Stereoselective preparation and reactions of configurationally defined dialkylzinc compounds

Article abstract of DOI:10.1002/1521-3765(20000804)6:15<2748::AID-CHEM2748>3.0.CO;2-Q

The reaction of cyclic and open-chain diastereomerically pure secondary organoboranes with diisopropylzinc allows the preparation of secondary dialkylzinc reagents with good to excellent retention of configuration as shown by deuterolysis and Cu^I- and Pd⁰-mediated reactions with electrophiles. The importance of a high boron-zinc exchange rate to obtain high diastereoselectivity has been shown. Improvement of the configurational stability and stereomeric purity of the zinc intermediates has been obtained by using mono-isopinocampheylborane ((-)-IpcBH₂) providing optically active dialkylzinc compounds (up to 96% ee) with enhanced diastereoselectivities.

Full text of DOI:10.1002/1521-3765(20000804)6:15<2748::AID-CHEM2748>3.0.CO;2-Q

FULL PAPER
Stereoselective Preparation and Reactions of Configurationally Defined
Dialkylzinc Compounds
Andreas Boudier, Christophe Darcel, Felix Flachsmann, Laurent Micouin,
Martin Oestreich, and Paul Knochel*[a]
Abstract: The reaction of cyclic and open-chain diastereomerically pure secondary
organoboranes with diisopropylzinc allows the preparation of secondary dialkylzinc
reagents with good to excellent retention of configuration as shown by deuterolysis
and CuI- and Pd0-mediated reactions with electrophiles. The importance of a high
boron ± zinc exchange rate to obtain high diastereoselectivity has been shown.
Improvement of the configurational stability and stereomeric purity of the zinc
intermediates has been obtained by using mono-isopinocampheylborane ((À)-
IpcBH2) providing optically active dialkylzinc compounds (up to 96% ee) with
enhanced diastereoselectivities.
Keywords: boron ± zinc exchange ´
organozinc compounds
´
stereo-
selective synthesis ´ zinc
Introduction
Results and Discussion
Organometallic species bearing a chiral carbon center at-
tached to the metal center are important chiral intermediates,
since after reaction with an organic electrophile, a variety of
chiral organic products is obtained. The preparation of chiral
organolithiums bearing a heteroatom in the a-position to the
carbon ± lithium bond has been an active research field and
led to configurationally stable organometallic compounds
which proved to be of a great utility in organic synthesis.[1]
Unfortunately, the absence of a heteroatom at the a-
position led to configurationally unstable organolithium
compounds. It is anticipated that organometallic compounds
bearing a more covalent carbon ± metal bond should be
configurationally more stable.[2] Recently, we have reported
that several cyclic secondary organozinc derivatives are
configurationally stable and that the reaction with electro-
philes takes place under high retention of configuration.[3, 4a]
Herein, we report our results on the preparation and reactions
of configurationally defined cyclic and acyclic diorganozinc
compounds.[4a, 4b] Furthermore we present our studies on the
preparation of enantiomerically enriched diorganozinc com-
pounds (up to 97%ee) and their CuI- or Pd0-mediated
reactions with electrophiles.
We envisioned a general method for the preparation of
secondary organozinc compounds and the study of their
configurational stability. Three main problems exist in such an
approach. First, the conversion of the starting material A to
the chiral zinc reagent
B should be stereoselective
(Scheme 1). Second, under the reaction conditions used
E
H
X
H
?
Zn or
R2Zn
XZn
R1
?
EX
H
R1
R2
R1
R2
R2
A
B
D
stereoselective
reactions with
electrophiles
stereoselective
preparation
?
H
ZnX
R2
R1
C
configurational stability
under the reaction conditions
Scheme 1. Configurational stability of organozinc compounds.
[a] Prof. Dr. P. Knochel, Dipl.-Chem. A. Boudier, Dr. C. Darcel,
Dr. F. Flachsmann, Dr. L. Micouin, Dipl.-Chem. M. Oestreich
Institut für Organische Chemie, Ludwig-Maximilians-Universität
Butenandtstrasse 5-13, 81377 München (Germany)
Fax : (‡49)89-2180-7680
(solvent, temperature, additives), the zinc intermediate B
should be configurationally stable and not interconvert to the
epimeric organometallic C. Finally, the organozinc species B
should react stereoselectively with a broad range of electro-
philes to products D.
E-mail: P.Knochel@cup.uni-muenchen.d
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Chem. Eur. J. 2000, 6, No. 15

2748±2761
A synthetically useful process only results, if all these
conditions are fulfilled. Below we will report such a successful
reaction sequence based on a stereoselective boron ± zinc
exchange. The oxidative addition of an alkyl iodide to metallic
zinc, which proceeds via radical intermediates, can be used in
some cases for the stereoselective preparation of zinc organo-
metallics, but is far from being general.[3a] We have found that
the boron ± zinc exchange reaction gives better results.[5] This
reaction allows the efficient conversion of primary alkyldie-
thylboranes to the corresponding dialkylzinc compounds by
treatment with diethylzinc. In the case of secondary alkyldie-
thylboranes, we have found that the use of diethylzinc leads in
several cases to a slow and equilibrated reaction, however by
using the secondary diorganozinc iPr2Zn for performing the
exchange, a faster reaction is observed (Scheme 2).[6]
Similarly, the hydroboration product of the silylated cyclo-
pentenol 3 reacts to give the corresponding zinc reagent 4 in
36% yield using Et2Zn (258C, 0.5 h), whereas 67% conver-
sion is obtained with iPr2Zn.
The hydroboration of various trisubstituted cyclopentene
or cyclohexene derivatives 5 with Et2BH provides the trans-
organoboranes 6 (Et2BH, 3 equiv, 408C, 4 d, Scheme 4).[5]
Subsequently we found that a shorter reaction time at a higher
temperature (508C, 18 h) is usually sufficient to complete the
hydroboration of trisubstituted olefins.
R
R
R
R
D
ii
i
iii
BEt2
Zn-i-Pr
5
6
7
8
R = Me, Ph
slow
Me
R-BEt2
R-BEt2
+
+
Et2Zn
RZnEt
+
Et3B
+ Et2BiPr
Me
Ph
Ph
X
X
fast
iPr2Zn
X
RZni-Pr
X
Scheme 2. The boron ± zinc exchange of secondary alkyldiethylboranes.
6a : BEt2
X = 7a : ZniPr
6b : BEt2
7b : ZniPr
6c : BEt2
7c : ZniPr
8c : D, 61 %
6d : BEt2
7d : ZniPr
8d : D, 60 %
8a : D, 56 % 8b : D, 56 %
Thus, diethylborylcyclododecane (1), prepared by the
reaction of Et2BH with cyclododecene (408C, 4 d),[7] does
not react at all with Et2Zn, but smoothly reacts with iPr2Zn
(2 equiv, ca. 5m in Et2O, 25 8C, 8 h) providing the desired
mixed isopropylcyclododecylzinc compound 2a in about 85%
yield (as determined by iodolysis experiments) (Scheme 3).
Scheme 4. Preparation and deuterolysis of configurationally defined zinc
reagents. i) Et2BH, 408C, 4 d; ii) iPr2Zn, À10 to 258C; iii) D2O, THF,
À788C.
The treatment of the compounds 6 with iPr2Zn (ca. 5m in
Et2O) provides mixed isopropylcycloalkylzinc intermediates
of type 7 which by treatment with D2O in THF generate the
trans-monodeuterated products 8a ± d with good to excellent
trans:cis ratios (Table 1). The use of iPr2Zn allows for the first
time the generation of stereochemically well defined secon-
dary diorganozinc compounds.[8]
Zn-R
BEt2
2 R2Zn
3
Et2BH
25 °C, 8 h
40 °C, 4d
1
2a : R = iPr: 85 %
2b : R = Et: no reaction
Table 1. Influence of the B ± Zn exchange conditions on the stereo-
selectivity of 8.
OTIPS
OTIPS
ZnR
OTIPS
3 Et2BH
2 R2Zn
Entry
5
8
T
[8C][a]
t
trans:cis[c]
Yield
[%][d]
[h][b]
25 °C, 0.5 h
BEt2
1
2
3
4
5
a
b
b
c
a
b
b
c
25
25
7
7
10
10
10
100:0
87:13
98:2
99:1
97:3
56
54
56
61
60
3
4a : R = iPr; 67 %
4b : R = Et; 36 %
À 10
25
Scheme 3. Relative ratio of the boron ± zinc exchange with Et2Zn and
d
d
À 10
iPr2Zn.
[a] Temperature required for the boron ± zinc exchange reaction. [b] Time
required for the boron ± zinc exchange reaction. [c] The trans:cis ratio was
determined by 2H NMR spectroscopy. [d] Overall yield of analytically pure
products based on olefin 5.
Abstract in German: Durch die Reaktion zyklischer und
offenkettiger diastereomerenreiner sekundärer Organoborane
mit Diisopropylzink gelangt man zu sekundären Dialkylzink-
verbindungen mit guter bis hervorragender Retention der
Konfiguration. Dies wird anhand von Deuterolyseexperimen-
ten und CuI- und Pd0-vermittelten Reaktionen mit Elektro-
philen bewiesen. Die Notwendigkeit eines schnellen Bor-
Zinkaustauschs zur Erlangung hoher Diastereoselektivitäten
wird dargelegt. Des weiteren konnte, durch die Verwendung
von (À)-IpcBH2 als chiralem Hydroborierungsreagens, sowohl
ein Zugang zu optisch angereicherten Dialkylzinkverbindun-
gen gefunden (bis zu 96%ee), als auch die Diastereoselektivi-
täten verbessert werden.
The trans:cis ratio of the deuterated products was deter-
2
mined by using H NMR spectroscopy. The performance of
the deuterolysis at À788C is essential for the diastereoselec-
tivity of the quenching reaction. Thus, quenching of the
dialkylzinc compound 7c with a solution of D2O in THF at
À788C furnishes the deuterated product with a trans:cis ratio
of 99:1, whereas deuterolysis at 08C yields a trans:cis ratio of
94:6. On the other side, phenylcyclohexene (5a) gives via this
sequence pure trans-2-deuterio-1-phenylcyclohexane (8a) by
operating at 258C. It was observed that in some cases better
Chem. Eur. J. 2000, 6, No. 15
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P. Knochel et al.
