O-DPPB-directed copper-mediated and -Catalyzed allylic substitution with grignard reagents

Article abstract of DOI:10.1002/chem.200600225

The ortho-diphenylphosphanylbenzoyl (o-DPPB) group was explored as a directing leaving group in copper-mediated and copper-catalyzed allylic substitution with Grignard reagents. Complete control of chemo-, regio- and stereoselectivity with complete syn-1,3-chirality transfer was observed as a result of the directed nature of the reaction. No excess of or ganometallic reagent is required and the directing group can be recovered quantitatively. Coordination studies in the solid state and in solution have shown that two substrates are bound via the phosphine function of the directing group at copper. Dynamic NMR experiments in solution are in agreement with a ligand-exchange process at copper, a prerequisite for the development of a substoichiometric process.

Full text of DOI:10.1002/chem.200600225

FULL PAPER
DOI: 10.1002/chem.200600225
o-DPPB-Directed Copper-Mediated and -Catalyzed Allylic Substitution with
Grignard Reagents**
Peter Demel, Manfred Keller, and Bernhard Breit*[a]
Abstract: The ortho-diphenylphospha-
nylbenzoyl (o-DPPB) group was ex-
plored as a directing leaving group in
copper-mediated and copper-catalyzed
allylic substitution with Grignard re-
agents. Complete control of chemo-,
regio- and stereoselectivity with com-
plete syn-1,3-chirality transfer was ob-
ganometallic reagent is required and
the directing group can be recovered
quantitatively. Coordination studies in
the solid state and in solution have
shown that two substrates are bound
via the phosphine function of the di-
recting group at copper. Dynamic
NMR experiments in solution are in
agreement with
a
ligand-exchange
process at copper, a prerequisite for
the development of a substoichiometric
process.
Keywords: allylic substitution
·
asymmetric synthesis grignard
·
reagents · organocopper reagents ·
synthetic methods
served as
a result of the directed
nature of the reaction. No excess of or-
Introduction
have proven to be useful. However, both systems suffer
from drawbacks. For instance, control over alkene geometry
upon reaction of acyclic derivatives is often unsatisfactory,
so that chirality transfer is incomplete.[1] Furthermore, in
many cases an excess of the organometallic reagent is re-
quired, which is particularly undesirable if valuable organic
residues are to be transferred.[4,5] Notably, the directing leav-
ing group is generally irreversibly lost in the overall process.
In previous work we have identified the ortho-diphenyl-
phosphanylbenzoyl (o-DPPB)-group as a multifunctional re-
agent-directing group (Scheme 1).[6] Several late transition-
metal catalyzed or mediated processes such as hydroformy-
lation,[7] rhodium catalyzed domino processes,[8] palladium
catalyzed atropselective biaryl coupling,[9] palladium cata-
lyzed allylic substitution[10] as well as conjugate addition of
organocopper reagents[11] have been described.
Synthetic transformations which allow the regio- and stereo-
selective construction of a desired carbon skeleton in a pre-
dictable and reliable fashion are of fundamental importance
for organic synthesis. In this respect the allylic substitution
with organocopper reagents is an attractive operation since
in contrast to many other transition-metal catalyzed allylic
substitutions it allows the introduction of hard nucleophiles
such as alkyl, alkenyl and aryl substituents.[1] However, the
simultaneous control of regio- and stereochemistry is a diffi-
cult problem to solve, and only a few successful examples
are known.[2] One solution to this problem makes use of re-
agent-directing leaving groups which control the trajectory
of the incoming copper nucleophile to occur as an exclusive
g-attack.[1] Additionally, a directing leaving group reverses
the stereochemical course of the allylic substitution to occur
as a syn process in opposition to the natural anti attack rela-
tive to the leaving group.[3] Among the leaving groups evalu-
ated for this purpose, carbamates[4] and benzothiazoles[5]
We herein report in full detail on the exploration of the
o-DPPB group as a reagent-directing leaving group for
regio- and stereoselective allylic substitution with organo-
[a] Dr. P. Demel, Dr. M. Keller,+ Prof. Dr. B. Breit
Institut für Organische Chemie und Biochemie
Albert-Ludwigs-Universität Freiburg
Albertstrasse 21, 79104 Freiburg (Germany)
Fax : (+49)761 203 8715
E-mail: bernhard.breit@organik.chemie.uni-freiburg.de
[+] X-ray crystal structure analysis of 34.
Scheme 1. o-DPPB-directed allylic substitution with organocopper re-
[**] o-DPPB-Directed Copper-Mediated Allylic Substitution: Part 1.
agents.
Chem. Eur. J. 2006, 12, 6669 – 6683
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6669

copper reagents.[12] Specifically, experiments towards opti-
mized reaction conditions as well as those clarifying the role
of the o-DPPB group are described. Limit and scope of the
regioselectivity of the o-DPPB-directed allylic substitution
has been evaluated, and experiments clarifying the stereo-
chemical course of the directed allylic substitution are pre-
sented. Furthermore, the coordination behavior of the allylic
o-DPPB esters towards copper(I) was studied in solution as
well as the solid state. Finally, first results employing sub-
stoichiometric amounts of copper(I) salts are reported.
We next turned our attention to organocopper reagents
which should have both lower reactivity in combination with
a pronounced affinity for phosphine coordination.[1,13] First,
the “lower-order cyanocuprate” was looked at, since it is
known to provide an intrinsically higher SN2’ selectivity.[1,13]
Accordingly, the g-substitution product 3 was obtained in a
97:3 ratio (Table 1, entry 4). However, the reaction rate was
rather low.
In order to ensure a complete intramolecular transfer of
the organocopper reagent we wondered whether a precom-
plexation of a copper(I) salt by the o-DPPB ester prior to
the generation of the organocopper reagent could be the
solution. In fact, best results were obtained when the o-
DPPB ester 1 was pretreated with one equivalent of copper
bromide dimethyl sulfide. Subsequent addition of 1.1 equiv-
alents of methyl magnesium iodide at room temperature in
diethyl ether led within less then two minutes to the quanti-
tative formation of the SN2’ substitution product 3 exclusive-
ly with complete control of alkene geometry (Table 1,
entry 5). When CH-benzoate 2 was subjected to identical
conditions, six hours were required to achieve a conversion
of 80%. Furthermore, the reaction displayed a dramatically
reduced chemo-, regio- and stereoselectivity. Hence, both
observations, the striking differences in chemo-, regio- and
diastereoselectivity as well as the significant rate accelera-
tion underline the role of the o-DPPB group to function as
a reagent-directing leaving group. Most interestingly, only
one equivalent of Grignard reagent was necessary in order
to achieve a quantitative reaction, which renders this
method most attractive for transfer of valuable organic resi-
dues.[14,15]
Results and Discussion
Development of the o-DPPB-directed allylic substitution:
Orientating experiments: Our investigations began with the
allylic-o-DPPB ester (ꢀ)-1. This substrate was chosen since
it is structurally not biased towards preference of either a-
or g-attack to give alkenes 3 and 4, respectively (Table 1).
Regioselectivity of the o-DPPB directed allylic substitution:
Next, generality of the o-DPPB-directed regio- and stereo-
selective allylic substitution was probed with respect to the
nature of the organic residue to be transferred. Thus, both
n-butyl magnesium chloride as well as isopropyl magnesium
bromide furnished the SN2’ substitution product 3 with ex-
cellent regio- and stereoselectivity (Table 2, entries 1 and 2).
However, the SN2’ selectivity dropped when phenylmagnesi-
um bromide was used. Interestingly, slowing down the addi-
tion rate of the Grignard reagent to the copper(I)-precom-
plexed substrate 2 led to excellent regioselectivity (Table 2,
First experiments were conducted with Gilman cuprates.
When allylic o-DPPB ester 1 was treated with two equiva-
lents of dimethylcuprate at ꢁ208C a quantitative conversion
was observed with formation of a 3:1 mixture of SN2’ substi-
tution product 3 and SN2 product 4 (Table 1, entry 1). Low-
ering the reaction temperature did not prove beneficial with
respect to regioselectivity (Table 1, entry 2). In order to see
whether this result was due to a directing effect of the o-
DPPB group the CH-derivative 2 was employed (Table 1,
entry 3). Here, the benzoate function should have similar
electronic and steric properties
except for the lack of capability
for metal coordination, and
hence for the ability to direct
the organocopper reagent. As a
result, substrate 2 gave almost
the same regioselectivity of
78:22 (Table 1, entry 3) as
found for the o-DPPB ester 1.
This suggests that for the dime-
thylcuprate reagent, the allylic
substitution of o-DPPB ester 1
does not proceed via a directed
reaction pathway.
Table 1. Results of the reaction of allylic benzoates 1 and 2 with different methylcopper reagents [see
Eq. (1)].
Entry
Equiv. [MR]
X
T [8C]
t [h]
Yield[a]
[%]
Ratio of 3[b]:4:5
1
2
3
4
5
6
7
2 Me2CuLi·LiI
2 Me2CuLi·LiI
2 Me2CuLi·LiI
2 MeCu(CN)Li
1 CuBr·SMe2/1.1 MeMgI
1 CuBr·SMe2/1.1 MeMgI
2.5 MeMgI
P
P
CH
P
ꢁ20
ꢁ80
ꢁ20
ꢁ20
RT
3
6
3
65
>95
>95
>95
>95
75:25:–
74:26:–
78:22:–
95:5:–
>99:1:–
42[d]:15:21
–:–:>99
P
2min
>95
[c]
CHRT
P
6
80
RT
48
98[e]
[a] GC yield. [b] E/Z >99:1. [c] Conversion. [d] The SN2’ product 3 was obtained as a E/Z mixture (64:36). [e]
Isolated yield after aqueous work-up and flash chromatography.
6670
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Chem. Eur. J. 2006, 12, 6669 – 6683

Allylic Substitution
FULL PAPER
Table 2. Results of the o-DPPB-directed copper-mediated allylic substi-
tution of o-DPPB ester 1 with Grignard reagents [Eq. (1)].
of the directed process may be slower which may result in
the accumulation of the corresponding cuprate reagent,
which would react via a non-directed pathway resulting in a
diminished regioselectivity. Hence, slowing down the
Grignard addition rate could avoid formation and accumula-
tion of the cuprate reagent, and would ensure directed and
hence selective allylic substitution via the organocopper re-
agent.
Entry Equiv. [MR][a]
t
Yield[b]
[%]
Ratio[c]
[d]:4:5
[h]
3
1
2
3
4
5
6
7
1 CuBr·SMe2/1.1 nBuMgCl
2
2
2
2
5
0.5
2
98
84
94
90
84
94
81
>99:1:–
97:3:–
88:12:–
93:7:–
97:3:–
97:3:–
1 CuBr·SMe2/1.1 iPrMgBr
1 CuBr·SMe2/1.1 PhMgBr
0.5 CuBr·SMe2/1.1 PhMgBr
0.5 CuBr·SMe2/1.1 PhMgBr[e]
0.5 CuBr·SMe2/1.2 PhMgBr[f]
0.5 CuBr·SMe2/1.1 (2-prope-
nyl)MgBr[g]
An obvious limitation at the present stage of this method
is the reaction with allyl-Grignard reagent. In this case nei-
ther SN2’ (3) nor SN2 product 4 were observed. Instead,
85:15:–
8
9
0.5 CuBr·SMe2/1.1 (2-prope-
4
2
73
87
94:6:–[i]
nyl)MgBr[h]
quantitative formation of allylic alcohol
(Table 2, entry 9).
5 was noted
0.5 CuBr·SMe2/2.1 allylMgBr
–:–:>99
Next, regioselectivity as a function of substrate structure
was studied. A series of primary allylic alcohols was trans-
formed into the corresponding o-DPPB esters 6–9. Employ-
ing the protocol of the directed allylic substitution in general
excellent SN2’ regioselectivities and yields were observed
(Table 3). Irrespective of double-bond geometry [compare
geraniol and nerol o-DPPB ester 8 and 9 (Table 3, entries 3–
6)] excellent regioselectivity with concomitant construction
of quaternary carbon centers was observed.
A series of secondary allylic o-DPPB esters starting from
acyclic secondary allylic alcohols was prepared and subject-
ed to the conditions of the directed allylic substitution
(Table 4). Again, excellent levels of regioselectivity were
found and isolated yields of the corresponding SN2’ products
[a] All reactions were performed with (ꢀ)-1 (X=P) at room temperature
(258C) in Et2O (0.05m), if not otherwise quoted. [b] Isolated yield after
aqueous work-up and flash chromatography. [c] GC Analysis of the
crude product mixture. [d] E/Z >99:1. [e] c
time (PhMgBr)=300 min. [f] As for [e] but substrate 1 was used in di-
chloromethane solution, c (CH2Cl2)=0.05m. [g] c(Et2O)=0.01m, addition
time [(2-propenyl)MgBr, c=0.11 molLꢁ1]=5 min. [h] c
(Et2O)=0.05m,
A
AHCTREUNG
AHCTREUNG
addition time [(2-propenyl)MgBr, c=0.122 molLꢁ1]=180 min. [i] GC
Analysis showed a mixture (60:40) of the substitution products 3/4 and
the elimination products (E,E)-1-phenyl-1,3-pentadiene, (E,Z)-1-phenyl-
1,3-pentadiene and (E)-5-phenyl-1,3-pentadiene.[17] The relative ratio of
the dienes was 40:17:43.
entries 5 and 6). The best yield for this reaction was ach-
ieved when a solvent mixture of dichloromethane and dieth-
yl ether was used (Table 2,
Table 3. o-DPPB-directed copper-mediated allylic substitution of primary o-DPPB esters with Grignard re-
agents.
entry 6). Employing similar re-
action conditions, transfer of an
alkenyl residue (2-propenyl)
was achieved with high SN2’ se-
lectivity (Table 2, entry 8).
Entry[a]
o-DPPB-ester[b]
RMgX (equiv)
MeMgI
Product
SN2’/SN2[c]
>99:1
Yield[d]
99
A
unified explanation of
these observations may suggest
that only organocopper re- 1[e]
agents (RCu) are capable to
react via the highly selective o-
DPPB-directed pathway.[16] On
(1.6)
MeMgI
(1.1)
2[f]
92:8
99
AHCTREUNG
the other hand, experiments
from above (Table 1, entries 1–
3) suggest that cuprate species
MeMgI
(1.2)
3[g]
95:5
91
80
(R2Cuꢁ) react via a non-direct-
AHCTREUNG
ed unselective intermolecular
pathway. Hence, in case of the
more nucleophilic alkyl copper
EtMgBr
(1.2)
4[h]
>98:2
AHCTREUNG
reagents (Table 2, entries 1, 2),
the rate of the directed allylic
substitution is greater than the
rate of a competing cuprate for-
mation followed by a non-di-
rected unselective pathway,
EtMgBr
(1.2)
5[h]
>98:2
>99:1
95
87
AHCTREUNG
nBuMgBr
(1.2)
6[i]
AHCTREUNG
even under fast addition rates
[a] The Grignard reagents in Et2O were added to the reaction mixture using a syringe pump. [b] For prepara-
tion of o-DPPB esters see Experimental Section. [c] Determined by GC (CPSil5CB, 30 m, 0.32 mm ID,
Chrompack). [d] Isolated yield after aqueous work-up and chromatographic purification. [e] c(substrate)=
of the alkyl-Grignard reagent.
However, in case of the less nu-
cleophilic aryl- and alkenyl–or-
0.01m,
c
N
c(Grignard)=0.1m,
E
ganometallic reagents the rate Grignard addition time 240 min. [g] c
G
U
ACHTREUNG
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6671

