energy change between TSs A and B when going
from gas phase to solution.
(
4
RR)-isomer, we transformed the homoallylic ether mixture
b into allyl ethers 6 with one stereogenic center less
[10]
(
Scheme 4, a). Allyl ether 6 proved to be a mixture of dia-
the relevant TSs in allylations
with 2d and 2e are also TSs A3
and B . The energy difference
3
between TSs A and B increas-
3
3
es further as the size of the sub-
stituent in the g-position of 2
increases, leading to an even in-
creased selectivity. The energy
of TSs B remain larger in the
case of E-configured silanes in
relation to the corresponding NH
3
Scheme 4. Transformations of the homoallylic ether mixture for the determination of the minor isomer stereo-
chemistry: a) 1. O , PPh , 96%; 2. NaBH , MeOH; 3. o-NO -C -SeCN, then H , 76% (2 steps). b) Na,
(l), then MeOH, ꢀ80%.
3
3
4
2
4
H
6
2 2
O
3
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Stereoselective Allylation of Ketones
FULL PAPER
stereomers, proving that the homoallylic ether isomers 4b
differ in their configuration at C-4, ruling out (RR)-4b.
In another experiment, 4b was treated with sodium in
liquid ammonia to cleave the auxiliary moiety and to give
homoallylic alcohols 7 (Scheme 4, b) which were found to
be enantiomers. Thus, both initially formed homoallylic
ether isomers have anti configuration, and the minor isomer
has (RS)-configuration.
leading to each of the four possible stereoisomers gave overall rate con-
stants, the ratio of which corresponds to the predicted ratio of product
isomers. In this respect, only TSs with a relative energy of less than
À1
6
kJmol (termed “relevant TSs”) may contribute more than 2% to the
product formation in the limiting case of only one lower-energy TS. In all
reported cases, there are more than one lower-energy TSs; consequently,
higher-energy TSs can be neglected without any loss of accuracy.
For the calculation of activation energies, the TS energies were refined
with single-point calculations by employing the larger basis set 6–311++
G ACHUTNRGNENUG( 2d,p). For selectivities, there was no significant change by using the
For the pentenylation, we performed the reaction with
acetone and obtained an 84:16 mixture of diastereomers,
which is almost identical to the 86:14 mixture obtained in
the case of butanone. Since the acetone-derived products
lack the stereogenic center in the 4-position, we conclude
that the butanone-derived diastereomers differ in their con-
figuration at C-3, which rules out (RR)-4c (the main isomer
was assigned the (RS)-stereochemistry by X-ray analysis). In
analogy to the crotylation, we therefore conclude that the
minor isomer is the second anti isomer, namely (SR)-4c.
Thus, we found that the reaction is exclusively anti-selec-
tive in all cases, with a switch between main and minor
isomer configuration when going from crotylation to pente-
nylation.
larger basis set; all given relative TS energies Grel were calculated with
the 6-31+G(d) basis set.
Acknowledgements
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: September 14, 2008
Published online: January 2, 2009
1712
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Chem. Eur. J. 2009, 15, 1706 – 1712