FULL PAPER
results are obtained by performing the boron ± zinc exchange
at À108C (Table 1). Thus, with phenylcyclopentene (5b), a
trans:cis ratio of 87:13 is obtained for the deuterated product
8b, if the boron ± zinc exchange is performed at 258C, while a
trans:cis ratio of 98:2 is obtained by performing the reaction at
À108C. Similar results are obtained for 5d. However, in the
case of 5c, an excellent selectivity could be obtained by
performing the boron ± zinc exchange at 258C. The reasons
for the better stereoselectivity of the boron ± zinc exchange at
08C or À108C compared to room temperature are not
completely clear. The partial epimerization observed by
carrying out the reaction at 258C may be due to radical side
reactions induced by Et3B. A practical problem arises when
the boron ± zinc exchange is slow. In these cases, this reaction
has to be performed at 258C which unfortunately may lead to
substantial epimerization. The formation of the zinc reagents
7 during the boron ± zinc exchange was monitored by quench-
ing reaction aliquots with an aqueous 3m NaOH solution and
subsequent oxidation with aqueous 30% H2O2. With this
procedure, the zinc reagent is protonated affording the
corresponding hydrocarbon while the residual organoborane
is oxidized to the corresponding alcohol. The ratio between
this hydrocarbon and the alcohol can be easily determined by
GC analysis and provides the conversion of the reaction with
good accuracy. Typical conversions of most reactions were in
the range between 60% and 80%. To prove the stereo-
selectivity of the boron ± zinc exchange reaction, we have
hydroborated the open-chain E- and Z-olefins 9 ± 11 and
performed the boron ± zinc exchange reaction followed by
deuterolysis (Scheme 5).[4b]
Me
Me
D
Me
Me
Zn
i,ii
iii
Me
OMe
Me
OMe
i-Pr
O
Me
12 : 59 %
anti:syn >99:1
Z-11
13 : 74 % conversion
Me
Me
Me
Me
D
Me
i,ii
iii
Zn
Me
OMe
i-Pr
O
OMe
Me
12 : 45 %
anti:syn = 23:77
E-11
14 : 51 % conversion
Scheme 6. Diastereoselective deuterolysis of chiral secondary dialkylzinc
compounds(only the major diastereomer is represented). i) Et2BH
(3 equiv), 258C, 14.5 h; ii) iPr2Zn (2 equiv), 08C, 3 h; iii) D2O, THF,
À788C.
respectively, after 1.5 h reaction time. This acceleration may
be due to a precomplexation of iPr2Zn to the methoxy group
leading to the chelate-stabilized zinc reagents 13 and 14. This
behavior is quite general and the presence of an ether function
À
in close proximity to the carbon boron bond accelerates
dramatically the rate of the exchange reaction. The above
results illustrate the stereoselectivity of the boron ± zinc
exchange reaction for open-chain secondary dialkylzinc com-
pounds. Interestingly, the deuterolysis of secondary zinc
reagents such as trans-isopropyl-(2-phenylcyclopentyl)zinc
(7b), which was stored for one week at 58C, proceeded with
the same trans:cis selectivity of 98:2 showing that stock
solutions of these zinc reagents may be prepared and stored at
low temperature.
Me
R2
Me
R2
Me
À
The stereoselective formation of new carbon carbon bonds
Me
R1
R1
with these secondary zinc reagents was also investigated.
Especially, the copper(i)-mediated allylation of cyclic zinc
reagents 7 was studied in some detail. Although the reaction
of organozinc compounds with allylic halides is slow, a rapid
reaction occurs if the dialkylzinc compound is first trans-
metalated with the THF-soluble copper salt CuCN ´ 2LiCl.[9]
Therefore, we studied the influence of transmetalation
reactions on the configuration of the indenylzinc reagent 7c.
First we found that the treatment of 7c with ZnBr2 (2 equiv,
À788C, 0.5 h) leads to a significant isomerization after
deuterolysis. The trans:cis ratio was 92:8 compared to 99:1
before the addition of ZnBr2, showing that the addition of
ZnBr2 considerably reduces the configurational stability of
the secondary alkylzinc compound 7c. On the other hand,
addition of CuCN ´ 2LiCl (2 equiv) leading to the zinc ± cop-
per reagent 15, followed by deuterolysis, furnishes the
deuterated indene 8c with a trans:cis ratio of 99:1 (Scheme 7).
Subsequent addition of ZnBr2 (2 equiv, À788C, 15 min) did
not lead to any epimerization and afforded after deuterolysis
8c with an unchanged trans:cis ratio of 99:1. Finally,
generation of the zinc ± copper reagent 15 at À788C and
warming up to 08C over 15 min, led to substantial isomer-
ization of the organometallic compound 15.
E-9 : R1 = R2 = H
Z-9 : R1 = R2 = H
E-10 : R1 = MeO; R2 = H
E-11 : R1 = H; R2 = MeO
Z-10 : R1 = MeO; R2 = H
Z-11 : R1 = H; R2 = MeO
Scheme 5. Acyclic olefins used for the B ± Zn exchange reaction.
Unfortunately, for the olefins 9 and 10 no separation of the
deuterium signals in 2H NMR spectroscopy could be ob-
tained. However, in the case of the alkenes E- and Z-11, a
2H NMR determination was possible showing that Z-11
undergoes the deuterolysis with >99% anti-diastereoselec-
tivity if the boron ± zinc exchange is performed at 08C
furnishing the anti-product (anti-12) (Scheme 6). By using
the E-isomeric alkene (E-11), the syn-diasteromer (syn-12) is
produced as the major product with a selectivity of syn:anti of
77:23. In contrast, by performing the boron ± zinc exchange at
258C, lower stereoselectivities were obtained, respectively a
syn:anti ratio of 22:78 starting with Z-11 and a syn:anti ratio of
73:27 starting with E-11. Interestingly, the presence of an
ortho-methoxy substituent significantly accelerates the bor-
on ± zinc exchange reaction. In fact, 68% conversion was
observed for E-11 after 1.5 h at 258C.
For the para-substituted E-10 and the unsubstituted ana-
logue E-9, corresponding conversions are only 36% and 40%,
With these results in hand, we performed the allylation of
the zinc reagent 7c after transmetalation with CuCN ´ 2LiCl
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Configurationally Defined Dialkylzinc Compounds
2748±2761
Table 2. Stereoselective reactions of the zinc reagents 7 with carbon
Me
Me
Me
electrophiles after transmetalation with CuCN ´ 2LiCl.
i, ii
ii
D
D
Zni-Pr
Entry
7
Product
16
trans:cis Yield
ratio
[%][a]
7c
8c
8c
trans:cis = 92:8
trans:cis = 99:1
CuCN·2LiCl,
- 78 °C
1
c
16a
95:5
58
Me
iii, ii
ii
8c
8c
M
2
a
16b
98:2
46
trans:cis = 89:11
trans:cis = 99:1
15, M = Cu(CN)ZniPr
3
4
5
b
a
b
16c
16d
16e
95:5
96:4
91:9
36
35
48
i, ii
8c
trans:cis = 99:1
Scheme 7. Transmetalations of secondary alkylzinc reagents. i) ZnBr2,
À788C; ii) D2O, THF, À788C; iii) À788C to 08C, 15 min.
(2 equiv, À788C, 20 min) and obtained the desired trans-
allylated product 16a in 58% yield and a trans:cis ratio of 95:5
showing that little isomerization occurs during the allylation
step (Table 2, entry 1). Attempts to improve this stereo-
selectivity by changing the reaction conditions (temperature,
rate of addition, addition of cosolvents like N-methylpyrro-
lidinone or pyridine) failed. Furthermore, the use of allylating
reagents other than allyl bromide (allyl diethylphosphate or
allyl iodide) also resulted in lower trans:cis ratios (90 ± 85:10 ±
15).
6
7
8
9
c
16 f
16g
16h
16i
93:7
88:12
91:9
96:4
45
42
44
41
b
a
b
A range of other allylation reactions was performed using
various allylic bromides and the cyclic organozinc reagents
7a ± c leading to diastereoselectivities better than 91:9 and up
to 98:2 (Table 2, entry 2). The use of propargyl bromide
furnishes the expected allene 16g in 42% yield and a trans:cis
ratio of 88:12. Cross-coupling reactions with alkynyl bromides
provide the corresponding alkynes 16h ± l in 27 ± 48% yield
and up to 96:4 trans:cis ratio.[10] Addition to ethyl propiolate
or dimethyl acetylenedicarboxylate furnishes the unsaturated
esters 16m, n again with diastereoselectivities of ca. 90:10
(Table 2entries 13 and 14). Finally, a palladium-catalyzed
benzoylation of 7c ([Pd(dba)2] 5 mol%, P(o-Tol)3 20 mol%,
258C, 11 h) furnishes the trans-phenylketone 16o (41%,
trans:cis ˆ 89:11).
10
11
c
c
16j; R ˆ Ph
16k; R ˆ Bu
16l; R ˆ 1-cyclo-
hexenyl
93:7
93:7
42
27
12
c
89:11
48
13
c
16m
16n
16o
90:10
41
14
15
c
c
89:11
89:11
31
41
The allylation reactions were also performed on the open-
chain secondary dialkylzinc systems. Thus, the hydroboration
of both E-9 and Z-9 with Et2BH, followed by the boron ± zinc
exchange with iPr2Zn (3 equiv) at 258C for 3 ± 4 h, furnishes
the expected epimeric zinc reagents syn-17 and anti-17
(Scheme 8) which were transmetalated with CuCN ´ 2LiCl at
À788C and treated with allyl bromide affording the desired
allylated products, respectively syn- and anti-18 with the ratios
78:22 and 19:81 showing also the stereoselectivity of the
allylation reaction in open-chain systems.
Attempts to improve these selectivities, by lowering the
reaction temperature of the boron ± zinc exchange to 08C or
changing the allylation reaction conditions, failed. Further-
more, E- and Z-2-(4-methoxyphenyl)-but-2-ene (E-10, Z-10),
for which the boron ± zinc exchange of the intermediate
borane was slow, undergo stereoconvergent allylation reac-
[a] Yield of analytically pure product based on the starting olefin.
tions leading to the same mixture of diastereomeric allylated
products. On the other hand, E- and Z-2-(2-methoxyphenyl)-
but-2-ene (E-11, Z-11) furnish intermediate organoboranes,
which undergo a fast boron ± zinc exchange. Thus, by per-
forming the boron ± zinc exchange at 08C for 3 h (68%
conversion) followed by transmetalation with CuCN ´ 2LiCl
and allylation, the two diastereomeric allylated products 19
were obtained respectively with a selectivity of syn:anti of
24:76 starting from Z-11 and syn:anti of 81:19 starting from
E-11 (Scheme 9). An ortho-methoxy group in alkenes 11
enhances the ratio of the boron ± zinc exchange, whereas the
presence of a methoxy group in para-position in olefins 10
lowers the rate of the boron ± zinc exchange and may be
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P. Knochel et al.
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Me
Me
Me
Me
Me
i, ii
iii
Zni-Pr
O
Ph
Ph
Ph
i
Me
Me
Me
Me
86 %
Me
X
Z-9
anti -17
anti-18 : 50 %
syn:anti = 19:81
18, syn:anti =78:22
20, X = H, syn:anti = 77:23
21, X = OH
ii (77 %)
Me
Me
Me
i, ii
Me
iii
Zni-Pr
Ph
Ph
NOE
Ph
Me
Me
Me
Me
O
HA
HB
HA
HB
Me
iii, iv
21
E-9
syn -17
syn-18 : 36 %
syn:anti = 78:22
Me
+
59 %
Scheme 8. Diastereoselective allylation of chiral open chain secondary
zinc reagents. i) Et2BH (3 equiv), 258C, 13 h; ii) iPr2Zn (3 equiv), 258C, 4 h;
iii) CuCN ´ 2LiCl (2 equiv), allyl bromide (2 equiv), À788C to 258C.
O
cis-22
trans-22
78:22
Scheme 10. i) O3, then Me2S; ii) NaClO2 , 2-methylbut-2-ene, NaH2PO4 in
tBuOH, 258C, 1 h; iii) SOCl2, 608C, 1 h; iv) AlCl3 (1.25 equiv) in 1,2-
dichloroethane, 258C, 4 h.