B. Breit et al.
Table 4. o-DPPB-directed copper-mediated allylic substitution of secondary o-DPPB esters with Grignard re-
agents.
To explore chirality transfer
in acyclic systems, enantiomeri-
cally pure allylic o-DPPB esters
(ꢁ)-(E)-15 and (+)-(Z)-15 were
chosen.
The enantiomerically pure E
alcohol (ꢁ)-(E)-29 was accessed
through an efficient enzymatic
kinetic resolution of the race-
mic alcohol (ꢀ)-(E)-29 employ-
ing Novozym 435.[21] Esterifica-
tion with o-DPPBA under Steg-
lich conditions[22] furnished the
enantiomerically pure allylic o-
Entry[a]
o-DPPB-ester[b]
RMgX
MeMgI
Product
SN2’/SN2[c]
(SN2’:E/Z)
Yield[d]
AHCTREUNG
97:3
1
84
AHCTREUNG
>99:1
2
3
4
5
MeMgI
MeMgI
MeMgI
MeMgI
88
82
A
95:5
(>95:5)
U
DPPB
(Scheme 5.)
ester
(ꢁ)-(E)-15
97:3
The corresponding cis-config-
ured ester (+)-(Z)-15 could be
prepared starting from propar-
gylic alcohol (ꢀ)-30. Thus, cis-
hydrogenation employing Lin-
dlarꢁs catalyst followed by enzy-
matic kinetic resolution em-
ploying Novozym 435, and es-
terification furnished the allylic
o-DPPB ester (+)-(Z)-15 in
97% ee. The absolute configu-
ration of (+)-(Z)-29 was deter-
86
A
>99:1
(>99:1)
68[e]
G
99:1
(>99:1)
6
nBuMgBr
99
A
[a] The Grignard reagents (0.5–1.11m in Et2O) were added to the reaction mixture during 15-20 min using a
syringe pump; c(substrate)=0.05m. [b] For preparation of o-DPPB esters see Experimental Section. [c] Deter-
mined by GC (CPSil5CB, 30 m, 0.32 mm ID, Chrompack). [d] Isolated yield after aqueous work-up and chro-
matographic purification. [e] Low yield due to high volatility of product.
were generally high, with the exception of highly volatile
products [(Table 4, entry 5, (ꢀ)-22].
Stereochemistry of the o-DPPB-directed allylic substitution:
In order to probe the stereochemistry of the o-DPPB-direct-
ed allylic substitution we chose the cis- and trans-cyclohexe-
nol-o-DPPB esters 27 as model substrates. Thus, Birch re-
duction of ortho-isopropylanisol 24 followed by acid-cata-
lyzed double-bond isomerization furnished the known
enone 25 in 44% overall yield according to a known proce-
dure.[18] Stereoselective reduction to give cis-26 was achieved
employing DIBAL as the reducing agent. Conversely, lithi-
um aluminum hydride furnished trans-26. Esterification of
alcohols 26 with ortho-diphenylphosphanyl benzoic acid fol-
lowing the Keck protocol[19] gave the desired o-DPPB esters
cis- and trans-27 in good yields (Scheme 2).
When cis-27 and trans-27 were independently subjected to
the conditions of the directed allylic substitution with
methyl magnesium bromide, in both cases a completely syn-
selective nucleophile transfer was observed to give cis- and
trans-menthene (28), respectively (Schemes 3 and 4).
Interestingly, even for trans-27 a complete 1,3-chirality
transfer was observed, even though in this case the substrate
has to pass a reactive conformation which places the iso-
propyl substituent in a pseudo-axial position (Scheme 4) in
Scheme 2. Preparation of cyclic o-DPPB esters cis- and trans-27.
mined through reductive transformation to the known alco-
hol (+)-31 (Scheme 6).[23]
Subjection of (ꢁ)-(E)-15 (99% ee) to the conditions of
the directed allylic substitution with methyl magnesium
iodide furnished in almost quantitative yield the SN2’ prod-
uct (+)-19 in perfect region-, stereoselectivity and in enan-
tiomerically pure form (99% ee).
order to fulfil stereoelectronic requirements [optimal p(C=
A
[3,20]
ꢁ
C)/s*
A
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Allylic Substitution
FULL PAPER
Scheme 6. Preparation of (+)-(Z)-15 and determination of absolute con-
figuration.
Scheme 3. syn-Selective o-DPPB-directed allylic substitution of cis-27.
lowing a syn-SN2’ pathway had occurred, which can be ra-
tionalized through a reactive conformation which minimizes
A1,3 strain[25] (32B vs 32A) and orients the o-DPPB leaving
in
a stereoelectronically favorable position (see 32B,
Scheme 7).
Scheme 4. syn-Selective o-DPPB-directed allylic substitution of trans-27.
Scheme 7. syn-Selective o-DPPB-directed allylic substitution of acyclic
(ꢁ)-(E)-15 and proposed reactive conformation 32B.
Scheme 5. Preparation of (ꢁ)-(E)-15.
Accordingly, a switch of the alkene geometry in the start-
ing allylic ester 15 from E to Z configuration should give
access to the optical antipode, (ꢁ)-19, starting from sub-
strates (ꢁ)-(E)-15 and (+)-(Z)-15 with the same absolute
configuration. Indeed, subjection of (+)-(Z)-15 to the condi-
tions of the directed allylic substitution furnished (ꢁ)-19,
with perfect 1,3-chirality transfer according to the directed
syn-substitution pathway. Hence, the directed allylic substi-
tution protocol employing o-DPPB-esters of secondary allyl-
ic alcohols occurs with perfect 1,3-chirality transfer for both,
structurally defined cyclic systems as well as for conforma-
tionally more flexible acyclic derivatives. In the latter case
the reaction enables the stereospecific construction of a ter-
tiary stereogenic carbon center as a function of alkene ge-
ometry (Scheme 8).
Interestingly, the o-DPPBA could be recovered almost
quantitatively during the work-up process (see Experimental
Section for details).
The absolute configuration of (+)-19 could be determined
upon oxidative cleavage of the alkene through ozonolysis
followed by reductive (NaBH4) workup to give the known
alcohol (+)-33.[24] Hence, a perfect 1,3-chirality transfer fol-
Chem. Eur. J. 2006, 12, 6669 – 6683
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6673

B. Breit et al.
Table 5. Selected bond lengths [Š], bond and torsion angles [8] for [(ꢁ)-
(E)-15]2CuBr (34) and [(Ph3P)3CuBr].
34
A
ꢁ
ꢁ
Cu P1
ꢁ
Cu P2
2.2390
2.2278
2.3464
126.8
114.7
118.5
117.8
108.7
P Cu
2.353
ꢁ
ꢁ
Cu Br1
Cu Br
2.481
110.2
108.6
P1-Cu-P2
P-Cu-P
P1-Cu-Br
P2-Cu-Br
O12-C33-C34-C35
O22-C83-C84-C85
P-Cu-Br
ꢁ
strates show an almost coplanar orientation of the s(C O)
A
Scheme 8. syn-Selective o-DPPB-directed allylic substitution of acyclic
(+)-(Z)-15 and proposed reactive conformation.
bond of the o-DPPB ester with respect to the alkene p
system as a result of minimizing A1,3 strain (torsion angle
O22-C83-C84-C85 108.78).[25] Hence, in the copper complex
34 the allylic o-DPPB substrates occupy a conformation
which fulfils the stereoelectronic requirements for the di-
rected allylic substitution in almost ideal manner, and is
thus in agreement with the postulated reactive conformation
32B (see Figure 2 and Scheme 7).
Coordination behavior of allylic o-DPPB esters towards
copper(I) salts: In order to learn about the nature of the at-
tractive interaction between the directing o-DPPB group
and a copper(I) center, we studied the coordination behav-
ior of (ꢁ)-(E)-15 in the presence of a copper(I) salt. Thus,
reaction of two equivalents of (ꢁ)-(E)-15 with copper bro-
mide dimethylsulfide in dichloromethane at room tempera-
ture gave in quantitative yields [(ꢁ)-(E)-15]2CuBr (34).
From a suitable single crystal an X-ray crystal structure
analysis could be obtained (Figure 1, Table 5). Thus, the
copper center shows trigonal-planar coordination geometry
with two substrates (ꢁ)-(E)-15 h1-coordinated via the phos-
phine donor and one bromide ligand. The structure and ge-
ometry of complex 34 differs significantly from the known
[Cu(PPh3)3Br] complex which displays tetrahedral geome-
U
try.[26] The lower coordination number for 34 may be ration-
alized on the basis of increased steric demand of phosphine
(ꢁ)-(E)-15. Interestingly, in complex 34 both phosphine sub-
Figure 2. Postulated reactive conformation for the directed allylic substi-
tution 32B and conformation of (ꢁ)-(E)-15 in the solid-state structure of
copper complex 34.
In fact, in most reactions shown above 0.5 equivalents of
copper(I) salt lead to optimal selectivities. This suggests that
both substrates coordinated to copper(I) undergo the direct-
ed reaction pathway.
Ligand exchange of allylic o-DPPB esters on a copper(I)
center: An interesting aspect would be to develop the stoi-
chiometric-directed process into a copper-catalyzed variant.
However, a prerequisite would be that the phosphine func-
tion of the o-DPPB group would allow for reversible bind-
ing of a copper(I) center. In order to learn about this possi-
bility, we studied the coordination behavior of (ꢁ)-(E)-15 in
the presence of 0.25 equivalents of copper bromide dime-
thylsulfide employing temperature dependent 31P NMR
spectroscopy (Figure3).
At 213 K two signals can be observed: A broad singlet at
d=ꢁ3.3 for the copper complex 34 and a sharp singlet for
the free phosphine, the o-DPPB ester (ꢁ)-(E)-15. Upon
warming the two signals show coalescence at T = 316
(ꢀ2) K and merge at 353 K into a broad singlet. This behav-
Figure 1. POV-ray plot of [(ꢁ)-(E)-15]2CuBr (34) in the solid state.
6674
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Chem. Eur. J. 2006, 12, 6669 – 6683

Allylic Substitution
FULL PAPER
Conclusions
The present study introduces
the ortho-diphenylphosphanyl
benzoate function (o-DPPB) as
an efficient directing leaving
group for copper-mediated al-
lylic substitution with Grignard
reagents. Optimal levels of re-
gioselectivity and syn-1,3-chiral-
ity transfer can be obtained
with 0.5 equivalents of copper
salt and stoichiometric amounts
of Grignard reagent, and the di-
recting o-DPPB group can be
recovered during the work-up
process as the corresponding
carboxylic acid (o-DPPBA)
almost quantitatively. Coordina-
tion studies in the solid state
and solution have shown that
two substrates are bound via
the phosphine function of the
directing group at copper. Dy-
namic NMR experiments in sol-
ution are in agreement with a
ligand exchange process at
Figure 3. Dynamic behavior of (ꢁ)-(E)-15 and [(ꢁ)-(E)-15]2CuBr (34), temperature dependent 31P NMR spec-
tra.
ior can be rationalized as a result of rapid ligand exchange
on copper(I). Employing a line shape analysis[27] the free ac-
tivation energy could be estimated to 16.7 kcalmolꢁ1.
Hence, the ligand exchange proceeds at room temperature
with a rate of k298 K = 13.1 sꢁ1 which suggests that experi-
ments employing substoichiometric quantities of copper(I)
salt should be possible.
copper, a prerequisite for the development of a catalytic
process.
Hence, the copper-mediated o-DPPB-directed allylic sub-
stitution is an interesting synthetic methodology for the ster-
eospecific construction of tertiary stereogenic carbon centers
and thus may become an attractive alternative to established
enolate alkylation chemistry.
Copper-catalyzed o-DPPB directed allylic substitution with
Grignard reagents: In fact, lowering the amount of copper
bromide to 0.2 equiv gave the allylic substitution product
(+)-19 in 85% yield in a regioselectivity of 96:4 and E/Z se-
lectivity of 95:5 in 99% ee, which is only slightly worse com-
pared with the results obtained from the stoichiometric var-
iant (compare Schemes 9 and 7). However, any further re-
duction of the amount of copper salt lead so far to lower se-
lectivities and to the formation of increasing amounts of al-
lylic alcohol 29 resulting from an undesired attack of the
Grignard reagent at the ester carbonyl function. Thus, in
case when highest levels of selectivity are in demand, the
stoichiometric process employing 0.5 equiv of copper(I) salt
should be preferred.
Experimental Section
General methods: Reactions were performed in flame-dried glassware
under argon (purity >99.998%). The solvents were dried by standard
procedures, distilled and stored under argon. Copper bromide dimethyl
sulfide was purchased from Aldrich (99%) and stored at 48C under
argon. All temperatures quoted are uncorrected. 1H, 13C NMR spectra:
Bruker ARX 200, Bruker DRX 300, Varian Mercury 300, Bruker AM
400, Bruker DRX 500 with tetramethylsilane (TMS) or chloroform
(CHCl3) as internal standards. 31P NMR spectra: Bruker ARX 200,
Bruker DRX 500, Varian Mercury 300 with 85% H3PO4 as external
standard. Melting points: Dr. Tottoli (Büchi) melting point apparatus. El-
emental Analyses: Elementaranalysen GmbHelementar vario EL. Opti-
cal rotation: Perkin–Elmer PE 241 or PE 342. Achiral Analytical GC:
Hewlett Packard HP5880A or Varian CP3800. Chiral Analytical GC:
Hewlett Packard HP5880A, Hewlett Packard HP5990A, CE Instruments
GC8000TOP. Flash chromatography: silica gel Si 60, E. Merck AG, Darm-
stadt, 40–63 mm.
The following compounds were prepared following literature procedures:
ortho-Diphenylphosphanylbenzoic acid (o-DPPBA),[28] benzhydrylbenzo-
ic acid,[29] (ꢀ)-(E)-1-phenyl-3-penten-2-ol,[30] cyclohexyl-2-propene-1-
ol,[31] (E)-3-hydroxy-oct-4-enoic acid tert-butyl ester,[32] (E)-3-hydroxy-5-
phenyl-pent-4-enoic acid tert-butyl ester,[33] 2,5-dimethyl-2-hexen-4-ol,[34]
2-isopropyl-anisole (24),[35] 6-isopropylcyclohex-2-en-1-one [(ꢀ)-25],[18]
Scheme 9. Copper-catalyzed o-DPPB-directed allylic substitution.
Chem. Eur. J. 2006, 12, 6669 – 6683
ꢀ 2006 Wiley-VCHVerlag GmbH& Co. KGaA, Weinheim
www.chemeurj.org
6675

B. Breit et al.
(ꢀ)-(E)-1-phenyl-1-penten-3-ol [(ꢀ)-(E)-29],[36] (ꢀ)-1-phenyl-1-pentin-3-
ol [(ꢀ)-30].[37]
(ꢁ)-(E)-29: 1HNMR (400.136 MHz, CDCl 3): d=0.94 (t, J=7.4 Hz, 3H,
CH3), 1.55–1.78 (m, 3H, CH2, OH), 4.23 (pq, J=6.4 Hz, 1H, CH), 6.21
(dd, J=15.9, 6.6 Hz, 1H), 6.58 (d, J=15.9 Hz, 1H, CH), 7.19–7.41 ppm
(m, 5H, Ar-H); 13C NMR (100.629 MHz, CDCl3): d=9.7, 30.2, 74.4, 126.5
(2C), 127.6, 128.6 (2C), 130.4, 132.3, 136.8 ppm; [a]2D0 =ꢁ7.0 (c=2.43,
Preparation of allylic alcohols
trans-(1R*,6R*)-6-Isopropyl-2-cyclohexen-1-ol (trans-26):[38] Enone (ꢀ)-
25 (1.321 g, 9.56 mmol) in Et2O (1 mL) was added slowly at ꢁ788C to a
magnetically stirred suspension of LiAlH4 (381 mg, 10.04 mmol) in Et2O
(20 mL) and the reaction mixture was stirred for further 3.5 h at this tem-
perature. Subsequently, the reaction mixture was warmed to room tem-
perature and the reaction was quenched by careful addition of water
(0.36 mL), stirred for further 30 min followed by successive addition of
2n NaOH(0.36 mL) and water (0.36 mL). The resulting mixture was ex-
tracted with Et2O (4”50 mL) and the combined organic phases were
washed with brine (20 mL) and dried (MgSO4). All volatile components
were removed in vacuo and the residue was purified through flash chro-
matography (petroleum ether/Et2O 95:5 ! 85:15) to give trans-26 as a
colorless oil (837 mg, 62%, dr 96:4). 1HNMR (200.132 MHz, CDCl 3):
d=0.85 (d, J=7.0 Hz, 3H, CH3), 0.97 (d, J=7.0 Hz, 3H, CH3), 1.31 (m,
CHCl3); GC analysis [Betadex 110, Supelco, 408C (15 min), 48Cminꢁ1
,
1508C (60 min)]: tR[(+)-(E)-29]=60.96 min, not detected; tR[(ꢁ)-(E)-
29]=61.26 min, 100%. The analytical data corresponded to those report-
ed previously.[21]
(E)-29-OAc: 1HNMR (400.136 MHz, CDCl 3): d=0.87 (pt, 3H, J=
7.7 Hz, CH3), 1.64 (pq, 1H, J=7.3 Hz, CH2), 1.68 (pq, 1H, J=7.3 Hz,
CH2), 2.00 (s, 3H, CH3), 5.27 (pq, 1H, J=6.9 Hz, CH), 6.04 (dd, 1H, J=
15.9, 7.3 Hz, CH), 6.52 (d, 1H, J=15.9 Hz, CH), 7.13–7.33 ppm (m, 5H,
Ar-H); 13C NMR (100.624 MHz, CDCl3): d=9.5, 21.3, 27.6, 76.0, 126.5
(2C), 127.6, 127.8, 128.5 (2C), 132.5, 136.4, 170.3 ppm. The analytical
data correspond to those reported previously.[21]
(+)-(S,Z)-1-Phenyl-1-penten-3-ol [(+)-(Z)-29]: According to the proce-
dure described above for (ꢁ)-(E)-29, from (ꢀ)-(Z)-29 (1.20 g, 7.4 mmol,
E/Z 3:97), vinyl acetate (8 mL) and Novozym 435 (100 mg) was obtained
after 70 h at ambient temperature (+)-(Z)-29 (516 mg, 44%, E/Z 3:97, ee
2H, CH ), 1.54 (brs, 1H, OH), 1.68 (m, 1H, CH), 2.03 (m, 3H, CH2,
2
CH), 4.05 (m, 1H, CH), 5.66 (ddd, J=9.9, 4.1, 2.2 Hz, 1H, CH),
5.78 ppm (m, 1H, CH); 13C NMR (75.469 MHz, CDCl3): d=17.2, 20.7,
21.0, 25.3, 26.6, 48.0, 68.9, 129.5, 131.0 ppm. The analytical data corre-
spond to those reported previously.[39] Analytical GC (OV1, 508C
(1 min), 108Cminꢁ1, 2008C (14 min)): cis-26 (tR =9.05 min); trans-26 (tR =
9.29 min), 6-isopropyl-2-cyclohexenone (25)(tR=10.36 min).
>97%). The corresponding acetate Z-29-OAc was not isolated. [a]D21
=
+52.9 (c=1.71, CHCl3). HPLC (Chiralcel OD-H, n-hexane/isopropanol
9:1, 0.5 mLminꢁ1, 258C, 254 nm): tR[(+)-(Z)-29]=10.83 min, 98.6%; tR
[(ꢁ)-(Z)-29]=18.59 min, not detected; tR[undefined by-product]=
17.72 min, 1.4%.
cis-(1R*,6S*)-6-Isopropyl-2-cyclohexen-1-ol (cis-26): A solution of enone
25 (1.38 g, 10 mmol) in benzene (2 mL) was added slowly at 08C to a
hexane solution of DIBAL (1.0m, 20 mL) in benzene (10 mL). After fur-
ther stirring for 4 h at this temperature the reaction was quenched upon
addition of a sat. aq. solution of Rochelle salt (40 mL). The organic
phase was separated and the aqueous phase extracted with Et2O (3”
60 mL). The combined organic phases were washed successively with
water (40 mL), brine (40 mL) and were dried (MgSO4). All volatile com-
ponents were removed in vacuo and the residue was purified through
flash chromatography (petroleum ether/ethyl acetate) to give cis-26 as a
colorless oil (580 mg, 41%, dr 95:5) which crystallized upon standing at
room temperature. M.p. 428C (lit.[40] 43–458C); 1HNMR (200.132 MHz,
CDCl3): d=0.97 (d, J=6.6 Hz, 3H, CH3), 1.02 (d, J=6.6 Hz, 3H, CH3),
1.13 (m, 1H), 1.29 (m, 1H), 1.69 (m, 2H), 1.98 (m, 1H, CH2), 2.15 (m,
(+)-(S)-1-Phenylpentan-3-ol [(+)-31]: Pd/C (10% Pd, 5.2 mg, 4.9 mmol)
was suspended in methanol (3 mL) and stirred 15 min under an atmos-
phere of hydrogen (balloon). Subsequently, a solution of (+)-(Z)-29
(64 mg, 0.4 mmol) in methanol (2 mL) was added via syringe and the sus-
pension was allowed to stir for further 24 h at ambient temperature. The
reaction mixture was filtered over a plug of methanol-wetted Celite and
washed with additional methanol (5 mL). Azeotropic removal of metha-
nol with Et2O furnished pure saturated alcohol (+)-31 as white needles.
1
M.p. 338C (lit.[23b] 36–388C); HNMR (300.135 MHz, CDCl 3): d=0.95 (t,
J=7.4 Hz, 3H, CH3), 1.38 (m, 1H, OH), 1.53 (m, 2H, CH2), 1.7 (m, 2H,
CH2), 2.69 (dd, J=13.6, 6.6 Hz, 1H, CH2), 2.82 (dd, J=13.6, 5.9 Hz, 1H,
CH2), 3.58 (m, 1H, CH), 7.21 (m, 3H, Ar-H), 7.31 (m, 2H, Ar-H);
13C NMR (75.476 MHz, CDCl3): d=9.8, 30.3, 32.1, 38.6, 72.7, 125.8,
128.39 (2C), 128.41 (2C), 142.2; [a]2D1 =+23.4 (c=1.37, CHCl3) [lit.[23b]
[a]2D5 =+23.8 (c=3.01, CHCl3)]. The analytical data correspond to those
reported previously.[23]
1H, CH ), 4.16 (brs, 1H, CH(OH)), 5.90 ppm (m, 2H, CH=CH). The
2
proton resonance of the hydroxyl group could not be detected. 13C NMR
(75.469 MHz, CDCl3): d=20.2 (CH3), 20.8(CH3), 20.9, 26.6, 28.5, 46.5,
N
54.6, 128.9, 131.7 ppm. The analytical data correspond to those reported
General procedure for the synthesis of o-DPPB-esters following the
Steglich protocol:[22] o-DPPBA (1 equiv), DMAP (1 equiv) and DCC
(1 equiv) were successively added to a solution of the allylic alcohol
(1 equiv) in CH2Cl2 (0.5m). The resulting mixture was stirred at ambient
temperature until TLC showed complete consumption of the starting ma-
terial. The reaction mixture was filtered through a plug of CH2Cl2-wetted
Celite and washed with additional CH2Cl2. An appropriate amount of
silica gel was added to the filtrate, which was then concentrated to dry-
ness. Flash chromatography with petroleum ether/ethyl acetate provided
the o-DPPB-esters as slightly yellow to colorless, highly viscous oils or
solids.
previously.[40]
(ꢀ)-(Z)-1-Phenyl-1-penten-3-ol [(ꢀ)-(Z)-29]:
A
solution of (ꢀ)-30
(2.37 g, 14.8 mmol) in ethyl acetate (50 mL) was treated subsequently
with quinoline (2.5 mL) and Pd/CaCO3/Pb (240 mg; 5% Pd, 0.11 mmol)
and placed under an atmosphere of hydrogen (balloon) and the mixture
was stirred vigorously for 18.5 h at room temperature. Subsequently, the
reaction mixture was filtered through a plug of Celite and washed with
ethyl acetate (20 mL). The organic phase was washed successively with
aqueous HCl (10%, 3”50 mL), water (30 mL) and was dried (MgSO4).
After removal of all volatile components in vacuo the remaining crude
product was purified by Kugelrohr distillation (808C, 0.01 mbar) to give
General procedure for the synthesis of o-DPPB-esters following the
Keck protocol:[19] o-DPPBA (1 equiv), DMAP (0.5 equiv), DMAP·HCl
(0.5 equiv) and DCC (1.3 equiv) were successively added to a solution of
the allylic alcohol (1 equiv) in CH2Cl2 (0.1m) and the resulting mixture
was stirred at ambient temperature until TLC showed complete con-
sumption of the starting material. The reaction mixture was filtered
through a plug of CH2Cl2-wetted Celite and washed with additional
CH2Cl2. An appropriate amount of silica gel was added to the filtrate,
which was then concentrated to dryness. Flash chromatography with pe-
troleum ether/ethyl acetate provided the o-DPPB-esters as slightly
yellow to colorless, highly viscous oils or solids.
(ꢀ)-(Z)-29 (2.09 g, 87%, E/Z 3:97) as
a
colorless oil. 1HNMR
(300.135 MHz, CDCl3): d=0.96 (t, J=7.7 Hz, 3H, CH3), 1.54 (d, J=
3.7 Hz, 1H, OH), 1.63 (m, 2H, CH2), 4.51 (m, 1H, CH), 5.67 (dd, J=
11.8, 9.6 Hz, 1H, CH), 6.58 (d, J=11.8 Hz, 1H, CH), 7.20–7.40 ppm (m,
5H, Ar-H); 13C NMR (75.476 MHz, CDCl3): d=9.7, 30.5, 69.2, 127.2,
128.3 (2C), 128.8 (2C), 131.3, 134.4, 136.7 ppm. Analytical data corre-
spond to those reported previously.[37]
(ꢁ)-(S,E)-1-Phenyl-1-penten-3-ol [(ꢁ)-(E)-29]:[21] Novozym 435 (200 mg)
was added to a solution of (ꢀ)-(E)-29 (1.62 g, 10.0 mmol) in vinyl acetate
(15 mL) and the resulting suspension was gently shaken for 136 h at am-
bient temperature. The enzyme was filtered and washed with Et2O. The
combined organic phases were evaporated and the residue purified by
flash chromatography to give (E)-29-OAc (899 mg, 44%, ee not deter-
mined) and the enantiomerically pure allylic alcohol (ꢁ)-(E)-29 (794 mg,
49%, ee >99%), both as colorless oils.
(ꢀ)-(E)-2-[2-(Diphenylposphanyl)benzoyloxy]-1-phenyl-3-pentene [(ꢀ)-
1
(X=P)]: Starting from (ꢀ)-(E)-1-phenyl-3-penten-2-ol (1.098 g,
6.77 mmol) was obtained (ꢀ)-1 (2.81 g, 92%) as a pale yellow, highly vis-
1
cous oil following the Steglich protocol. HNMR (300.133 MHz, CDCl 3):
d=1.49 (pd, J=6.5 Hz, 3H, CH3), 2.71 (dd, J=13.7, 6.6 Hz, 1H, CH2),
6676
www.chemeurj.org
ꢀ 2006 Wiley-VCHVerlag GmbH& Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 6669 – 6683