Me
Me
Me
Me
iv
i, ii
Me
OMe
Me
Zn
boration/ boron ± zinc exchange sequence which should lead
to enantiomerically enriched organozinc reagents. Mono-
isopinocampheylborane ((À)-IpcBH2) (23) is the reagent of
choice for conducting asymmetric hydroborations with tri-
substituted olefins.[13] First experiments with methylcyclohex-
ene (5e) revealed that the intermediate organyl-isopinocam-
pheylborane (24a) did not give any boron ± zinc exchange
after treatment with iPr2Zn (Scheme 11).
OMe
iPr
O
Me
Z-11
14 : 68 % conversion
19 : syn:anti = 24:76
Me
Me
Me
Me
Me
iv
i, ii
Zn
Me
iPr
OMe
O
OMe
Me
15 : 40 % conversion
19 : syn:anti = 81:19
E-11
Me
Me
Me
Scheme 9. i) Et2BH (3 equiv), 258C, 15 h; ii) iPr2Zn 3 equiv), 08C, 3 h; iii)
iPr2Zn (3 equiv), 08C, 3.5 h; iv) CuCN ´ 2LiCl (2 equiv), allyl bromide
(2 equiv), À788C to 258C.
(–)-IpcBH2, Et2O
48 h, -30 °C
Et2BH
16 h, 50 °C
B(R)Et
BHIpc
5e
25e
24e: 96 %ee
after recrystallization
R = Et, H
Me
+
responsible for the stereoconvergent allylation results. To
prove the deleterious influence of a polar ether function for
the performance of the boron ± zinc exchange, we have added
para-methylanisole (1 equiv) to the alkene E-9 (after hydro-
boration) which leads to a nonstereoselective boron ± zinc
exchange and to a 43:57 mixture of the syn:anti product 18
(compared to a syn:anti ratio of 78:22; Scheme 8).
B(R)Et
26
i) iPr2Zn, 25 °C
ii) CuCN·2LiCl,
-78 °C
Me
iii) allyl bromide
Zn-iPr
The relative configuration of the products 18 obtained after
allylation was established by treating a syn:anti mixture
(78:22) of 18 with O3 (CH2Cl2, À788C, 20 min), followed by a
reductive work-up leading to the aldehyde 20 (86% yield,
Scheme 10). Further oxidation of 20 with NaClO2 in the
presence of 2-methylbut-2-ene and NaH2PO4 in tBuOH
(258C, 1 h) furnishes the carboxylic acid 21 in 77% yield.[11]
This acid was converted to the corresponding acid chloride
(SOCl2, neat, 608C, 1 h), which was cyclized under Friedel ±
Crafts conditions (AlCl3, 1,2-dichloroethane, 258C, 4 h) lead-
ing to a trans-cis mixture (78:22) of the a-tetralone 22 in 59%
yield. Both the major trans isomer and the minor cis isomer
could be unequivocally identified by NMR spectroscopy.
Having found an access to configurationally defined cyclic
and acyclic diorganozinc compounds, we envisioned an
asymmetric route allowing to prepare enantiomerically en-
riched diorganozinc compounds. Since the pioneering work of
Brown, asymmetric hydroboration has become a powerful
tool in organic synthesis and numerous papers have been
published.[12] We therefore thought of an asymmetric hydro-
27e
Me
Me
+
29
28a: 96 %ee
94 %de
Scheme 11. Ligand redistribution on boron and further reactions.
This lack of reactivity might be due to steric hindrance
around the boron atom. This problem could be circumvented
by a ligand redistribution reaction on boron employing excess
Et2BH (ca. 7m in Me2S) to the optically active organo-
isopinocampheylborane 24e.[5] On heating 24e for 16 h at
508C with excess Et2BH as solvent (3 ± 6 equiv), a redistrib-
ution of the ligands on boron takes place affording a mixture
of ethyl- and diethylorganoboranes 25e together with ethyl-
and diethyl-isopinocampheylboranes 26. After the excess
Et2BH had been evaporated, the residual organoboranes were
treated with iPr2Zn (3 equiv) to afford the enantiomerically
enriched organozinc compounds 27. Subsequent transmetala-
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Configurationally Defined Dialkylzinc Compounds
2748±2761
tion with CuCN ´ 2LiCl (1 equiv) and addition of allyl
bromide provided (1S, 2R)-1-(1-propen-3-yl)-2-methylcyclo-
hexane 28a (94 %de, 96 %ee,). Unfortunately, products
derived from 1-methylcyclohexene could not be obtained in
analytically pure form because of the inseparable by-product
29 derived from pinane (see Table 3, entries 1 ± 3). In all the
other cases the pinane-derived by-product could easily be
separated by flash chromatography.[14]
Me
Me
OH
Me
(–)-IpcBH2, -30 °C
i,ii
BHIpc
Et2O, 48 h
5c
24c
30 : 54 %ee
ii
Me
OH
30 : 54 %ee
Scheme 12. i) Et2BH, 508C, 16 h; ii) aq. NaOH/H2O2.
Table 3. Stereoselective reactions of the optically enriched zinc reagents
27 with carbon electrophiles after transmetalation with CuCN ´ 2LiCl.
Entry
27
Product
28
trans:cis
ratio
ee[a]
Yield
[%][b]
the cyclic olefins 5a ± f, we obtained the chiral organozinc
species 27a ± f. After transmetalation to copper, the reaction
with a variety of electrophiles (allylic halides, acid chlorides,
1-bromoalkynes) afforded the products 28a ± i with excellent
diastereomeric ratios (d.r. 93:7) and moderate to excellent
enantioselectivities (up to 96%ee) (see Table 3).[15]
[c]
1
2
e
e
28a
28b
98:2
93:7
94
96
[c]
[c]
Importantly, extension of this procedure to the acyclic
olefins Z-9 and E-9 afforded products with significantly higher
diastereoselectivities than those obtained by the achiral
hydroboration method presented in the first part of this
paper. Thus, the reaction of Z-2-phenyl-2-butene (Z-9) with
(À)-IpcBH2 (23, À358C, 48 h), followed by the equilibration
with Et2BH (508C, 16 h) and the boron ± zinc exchange
(iPr2Zn, 258C, 5h), furnishes the intermediate zinc reagent
anti-31, which after CuI-mediated allylation affords the
desired product anti-32 in 40% yield with high diastereose-
lectivity (syn:anti 7:93) and 74%ee. Respectively, starting
with E-9 the product syn-32 is obtained in 42% yield with a
syn:anti ratio of 94:6 and 46%ee (Scheme 13).
3
4
5
e
a
b
28c
28d
28e
94:6
97:3
97:3
96
20
94
45
47
6
7
f
28 f
28g
98:2
97:3
84
66
77
40
c
8
9
c
28h
28i
99:1
98:2
64
42
43
40
Me
Me
Zni-Pr
iv,v
i-iii
Z-9
Me
Me
d
anti-31
anti-32a: 40%
syn:anti = 7 : 93
74 %ee
[a] Enantiomeric ratio of the major diastereomer determined by GC
analysis on a chiral b-cyclodextrin column. [b] Yield of analytically pure
product based on the starting olefin. [c] Desired products are contaminated
by pinene-derived products with electrophiles.
Me
Me
Zni-Pr
i-iii
iv,v
E-9
Me
Me
syn-32a: 42%
syn:anti = 94 : 6
46 %ee
syn-31
The enantiomeric ratio could be determined by GC analysis
on a chiral b-cyclodextrin column. We have verified that the
enantioselectivity of the initial asymmetric hydroboration is
conserved in this redistribution process by the following
experiment: methylindene 5c was hydroborated with (À)-
IpcBH2 (23, 0.7m in Et2O, 1 equiv, À308C) affording the
optically active organoborane 24c. An aliquot was directly
oxidized with aqueous 3m NaOH/aqueous 30% H2O2 to
afford the alcohol 30. A second aliquot was first heated with
excess Et2BH (508C, 16 h) then also oxidized to the alcohol
30. In both cases, the enantiomeric ratio of the alcohol 30 was
77:23 showing that the enantioselectivity is conserved during
this equilibration step (Scheme 12).
Scheme 13. i) (À)-IpcBH2 (1 equiv), 48 h, À308C; ii) Et2BH (3 equiv),
16 h, 508C then vacuo; iii) iPr2Zn (3 equiv), 5 h, 258C then vacuo; iv)
CuCN ´ 2LiCl, THF, À788C; v) allyl bromide, À788C.
These diastereoselectivities are significantly higher than
those obtained with the achiral hydroboration procedure (see
Scheme 8). The quenching with different electrophiles is
possible and provides products 32 with good to excellent
retention of configuration (Table 4).[15]
Pd0-catalyzed reactions of the optically active diorganozinc
compounds 27 and 31 have also been examined. Pd0-catalyzed
cross-couplings of 27 with E-1-iodo-hex-1-ene and acylations
using pentanoyl and benzoyl chloride afforded products of
By employing this asymmetric one-pot sequence (asym-
metric hydroboration/equilibration/ boron ± zinc exchange) to
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FULL PAPER
Table 4. Stereoselective reactions of the optically enriched zinc reagents
31 with carbon electrophiles after transmetalation with CuCN ´ 2LiCl.
Table 5. Stereoselective reactions of the optically enriched zinc reagents
27 with carbon electrophiles after transmetalation with Pd0.
En- 31
try
Product
32
anti:syn ee[a] Yield
ratio
Entry 27
Product
33 trans:cis ratio ee[a] Yield [%][b]
[%][b]
1
c
33a 99:1
56 35
1
2
3
4
5
6
7
8
anti
anti-32a 92:8
anti-32b 90:10
anti-32c 94:6
anti-32d 97:3
74
74
82
56
46
44
46
56
40
2
3
4
d
f
33b 99:1
33c 98:2
33d 92:8
52 41
83 40
64 39
anti
anti
anti
syn
syn
syn
syn
38
41
41
42
35
35
38
c
5
6
d
f
33e 92:8
33 f 99:1
60 43
81 58
syn-32a
syn-32b
syn-32c
syn-32d
6:94
2:98
7
8
anti-31
33g 90:10
33h 95:5
88 45
60 41
11:89
5:95
c
[a] Enantiomeric ratio of major diastereomer determined by GC analysis
on a chiral b-cyclodextrin column. [b] Yield of analytically pure products
based on the starting olefin.
[a] Enantiomeric ratio of ther major diastereomer determined by GC
analysis on a chiral b-cyclodextrin column. [b] Yield of analytically pure
products based on the olefin.
by Pd0-catalyzed acylations
were lower than those obtained
NOE
NOE
type 33. We were very pleased to find that cyclic diorganozinc
compounds 27 gave excellent trans:cis ratios (d.r. 98:2) under
the reaction conditions (258C, 16 h) of the cross-coupling,
Me
HA
with CuI-mediated acylations.
The trans relationship of the
vinylation products could be
proven in the case of 33b. For
this compound, a COSY-NMR
experiment showed a NOE cor-
relation between the benzylic
HC
HB
Bu
À
without any epimerization of the C Zn bond (see Scheme 14
and Table 5).[16] In general, the diastereoselectivities obtained
Scheme 15. Determination of
stereochemistry of 33b by CO-
SY-NMR spectroscopy.
MeO
MeO
MeO
iv
i-iii
methyl group and HB as well as a NOE correlation between
HA and the vinylic proton HC (Scheme 15).
ZniPr
5f
27f
O
33f : 58%
trans:cis = 99 : 1
81 %ee
Conclusion
In summary, we have shown that the boron ± zinc exchange is
an appropriate method for the preparation of both stereo-
chemically defined cyclic and acyclic diorganozinc com-
pounds. The choice of the reaction conditions and a high
boron ± zinc exchange rate are essential for obtaining a good
stereoselectivity as shown by D2O-quenching experiments.
An achiral method using a hydroboration/boron ± zinc ex-
change sequence proceeds with good stereoselectivities for
cyclic substrates (d.r. 88:12) but only moderate diastereose-
lectivities are obtained for acyclic substrates (d.r. 76:24).
Bu
ZniPr
v
i-iii
27d
33b : 41%
trans:cis = 99 : 1
56 %ee
5d
Scheme 14. i) (À)-IpcBH2, 48 h, À308C; ii) Et2BH, 16 h, 508C then vacuo;
iii) iPr2Zn, 5 h, 258C then vacuo; iv) [Pd(dba)2] (2 mol%), P(o-tolyl)3
(4 mol%), pentanoyl chloride, dioxane , 08C to 258C, 16 h; v) [Pd(dba)2]
(2 mol%), P(o-tolyl)3 (4 mol%), E-1-iodohexene, THF, 08C then 258C,
16 h.
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Chem. Eur. J. 2000, 6, No. 15

Configurationally Defined Dialkylzinc Compounds
2748±2761
1H), 6.90 ± 6.71 (m, 3H), 5.45 (qd, J ˆ 3.8, 1.4 Hz, 1H), 3.66 (s, 3H), 1.84 (br
s, 3H), 1.31 (dt, J ˆ 4.0 Hz, J ˆ 1.4 Hz, 3H); 13C NMR (CDCl3, 50 MHz):
d ˆ 159.0, 137.2, 133.3, 132.4, 130.3, 124.9, 122.9, 131.3, 57.8, 26.9, 17.2; MS
An extension of this method to optically active diorgano-
zinc species was found by employing a one-pot sequence of
asymmetric hydroboration/equilibration/boron ± zinc ex-
change. This asymmetric reaction sequence provides better
diastereoselectivities both with cyclic (d.r.) 93:7 and upto 99:1
and acyclic (d.r.) 89:11 and upto 98:2 substrates. Furthermore,
the enantioselectivity of the initial asymmetric hydroboration
is conserved in this one-pot process and ranges from 44 to
96 %ee depending on the starting olefin.
The effectiveness of these two methods could be demon-
strated by showing that a variety of products are obtained by
the CuI- or Pd0-mediated reactions of these configurationally
stable cyclic or acyclic diorganozinc compounds. The above
results represent the first general method for preparing chiral
main group organometallic compounds through the stereo-
selective reaction with several classes of electrophiles.
‡
(EI): m/z (%): 162 (100) [M ], 147 (28), 131 (22), 105 (22), 91 (45);
elemental analysis calcd for C11H14O (162.23): C 81.44, H 8.70; found: C
81.53, H 8.42.
E-11: IR (film): nÄ ˆ 2918 (s), 1596 (m), 1578 (m), 1489 (vs), 1461 (vs), 1435
(vs), 1377 (m), 1257 (vs), 1230 (vs), 1180 (m), 1030 (vs), 752 (vs); 1H NMR
(CDCl3, 200 MHz): d ˆ 7.33 ± 7.21 (m, 2H), 7.01 ± 6.82 (m, 2H), 5.64 (q, J ˆ
6.0 Hz, 1H), 3.89 (s, 3H), 2.07 (s, 3H), 1.86 (d, J ˆ 6.7 Hz, 3H); 13C NMR
(CDCl3, 50 MHz): d ˆ 156.9, 135.9, 135.3, 129.9, 127.9, 124.1, 120.8, 110.9,
55.6, 17.0, 14.2; elemental analysis calcd for C11H14O (162.23): C 81.44, H
8.70; found: C 81.27, H 8.50.
Z- and E-1-methoxy-4-(1-methyl-1-propenyl)benzene (10): Following the
same procedure as above, the crude product (33.0 g; 74%) was obtained
from 4-methoxyacetophenone (40.4 g). Distillation over a spinning band
column afforded the Z isomer (6 g; Z:E ˆ 98:2) at b.p. 102 ± 1058C/
19 mmHg and the E isomer (8 g; E:Z ˆ 97:3) at b.p. 120 ± 1228C/19 mmHg,
besides fractions of mixtures (11 g). Spectroscopic and physical data are in
accordance with those already reported.[16]
General procedure I: Deuteration of zinc reagents 7: A 25-mL two-necked-
flask equipped with a rubber septum and an argon inlet was charged with
the olefin (10 mmol). After degassing the olefin, diethylborane (2.94 g,
30 mmol, 3.0 equiv) was added dropwise over 10 min by syringe at 258C.
The resulting mixture was stirred for 4 d at 408C. The excess diethylborane
was distilled off (258C, 1 mmHg, 3 h). iPr2Zn (4 mL, 20 mmol, 2 equiv) was
carefully added by syringe at 258C. For the boron ± zinc exchange, the
reaction mixture was stirred at 258C for 7 h, during which time the flask was
covered with aluminum foil to exclude light. The excess iPr2Zn was distilled
off (258C, 1 mmHg, 1 h), the flask was equipped with an internal
thermometer, and the organozinc compound was diluted with dry THF
(15 mL) and cooled to À788C. Deuterium oxide (3.0 g) was added slowly.
Then the mixture was stirred at À788C for 15 min, warmed to 258C, and
worked-up as usual. The crude product was purified by flash chromatog-
raphy (hexanes).
Experimental Section
General considerations: Unless otherwise indicated, all reactions were
carried out under argon. Solvents (THF, diethyl ether) were dried and
freshly distilled over sodium/benzophenone. Reactions were monitored by
liquid-gas chromatography (GC) or thin-layer chromatography (TLC)
analysis of hydrolyzed aliquots. The ratios between diastereomers were
1
determined by H NMR spectroscopy and/or GC analysis.
Starting materials: The following starting materials were prepared accord-
ing to literature procedures: ethyl a-(bromomethyl)acrylate,[17] 1-phenyl-
cyclopent-1-ene (5b),[18] 1-methyl-3H-indene (5c),[19] 3,4-dihydro-1-meth-
ylnaphthalene (5d),[19] E-2-phenylbut-2-ene (E-9),[20] Z-2-phenylbut-2-ene
(Z-9),[20] E-2-(2-p-anisyl)-but-2-ene (E-10),[21] Z-2-(2-p-anisyl)-but-2-ene
(Z-10), [21] E-3-methyl-5-phenylpent-2-ene (E-12),[22] Z-3-methyl-5-phenyl-
pent-2-ene (Z-12).[22]
trans-2-Deuterio-1-phenylcyclohexane (8a): Deuteration of 1-phenyl-1-
cyclohexene (5a) (1.500 g, 9.5 mmol) according to general procedure I
afforded 8a as a clear oil (0.850 g, 56% yield). For the boron ± zinc
exchange, the reaction mixture was stirred at 258C for 7 h; IR (film): nÄ ˆ
3062 (w), 3027 (m), 2925 (vs), 2854 (vs), 2165 (w), 1602 (m), 1584 (m), 1493
(s), 1447 (s), 754 (s); 1H NMR (CDCl3, 300 MHz): d ˆ 7.45 ± 7.33 (m, 5H),
2.69 ± 2.61 (m, 1H), 2.03 ± 1.91 (m, 4H), 1.62 ± 1.43 (m, 5H); 13C NMR
(CDCl3, 75 MHz): d ˆ 148.0, 128.2 (2C), 127.9 (2C), 126.0, 44.5, 34.4, 34.1 (t,
1JCD ˆ 19.6 Hz), 26.9, 26.8, 26.2; 2H NMR (CD2Cl2, 77 MHz): d ˆ 1.95
Preparation of the starting materials
Diisopropylzinc: A 1.3m solution of isopropylmagnesium bromide in
diethyl ether was prepared from 2-bromopropane (38.8 g, 0.32 mol) and
magnesium (8.5 g, 0.35 mol) and transferred by cannula to a 500 mL
2-necked flask. Zinc bromide (35.5 g, 0.16 mol) was dried (1208C, 1 mmHg,
2 h) and dissolved in diethyl ether (150 mL, ca. 30 min). This solution was
carefully added to the Grignard reagent at 08C and the resulting biphasic
mixture was stirred vigorously overnight. After most of the diethyl ether
had been distilled off at 40 ± 508C (ca. 2 h), a Schlenk-tube equipped with a
magnetic stirring bar was connected to the distillation apparatus and cooled
with liquid nitrogen. Vacuum was applied (1 mmHg) and a mixture of
diisopropylzinc and diethyl ether was distilled from the remainig salts by
slowly raising the temperature from 258C to 1008C (ca. 2 h). After the
condensate was warmed to 258C, excess diethyl ether was evaporated by
slowly lowering the pressure to 20 mmHg under stirring over 1 h. The
diisopropylzinc thus obtained (18 mL, ca. 60%) contained 10 ± 15% diethyl
ether (1H NMR) and was about 5m (titration with 1m I2 solution in
tetrahydrofuran). It should be kept under exclusion of light.
‡
(trans-D); MS (EI): m/z (%): 161 (97) [M ], 118 (50), 117 (94), 105 (63), 104
(100), 92 (39), 91 (68); elemental analysis calcd for C12H15D (161.26): C
89.38, H/D 10.62; found: C 89.14, H/D 10.52.
trans-2-Deuterio-1-phenylcyclopentane (8b): Deuteration of 1-phenylcy-
clopent-1-ene (5b) (1.50 g, 10.4 mmol) according to general procedure I
afforded 8b as a clear oil (0.850 g, 56% yield) with a trans ± cis ratio of 98:2.
For the boron ± zinc exchange, the reaction mixture was stirred at 08C for
10 h; IR (film): nÄ ˆ 3062 (w), 3029 (m), 2954 (vs), 2871 (s), 1603 (m), 1492
(m), 1453 (m), 1030 (w), 756 (s); 1H NMR (CDCl3, 300 MHz): d ˆ 7.40 ±
7.25 (m, 5H), 3.12 ± 3.03 (m, 1H), 2.22 ± 2.14 (m, 1H), 1.91 ± 1.68 (m, 6H);
13C NMR (CDCl3, 75 MHz): d ˆ 146.3, 128.2 (2C), 127.1 (2C), 125.6, 45.9,
1
34.6, 34.2 (t, JCD ˆ 20.0 Hz), 25.5, 25.4; 2H NMR (CD2Cl2, 77 MHz): d ˆ
Z- and E-1-methoxy-2-(1-methyl-1-propenyl)benzene (11): A solution of
2-methoxyacetophenone (24.8 g, 0.16 mol) in diethyl ether (50 mL) was
added at 258C dropwise over 30 min to the Wittig reagent prepared from
triphenylethylphosphonium bromide (61.8 g, 0.17 mol) and butyllithium
(1.45m solution in hexane, 115 mL, 0.17 mol) in diethyl ether (350 mL). The
resulting yellow suspension was stirred at 258C for 14 h. After evaporation
of the solvents, the residue was taken up in hexane, successively washed
with water, water/MeOH (2:1) mixture, and brine. After drying (MgSO4),
11 was obtained (25 g; 90%), which was distilled over a 1 m long spinning
band column. Besides fractions of mixtures (6 g), the Z isomer (7 g; Z:E ˆ
97:3) was isolated at b.p. 116 ± 1208C/17 mmHg and the E isomer (2 g;
E:Z ˆ 98:2) at b.p. 135 ± 1378C/17 mmHg. The two isomers were unequiv-
ocally asigned by NOESY-experiments.