Allylic Substitution
FULL PAPER
2.84 (dd, J=13.7, 6.6 Hz, 1H, CH2), 5.24 (m, 1H, CH), 5.47 (m, 2H, 2”
CH), 6.81 (m, 1H, Ar-H), 7.17 (m, 17H, Ar-H), 7.90 (m, 1H, Ar-H);
13C NMR (75.469 MHz, CDCl3): d=17.6, 40.9, 76.3, 126.3, 128.06, 128.11,
128.4 (d, JC,P =7.4 Hz, 4C), 128.48 (d, JC,P =1.7 Hz, 2C), 128.50, 129.6
(4C), 130.5 (d, JC,P =2.8 Hz), 131.5, 134.0 (d, JC,P =20.4 Hz, 2C), 134.1 (d,
32.1, 61.8, 119.1, 123.6, 128.1, 128.4 (d, JC,P =7.3 Hz, 4C), 128.5 (2C),
130.6 (d, JC,P =2.9 Hz), 131.7, 132.0, 133.9 (d, JC,P =20.4 Hz, 4C), 134.2,
134.8 (d, JC,P =20.4 Hz), 138.1 (d, JC,P =10.2 Hz, 2C), 140.2 ppm (d, JC,P
=
27.6 Hz), 142.2, 166.8; 31P NMR (121.449 MHz, CDCl3): d = ꢁ4.4 ppm;
elemental analysis calcd (%) for C29H31O2P (442.53): C 78.71, H7.06;
found: C 78.40, H7.20.
J
C,P =20.9 Hz, 2C), 134.9 (d, JC,P =19.2 Hz), 134.2, 137.1, 138.16 (d, JC,P =
11.9 Hz), 138.18 (d, JC,P =11.9 Hz), 140.2 (d, JC,P =27.1 Hz), 165.9 (d,
J
ysis calcd (%) for C30H27O2P (450.51): C 79.98, H6.04; found: C 79.95, H
6.12.
(ꢁ)-(S,E)-3-[(Diphenylphosphanyl)benzoyloxy]-1-phenyl-1-pentene [(ꢁ)-
(E)-15]: Starting from (ꢁ)-(S,E)-1-phenyl-1-penten-3-ol [(ꢁ)-(E)-29]
(370 mg, 2.28 mmol, ee >99%) was obtained o-DPPB ester (ꢁ)-(E)-15
(960 mg, 94%, ee >99%) as a colorless, highly viscous oil following the
Steglich protocol. 1HNMR (500.135 MHz, CDCl 3): d=0.88 (pt, J=
7.4 Hz, CH3, 3H), 1.65 (psept, J=7.4 Hz, 1H), 1.74 (psept, J=7.4 Hz,
1H), 5.46 (m, 1H, CH), 5.99 (dd, J=16.1, 8.0 Hz, 1H, CH), 6.55 (d, J=
16.1 Hz, 1H, CH), 6.90 (m, 1H, Ar-H), 7.21–7.46 (m, 17H, Ar-H),
8.10 ppm (m, 1H, Ar-H); 13C NMR (125.771 MHz, CDCl3): d=9.6, 27.6,
77.3, 126.6 (2C), 127.3, 127.8, 128.2, 128.39 (d, JC,P =7.3 Hz, 2C), 128.41
(d, JC,P =7.4 Hz, 2C), 128.42 (2C), 128.5 (2C), 130.7 (d, JC,P =2.8 Hz),
131.8, 132.7, 133.90 (d, JC,P =19.8 Hz, 2C), 133.93 (d, JC,P =20.7 Hz, 2C),
134.3, 134.9 (d, JC,P =19.8 Hz), 136.4, 138.0 (d, JC,P =11.3 Hz), 138.2 (d,
C,P =2.3 Hz); 31P NMR (121.495 MHz, CDCl3): d=ꢁ4.5; elemental anal-
(ꢀ)-(E)-2-(2-Benzhydrylbenzoyloxy)-1-phenyl-3-pentene [(ꢀ)-2 (X=
CH)]: Starting from (ꢀ)-(E)-1-phenyl-3-penten-2-ol (402 mg, 2.48 mmol)
and benzhydrylbenzoic acid (715 mg, 2.48 mmol) was obtained (ꢀ)-2
(968 mg, 2.24 mmol, 90%) as a colorless, highly viscous oil following the
Steglich protocol. 1HNMR (300.133 MHz, CDCl 3): d=1.53 (m, 3H,
CH3), 2.82 (d, J=6.6 Hz, 2H, CH2), 5.31 (m, 1H, CH), 5.52 (m, 2H, 2”
CH), 6.52 (s, 1H, CH), 7.02 (m, 4H, Ar-H), 7.22 (m, 14H, Ar-H), 7.66
(m, 1H, Ar-H); 13C NMR (75.469 MHz, CDCl3): d=17.7, 41.0, 52.0, 75.7,
126.10, 126.12, 126.14, 126.4, 128.15 (4C), 128.21 (4C), 128.6, 129.3 (3C),
129.5, 129.7, 130.1, 130.8, 131.1, 131.5, 137.2, 143.8, 143.9, 144.2, 167.1; el-
emental analysis calcd (%) for C31H28O2 (432.55): C 86.08, H6.52; found:
C 86.35, H6.51; HRMS (FAB +): m/z: calcd for C31H28O2: 433.2168;
found 433.2177 [M+H]+.
J
C,P =11.3 Hz), 140.1 (d, JC,P =27.3 Hz), 166.2 ppm (d, JC,P =1.0 Hz);
31P NMR (202.456 MHz, CDCl3): d=ꢁ4.7 ppm; [a]2D0 = ꢁ53.7 (c=1.9,
CHCl3); elemental analysis calcd (%) for C30H27O2P (450.51): C 79.98, H
6.04; found: C 79.72, H6.08.
(ꢀ)-(E)-3-[(Diphenylphosphanyl)benzoyloxy]-1-phenyl-1-pentene [(ꢀ)-
(E)-15]: Starting from (ꢀ)-(E)-1-phenyl-1-penten-3-ol [(ꢀ)-(E)-29]
(623 mg, 3.84 mmol, ee >99%) was obtained o-DPPB ester (ꢀ)-(E)-15
(1.365 g, 79%) as a yellowish highly viscous oil following the Steglich
protocol.
(E)-3-Cyclohexyl-1-[(2-diphenylphosphanyl)benzoyloxy)-2-propene (6):
Starting from (E)-3-cyclohexyl-2-propen-1-ol (351 mg, 2.50 mmol) was
obtained o-DPPB ester 6 (1.020 g, 95%) as a colorless powder following
the Steglich protocol. M.p. 878C; 1HNMR (400.136 MHz, CDCl 3): d=
1.16 (m, 5H), 1.68 (m, 5H), 1.92 (m, 1H), 4.58 (d, J=6.4 Hz, 2H), 5.41
(dtd, J=15.5, 6.5, 1.3 Hz, 1H), 5.67 (dd, J=15.5, 6.9 Hz, 1H), 6.92 (m,
1H), 7.22–7.42 (m, 12H), 7.37 ppm (m, 1H); 13C NMR (100.624 MHz,
CDCl3): d=25.9 (2C), 26.1, 32.5 (2C), 40.3, 66.2, 121.2, 128.1, 128.4 (d,
(+)-(3S,Z)-3-[(Diphenylphosphanyl)benzoyloxy]-1-phenyl-1-pentene
[(+)-(Z)-15]: Starting from (+)-(3S,Z)-1-Phenyl-1-penten-3-ol [(+)-(Z)-
29] (392 mg, 2.42 mmol, E/Z 3:97 (NMR), ee >97%) was obtained o-
DPPB ester (+)-(Z)-15 (832 mg, 76%, E/Z 3:97 (NMR), ee >97%) as a
colorless, highly viscous oil following the Steglich protocol. 1HNMR
(250.135 MHz, CDCl3): d=0.78 (t, J=7.5 Hz, 3H, CH3), 1.61 (m, 2H,
CH2), 5.50 (dd, J=11.8, 9.3 Hz, 1H, CH), 5.79 (dpt, J=9.3, 6.3 Hz, 1H,
CH), 6.50 (d, J=11.8 Hz, 1H, CH), 6.90 (m, 1H, Ar-H), 7.29 (m, 17H,
Ar-H), 8.04 ppm (m, 1H, Ar-H); 13C NMR (75.476 MHz, CDCl3): d=9.4,
27.8, 73.6, 127.2, 128.1, 128.3 (2C), 128.39 (d, JC,P =6.8 Hz, 2C), 128.41
J
J
C,P =7.3 Hz, 4C), 128.5 (2C), 130.6 (d, JC,P =2.9 Hz), 131.8, 133.9 (d,
C,P =20.3 Hz, 4C), 134.3 (2C), 134.7 (d, JC,P =19.2 Hz), 138.1 (d, JC,P
C,P =26.6 Hz), 142.0, 166.7 ppm; 31P NMR
=
11.6 Hz), 140.3 (d,
J
(121.464 MHz, CDCl3): d=ꢁ4.6 ppm; elemental analysis calcd (%) for
C28H29O2P (428.50): C 78.48, H6.82; found: C 78.22, H6.65.
(E)-1-[(2-Diphenylphosphanyl)benzoyloxy)-3-phenyl-2-propene
(7):
Starting from cinnamyl alcohol (671 mg, 5.0 mmol) was obtained
7
(d, JC,P =6.7 Hz, 2C), 128.5 (2C), 128.6 (2C), 129.8, 130.6 (d, JC,P
2.8 Hz), 131.7, 131.9, 133.92 (d, JC,P =20.9 Hz, 2C), 133.98 (d, JC,P
=
=
=
(1.770 g, 84%) as a slightly yellow powder following the Steglich proto-
col. M.p. 95–988C; 1HNMR (400.136 MHz, CDCl 3): d=4.80 (dd, J=6.5,
1.3 Hz, 2H), 6.16 (dt, J=15.9, 6.5 Hz, 1H), 6.60 (d, J=15.9 Hz, 1H), 6.93
(m, 1H), 7.22 (m, 17H), 8.09 ppm (m, 1H); 13C NMR (100.624 MHz,
CDCl3): d=65.8, 123.1, 126.7 (2C), 128.0 (2C), 128.2 (2C), 128.5 (d,
20.9 Hz, 2C), 134.2, 135.0 (d,
JC,P =19.2 Hz), 136.3, 138.1 (d, JC,P
11.3 Hz), 138.2 (d, JC,P =11.9 Hz), 140.0 (d, JC,P =27.1 Hz), 166.2 ppm (d,
J
C,P =2.3 Hz); 31P NMR (101.261 MHz, CDCl3): d=ꢁ6.5 ppm; [a]D16
=
+133.48 (c=5.04, CHCl3); elemental analysis calcd (%) for C30H27O2P
J
C,P =7.3 Hz, 4C), 128.6 (2C), 130.8, 131.9, 133.9 (d, JC,P =20.4 Hz, 4C),
(450.51): C 79.98, H6.04; found: C 79.72, H5.92.
139.3 (2C), 134.5 (d, JC,P =18.9 Hz), 136.3, 138.0 (d, JC,P =11.6 Hz, 2C),
140.4 (d, JC,P =27.6 Hz), 166.7 ppm; 31P NMR (121.464 MHz, CDCl3): d=
ꢁ4.10 ppm; elemental analysis calcd (%) for C28H23O2P (422.45): C 79.61,
H5.49; found: C 79.46, H5.50.
(ꢀ)-(3S,Z)-3-[(Diphenylphosphanyl)benzoyloxy]-1-phenyl-1-pentene [(ꢀ)-
(Z)-15]: Starting from (ꢀ)-(Z)-1-Phenyl-1-penten-3-ol [(ꢀ)-(Z)-29]
(585 mg, 3.61 mmol) was obtained o-DPPB ester (ꢀ)-(Z)-15 (1.455 g,
90%) as a yellowish, highly viscous oil following the Steglich protocol.
(E)-1-[(2-Diphenylphosphanyl)benzoyloxy]-3,7-dimethyl-2,6-octadiene
(8): Starting from geraniol (439 mg, 2.85 mmol) was obtained o-DPPB
ester 8 (1.039 g, 82%) as a slightly yellow highly viscous oil following the
Steglich protocol. 1HNMR (400.136 MHz, CDCl 3): d = 1.60 (s, 3H),
1.64 (s, 3H), 1.68 (s, 3H), 1.99 (m, 2H), 2.07 (m, 2H), 4.67 (d, J=7.3 Hz,
2H), 5.08 (m, 1H), 5.26 (m, 1H), 6.92 (m, 1H), 7.25–7.33 (m, 10H), 7.37
(m, 2H), 8.05 ppm (m, 1H); 13C NMR (100.624 MHz, CDCl3): d = 16.4,
17.7, 26.3, 39.5, 62.1, 118.2, 123.8, 128.1, 128.4 (d, JC,P =7.3 Hz, 4C), 128.5
(2C), 130.6 (d, JC,P =2.9 Hz), 131.67, 131.71, 133.9 (d, JC,P =21.8 Hz, 4C),
134.2, 134.8 (d, JC,P =18.9 Hz), 138.1 (d, JC,P =11.6 Hz, 2C), 140.2 (d,
(ꢀ)-(E)-3-[2-(Diphenylphosphanyl)benzoyloxy]-oct-4-enoic acid tert-
butyl ester [(ꢀ)-16]: Starting from (E)-3-hydroxy-oct-4-enoic acid tert-
butyl ester[32] (544 mg, 2.54 mmol) was obtained (ꢀ)-16 (936 mg, 73%) as
a slightly green-yellow highly viscous oil following the Steglich protocol.
1HNMR (300.133 MHz, CDCl 3): d=0.85 (t, J=7.4 Hz, 3H), 1.30 (m,
2H), 1.37 (s, 9H), 1.92 (pq, J=6.6 Hz, 2H), 2.43 (dd, J=15.1, 6.6 Hz,
1H), 2.59 (dd, J=15.1, 7.7 Hz, 1H), 5.32 (ddt, J=15.4, 7.0, 1.5 Hz, 1H),
5.69 (m, 2H), 6.89 (m, 1H), 7.18–7.42 (m, 12H), 8.06 ppm (m, 1H);
13C NMR (75.476 MHz, CDCl3): d=13.6, 21.9, 28.0 (3C), 34.2, 41.1, 72.3,
J
C,P =26.2 Hz), 142.0, 166.9 ppm; 31P NMR (121.449 MHz, CDCl3): d =
80.8, 126.8, 128.1, 128.2 (d, JC,P =6.8 Hz, 4C), 128.5 (2C), 130.7 (d, JC,P
=
ꢁ4.4 ppm; elemental analysis calcd (%) for C29H31O2P (442.53): C 78.71,
2.8 Hz), 131.8, 133.88 (d, JC,P =20.4 Hz, 2C), 133.91 (d, JC,P =20.4 Hz,
2C), 134.3, 134.7 (d, JC,P =19.2 Hz), 135.0, 138.1 (d, JC,P =11.9 Hz), 138.2
H7.06; found: C 78.43, H7.13.
(d,
JC,P =11.9 Hz), 140.2 (d, JC,P =27.7 Hz), 165.5 (d, JC,P =2.3 Hz),
(Z)-1-[(2-Diphenylphosphanyl)benzoyloxy]-3,7-dimethyl-2,6-octadiene
[9]: Starting from nerol (771 mg, 5.00 mmol) was obtained o-DPPB ester
9 (1.708 g, 77%) as a slightly yellow highly viscous oil following the Steg-
lich protocol. 1HNMR (400.136 MHz, CDCl 3): d = 1.57 (s, 3H), 1.65 (s,
3H), 1.71 (m, 3H), 2.05 (m, 4H), 4.65 (d, J=7.3 Hz, 2H), 5.06 (m, 1H),
5.26 (td, J=7.3, 1.3 Hz, 1H), 6.92 (m, 1H), 7.22–7.40 (m, 12H), 8.04 ppm
(m, 1H); 13C NMR (100.624 MHz, CDCl3): d = 17.6, 23.9, 25.6, 26.6,
169.0 ppm; 31P NMR (121.496 MHz, CDCl3): d=ꢁ4.9 ppm; elemental
analysis calcd (%) for C31H35O4P (502.58): C 74.08, H7.02; found: C
73.89, H6.98.
(E)-3-[2-(Diphenylphosphanyl)benzoyloxy]-5-phenyl-pent-4-enoic
acid
tert-butyl ester [(ꢀ)-17]: Starting from (E)-3-hydroxy-5-phenyl-pent-4-
enoic acid tert-butyl ester[33] (2.00 g, 8.05 mmol) was obtained (ꢀ)-17
Chem. Eur. J. 2006, 12, 6669 – 6683
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6677