‡
2.10 (trans-D), 1.73 (cis-D); MS (EI): m/z (%): 147 (96) [M ], 117 (100), 105
(78), 104 (93), 92 (40), 91(53); elemental analysis calcd for C11H13D
(147.23): C 89.74, H/D 10.26; found: C 89.40, H/D 10.48.
trans-2-Deuterio-1-methyl-2,3-dihydro-1H-indene (8c): Deuteration of
1-methyl-3H-ind-1-ene (5c) (1.00 g, 7.68 mmol) according to general
procedure I afforded 8c as a clear oil (0.620 g, 61% yield) with a trans ±
cis ratio of 99:1. For the boron ± zinc exchange, the reaction mixture was
stirred at 258C for 5 h; IR (film): nÄ ˆ 3070 (m), 3022 (m), 2958 (vs), 2869 (s),
2850 (s), 2196 (w),1492 (m), 1478 (m), 1461 (s), 1374 (m), 1324 (w), 1297
(w), 757 (vs); 1H NMR (CDCl3, 300 MHz): d ˆ 7.36 ± 7.25 (m, 4H), 3.37 ±
3.27 (m, 1H), 3.09 ± 3.00 (m, 2H), 1.81 ± 1.77 (m, 1H), 1.48 (d, J ˆ 6.8 Hz,
3H); 13C NMR (CDCl3, 75 MHz): d ˆ 147.7, 143.8, 126.1, 128.08, 124.3,
123.1, 39.5, 34.4 (t, 1JCD ˆ 20.0 Hz), 31.5, 19.9; 2H NMR (CD2Cl2, 77 MHz):
Z-11: IR (film): nÄ ˆ 2961 (s), 2935 (s), 1598 (m), 1579 (m), 1491 (s), 1460 (s),
‡
1433 (s), 1244 (vs), 1028 (s); 1H NMR (CDCl3, 200 MHz): d ˆ 7.15 ± 7.05 (m,
d ˆ 2.38 (trans-D), 1.66 (cis-D); MS (EI): m/z (%): 133 (96) [M ], 118 (100),
Chem. Eur. J. 2000, 6, No. 15
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2755

P. Knochel et al.
FULL PAPER
117 (12), 116 (16), 85 (15), 84 (27), 49 (21); elemental analysis (%) calcd for
C10H11D (133.21): C 90.17, H/D 9.83; found: C 89.95, H/D 9.94.
(vs); 1H NMR (CDCl3, 300 MHz): d ˆ 7.23 ± 7.15 (m, 4H), 6.00 ± 5.86 (m,
1H), 5.17 ± 5.06 (m, 2H), 3.08 (dd, J ˆ 15.8 Hz, J ˆ 7.8 Hz, 1H), 2.96 ± 2.84
(m, 1H), 2.63 (dd, J ˆ 15.8 Hz, J ˆ 8.8 Hz, 1H), 2.54 ± 2.45 (m, 1H), 2.17 ±
2.28 (m, 1H), 2.14 ± 2.01 (m, 1H), 1.36 (d, J ˆ 6.8 Hz, 3H); 13C NMR
(CDCl3, 75 MHz): trans product: d ˆ 148.2, 142.6, 137.5, 126.2 (2C), 124.4,
123.2, 115.5, 48.4, 44.74, 38.4, 37.7, 18.5; cis product: 149.2, 142.3, 138.0,
126.2 (2C), 124.4, 123.5, 115.3, 43.0, 41.7, 36.5, 34.4, 15.2; MS (EI): m/z (%):
172 (2) [M ], 143 (17), 131 (23), 130 (100), 129 (25), 115 (22), 91 (16);
elemental analysis (%) calcd for C13H16 (172.27): C 90.64, H 9.36; found: C
90.39, H 9.64.
trans-2-Deuterio-1-methyl-1,2,3,4-tetrahydronaphthalene (8d): Deutera-
tion of 3,4-dihydro-1-methylnaphthalene (5d) (1.50 g, 10.4 mmol) accord-
ing to general procedure I afforded 8d as a clear oil (0.900 g, 59% yield)
with a trans ± cis ratio of 97:3. For the boron ± zinc exchange, the reaction
mixture was stirred at 08C for 10 h; IR (film): nÄ ˆ 3062 (w), 3018 (w), 2960
(m), 2929 (m), 2871 (m), 1490 (m), 1447 (m), 754 (s), 726 (m); 1H NMR
(CDCl3, 300 MHz): d ˆ 7.29 ± 7.21 (m, 4H), 3.11 ± 3.02 (m, 1H), 2.99 ± 2.87
(m, 2H), 2.12 ± 2.02 (m, 2H), 1.74 ± 1.69 (m, 1H), 1.58 (d, J ˆ 7.1 Hz, 3H);
13C NMR (CDCl3, 75 MHz): d ˆ 142.1, 136.8, 129.0, 128.0, 125.6, 125.4, 32.4,
‡
trans-1-Allyl-2-phenylcyclohexane (16b): Reaction of with 1-phenylcyclo-
hex-1-ene (5a) and 3-bromoprop-1-ene according to general procedure II
afforded 16b as a clear oil (0.921 g, 46% yield) with a trans ± cis ratio of
98:2. For the boron ± zinc exchange, the reaction mixture was stirred at
258C for 7 h; IR (film): nÄ ˆ 3076 (m), 3064 (m), 3027 (s), 2925 (vs), 2854
(vs), 1640 (m), 1493 (s), 1447 (s), 996 (m), 909 (s), 756 (vs), 700 (vs);
1H NMR (CDCl3, 300 MHz): d ˆ 7.31 ± 7.26 (m, 2H), 7.20 ± 7.15 (m, 3H),
5.72 ± 5.60 (m, 1H), 4.93 ± 4.82 (m, 2H), 2.26 ± 2.18 (m, 1H), 2.00 ± 1.91 (m,
2H), 1.85 ± 1.78 (m, 3H), 1.69-1.58 (m, 2H), 1.53-1.27 (m, 3H), 1.11 ± 0.93
(m, 1H); 13C NMR (CDCl3, 75 MHz): d ˆ 146.5, 137.2, 128.3, 128.3, 127.6
(2C), 125.9, 115.5, 50.4, 43.2, 38.7, 36.1, 32.0, 26.9, 26.5; MS (EI): m/z (%):
1
31.2 (t, JCD ˆ 19.4 Hz) 29.9, 22.9, 20.1; 2H NMR (CD2Cl2, 77 MHz): d ˆ
‡
2.06 (trans-D), 1.67 (cis-D); MS (EI): m/z (%): 147 (3) [M ], 133 (10), 132
(100), 131 (29), 118 (17), 117 (13), 92 (11), 91 (96); elemental analysis (%)
calcd for C11H13D (147.23): C 89.74, H/D 10.26; found: C 89.50, H/D 9.95.
anti-2-(2-Methoxybenzene)-3-deuteriobutane (anti-12): Deuteration of
cis-2-(o-anisyl)-but-2-ene (Z-11) (0.20 g, 1.23 mmol) according to general
procedure I afforded anti-12 as a clear oil (0.120 g, 59% yield) with a syn ±
anti ratio of < 1: > 99. After 3.25 h at 08C, the boron ± zinc conversion was
74%; IR (film): nÄ ˆ 3065 (w), 3030 (w), 2962 (s), 2932 (m), 2874 (m), 2835
(m), 1600 (s), 1585 (w), 1491 (s), 1462 (s), 1439 (m), 1240 (vs), 1174 (w),
1096 (w), 1051 (w), 1032 (m), 751 (s); 1H NMR (CDCl3, 200 MHz): d ˆ
7.10 ± 7.03 (m, 2H), 6,90 ± 6,70 (m, 2H), 3.63 (s, 3H), 3.03 (sext, J ˆ 7.0 Hz,
1H), 1.68 ± 1.34 (m, 1H), 1.11 (d, J ˆ 7.0 Hz, 3H), 0.76 (t, J ˆ 6.9 Hz, 3H);
13C NMR (CDCl3, 50 MHz): d ˆ 157.1, 135.9, 126.7, 126.4, 120.5, 110.4,
55.3, 33.5, 29.8, 20.4, 12.1; 2H NMR (CHCl3, CDCl3, 77 MHz): d ˆ 1.62; MS
‡
200 (6) [M ], 159 (18), 158 (72), 117 (25), 104 (34), 91 (100), 81 (22);
elemental analysis (%) calcd for C15H20 (200.32) : C 89.94, H 10.06; found:
C 89.72, H 9.99.
trans-1-Allyl-2-phenylcyclopentane (16c): reaction of 1-phenylcyclopent-
1-ene (5b) and 3-bromoprop-1-ene according to general procedure II
afforded 16c as a clear oil (0.671 g, 36% yield) with a trans ± cis ratio of
95:5. For the boron ± zinc exchange, the reaction mixture was stirred at 08C
for 10 h; IR (film): nÄ ˆ 3029 (w), 2954 (s), 2873 (s), 1640 (w), 1493 (m), 1453
‡
‡
(EI): m/z (%): 165 (6) [M ], 164 (18) [M À 1], 136 (14), 135 (100), 105 (16);
elemental analysis (%) calcd for C11H15DO (165.25): C 79.96, H/D 10.36;
found: C 80.22, H/D 9.96.
1
(m), 994 (m), 911 (s), 756 (s), 700 (vs); H NMR (CDCl3, 300 MHz): d ˆ
syn-2-(2-Methoxybenzene)-3-deuteriobutane (syn-12): Deuteration of
trans-2-(o-anisyl)-but-2-ene (E-11) (0.15 g, 0.9 mmol) according to general
procedure I afforded syn-12 as a clear oil (0.067 g, 45% yield) with a syn ±
anti ratio of 77:23. After 3.25 h at 08C, the boron ± zinc conversion was
51%; IR (film): nÄ ˆ 3065 (w), 3030 (w), 2962 (s), 2932 (m), 2874 (m), 2835
(m), 1600 (s), 1585 (w), 1491 (s), 1462 (s), 1439 (m), 1240 (vs), 1174 (w),
1096 (w), 1051 (w), 1032 (m), 751 (s); 1H NMR (CDCl3, 200 MHz): d ˆ
7.10 ± 7.03 (m, 2H), 6,87 ± 6,78 (m, 2H), 3.72 (s, 3H), 3.03 (sext, J ˆ 7.0 Hz,
1H), 1.68 ± 1.34 (m, 1H), 1.11 (d, J ˆ 7.0 Hz, 3H), 0.76 (t, J ˆ 6.9 Hz, 3H);
13C NMR (CDCl3, 50 MHz): d ˆ 157.1, 135.9, 126.7, 126.4, 120.5, 110.4, 55.3,
33.5, 29.8, 20.4, 12.1; 2H NMR (CHCl3, CDCl3, 77 MHz): d ˆ 1.70; MS (EI):
7.39 ± 7.20 (m, 5H), 5.88 ± 5.74 (m, 1H), 5.07 ± 4.96 (m, 2H), 2.67 ± 2.61 (m,
1H), 2.31 ± 2.20 (m, 1H), 2.18 ± 1.76 (m, 5H), 1.47 ± 1.41 (m, 2H), 0.97 ± 0.87
(m, 1H); 13C NMR (CDCl3, 75 MHz): d ˆ 145.5, 137.8, 128.3 (2C), 127.6
(2C), 125.9, 115.1, 52.3, 47.7, 28.3, 35.5, 31.8, 24.1; MS (EI): m/z (%): 186 (2)
‡
[M ], 145 (23), 144 (100), 143 (15), 104 (50), 91 (79); elemental analysis (%)
calcd for C14H18 (186.29): C 90.26, H 9.74, found: C 90.17, H 9.78.