B. Breit et al.
(3.883 g, 7.24 mmol, 90%) as a slightly yellow highly viscous oil following
the Steglich protocol. 1HNMR (500.135 MHz, CDCl 3): d=1.37 (s, 9H),
2.56 (dd, J=15.4, 6.7 Hz, 1H), 2.70 (dd, J=15.4, 7.4 Hz, 1H), 5.89 (m,
1H), 6.02 (dd, J=16.1, 7.4 Hz, 1H), 6.60 (d, J=16.1 Hz, 1H), 6.91 (m,
1H), 7.21–7.41 (m, 17H), 8.08 ppm (m, 1H); 13C NMR (125.771 MHz,
CDCl3): d=28.0 (3C), 41.0, 72.2, 81.0, 125.9, 126.7 (2C), 128.0, 128.2,
128.4 (m, 6C), 128.53, 128.55, 130.8, 131.9, 133.2, 133.9 (d, JC,P =10.4 Hz,
3C), 134.3, 134.5 (d, JC,P =18.5 Hz, 2C), 136.1, 137.9 (d, JC,P =10.4 Hz),
138.1 (d, JC,P =11.3 Hz), 140.3 (d, JC,P =27.3 Hz), 165.5 (d, JC,P =1.9 Hz),
168.7 ppm; 31P NMR (121.495 MHz, CDCl3): d=ꢁ4.7 ppm; elemental
analysis calcd (%) for C34H33O4P (536.60): C 76.10, H6.20; found: C
75.86, H6.19.
mixture was stirred for 10 min, the organic phase was separated and the
aqueous phase was extracted with Et2O (2”20 mL). The combined or-
ganic phases were washed with brine, dried (MgSO4), and the solvent
was removed in vacuo to give (ꢀ)-(E)-4-methyl-1-phenyl-2-pentene
[(ꢀ)-2] and (ꢀ)-(E)-2-methyl-1-phenyl-3-pentene [(ꢀ)-3] as an insepara-
ble mixture in a ratio of 75:25. Analytical GC (Carbovax, Hewlett Pack-
ard; 508C, 1 min, 108Cminꢁ1
,
2008C, 14 min): tR[(ꢀ)-3]=10.36 min,
tR[(ꢀ)-4]=10.01 min, GC yield: >95%; (ꢀ)-3 (R=Me): 1HNMR
(200.131 MHz, CDCl3): d=1.05 (d, J=6.8 Hz, 6H), 2.33 (m, 1H), 3.37
(pd, J=4.8 Hz, 2H), 5.54–5.59 (m, 2H), 7.21–7.38 ppm (m, 5H);
13C NMR (50.328 MHz, CDCl3) d=22.6 (2C), 31.0, 39.0, 125.7, 125.8,
128.1 (2C), 128.5 (2C), 139.2, 141.2 ppm. The analytical data correspond
to those reported previously.[41]
(ꢀ)-2,5-Dimethyl-4-[2-(diphenylphosphanyl)benzoyloxy]-2-hexene [(ꢀ)-
18]: Starting from 2,5-dimethyl-2-hexen-4-ol[34] (1.28 g, 10.0 mmol) was
obtained (ꢀ)-18 (2.42 g, 58%) as a yellowish glass following the Steglich
protocol. 1HNMR (300.066 MHz, CDCl 3): d = 0.75 (d, J=7.3 Hz, 6H),
1.54 (d, J=1.2 Hz, 3H), 1.58 (d, J=1.0 Hz, 3H), 1.72 (m, 1H), 4.92 (m,
1H), 5.33 (dd, J=9.4, 6.9 Hz, 1H), 6.81 (m, 1H), 7.12–7.34 (m, 12H),
7.98 ppm (m, 1H); 13C NMR (100.624 MHz, CDCl3): d = 17.9, 18.4, 18.6,
(ꢀ)-4 (R=Me): 1HNMR (300.13 MHz, CDCl 3): d=0.94 (d, J=6.6 Hz,
3H), 1.62 (m, 3H), 2.43 (m, 2H), 2.65 (dd, J=12.87, 6.25 Hz, 1H), 5.35–
5.4 (m, 2H), 7.2 ppm (m, 5H); 13C NMR (75.48 MHz, CDCl3): d=17.9,
19.9, 38.3, 43.8, 123.1, 125.6, 128.0 (2C), 129.2 (2C), 136.7, 141.0 ppm.
The analytical data correspond to those reported previously.[42]
Reaction of (ꢀ)-1 (X=P) with Me2CuLi·LiI at ꢁ808C (Table 1, entry 2,
R=Me): Following the above described procedure from (ꢀ)-1 (300 mg,
0.666 mmol) (ꢀ)-3 and (ꢀ)-4 were obtained after 6 h at ꢁ808C in a ratio
of 74:26. Analytical GC (Carbovax, Hewlett Packard; 508C, 1 min,
25.8, 32.5, 71.1, 121.7, 128.0, 128.3 (d, JC,P =7.3 Hz, 2C), 128.38 (d, JC,P
=
5.8 Hz, 2C), 128.43 (2C), 130.6, 131.6, 134.0 (d, JC,P =20.4 Hz, 5C), 134.2,
137.7, 138.3 (d, JC,P =11.6 Hz), 138.4 (d, JC,P =11.6 Hz), 140.2 (d, JC,P
=
27.6 Hz), 166.2 ppm; 31P NMR (121.474 MHz, CDCl3): d = ꢁ3.4 ppm; el-
emental analysis calcd (%) for C27H29O2P (416.49): C 77.86, H7.13;
found: C 77.55, H7.02.
108Cminꢁ1
GC yield: >95%.
,
2008C, 14 min): tR[(ꢀ)-2]=10.28 min, tR[(ꢀ)-3]=9.96 min,
Reaction of (ꢀ)-2 (X=CH) with Me2CuLi·LiI (Table 1, entry 3, R=
Me): Following the above described procedure from (ꢀ)-2 (222 mg,
0.51 mmol) (ꢀ)-3 and (ꢀ)-4 were obtained after 3 h at ꢁ208C in a ratio
of 78:22. Analytical GC (Carbovax, Hewlett Packard; 508C, 1 min,
108Cminꢁ1, 2008C, 14 min): tR[(ꢀ)-3]=10.94 min, tR[(ꢀ)-4]=10.61 min,
GC yield: >95%.
(ꢀ)-(1R*,6R*)-1-[(Diphenylphosphanyl)benzoyloxy]-6-isopropyl-2-cyclo-
hexene [(ꢀ)-cis-27]: Starting from (ꢀ)-cis-26 (573 mg, 4.09 mmol, cis/
trans 99:1) was obtained (ꢀ)-cis-27 (1.494 g, 85%, cis/trans 97:3, deter-
mined by NMR) as a colorless, highly viscous oil following the Keck pro-
tocol. 1HNMR (300.135 MHz, CDCl 3): d=0.78 (d, J=6.6 Hz, 3H, CH3),
0.91 (d, J=6.6 Hz, 3H, CH3), 1.20 (m, 1H), 1.49 (m, 2H), 1.73 (m, 1H),
2.01 (m, 1H), 2.15 (m, 1H), 5.35 (m, 1H, CH), 5.77 (m, 1H, CH), 5.89
(m, 1H, CH), 6.88 (m, 1H, Ar-H), 7.22–7.36 (m, 12H, Ar-H), 8.02 ppm
(m, 1H, Ar-H); 13C NMR (75.476 MHz, CDCl3): d=20.7, 20.8 (2C), 26.4,
28.6, 44.1, 68.5, 124.9, 128.0, 128.31 (2C), 128.36 (d, JC,P =7.9 Hz, 4C),
130.4 (d, JC,P =2.8 Hz), 131.7, 133.2, 133.6, 134.0 (d, JC,P =16.4 Hz), 134.1
Reaction of (ꢀ)-1 (X=P) with MeCu(CN)Li (Table 1, entry 4, R=Me):
Following the above described procedure from (ꢀ)-1 (200 mg,
0.444 mmol) (ꢀ)-3 and (ꢀ)-4 were obtained after 65 h at ꢁ208C with
MeCu(CN)Li[43] in a ratio of 95:5. Analytical GC (Carbovax, Hewlett
Packard; 508C, 1 min, 108Cminꢁ1, 2008C, 14 min): tR[(ꢀ)-3]=10.79 min,
tR[(ꢀ)-4]=10.48 min, GC yield: >95%.
(d, JC,P =20.4 Hz, 2C), 134.7 (d, JC,P =18.1 Hz, 2C), 138.23 (d, JC,P
=
Reaction of (ꢀ)-1 (X=P) with copper(I) bromide dimethyl sulfide/
methyl magnesium iodide (Table 1, entry 5, R=Me): To a solution of
(ꢀ)-1 (100 mg, 0.22 mmol) in Et2O (4.4 mL, 0.05m) at room temperature
was added copper(I) bromide dimethyl sulfide (46 mg, 0.22 mmol,
1.0 equiv) in one portion. The resulting yellow solution was stirred for
5 min after which a 1.29m solution of methyl magnesium iodide in Et2O
(0.21 mL, 0.27 mmol, 1.2 equiv) was added within 0.5 min. The resulting
bright yellow suspension was stirred vigorously. After 2 min TLC showed
quantitative consumption of starting material. The reaction was quenched
by successive addition of a saturated aqueous NH4Cl solution (4 mL) and
an aqueous ammonia solution (12.5%, 2 mL) followed by the addition of
Et2O (10 mL). The mixture was stirred for 10 min, the organic phase was
separated and the aqueous phase was extracted twice with Et2O (20 mL
each). The combined organic phases were washed with brine, dried
(MgSO4) and the solvent removed in vacuo to give (ꢀ)-3 (R=Me) in a
regioselectivity of >99:1. Analytical GC (Carbovax, Hewlett Packard;
508C, 1 min, 108Cminꢁ1, 2008C, 14 min): tR[(ꢀ)-3]=10.66 min, tR[(ꢀ)-
4]=10.36 min, GC yield: >95%.
12.4 Hz), 138.24 (d, JC,P =11.3 Hz), 140.7 (d, JC,P =27.1 Hz), 166.2 ppm (d,
J
analysis calcd (%) for C28H29O2P (428.50): C 78.48, H6.82; found: C
78.36, H6.98.
C,P =2.8 Hz); 31P NMR (202.468 MHz, CDCl3): d=ꢁ4.3 ppm; elemental
(ꢀ)-(1R*,6S*)-1-[(Diphenylphosphanyl)benzoyloxy]-6-isopropyl-2-cyclo-
hexene [(ꢀ)-trans-27]: Starting from (ꢀ)-trans-26 (187 mg, 1.33 mmol,
anti/syn 94:6) was obtained (ꢀ)-trans-27 (528 mg, 1.23 mmol, 93%, anti/
syn 92:8, determined by NMR) as a colorless, highly viscous oil following
the Keck protocol. 1HNMR (200.131 MHz, CDCl 3): d=0.79 (d, J=
6.8 Hz, 3H, CH3), 0.91 (d, J=6.8 Hz, 3H, CH3), 1.29–1.78 (m, 4H), 2.07
(m, 2H), 5.48 (m, 2H), 5.82 (m, 1H), 6.95 (m, 1H, Ar-H), 7.30–7.43 (m,
12H, Ar-H), 8.08 ppm (m, 1H, Ar-H); 13C NMR (74.469 MHz, CDCl3):
d=17.6, 20.7, 20.9, 24.7, 28.1, 43.8, 72.5, 126.6, 128.0, 128.38 (d, JC,P
7.4 Hz, 4C), 128.40 (2C), 130.5 (d, JC,P =2.8 Hz), 131.1, 131.7, 133.8 (d,
C,P =12.9 Hz), 134.08 (d, C,P =13.1 Hz, 2C), 134.1, 134.8 (d, JC,P
18.4 Hz, 2C), 138.1 (d, C,P =11.4 Hz, 2C), 140.1 (d, C,P =27.2 Hz),
166.8 ppm (d,
C,P =2.6 Hz); 31P NMR (81.018 MHz, CDCl3):
ꢁ3.1 ppm; elemental analysis calcd (%) for C28H29O2P (428.50): C 78.48,
=
J
J
=
J
J
J
d =
Reaction of (ꢀ)-2 (X=CH) with copper(I) bromide dimethyl sulfide/
methyl magnesium iodide (Table 1, entry 6, R=Me): Copper(I) bromide
dimethyl sulfide (72 mg, 0.35 mmol, 1.0 equiv) was added in one portion
at ambient temperature to a solution of (ꢀ)-2 (150 mg, 0.35 mmol) in
Et2O (7 mL, 0.05m). After the resulting white suspension was stirred for
5 min a 0.5m solution of methyl magnesium iodide in Et2O (0.77 mL,
0.39 mmol, 1.1 equiv) was added within 0.5 min and the resulting slight
yellow-orange suspension stirred vigorously for further 6 h at which time
TLC showed no further reaction progress. The reaction was quenched by
successive addition of sat. aq. NH4Cl (8 mL), and aq. NH3 (12.5%, 4 mL)
followed by the addition of Et2O (20 mL) and tert-butyl acetate (50 mL,
43.1 mg, 0.37 mmol) as an internal standard for NMR. The mixture was
stirred for 10 min, the organic phase was separated and the aqueous
phase was extracted twice with Et2O (20 mL). The combined organic
H6.82; found:
C
78.36, H6.98.; HR-MS (FAB
+): m/z: calcd for
C28H29O2P: 429.1983; found: 429.1970 [M+H]+.
Allylic substitution reactions
Reaction of (ꢀ)-1 (X=P) with Me2CuLi·LiI at ꢁ208C (Table 1, entry 1,
R=Me): A 1.45m methyl lithium solution in Et2O (1.76 mL, 2.66 mmol)
was added dropwise at ꢁ58C to
a suspension of copper(I) iodide
(254 mg, 1.33 mmol) in Et2O (17 mL) and stirred for further 30 min.
After cooling to ꢁ208C a solution of (ꢀ)-1 (300 mg, 0.67 mmol) in Et2O
(3.5 mL) was added dropwise during 10 min und the resulting yellow sus-
pension was stirred for 2 h until TLC showed complete consumption of
the starting material. The reaction was quenched by successive addition
of a saturated aqueous NH4Cl solution (13 mL) and an aqueous ammonia
solution (12.5%, 10 mL) followed by the addition of Et2O (35 mL). The
6678
www.chemeurj.org
ꢀ 2006 Wiley-VCHVerlag GmbH& Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 6669 – 6683