trans-Ethyl-2-[2'-phenylcyclohexylmethyl]acrylate (16d): Reaction of
1-phenylcyclohex-1-ene (5a) and ethyl 2-(bromomethyl)acrylate according
to general procedure II afforded 16d as a clear oil (0.953 g, 35% yield) with
a trans ± cis ratio of 96:4. For the boron ± zinc exchange, the reaction
mixture was stirred at 258C for 7 h; IR (film): nÄ ˆ 2910 (w), 2840 (s), 1717
(vs), 1610 (m), 1590 (m), 1480 (s), 1430 (s), 1325 (m), 1300 (s), 1250 (vs),
1030 (s), 745 (s); 1H NMR (CDCl3, 200 MHz): d ˆ 7.21 ± 7.09 (m, 5H), 6.00
(s, 1H), 5.25 (s, 1H), 4.08 (q, J ˆ 7.1 Hz, 2H), 2.21 (d, J ˆ 11.6 Hz, 2H), 1.18
(d, J ˆ 7.1 Hz, 3H), 2.06 ± 0.70 (m, 10H); 13C NMR (CDCl3, 75 MHz): d ˆ
167.3, 146.1, 139.4, 128.2, 127.7, 125.9, 125.8, 60.3, 51.4, 40.8, 37.4, 36.2, 31.8,
‡
‡
m/z (%): 165 (10) [M ], 164 (15) [M À 1], 136 (12), 135 (100), 105 (24), 91
(14), 77 (10); elemental analysis (%) calcd for C11H15DO (165.240): C
79.96; H, D 10.36, found: C 80.22; H, D 9.96.
General procedure II: CuI-catalyzed reactions of zinc reagents 7 with
electrophiles: A 25-mL two-necked-flask equipped with a rubber septum
and an argon inlet was charged with the olefin (10 mmol). After degassing
the olefin, diethylborane (prepared from triethylborane and borane ±
methyl sulfide complex (2.94 g, 30 mmol, 3.0 equiv) was added dropwise
over 10 min by syringe at 258C. The resulting mixture was stirred for 4 d at
408C. Excess diethylborane was distilled off (258C, 1 mmHg, 3 h). iPr2Zn
(4 mL, 20 mmol, 2.0 equiv) was carefully added via syringe at 258C. The
reaction mixture was stirred at the indicated temperature with exclusion of
light. Meanwhile a mixture of CuCN (20 mmol, 2.0 equiv) and LiCl
(40 mmol, 4 equiv) was dried in vacuo (1308C, 3 h). The copper and lithium
salts were dissolved in dry THF (20 mL) and cooled to À788C. Then the
excess of iPr2Zn was distilled off (258C, 1 h) covering the flask with
aluminium foil to exclude light. The flask was equipped with an internal
thermometer and the organozinc compound was diluted with dry THF
(40 mL) and cooled to À788C. The previously prepared CuCN ´ 2LiCl
solution was added. The reaction mixture was stirred at À788C for 20 min
and the electrophile (20 mmol, 2.0 equiv) in dry THF (10 mL) was added
dropwise over 20 min keeping the temperature below À708C. The reaction
mixture was stirred at À708C for 20 min, warmed up to 258C and worked-
up as usual. The crude product was purified by flash-chromatography
(hexanes).
‡
27.0, 26.2, 14.1; MS (EI): m/z (%): 272 (15) [M ], 159 (24), 158 (39), 117
(20), 115 (14), 114 (25), 92 (10), 91 (100), 86 (19), 80 (15); HRMS calcd for
C18H24O2: 272.1763, found 272.1776
trans-Ethyl-2-[2'-phenylcyclopentylmethyl]acrylate (16e): Reaction of
1-phenylcyclopent-1-ene (5b) and ethyl 2-(bromomethyl)-acrylate accord-
ing to general procedure II afforded 16e as a clear oil (1.240 g, 48% yield)
with a trans ± cis ratio of 91:9. For the boron ± zinc exchange, the reaction
mixture was stirred at 08C for 10 h; IR (film): nÄ ˆ 3062 (w), 3029 (m), 2956
(vs), 2871 (s), 1717 (vs), 1630 (m), 1493 (m), 1453 (s), 1368 (s), 1331 (m),
1
1302 (s), 1179 (vs), 1123 (s), 1030 (s), 756 (s), 700 (vs); H NMR (CDCl3,
300 MHz): d ˆ 7.27 ± 7.11 (m, 5H), 6.03 (m, 1H), 5.41 (m, 1H), 4.11 ± 4.05
(q, J ˆ 7.2 Hz, 2H), 2.57 ± 2.42 (m, 2H), 2.13 ± 2.03 (m, 3H), 1.92 ± 1.88 (m,
1H), 1.74 ± 1.63 (m, 3H), 1.27 ± 1.23 (m, 1H), 1.18 (t, J ˆ 7.4 Hz, 3H);
13C NMR (CDCl3, 75 MHz): d ˆ 167.3, 145.0, 140.3, 128.3 (2C), 127.8 (2C),
125.9, 125.0, 60.4, 52.8, 46.2, 36.7, 35.6, 31.9, 23.8, 14.1; MS (EI): m/z (%):
‡
258 (31) [M ], 212 (19), 145 (73), 144 (100), 143 (21), 117 (29), 115 (26), 114
(45), 104 (80), 91 (98), 86 (41), 67 (18); elemental analysis (%) calcd for
C17H22O2 (258.36): C 79.03, H 8.58; found: C 78.96, H 8.69.
trans-Ethyl-2-[1'-methyl-2',3'-dihydro-1H-2-indenylmethyl)]
acrylate
trans-2-Allyl-1-methyl-2,3-dihydro-1H-indene (16a): Reaction of 1-meth-
yl-3H-ind-1-ene (5c) and 3-bromoprop-1-ene according to general proce-
dure II afforded 16a as a clear oil (0.999 g, 58% yield) with a trans:cis ratio
of 95:5; IR (film): nÄ ˆ 3076 (s), 3045 (m), 3022 (s), 2958 (vs), 2902 (vs), 2869
(vs), 2840 (vs), 1642 (s), 1478 (vs), 1461 (s), 996 (s), 911 (vs), 770 (vs), 743
(16 f): Reaction of 1-methyl-3H-ind-1-ene (5c) and ethyl 2-(bromomethy-
l)acrylate according to general procedure II afforded 16 f as a clear oil
(1.100 g, 45% yield) with a trans ± cis ratio of 93:7. After 9 h at room
temperature, the boron ± zinc conversion was 72%; IR (film): nÄ ˆ 3070 (w),
3020 (w), 2957 (m), 2931 (m), 2870 (m), 1717 (vs), 1630 (s), 1476 (m), 1459
2756
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
0947-6539/00/0615-2756 $ 17.50+.50/0
Chem. Eur. J. 2000, 6, No. 15

Configurationally Defined Dialkylzinc Compounds
2748±2761
(m), 1369 (m), 1323 (m), 1300 (m), 1258 (m), 1180 (vs); 1H NMR (CDCl3,
300 MHz): d ˆ 7.20-7.05 (m, 4H), 6.18 (d, J ˆ 1.3 Hz, 1H), 5.56 (d, J ˆ
1.1 Hz, 1H), 4.28 ± 4.14 (m, 2H), 3.10 ± 2.05 (m, 6H), 1.40 ± 1.20 (m, 6H);
13C NMR (CDCl3, 75 MHz): d ˆ 167.3, 148.0, 142.4, 140.1, 128.9, 126.3,
125.5, 124.3, 123.3, 47.5, 45.1, 37.8, 36.8, 18.5, 14.3; MS (EI): m/z (%): 245 (5)
[M ‡H], 244 (30) [M ], 215 (16), 143 (13), 131 (93), 130 (100), 129 (24), 128
(16), 116 (12), 115 (33), 114 (23), 91 (20), 86 (33); HRMS calcd for
C16H20O2: 244.1463, found 244.1464.
d ˆ 146.7, 141.8, 126.4, 124.1, 122.9, 81.9, 81.2, 46.8, 39.8, 39.2, 31.2, 21.9, 18.5,
‡
‡
17.4, 13.7; MS (EI): m/z (%): 213 (10) [M ‡H], 212 (51) [M ], 170 (51), 169
(22), 165 (10), 156 (23), 155 (100), 154 (19), 153 (16), 152 (18), 143 (38), 142
(35), 141 (83), 130 (55), 129 (53), 128 (21), 117 (13), 115 (26), 91 (16), 55
(12); HRMS calcd for C16H20: 212.1565, found: 212.1565.
‡
‡
trans-2-(2'-Cyclohexyl-1'-ethynyl)-1-methyl-2,3-dihydro-1H-indene (16l):
Reaction of 1-methyl-3H-ind-1-ene (5c) and 2-bromo-1-(1-cyclohexenyl)-
acetylene according to general procedure II afforded 16l as a yellow oil
(1.144 g, 48% yield) with a trans ± cis ratio of 89:11. After 4.5 h at room
temperature, the boron ± zinc conversion was 73%; IR (film): nÄ ˆ 3069 (w),
3022 (w), 2931 (vs), 2867 (m), 2210 (w), 1674 (m), 1588 (w), 1476 (m), 1459
(m), 744 (s); 1H NMR (CDCl3, 300 MHz): d ˆ 7.25 ± 7.00 (m, 4H), 6.07
(sext, J ˆ 2.0 Hz, 1H), 3.10 ± 2.65 (m, 4H), 2.10 ± 1.95 (m, 4H), 1.75 ± 1.45
(m, 4H), 1.41 (d, J ˆ 6.8 Hz, 3H); 13C NMR (CDCl3, 75 MHz): d ˆ 146.6,
141.7, 133.7, 126.5, 124.1, 122.9, 120.98, 88.9, 83.2, 46.8, 40.2, 39.17, 29.7, 25.6,
trans-1-[2-(1, 2-Propadienyl)cyclopentyl]benzene (16g): Reaction of
1-phenylcyclopent-1-ene (5b) and 3-bromopropyne (80% in toluene)
according to general procedure II afforded 16g as a clear oil (0.774 g, 42%
yield) with a trans ± cis ratio of 88:12. For the boron ± zinc exchange, the
reaction mixture was stirred at 08C for 10 h; IR (film): nÄ ˆ 3062 (m), 3029
(m), 2956 (vs), 2871 (s), 1957 (s), 1603 (m), 1493 (m), 1453 (s), 843 (s), 754
(s), 700 (vs); 1H NMR (CDCl3, 300 MHz): d ˆ 7.39 ± 7.26 (m, 5H), 5.20 (q,
J ˆ 6.6 Hz, 1H), 4.78 ± 4.61 (m, 2H), 2.88 ± 2.79 (m, 1H), 2.67 ± 2.56 (m,
1H), 2.27 ± 2.08 (m, 2H), 1.94 ± 1.82 (m, 3H), 1.76 ± 1.63 (m, 1H); 13C NMR
(CDCl3, 75 MHz): trans product: d ˆ 207.9, 144.5, 128.2 (2C), 127.4 (2C),
125.9, 93.1, 75.5, 52.6, 46.54, 34.90, 32.58, 23.9; cis product: d ˆ 141.2, 128.7
(2C), 127.2 (2C), 127.1, 91.4, 74.9, 49.5, 43.3, 30.5, 29.1, 23.0; MS (EI): m/z
‡
‡
22.4, 21.6, 17.5; MS (EI): m/z (%): 237 (18) [M ‡H], 236 (100) [M ], 221
(50), 207 (14), 193 (33), 180 (13), 179 (37), 178 (23), 165 (22), 155 (17), 142
(13), 141 (16), 135 (28), 131 (14), 130 (99), 129 (29), 128 (20), 117 (10), 115
(25), 105 (23), 91 (33), 71 (22), 57 (27), 43 (22), 28 (47); HRMS calcd. for
C18H20: 236.1565, found: 236.1566.