Allylic Substitution
FULL PAPER
phases were washed with brine, dried (MgSO4) and the solvent removed
in vacuo. NMR spectroscopy of the crude product showed 80% conver-
sion (vs tert-butyl acetate, d=1.87 ppm). Column chromatography (silica
gel, pentane, then pentane/Et2O 95:5, then PE/EtOAc 4:1) yielded an in-
separable mixture of (ꢀ)-(E)-3 (R=Me), (ꢀ)-4 (R=Me) and (ꢀ)-(Z)-3
propyl magnesium bromide (0.54 mL, 0.38 mmol, 1.1 equiv) in Et2O
(7 mL) was obtained after column chromatography (pentane) (ꢀ)-3 (R=
iPr) (55 mg, 0.29 mmol, 84%) in a regioselectivity of 97:3. Analytical GC
(CP-SIL 5CB, Chrompack; 408C, 2 min, 108Cminꢁ1, 2008C, 12 min):
tR[(ꢀ)-2 (R=iPr)]=14.01 min, tR[(ꢀ)-3 (R=iPr)]=14.09 min; 1HNMR
(300.13 MHz, CDCl3): d=0.85 (d, J=6.6 Hz, 3H), 0.86 (d, J=6.6 Hz,
3H), 0.96 (d, J=7.0 Hz, 3H), 1.52 (m, 1H), 1.95 (m, 1H), 3.34 (d, J=
6.3 Hz, 2H), 5.47 (m, 2H), 7.23 ppm (m, 5H); 13C NMR (75.47 MHz,
CDCl3): d=17.5, 19.7, 19.9, 33.1, 39.2, 42.9, 125.8, 127.7, 128.3 (2C),
128.5 (2C), 136.4, 141.3 ppm; HRMS (EI, 70 eV): m/z: calcd for C14H20
188.1565; found 188.1564 [M]+.
(32 mg, 0.20 mmol, 57%) in
a ratio of 47:27:26 (determined by
1HNMR). Analytical GC (Chrompack, CP-SIL 5CB; 40 8C, 5 min,
108Cminꢁ1, 2008C, 9 min): tR[(ꢀ)-(E)-3 (R=Me)]=14.29 min, tR[(ꢀ)-4
(R=Me)] 13.89 min, tR[(ꢀ)-(Z)-3]=13.74 min. Additionally, starting ma-
terial (ꢀ)-2 (X=CH) (28 mg, 0.07 mmol, 19%) and (ꢀ)-(E)-1-phenyl-3-
penten-2-ol (12 mg, 0.07 mmol, 21%) were isolated.
(ꢀ)-(Z)-4-Methyl-1-phenyl-2-pentene
[(ꢀ)-(Z)-3]:
1HNMR
(ꢀ)-(E)-1,4-Diphenyl-2-pentene [(ꢀ)-3, R=Ph, Table 2, entry 6]: Starting
from (ꢀ)-1 (X=P) (222 mg, 0.49 mmol), copper(I) bromide dimethyl sul-
fide (50 mg, 0.24 mmol) and a 1.33m solution of phenyl magnesium bro-
mide (0.44 mL, 0.59 mmol, 1.2 equiv) in CH2Cl2 (0.05m, 9.8 mL) was ob-
tained after flash chromatography (pentane) (ꢀ)-3 (R=Ph) and (ꢀ)-4
(R=Ph) as an inseparable mixture (102 mg, 0.46 mmol, 94%) in a ratio
of 97:3. Analytical GC (CP-SIL 5CB, Chrompack; 408C, 2 min,
108Cminꢁ1, 2008C, 12 min): tR[(ꢀ)-3 (R=Ph)]=19.03 min, tR[(ꢀ)-4 (R=
(300.133 MHz, CDCl3): d=1.00 (d, J=6.6 Hz, 6H), 2.74 (m, 1H), 3.4 (d,
J=7.0 Hz, 2H), 5.2–5.45 (m, 2H), 7.1–7.3 ppm (m, 5H); 13C NMR
(75.469 MHz, CDCl3): d=23.2 (2C), 26.5, 33.6, 125.6, 125.8, 128.4 (2C),
136.1, 138.4 ppm; two carbon resonances of the aromatic system could
not be detected presumably due to overlap with the carbon resonances of
(ꢀ)-(E)-3 at 128.5 ppm. The analytical data correspond to those reported
previously.[42]
1
Control experiment of (ꢀ)-1 (X=P) with methyl magnesium iodide
(Table 1, entry 7, R=Me): A 0.83m solution of methyl magnesium iodide
in Et2O (1.29 mL, 1.07 mmol, 2.5 equiv) within 0.5 min was added at am-
bient temperature to a solution of (ꢀ)-1 (193 mg, 0.43 mmol) in Et2O
(9 mL, 0.05m). The resulting reaction mixture was stirred vigorously for
further 16 h until TLC showed complete consumption of starting materi-
al. The reaction was quenched by successive addition of a saturated aque-
ous NH4Cl solution (6 mL) followed by the addition of Et2O (20 mL).
The mixture was stirred for 10 min, the organic phase was separated and
the aqueous phase was extracted with Et2O (3”20 mL). The combined
organic phases were washed with brine, dried (MgSO4) and the solvent
was removed in vacuo. Flash chromatography (petroleum ether/ethyl ace-
tate 9:1) yielded (ꢀ)-(E)-1-phenyl-3-penten-2-ol (68 mg, 0.42 mmol,
98%).[30]
Ph)]=18.03 min. (ꢀ)-3 (R=Ph): HNMR (300.13 MHz, CDCl 3): d=1.47
(d, J=7.3 Hz, 3H), 3.47 (d, J=6.2 Hz, 2H), 3.55 (pquintet, J=6.8 Hz,
1H), 5.74 (pdt, J=15.3, 6.4 Hz, 1H), 5.83 (dd, J=15.3, 6.2 Hz, 1H), 7.13–
7.72 ppm (m, 10H); 13C NMR (125.76 MHz, CDCl3): d=21.4, 39.0, 42.2,
125.8, 125.9, 127.2, 127.7 (2C), 128.3 (2C), 128.4 (2C), 128.5 (2C), 136.6,
140.8, 146.2 ppm.
(ꢀ)-4 (R=Ph): 1HNMR (300.13 MHz, CDCl 3): d=1.72 (d, J=6.4 Hz,
3H), 3.09 (d, J=7.5 Hz, 2H), 5.45 ppm (m, 1H). One olefinic proton
signal as well as the resonance of the aromatic protons of (ꢀ)-4 could
not be resolved due to overlap with the major regioisomer (ꢀ)-3. The an-
alytical data correspond to those reported previously.[45]
(ꢀ)-(E)-2,3-Dimethyl-6-phenyl-1,4-hexadiene [(ꢀ)-3, R=2-propenyl,
Table 2, entry 7]: Starting from (ꢀ)-1 (X=P) (60 mg, 0.133 mmol), cop-
per(I) bromide dimethyl sulfide (13.7 mg, 0.067 mmol) and a 0.111m solu-
tion of 2-propenyl magnesium bromide (1.45 mL, 0.16 mmol, 1.2 equiv)
in Et2O (0.05m, 2.7 mL) was obtained after flash chromatography (pen-
tane) (ꢀ)-3 (R=2-propenyl) and (ꢀ)-4 (R=2-propenyl) as an insepara-
ble mixture (20 mg, 0.11 mmol, 81%) in a ratio of 85:15 in addition to
traces of inseparable impurities. Analytical GC (CP-SIL 5CB, Chrom-
pack; 408C, 2 min, 108Cminꢁ1, 2008C, 12 min): tR[(ꢀ)-3 (R=2-propen-
yl)]=15.25 min, tR[(ꢀ)-4 (R=2-propenyl)]=17.43 min; (ꢀ)-3 (R=2-pro-
General procedure for the copper-mediated allylic substitution with
Grignard reagents: Copper bromide dimethyl sulfide (0.5–1.0 equiv) was
added to a stirred solution of the allylic o-DPPB ester in the solvent indi-
cated (c=0.01–0.05m, see Tables 1–4, Schemes 3 and 4, 7 and 8 for de-
tails). After 15 min, the Grignard reagent (1.0–1.4 equiv) was added
during the specified time (syringe pump addition was used for addition
times greater than 5 min). After complete consumption of the starting
material (TLC control, the reaction was in most cases complete after the
Grignard addition was finished) the reaction was quenched with saturat-
ed aqueous NH4Cl solution (20 mLmmolꢁ1 ester) and 12.5% aqueous
NH3 solution (10 mL per mmol). After stirring for 5 min, the phases were
separated and the aqueous phase was extracted with Et2O (2”40 mL per
mmol). The combined organic phases were washed with brine
(40 mLmmolꢁ1), dried (MgSO4), and the solvent was removed carefully
to give in many cases already pure products. In some cases further purifi-
cation was achieved by flash chromatography (silica gel, pentane or pen-
tane/Et2O). The ratio of SN2’ and SN2 products was detected by analytical
GC of the crude reaction mixture.
1
penyl); HNMR (300.065 MHz, CDCl 3): d=1.12 (d, J=6.9 Hz, 3H, CH3-
C8), 1.70 (s, 3H, CH3-C7), 2.78 (m, 1H, CH-C3), 3.35 (d, J=6.4 Hz, 2H,
CH2-C6), 4.73 (m, 2H, CH2-C1), 5.47 (pdd, J=15.4, 6.9 Hz, 1H, CH-C4),
5.59 (pdt, J=15.4, 6.5 Hz, 1H, CH-C5), 7.26 ppm (m, 5H, Ar-H); MS
(EI, 70 eV): m/z (%): 186 (15) [M]+, 171 (61), 157 (21), 143 (24), 129
(21), 115 (31), 104 (18), 95 (100), 67 (90); HRMS (EI, 70 eV): m/z: calcd
for C14H18: 186.1409; found: 186.1412 [M]+.
Reaction of (ꢀ)-1 with allyl magnesium bromide (Table 2, entry 9, R=
allyl): Starting from (ꢀ)-1 (X=P) (88 mg, 0.195 mmol), copper(I) bro-
mide dimethyl sulfide (20.0 mg, 0.098 mmol) and a 1.07m solution of allyl
magnesium bromide (0.39 mL, 0.37 mmol, 2 equiv) in Et2O (3.9 mL) was
obtained after flash chromatography (cyclohexane/ethyl acetate 95:5)
(27.4 mg, 0.169 mmol, 87%) of the corresponding allylic alcohol (ꢀ)-(E)-
1-phenyl-3-penten-2-ol.
(ꢀ)-(E)-4-Methyl-1-phenyl-2-octene [(ꢀ)-3, R=nBu, Table 2, entry 1]:
Starting from (ꢀ)-1 (X=P) (257 mg, 0.57 mmol), copper(I) bromide di-
methyl sulfide (117 mg, 0.57 mmol) and a 0.46m solution of n-butyl mag-
nesium chloride (1.36 mL, 0.63 mmol) in Et2O (11.4 mL) was obtained
after column chromatography (pentane) (ꢀ)-3 (R=nBu) (113 mg,
0.56 mmol, 98%) as a colorless oil in a regioselectivity of >99:1. Analyti-
cal GC (CP-SIL 5CB, Chrompack; 408C, 2 min, 108Cminꢁ1, 2008C,
3-Cyclohexenyl-1-butene (10): Starting from o-DPPB-ester
6 (93 mg,
0.22 mmol), copper bromide dimethyl sulfide (22.5 mg, 0.11 mmol) and a
0.1m solution of methyl magnesium iodide (3.5 mL, 0.35 mmol, 1.6 equiv,
addition within 3.2 h) in Et2O (22 mL, 0.01m) was obtained after stirring
for 12 h the substitution product 10 (30 mg, 99%) in a regioselectivity of
SN2’/SN2 >99:1 after aqueous work-up and chromatographic purification
1
12 min): tR[(ꢀ)-3 (R=nBu)]=15.38 min; HNMR (500.13 MHz, CDCl 3):
d=0.88 (m, 3H), 0.97 (d, J=6.7 Hz, 3H), 1.27 (m, 6H), 2.09 (m, 1H),
3.32 (d, J=6.7 Hz, 2H), 5.38 (dd, J=15.1, 8.0 Hz, 1H), 5.51 (m, 1H),
7.17 (m, 3H), 7.25 ppm (m, 2H); 13C NMR (125.76 MHz, CDCl3): d=
14.1, 20.8, 22.8, 29.7, 36.7, 36.9, 39.1, 125.8, 126.8, 128.3 (2C), 128.5 (2C),
138.3, 141.3 ppm. The analytical data correspond to those reported previ-
ously.[44]
(silica gel, pentane). Analytical GC (CPSil5CB, 408C (5 min), 58Cminꢁ1
2008C (5 min)): tR[10]=12.19 min, tR
[SN2]=13.14 min; 1HNMR
,
AHCTREUNG
(400.136 MHz, CDCl3): d=0.96 (d, J=6.9 Hz, 3H), 1.04–1.35 (m, 6H),
1.59–1.76 (m, 5H), 1.95 (m, 1H), 4.90 (m, 1H), 4.99 (m, 1H), 5.71 ppm
(m, 1H); 13C NMR (100.614 MHz, CDCl3): d=17.1, 26.65 (2C), 26.69,
30.2, 30.4, 42.9, 43.5, 112.9, 143.6 ppm. The analytical data correspond to
those reported previously.[46]
(ꢀ)-(E)-4,5-Dimethyl-1-phenyl-2-hexene
[(ꢀ)-3,
R=iPr,
Table 2,
entry 2]: Starting from (ꢀ)-1 (X=P)(156 mg, 0.35 mmol), copper(I) bro-
mide dimethyl sulfide (71 mg, 0.35 mmol) and a 0.71m solution of iso-
Chem. Eur. J. 2006, 12, 6669 – 6683
ꢀ 2006 Wiley-VCHVerlag GmbH& Co. KGaA, Weinheim
www.chemeurj.org
6679