‡
(%): 184 (33) [M ], 169 (77), 156 (37), 155 (84), 141 (100), 117 (75), 115
trans-Ethyl-(E)-3-[1'-methyl-2',3'-dihydro-1H-2'-indenyl]-2-propenoate
(16m): Reaction of 1-methyl-3H-ind-1-ene (5c) and ethyl propiolate
according to general procedure II afforded 16m as a clear oil (0.944 g, 41%
yield) with a trans ± cis ratio of 90:10. After 5 h at room temperature, the
boron ± zinc conversion was 80%; IR (film): nÄ ˆ 3069 (w), 3020 (w), 2960
(m), 2933 (m), 2901 (m), 2871 (m), 2842 (m), 1718 (vs), 1652 (s), 1585 (w),
1475 (m), 1460 (m), 1369 (m), 1301 (m), 1280 (s), 1225 (m), 1182 (s), 1153
(s), 1110 (m), 1066 (m), 1037 (m), 985 (m), 746 (s); 1H NMR (CDCl3,
200 MHz): d ˆ 7.60 ± 6.95 (m, 5H), 5.59 (dd, J ˆ 15.5 Hz, J ˆ 0.7 Hz, 1H),
4.14 (q, J ˆ 7.1 Hz, 2H), 3.50 ± 2.50 (m, 4H), 1.30 ± 1.10 (m, 6H); 13C NMR
(CDCl3, 50 MHz): d ˆ 167.1, 151.1, 147.2, 141.1, 127.0, 124.6, 123.6, 122.1,
(45), 103 (22), 91 (74), 77 (37), 65 (20), 39 (19); elemental analysis (%) calcd
for C14H16 (184.28): C 91.25, H 8.75, found: C 91.41, H 8.56.
trans-1-Phenyl-2-(2-phenyl-ethynyl)cyclohexane (16h): Reaction of 1-phe-
nylcyclohex-1-ene (5a) and 1-bromo-2-phenylacetylene according to gen-
eral procedure II afforded 16h as a clear oil (1.146 g, 44% yield) with a
trans ± cis ratio of 91:9. For the boron ± zinc exchange, the reaction mixture
was stirred at 258C for 7 h; IR (film): nÄ ˆ 3040 (w), 3020 (w), 2940 (s), 2880
(m), 1620 (w), 1510 (s), 1450 (m), 780 (vs), 690 (s); 1H NMR.(CDCl3,
300 MHz): d ˆ 7.42 ± 7.17 (m, 10H), 2.68 ± 2.55 (m, 1H), 2.26 ± 1.96 (m, 1H),
1.87 ± 1.23 (m, 8H); 13C NMR (CDCl3, 75 MHz): trans product: d ˆ 145.4,
131,4, 128.1, 127.9, 127.6, 127.3, 126.2, 124.0, 93.3, 81.7, 50.2, 37.0, 34.1, 33.6,
26.6, 26.3; cis product: d ˆ 145.0, 131.4, 128.1, 128.0, 127.8, 127.6, 127.3,
128.2, 91.0, 84.3, 46.9, 36.1, 32.5, 27.2, 26.6, 21.5; MS (EI): m/z (%): 261 (21)
‡
60.7, 52.8, 45.1, 38.1, 17.6, 14.7; MS (EI): m/z (%): 231 (4) [M ‡H], 230 (31)
‡
[M ], 185 (18), 169 (16), 157 (18), 156 (16), 155 (13), 142 (17), 141 (26), 131
(14), 130 (100), 129 (21), 128 (14), 117 (21), 115 (28), 55 (30); HRMS calcd
for C15H18O2: 230.1307, found: 230.1311.
‡
‡
[M ‡H], 260 (100) [M ], 218 (28), 217 (64), 169 (24), 141 (39), 128 (54), 115
trans-Dimethyl-(Z) ± 2-[1'-methyl-2',3'-dihydro-1H-2'-indenyl]-2-butene-
dioate (16n): Reaction of 1-methyl-3H-ind-1-ene (5c) and dimethyl
acetylenedicarboxylate according to general procedure II afforded 16n as
a clear oil (0.937 g, 31% yield) with a trans ± cis ratio of 89:11. After 5 h at
room temperature, the boron ± zinc conversion was 73%; IR (film): nÄ ˆ
3069 (m), 3021 (m), 2955 (s), 2929 (m), 2869 (m), 1725 (vs), 1636 (s), 1586
(w), 1477 (s), 1458 (s), 1377 (s), 1271 (s), 1205 (vs); 1H NMR (CDCl3,
200 MHz): d ˆ 7.20 ± 7.00 (m, 4H), 6.72 (s, 1H), 3.90 (m, 1H), 3,68 (s, 3H),
3.67 (s, 3H), 3.60 ± 2.80 (m, 3H), 1.20 (d, J ˆ 11.8 Hz, 3H); 13C NMR
(CDCl3, 50 MHz): d ˆ 166.1, 165.0, 147.4, 146.0, 141.1, 127.1, 125.4, 125.3,
123.2, 122.1, 51.2, 50.8, 46.2, 43.1, 36.1, 17.0. MS (EI): m/z (%): 275 (2)
(39), 91 (61); HRMS cacld for C20H20: 260.156490, found: 260.15649.
trans-1-Phenyl-2-(2-phenyl-ethynyl)cyclopentane (16i): Reaction of
1-phenylcyclopent-1-ene (5b) and 1-bromo-2-phenylacetylene according
to general procedure II afforded 16i as a clear oil (1.01 g, 41% yield) with a
trans ± cis ratio of 96:4. For the boron ± zinc exchange, the reaction mixture
was stirred at 08C for 10 h; IR (film): nÄ ˆ 3062 (w), 3029 (m), 2960 (s), 2873
(m), 1600 (w), 1492 (s), 1453 (m), 756 (vs), 693 (vs); 1H NMR (CDCl3,
300 MHz): d ˆ 7.46 ± 7.39 (m, 5H), 7.33 ± 7.28 (m, 5H), 3.35 ± 3.17 (m, 1H),
2.98 ± 2.89 (m, 1H), 2.41 ± 2.27 (m, 2H), 2.14 ± 1.86 (m, 4H); 13C NMR
(CDCl3, 75 MHz): d ˆ 143.7, 131.5, 128.3, 128.1, 127.4, 127.2, 126.3, 124.1,
‡
93.0, 81.5, 53.2, 39.5, 33.8, 33.7, 24.2; MS (EI): m/z (%): 247 (19) [M ‡H],
‡
‡
[M ‡H], 274 (8) [M ], 243 (27), 242 (100), 215 (13), 214 (66), 199 (11), 183
(15), 182 (13), 155 (38), 154 (86), 153 (15), 141 (11), 130 (23), 129 (11), 128
(14), 117 (18), 115 (26), 91 (10); elemental analysis (%) calcd for C16H28O4
(302.36): C 70.06, H 6.61, found: C 70.18, H 6.65
‡
246 (100) [M ], 245 (22), 218 (39), 217 (64), 205 (17), 155 (26), 129 (21), 128
(59), 115 (35), 91 (26); elemental analysis (%) calcd for C19H18 (246.35): C
92.64, H 7.36; found: C 92.35, H 7.39.
trans-1-Methyl-2-(2'-phenyl-1'-ethynyl)-2,3-dihydro-1H-indene (16j): Re-
action of 1-methyl-3H-ind-1-ene (5c) and 1-bromo-2-phenylacetylene
according to general procedure II afforded 16j as a clear oil (0.976 g,
42% yield) with a trans ± cis ratio of 93:7. For the boron ± zinc exchange, the
reaction mixture was stirred at 08C for 10 h; IR (film): nÄ ˆ 3022 (m), 2960
(s), 2927 (m), 2869 (m), 2225 (w), 1598 (m), 1488 (s), 1478 (s), 1461 (s), 1443
(s), 791 (m), 754 (vs), 691 (vs); 1H NMR (CDCl3, 300 MHz): d ˆ 7.62 ± 7.59
(m, 2H), 7.56 ± 7.52 (m, 2H), 7.43 ± 7.24 (m, 5H), 3.39 ± 3.30 (m, 2H), 3.19 ±
3.11 (m, 1H), 3.01 ± 2.92 (m, 1H), 1.56 (d, J ˆ 6.8 Hz, 3H); 13C NMR
(CDCl3, 75 MHz): d ˆ 146.4, 141.5, 132.4 (2C), 131.6, 129.11, 128.5, 128.1
(2C), 126.6, 124.1, 122.9, 91.9, 81.6, 46.7, 40.2, 38.8, 17.6; MS (EI): m/z (%):
trans-1-Methyl-2,3-dihydro-1H-2-indenyl-phenylmethanone (16o): Reac-
tion of 1-methyl-3H-ind-1-ene (5c) (0.255 g, 2.0 mmol), diethylborane
(0.80 mL, 6.00 mmol, 3.0 equiv), iPr2Zn (0.78 mL, 3.9 mmol, 2.0 equiv).
After 6 h at room temperature, the boron ± zinc conversion was 61%. The
zinc reagent was then dissolved in dry THF (3 mL) and a solution of
[Pd(dba)2] (0.056 g, 0.1 mmol, 5 mol%) and P(o-Tol)3 (0.119 g, 0.4 mmol,
20 mol%) in dry THF (2 mL) was added. The mixture was stirred for 5 min
and a solution of benzoyl chloride (517 mg, 3.9 mmol, 2 equiv) in THF
(2 mL) was added dropwise. The mixture was stirred at room temperature
for 11 h and worked up as usual. Flash chromatography purification
(hexanes/ether 98:2) afforded the compound 16o as a clear oil (0.189 g,
41% yield) with a trans ± cis ratio of 89:11; IR (film): nÄ ˆ 3066 (m), 3024
(m), 2960 (s), 2929 (m), 2870 (m), 1719 (m), 1680 (vs), 1597 (m), 1581 (m),
1478 (m), 1449 (s), 1362 (m), 1271 (s), 1253 (s), 1233 (s), 1219 (s); 1H NMR
(CDCl3, 200 MHz): d ˆ 8.35 ± 7.00 (m, 9H), 4.00 ± 2.80 (m, 4H), 1.27 (d, J ˆ
6.6 Hz, 3H); 13C NMR (CDCl3, 50 MHz): 2 diastereoisomers d ˆ 201.8,
146.6, 140.7, 136.9, 133.0, 133.8, 129.6, 129.5, 128.7, 128.6, 128.5, 128.4, 128.3,
128.1, 127.9, 126.7, 126.6, 124.7, 124.1, 123.4, 123.2, 55.5, 55.4, 43.1, 42.1, 31.9,
‡
232 (56) [M ], 231 (23), 218 (19), 217 (97), 216 (21), 215 (37), 130 (32), 115
(32); HRMS calcd. for C18H16: 232.1251, found: 232.1209.
trans-2-(1'-Hexenyl)-1-methyl-2,3-dihydro-1H-indene (16k): Reaction of
1-methyl-3H-ind-1-ene (5c) and 1-bromohexyne according to general
procedure II afforded 16k as a clear oil (0.573 g, 27% yield) with a trans ±
cis ratio of 93:7. After 6.5 h at room temperature, the boron ± zinc
conversion was 48%; IR (film): nÄ ˆ 3069 (m), 3023 (m), 2956 (vs), 2932
(vs), 2871 (s), 2213 (w), 1608 (w), 1460 (m), 746 (m); 1H NMR (CDCl3,
300 MHz): d ˆ 7.65 ± 7.00 (m, 4H), 3.25 ± 2.00 (m, 6H), 1.60 ± 1.30 (m, 4H),
1.32 (d, J ˆ 6.6 Hz, 3H), 0.90 ± 0.80 (m, 3H); 13C NMR (CDCl3, 75 MHz):
‡
‡
26.6, 19.24, 17.33; MS (EI): m/z (%): 237 (16) [M ‡H], 236 (100) [M ], 222
(13), 221 (83), 131 (20), 130 (73), 115 (11), 107 (43), 105 (81), 91 (20), 77
(58), 28 (15); HRMS calcd. for C17H16O: 236.1201, found: 236.1201.