B. Breit et al.
3-Phenyl-1-butene (11): Starting from o-DPPB ester
7
(135 mg,
(125.758 MHz, CDCl3): d=13.8, 21.6, 25.5, 41.3, 125.9, 127.2 (2C), 128.3
(2C), 130.8, 133.9, 146.6 ppm.
0.32 mmol), copper bromide dimethyl sulfide (32.9 mg, 0.16 mmol), and
MeMgI (0.1m in Et2O, 4.8 mL, 0.48 mmol, addition within 4 h) in Et2O
(32 mL, 0.01m) was obtained crude 11 (conv. >95%) in a regioselectivity
of SN2’/SN2 92:8. Column chromatography (silica gel, pentane) gave pure
(ꢀ)-(E)-5-Methyloct-3-enoic acid tert-butyl ester [(ꢀ)-20]: Starting from
the o-DPPB ester (ꢀ)-16 (251 mg, 0.50 mmol), copper bromide dimethyl
sulfide (103 mg, 0.50 mmol) and a solution of MeMgI (1.17m in Et2O,
0.86 mL, 1.00 mmol, addition within 3 min) in Et2O (15 mL) was obtained
after 48 h at 08C after aqueous work-up and column chromatography
(silica gel, pentane/Et2O 95:5) (ꢀ)-20 (89 mg, 82%, SN2’/SN2 95:5) as a
colorless oil. Analytical GC (OV-1, 408C (5 min), 108Cminꢁ1, 2008C
11 (31 mg, 73%). Analytical GC (CPSil5CB, 408C (1 min), 108Cminꢁ1
,
2008C
(2 min):
tR[11]=8.16 min,
tR
A
1HNMR
(400.136 MHz, CDCl3): d=1.36 (d, J=7.3 Hz, 3H), 3.46 (m, 1H), 5.02
(dpt, J=10.3, 1.3 Hz, 1H), 5.04 (dpt, J=17.1, 1.3 Hz, 1H), 6.01 (ddd, J=
17.1, 10.3, 6.5 Hz, 1H), 7.15–7.35 ppm (m, 5H); 13C NMR (100.624 MHz,
CDCl3): d=20.8, 43.3, 113.2, 126.2, 126.8 (2C), 128.6 (2C), 143.4,
145.7 ppm. The analytical data correspond to those reported previous-
ly.[47]
(9 min):
tR
A
tR[(ꢀ)-20]=16.42 min;
1HNMR
(300.135 MHz, CDCl3): d=0.87 (t, J=7.0 Hz, 3H), 0.96 (d, J=6.6 Hz,
3H), 1.23 (m, 4H), 1.44 (s, 9H), 2.12 (psept, J=6.6 Hz, 1H), 2.92 (d, J=
5.9 Hz, 2H), 5.38 (dd, J=15.5, 6.6 Hz, 1H), 5.46 ppm (dt, J=15.5, 6.3 Hz,
1H); 13C NMR (75.476 MHz, CDCl3): d=14.1, 20.3, 20.5, 28.1 (3C), 36.4,
39.1, 39.4, 80.2, 120.4, 140.2, 171.6 ppm; HRMS (EI, 70 eV): m/z: calcd
for C13H24O2: 212.1776; found 212.1777 [M]+.
3,3,7-Trimethyl-1,6-octadiene (12): Starting from o-DPPB ester 8 (50 mg,
0.113 mmol), copper bromide dimethyl sulfide (12.3 mg, 0.06 mmol), and
MeMgI (0.83m in Et2O, 0.08 mL, 0.136 mmol, addition time 15 min) was
(ꢀ)-(E)-5-Phenyl-hex-3-enoic acid tert-butyl ester [(ꢀ)-21]: Starting
from the o-DPPB-ester (ꢀ)-17 (392 mg, 0.73 mmol), copper bromide di-
methyl sulfide (150 mg, 0.73 mmol), and MeMgI (0.50m in diethylether,
1.6 mL, 0.80 mmol, addition within 3 min) in Et2O (14.6 mL) was ob-
tained after aqueous work-up and column chromatography (silica gel,
pentane) (ꢀ)-21 (155 mg, 0.63 mmol, 86%, SN2’/SN2 97:3; E/Z[(ꢀ)-17]
97:3) as a clear colorless oil. Analytical GC (CPSil5CB, 408C (2 min),
obtained 12 (16 mg, 91%, SN2’/SN2 95:5 (GC), E/Z(SN2’) 92:8 (GC). Ana-
N
lytical GC (CPSil5CB; 408C, 5 min, 58Cminꢁ1, 2008C, 12 min): tR[12]=
12.52 min, tR[(Z)-SN2]=14.20 min, tr[(E)-SN2]=14.58 min; 1HNMR
(300.066 MHz, CDCl3): d = 0.99 (s, 6H), 1.29 (m, 2H), 1.58 (s, 3H), 1.67
(s, 3H), 1.88 (m, 2H), 4.90 (m, 2H), 5.09 (m, 1H), 5.77 ppm (m, 1H);
13C NMR (100.624 MHz, CDCl3): d = 17.5, 23.3, 25.6, 26.7 (2C), 36.6,
42.8, 110.3, 125.1, 131.0, 148.5 ppm. The analytical data correspond to
those reported previously.[48]
108Cminꢁ1
,
2008C (2 min)): tR[(ꢀ)-(Z)-21]=17.34 min, tR[(E)-SN2]=
18.05 min, tR[(ꢀ)-(E)-21]=18.63 min; 1HNMR (CDCl 3, 300.133 MHz):
d=1.36 (d, J=7.0 Hz, 3H), 1.44 (s, 9H), 2.96 (m, 2H), 3.47 (m, 1H),
[5.42 (dd, J=9.2, 7.0 Hz, 1H], 5.57 (dptd, J=15.5, 6.4, 1.1 Hz, 1H), 5.71
(ddpt, J=15.5, 6.6, 1.1 Hz, 1H), 7.29 ppm (m, 5H); 13C NMR (CDCl3,
75.469 MHz): d=21.1, 28.0 (3C), 39.2, 42.1, 80.4, 121.3, 126.0, 127.2 (2C),
128.3 (2C), 138.6, 145.7, 171.3 ppm; elemental analysis calcd (%) for
C16H22O2 (246.34): C 78.01, H9.00; found: C 78.02, H8.99.
3,7-Dimethyl-3-ethyl-1,6-octadiene (13): Starting from o-DPPB ester 8
(57 mg, 0.129 mmol), copper bromide dimethyl sulfide (14.4 mg,
0.07 mmol), and EtMgBr (1.02m in Et2O, 0.15 mL, 0.155 mmol, addition
time 15 min) was obtained 13 (17 mg, 80%, SN2’/SN2 >98:2, E/Z(SN2’)
G
92:8).
Starting from o-DPPB ester 9 (68 mg, 0.154 mmol), copper bromide di-
methyl sulfide (16.4 mg, 0.08 mmol), and EtMgBr (1.02m in Et2O,
0.18 mL, 0.185 mmol, addition time 15 min) were obtained 13 (24 mg,
(E)-2,2,5-Trimethyl-3-hexene [(ꢀ)-22]: Starting from o-DPPB-ester (ꢀ)-
18 (161 mg, 0.387 mmol), copper bromide dimethyl sulfide (39.7 mg,
0.193 mmol), and MeMgI (1.11m in Et2O, 0.38 mL, 0.425 mmol, addition
time 15 min) (ꢀ)-22 (33 mg, 68%, SN2’/SN2 >99:1, E/Z (SN2’) >99:1). In
deviation from the general procedure aqueous work-up was omitted. In-
stead, all volatile components of the crude reaction mixture were evapo-
rated in oil pump vacuo and condensed in a cold trap at ꢁ1968C. Ethere-
al solvent was removed upon distillation under ambient pressure to give
pure (ꢀ)-22. Analytical GC (CPSil5CB; 408C, 5 min, 58Cminꢁ1, 1008C,
13 min, 408Cminꢁ1, 2008C): tR =3.42 min (0.6%), tR[(ꢀ)-22]=4.32 min
(99.4%); 1HNMR (400.136 MHz, CDCl 3): d = 0.93 (d, J=6.9 Hz, 6H),
0.95 (s, 9H), 2.18 (m, 1H), 5.23 (dd, J=15.9, 6.5 Hz, 1H), 5.35 ppm (m,
1H); 13C NMR (100.624 MHz, CDCl3): d = 22.8 (2C), 29.9 (3C), 31.0,
32.5, 131.9, 138.4 ppm; MS (EI, 70 eV): m/z (%): 126 (12) [M]+, 111 (28),
83 (68), 70 (77), 69 (100), 55 (52).
0.146 mmol, 95%; SN2’/SN2 98:2 (GC), E/Z(SN2’) 97:3 (GC)). Analytical
E
GC (CPSil5CB; 408C, 5 min, 58Cminꢁ1, 2008C): tR[13]=16.2 min, tR[(Z)-
1
SN2]=17.00 min, tR[(E)-SN2]=17.4 min; HNMR (300.066 MHz, CDCl 3):
d = 0.78 (t, J=7.5 Hz, 3H), 0.94 (s, 3H), 1.30 (m, 4H), 1.58 (s, 3H), 1.67
(m, 3H), 1.86 (m, 2H), 4.89 (dd, J=17.6, 1.5 Hz, 1H), 4.99 (dd, J=10.9,
1.5 Hz, 1H), 5.09 (m, 1H), 5.67 ppm (dd, J=17.6, 10.9 Hz, 1H);
13C NMR (100.624 MHz, CDCl3): d = 8.3, 22.0 (2C), 22.8, 25.7, 33.0,
39.6, 40.4, 111.6, 125.2, 130.9, 147.2 ppm. The analytical data correspond
to those reported previously.[49]
2,6-Dimethyl-6-ethenyl-2-decene (14): Starting from o-DPPB ester
8
(51 mg, 0.115 mmol) and nBuMgBr (1.23m in Et2O, 0.11 mL, 0.138 mmol,
addition time 15 min) was obtained 14 (20 mg, 87%, SN2’/SN2 >99:1).
Analytical GC (CPSil5CB; 408C, 5 min, 58Cminꢁ1
,
2008C): tR[8]=
21.0 min,
tR[(Z)-SN2]=22.0 min,
tR[(E)-SN2]=22.4 min;
1HNMR
(ꢀ)-(E)-2,5,5-Trimethyl-3-nonene [(ꢀ)-(E)-23]: Starting from o-DPPB-
ester (ꢀ)-18 (121 mg, 0.290 mmol), copper bromide dimethyl sulfide
(30 mg, 0.145 mmol), and nBuMgBr (0.51m in Et2O, 0.63 mL, 0.32 mmol,
addition time 15 min) was obtained (ꢀ)-(E)-23 (50 mg, 99%, SN2’/SN2
>99:1, E/Z (SN2’) >99:1). Analytical GC (CPSil5CB; 408C, 5 min,
(400.136 MHz, CDCl3): d = 0.88 (t, J=7.3 Hz, 3H), 0.95 (s, 3H), 1.21
(m, 8H), 1.58 (s, 3H), 1.67 (s, 3H), 1.87 (m, 2H), 4.88 (dd, J=17.6,
1.7 Hz, 1H), 4.97 (dd, J=10.8, 1.7 Hz, 1H), 5.09 (m, 1H), 5.70 ppm (dd,
J=17.6, 10.7 Hz, 1H); 13C NMR (100.620 MHz, CDCl3): d = 14.1, 17.5,
22.6, 22.8, 23.5, 26.3, 39.4, 40.6, 40.8, 111.2, 125.2, 130.9, 147.5 ppm. The
analytical data correspond to those reported previously.[50]
58Cminꢁ1
, , 2008C): tR =12.25 min (1%),
1008C, 13 min, 408Cminꢁ1
tR[(ꢀ)-(E)-23]=14.06 min (98%), tR =15.24 min (1%); 1HNMR
(400.136 MHz, CDCl3): d = 0.81 (t, J=6.9 Hz, 3H), 0.86 (s, 6H), 0.89 (d,
J=6.4 Hz, 6H), 1.16 (m, 6H), 2.15 (m, 1H), 5.15 (dd, J=15.9, 6.0 Hz,
1H), 5.22 ppm (d, J=15.9 Hz, 1H); 13C NMR (100.624 MHz, CDCl3): d
= 14.1, 23.0 (2C), 23.5, 26.8, 27.5 (2C), 31.2, 35.2, 43.1, 133.1, 137.3 ppm;
HRMS (EI, 70 eV): m/z: calcd for C12H24: 168.1878; found 168.1878 [M]+
.
(ꢀ)-(E)-2-Phenyl-3-hexene [(ꢀ)-19]: Starting from o-DPPB ester (ꢀ)-
(E)-15 (256 mg, 0.57 mmol), copper bromide dimethyl sulfide (58.6 mg,
0.29 mmol) and MeMgI (0.96m in Et2O, 0.65 mL, 0.63 mmol, addition
time 15 min) was obtained after column chromatography (silica gel, pen-
tane) (ꢀ)-19 (84 mg, 92%, SN2’/SN2 97:3).
Starting from o-DPPB ester (ꢀ)-(Z)-15 (230 mg, 0.51 mmol), copper bro-
mide dimethyl sulfide (52 mg, 0.255 mmol) and MeMgI (0.96m in Et2O,
0.58 mL, 0.56 mmol, addition time 0.5 min, reaction time after Grignard
addition 30 min) was obtained after column chromatography (silica gel,
pentane) (ꢀ)-19 (72 mg, 88%, SN2’/SN2 99:1). Analytical GC (CPSil5CB;
Chirality transfer experiments
(ꢀ)-(3R*,6R*)-3-Isopropyl-6-methyl-1-cyclohexene (cis-menthene, cis-
28):[51] Starting from o-DPPB ester cis-27 (223 mg, 0.52 mmol, cis/trans
97:3), copper(I) bromide dimethyl sulfide (107 mg, 0.52 mmol), and
MeMgI (1.50m in Et2O, 0.38 mL, 0.57 mmol) in additional Et2O
(10.4 mL) was obtained cis-28 and trans-28 as an inseparable mixture
408C, 2 min, 108Cminꢁ1, 2008C, 12 min): tR[(E)-19]=11.17 min, tR
[SN2]=
G
11.82 min, tR[(Z)-19]=12.31 min; 1HNMR (500.132 MHz, CDCl 3): d=
0.98 (t, J=7.4 Hz, 3H), 1.33 (d, J=7.4 Hz, 3H), 2.03 (pquint, J=7.4 Hz,
2H), 3.41 (pquint, J=7.4 Hz, 1H), 5.49 (dpt, J=15.4, 6.0 Hz, 1H), 5.59
(dd, J=15.4, 6.69 Hz, 1H), 7.16–7.3 ppm (m, 5H); 13C NMR
(97:3). Analytical GC (CP-SIL 5CB, Chrompack; 408C, 5 min, 58Cminꢁ1
1608C, 1 min) tR[cis-28]=11.85 min, tR[trans-28]=11.63 min, GC yield
>95%; 1HNMR (CDCl 3, 500.135 MHz): d = 0.88 (d, J=6.7 Hz, 3H),
,
A
ACHTREUNG
6680
www.chemeurj.org
ꢀ 2006 Wiley-VCHVerlag GmbH& Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 6669 – 6683

Allylic Substitution
FULL PAPER
0.91 (d, J=6.7 Hz, 3H), 0.96 (d, J=7.4 Hz, 3H), 1.28 (m, 1H), 1.38 (m,
1H), 1.51 (m, 2H), 1.68 (m, 1H), 1.85 (m, 1H), 2.16 (m, 1H), 5.58 ppm
(m, 2H); 13C NMR (CDCl3, 125.771 MHz): d=19.8, 20.0, 21.2, 22.0, 28.9,
29.4, 32.2, 41.5, 129.9, 133.5 ppm. The 1Hand 13C NMR data correspond
to a sample of cis-menthene (cis-28) prepared from the corresponding
carbamate and Me5Cu3Li2 following a literature procedure.[51]
0.46 mmol) was added within 5 min and the bright yellow suspension was
stirred for further 2 h at room temperature. The reaction was quenched
by successive addition of a saturated aqueous NH4Cl solution (8 mL) and
an aqueous ammonia solution (12.5%, 10 mL) followed by the addition
of Et2O (10 mL). The mixture was stirred for 10 min, the organic phase
was separated and the aqueous phase was extracted twice with Et2O
(20 mL each). The combined organic phases were washed with brine,
dried (MgSO4) and the solvent removed in vacuo to give (ꢁ)-19 (57 mg,
0.36 mmol, 86%, SN2’/SN2 >99:1, E/Z (SN2’)>98:2, ee 93%) as a color-
less oil after column chromatography (pentane). Analytical GC (CP-SIL
5CB, Chrompack; 408C, 2 min, 108Cminꢁ1, 2008C, 12 min), tR[(ꢁ)-19]=
11.82 min (97%), (Z)-alkene isomer, tR =11.17 min (1%) and regioisom-
er (E)-1-phenyl-3-methyl-1-pentene, tR =12.31 min (2%). Chiral GC
(Permethyl-b-cyclodextrin, Chrompack; 658C), tR[(ꢁ)-19]=66.43 min
(ꢀ)-(3R*,6S*)-3-Isopropyl-6-methyl-1-cyclohexene
(trans-menthene,
trans-28): Starting from o-DPPB ester trans-27 (54 mg, 0.13 mmol, trans/
cis 92:8), copper(I) bromide dimethyl sulfide (26 mg, 0.13 mmol), and
MeMgI (1.27m in Et2O, 0.20 mL, 0.26 mmol) in additional Et2O (4 mL)
was obtained trans-28 and cis-28 as an inseparable mixture (92:8). Ana-
lytical GC (Carbovax, Hewlett Packard; 508C, 1 min, 108Cminꢁ1, 2008C,
14 min): tR
N
N
1HNMR (CDCl 3, 500.135 MHz): d=0.86 (d, J=6.7 Hz, 3H), 0.89 (d, J=
6.7 Hz, 3H), 0.95 (d, J=6.7 Hz, 3H), 1.10 (m, 1H), 1.24 (m, 1H), 1.56
(psept, J=6.7 Hz, 1H), 1.70 (m, 1H), 1.83 (m, 1H), 1.91 (m, 1H), 2.11
(m, 1H), 5.52 ppm (m, 2H); 13C NMR (CDCl3, 125.771 MHz): d=19.3,
19.6, 22.0, 25.6, 31.0, 32.0, 32.2, 41.9, 129.9, 134.0 ppm. The 1Hand
13C NMR data correspond to a sample of commercially available (Al-
drich) sample of trans-menthene (trans-28).
(96.3%), tR[(+)-17]=70.63 min (3.7%); [a]D20
=
ꢁ13.7 (c=3.12 in
CHCl3).
Ozonolysis of (+)-19 and reductive work-up: (+)-(R)-2-phenylpropanol
[(+)-33]: A solution of (+)-19 (67 mg, 0.42 mmol) in methanol (7 mL)
was cooled to ꢁ788C under a stream of oxygen. Subsequently, ozone was
bubbled through this solution for 7 min (the typical blue color appeared
and persisted after 1 min) followed by oxygen for further 3 min. Sodium
boron hydride (60 mg, 1.68 mmol) was added, the solution was allowed
to warm during 10 h to room temperature, and was stirred for further
24 h. The reaction mixture was poured into an aqueous HCl solution
(5%, 20 mL), followed by the addition of Et2O (10 mL). The organic
phase was separated and the aqueous phase was extracted with Et2O (3”
20 mL). The combined organic phases were washed with water and brine,
dried (MgSO4) and the solvent was removed in vacuo. Column chroma-
tography (silica gel, PE/EtOAc 4:1) furnished (+)-33 (21 mg, 0.15 mmol,
37%). [a]2D0 = +11.3 (c=0.95, CHCl3) {lit.[24] [a]2D0 = +14.3 (c=16.5,
CHCl3)}. Analytical and spectroscopic data correspond to those reported
previously.[24]
(+)-(2S,E)-2-Phenyl-3-hexene [(+)-19] with recovery of the o-DPPBA:
Copper bromide dimethyl sulfide (257 mg, 1.25 mmol, 1.0 equiv) in one
portion was added to a solution of o-DPPB ester (ꢁ)-(E)-15 (565 mg,
1.25 mmol, ee >99%) in Et2O (25 mL) and the resulting yellow suspen-
sion was stirred for 5 min at room temperature. A 1.06m ethereal solu-
tion of methyl magnesium iodide (1.3 mL, 1.38 mmol) was added within
5 min and the bright yellow suspension was stirred for further 2 h at
room temperature. The reaction was quenched by successive addition of
a saturated aqueous NH4Cl solution (8 mL) and an aqueous ammonia
solution (12.5%, 10 mL) followed by the addition of pentane/Et2O (5:1,
20 mL). The mixture was stirred for 10 min during which time a yellow
precipitate formed. The mixture was filtered and the residue washed with
additional pentane/Et2O (5:1, 20 mL). The organic phase of the filtrate
was separated and the aqueous phase was extracted with three further
portions of Et2O (10 mL each). The combined organic phases were
washed with brine, dried (MgSO4) and the solvent removed in vacuo.
Column chromatography (silica gel, PE/EtOAc 9:1) furnished (+)-19
[(ꢁ)-(E)-15]2CuBr (34): Copper(I) bromide dimethyl sulfide (39.9 mg,
0.194 mmol) in one portion was added to a solution of (ꢁ)-(E)-15
(175 mg, 0.388 mmol) in CH2Cl2 (1 mL). The reaction mixture was stirred
for about 5 min to give an intensive yellow solution. Removal of all vola-
tile components in oil pump vacuum gave 34 (203 mg, quant.) as a yellow
solid. M.p. 98–1058C; [a]D20
(300.063 MHz, CDCl3): d=0.73 (t, J=7.2 Hz, 6H, 2”CH3-C5), 1.57 (m,
=
ꢁ162.0 (c=2.35, CHCl3); 1HNMR
(184 mg, 92%, SN2’/SN2 99:1, E/Z(SN2’) 98:2, ee >99%). Analytical GC
C
(CP-SIL 5CB, Chrompack; 408C, 2 min, 108Cminꢁ1, 2008C, 12 min),
tR[(+)-19]=11.29 min (97%), (Z)-alkene isomer, tR = 11.10 min (1%)
and regioisomer (E)-1-phenyl-3-methyl-1-pentene, tR = 12.27 min (2%);
chiral GC (permethyl-b-cyclodextrin, Chrompack; 658C), tR[(+)-19]=
2H, 2”CH -C4), 5.05 (brs, 2”CH-C3), 5.95 (dd, J=15.9, 7.4 Hz, 2”-CH-
2
C2), 6.17 (d, J=16.1 Hz, 2”CH-C1), 6.76 (d, J=7.6 Hz, 2H, Ar-H), 7.05–
7.32 (m, 26H, Ar-H), 7.48 (d, J=7.0 Hz, 4H, Ar-H), 7.60 (d, J=6.4 Hz,
4H, Ar-H), 7.85 ppm (m, 2H, Ar-H); 31P NMR (121.450 MHz, CDCl3):
d=ꢁ0.3 ppm (brs).
69.07 min; [a]2D0
=
+10 (c=1.5, pentane); 1HNMR (500.132 MHz,
CDCl3): d=0.98 (t, J=7.4 Hz, 3H), 1.33 (d, J=7.4 Hz, 3H), 2.03 (pquint,
J=7.4 Hz, 2H), 3.41 (pquint, J=7.4 Hz, 1H), 5.49 (dpt, J=15.4, 6.0 Hz,
1H), 5.59 (dd, J=15.4, 6.69 Hz, 1H), 7.16–7.3 ppm (m, 5H); 13C NMR
(125.758 MHz, CDCl3): d=13.8, 21.6, 25.5, 41.3, 125.9, 127.2 (2C), 128.3
Temperature dependent NMR spectroscopy of [(ꢁ)-(E)-15]2CuBr
+
2 equiv (ꢁ)-(E)-15: A solution of (ꢁ)-(E)-15 (95 mg, 0.211 mmol) in
nBu2O (1.4 mL) was treated with copper(I) bromide dimethyl sulfide
(10.8 mg, 0.053 mmol) and stirred at room temperature for 5 min. The
yellow precipitate, which was formed immediately, was dissolved with ad-
ditional CH2Cl2 (0.6 mL). As a reference for the NMR spectroscopy ad-
ditional [D8]toluene (0.2 mL) was added to this mixture. An aliquot
(0.8 mL) of this solution was transferred into a flame-dried NMR tube
under an atmosphere of argon, and analyzed by 31P NMR spectroscopy
(121.450 MHz) at temperatures between 213 and 353 K. The coalescent
temperature was determined to TC =316 K (ꢀ2 K), see Table 6.
(2C), 130.8, 133.9, 146.6 ppm; HRMS (EI, 70 eV): m/z: calcd for C12H16
160.1256; found 160.1238 [M]+.
:
Recovery of 2-diphenylphosphanyl benzoic acid (o-DPPBA): The yellow
residue obtained in the filtration process above was dissolved in dichloro-
methane (20 mL), washed with water (10 mL), followed by addition of
pH4.75 buffer in methanol/water (1:1, 20 mL) and KCN (600 mg,
9.2 mmol) upon which the color of the organic phase changed from
yellow to colorless. The phases were separated and the aqueous phase
washed with three more portions of dichloromethane (10 mL each). The
combined organic phases were washed with water (20 mL), dried
(MgSO4) and the solvent removed in vacuo to give o-DPPBA as a pale
yellow solid (303 mg, 79%). Analytical data were identical to those re-
ported previously.[28]
Storage of the remaining solution for several days at room temperature
furnished slightly yellow crystals of 34 suitable for X-ray diffraction.
X-ray crystal structure analysis of [(ꢁ)-(E)-14]2CuBr (34): Crystal data:
C60H54BrCuO4P2·C7H8, M=1044.42, 0.2”0.2”0.15 mm3, orthorhombic,
space group P212121, a=10.32610(10), b=18.6890(4), c=29.2748(6) Š,
V=5649.58(18) Š3, Z=4, 1calcd =1.228 gcmꢁ3
,
qmax =27.488, MoKa
=
(ꢁ)-(2R,E)-2-Phenyl-3-hexene [(ꢁ)-19]: Copper bromide dimethyl sul-
fide (43 mg, 0.21 mmol) was added in one portion to a solution of o-
DPPB ester (+)-(Z)-15 (190 mg,
0.71073 Š, T=100(2) K, Data were collected on a Nonius KappaCCD
0.42 mmol, ee >97%) in Et2O
(8.4 mL) and the resulting yellow solu-
Table 6. Exchange rates determined with WinDynA.[27]
tion was stirred for 5 min at room tem-
perature. A 1.34m ethereal solution of
methyl magnesium iodide (0.35 mL,
T [K]
213
1.30
223
0.84
233
2.25
243
2.39
253
3.07
263
6.13
273
5.40
283
7.23
293
13.58
kT [sꢁ1
]
Chem. Eur. J. 2006, 12, 6669 – 6683
ꢀ 2006 Wiley-VCHVerlag GmbH& Co. KGaA, Weinheim
www.chemeurj.org
6681

B. Breit et al.
diffractometer, 39857 reflections collected, 12825 were independent
(Rint =0.0670), absorption correction was performed semi-empirical from
equivalents (m=1.193 mmꢁ1, min. transmission=0.960, max. transmis-
sion=1.037). The structure was solved by direct methods (SIR-97 (Gia-
covazzo, 1997)) and refined by full-matrix least squares on F2 (SHELXL-
97 (Sheldrick, 1997)). Application of Platon/SQUEEZE removed unas-
signed residual electron density due to disordered solvent.[52] The unit
Heckmann, S. K. Zahn, Chem. Eur. J. 2003, 9, 425–434; d) B. Breit,
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3
cell contains two voids of about 411 Š each. The total electron density
taken into account was 96 and 97 e¯, respectively, per void, equivalent to
two toluene molecules. The derived quantities (M, m and 1calcd) do not
contain the contribution from this disordered solvent. The Hatoms were
constructed in geometrically idealized positions and refined in a riding
model. Parameters=613, final R1=0.0395 [I>2s(I)] and wR2=0.0806
ꢁ3
(all data). Residual electron density=0.395 eŠ
.
CCDC-299832 contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
(+)-(S,E)-2-Phenyl-3-hexene [(+)-19] employing catalytic conditions (20
mol% copper(I) bromide dimethyl sulfide): Following the representative
procedure for (ꢁ)-19 described above from (ꢁ)-(E)-15 (276 mg,
0.61 mmol, ee >99%), copper(I) bromide dimethyl sulfide (25.1 mg,
0.12 mmol) and a 0.96m ethereal solution of methyl magnesium iodide
(0.70 mL, 0.67 mmol, 1.1 equiv, addition time 5 min, room temperature)
in Et2O (12.2 mL, 0.05m) was obtained after flash chromatography (pen-
tane) (+)-19 as an inseparable mixture with the SN2 regioisomer (76 mg,
0.47 mmol, 78%, ee >99%) in a ratio of 93:7 (E/Z[(+)-19] 93:7). Analyt-
ical GC (CP-SIL 5CB, Chrompack; 408C, 2 min, 108Cminꢁ1, 2008C,
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Acknowledgements
This work was supported by the Fonds der Chemischen Industrie, the
Deutsche Forschungsgemeinschaft and the Alfried-Krupp Award for
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Received: February 17, 2006
Published online: June 26, 2006
Chem. Eur. J. 2006, 12, 6669 – 6683
ꢀ 2006 Wiley-VCHVerlag GmbH& Co. KGaA, Weinheim
www.chemeurj.org
6683