Chem. Eur. J. 2000, 6, No. 15
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
0947-6539/00/0615-2757 $ 17.50+.50/0
2757

P. Knochel et al.
FULL PAPER
syn-1-(1,2-Dimethyl-4-pentenyl)benzene (syn-18): Reaction of E-2-phenyl-
but-2-ene (E-9) (0.250 g, 1.9 mmol) and 3-bromoprop-1-ene (0.458 g,
3.8 mmol, 2.0 equiv) according to general procedure II afforded syn-18 as
a clear oil (0.118 g, 36% yield) with a syn ± anti ratio of 78:22. After 4 h at
room temperature, the boron ± zinc conversion was 40%; IR (film): nÄ ˆ
3077 (m), 3064 (m), 3029 (m), 2967 (vs), 2928 (s), 2877 (s), 1639 (m), 1603
(w), 1494 (m), 1453 (s), 1377 (m), 1080 (m), 994 (m), 910 (s), 770 (m), 761
(m), 701 (s); 1H NMR (CDCl3, 300 MHz): d ˆ 7.40 ± 7.10 (m, 5H), 5.85 ±
5.65 (m, 1H), 5.10 ± 4.90 (m, 2H), 2.61 (quint, J ˆ 7.0 Hz, 1H), 2.20 ± 1.80
(m, 3H), 1.29 (d, J ˆ 7.0 Hz, 3H, anti isomer), 1.24 (d, J ˆ 7.0 Hz, 3H, syn
isomer), 0.91 (d, J ˆ 6.5 Hz, 3H, syn isomer), 0.76 (d, J ˆ 6.8 Hz, 3H, anti
isomer); 13C NMR (CDCl3, 75 MHz): d ˆ syn isomer: 147.0, 137.7, 128.2,
127. 7, 127. 1, 125.8, 115.7, 44.5, 39.5, 39.2, 19.0, 16.1; anti isomer: 146.2, 137.5,
128.1, 127.9, 127.1, 125.8, 115.8, 44.7, 39.2, 38.5, 21.8, 17.23; MS (EI): m/z
syn-3-Methyl-4-phenyl-pentanoic acid (21): The aldehyde 20 (0.180 mg,
1.0 mmol), was dissolved in tBuOH (20 mL), then 2-methyl-2-butene (5.1 g,
72.7 mmol) was added, followed by the solution of NaClO2 (1.36 g,
15.0 mmol) and NaH2PO2 ´ H2O (1.28 g, 9.3 mmol) in H2O (25 mL). After
1 h at 258C, the oxidation was complete. The tBuOH was evaporated at
reduced pressure (50 mmHg, 408C) and the residue extracted five times
with diethyl ether. After drying and evaporation, analytically pure acid 21
(0.150 g, 77%) was isolated as a viscous oil; IR (film): nÄ ˆ 3600 ± 3300 (b),
3028 (m), 1708 (vs), 1494 (m), 1453 (s), 1407 (m), 702 (vs); 1H NMR
(CDCl3, 200 MHz): d ˆ 9.85 (br, 1H), 7.26 ± 7.01 (m, 5H), 2.50 (quint., J ˆ
7.3, 1H), 2.30 ± 1.82 (m, 3H), 1.17 (d, J ˆ 7.0, 3H, major isomer), 1.18 (d, J ˆ
7.0, 3H, minor isomer), 0.92 (d, J ˆ 6.5, 3H, major isomer), 0,76 (d, J ˆ 6.5,
3H, minor isomer); 13C NMR (CDCl3, 50 MHz): major isomer: d ˆ 178.8,
144.7, 127.3, 126.8, 125.2, 43.7, 38.9, 35.4, 17.1, 16.0; minor isomer: d ˆ 178.8,
143.9, 127.3, 127.2, 126.5, 43.4, 38.0, 35.2, 17.3, 16.5; MS (EI): m/z (%): 192
‡
‡
(%): 175 (1) [M ‡H], 174 (8) [M ], 133 (14), 132 (45), 106 (38), 105 (100),
104 (11), 91 (42), 79 (15), 77 (20), 69 (11), 41 (15); elemental analysis (%)
calcd for C13H18: C 89.59, H 10.41, found: C 89.08, H 10.72.
‡
(14) [M ], 132 (37), 105 (100), 77 (8), 28 (14); HRMS calcd. for C12H16O2:
192.1150, found: 192.1152.
anti-1-(1,2-Dimethyl-4-pentenyl)benzene (anti-18): Reaction of Z-2-phe-
nylbut-2-ene (Z-9) (0.240 g, 1.8 mmol) and 3-bromoprop-1-ene (0.980 g,
8.0 mmol, 4.4 equiv) according to general procedure II afforded anti-18 as a
clear oil (0.160 g, 50% yield) with a syn ± anti ratio of 19:81. After 3.5 h at
room temperature, the boron ± zinc conversion was 67%; IR (film): nÄ ˆ
3074 (s), 3017 (s), 2967 (vs), 2918 (vs), 2875 (vs), 1644 (s), 1588 (m), 1488 (s),
3,4-Dimethyl-1,2,3,4-tetrahydro-1-naphthalene (22): Acid 21 (0.150 g,
0.8 mmol) was heated with SOCl2 (0.2 mL, 2.7 mmol, 3.5 equiv) to 608C
for 1 h (evolution of gases ceased). The excess SOCl2 was evaporated at
1 mmHg/258C for 20 min, then the brown residue was dissolved in 1,2-
dichloroethane (1 mL). AlCl3 (130 mg, 1.0 mmol, 1.2 equiv) was added at
once and the mixture stirred at 258C for 4 h. After quenching with an ice/
water mixture and acidification (1m aqueous HCl, pH 1), the product was
extracted with diethyl ether. Flash chromatography purification afforded
analytically pure tetralone 22 (0.080 g; 59%), cis:trans 22:78; IR (film): nÄ ˆ
2960 (s), 2880 (s), 1683 (vs), 1601 (s), 1454 (s), 1378 (m), 1285 (s); 1H NMR
(CDCl3, 200 MHz): trans isomer: d ˆ 7.93 (d, J ˆ 7.8 Hz, 1H), 7.43 (m, 1H),
7.26 ± 7.19 (m, 2H), 2.72 (quint, J ˆ 6.3 Hz, 1H), 2.47 (br s, 1H), 2.35 (dd,
J ˆ 16.4 Hz, J ˆ 9.2 Hz, 1H), 2.10 ± 2.04 (m, 1H); 1.34 (d, J ˆ 7.1 Hz, 3H),
1.02 (d, J ˆ 6.9 Hz, 3H); cis isomer: d ˆ 7.93 (d, J ˆ 7.8 Hz, 1H), 7.43 (m,
1H), 7.26 ± 7.19 (m, 2H), 2.98 ± 2.93 (m, 1H), 2.81 (dd, J ˆ 17.0 Hz, J ˆ
4.5 Hz, 1H), 2.49 (d, J ˆ 1.4 Hz, 1H), 2.45 ± 2.39 (m, 1H); 1.15 (d, J ˆ
7.2 Hz, 3H), 0.99 (d, J ˆ 6.5 Hz, 3H); 13C NMR (CDCl3, 50 MHz): trans
isomer: d ˆ 198.5, 148.1, 134.2, 132.0, 128.7, 127.5, 126.9, 43.8, 40.4, 35.9, 20.7,
16.23; cis isomer: d ˆ 198.6, 150.3, 134.1, 131.6, 128.6, 127.2, 126.8, 42.6, 38.6,
33.2, 18.2, 16.1; irradiation experiments (400 MHz, CDCl3): irradiation of
the methyl groups at d ˆ 1.34 (cis) and d ˆ 1.15 (trans), respectively, reveals
J ˆ 5.5 Hz for the benzylic proton at 2.72 for the trans isomer and J ˆ 3.8 Hz
for the benzylic proton at 2.98 ± 2.93 for the cis isomer; NOESY experi-
ments (CDCl3, 400 MHz): for the trans isomer cross-peak between
homobenzylic proton at d ˆ 2.10 ± 2.04 and the benzylic methyl group at
d ˆ 1.34 which is not observed for the cis isomer (d ˆ 2.45 ± 2.39 and 1.15);
1
1452 (vs), 1374 (s), 990 (m), 905 (vs), 770 (m), 748 (m), 699 (vs), H NMR
(300 MHz, CDCl3): 7.35 ± 7.30 (m, 2H), 7.24 ± 7.10 (m, 3H), 5.89 ± 5.78(m,
1H), 5.12 ± 5.04 (m, 2H), 2.65 (quint, 3J ˆ7.1, 1H), 2.34 ± 2.29 (m, 1H),
3
3
1.98 ± 1.76 (m, 2H), 1.32 (d, J ˆ7.1, 3H), 0.80 (d, J ˆ6.7, 3H); 13C NMR
(75 MHz, CDCl3): d ˆ 146.32(s), 137.61(d), 128.28(d), 128.18(d), 128.01(d),
127.78(d), 125.96(d), 115.96(t), 44.78(d), 39.37(d), 38.65(t), 19.11(q),
‡
17.36(q); MS (EI): m/z (%): 174 (2) [M ], 132 (16), 105 (100), 91 (16);
HRMS calcd. for C13H18: 174.1408, found: 174.1409.
syn-1-(1, 2-Dimethyl-4-pentenyl)-2-methoxybenzene (syn-19): Reaction of
E-2-phenylbut-2-ene (E-11) (0.280 g, 1.7 mmol) and 3-bromoprop-1-ene
(0.560 g, 4.6 mmol, 2.7 equiv) according to general procedure II afforded
syn-19 as a clear oil (0.140 g, 40% yield) with a syn ± anti ratio of 81:19.
After 3.5 h at room temperature, the boron ± zinc conversion was 62%; IR
(film): nÄ ˆ 3074 (m), 3029 (m), 2963 (vs), 2930 (vs), 2875 (s), 2836 (s), 1639
(m), 1599 (m), 1585 (m), 1492 (s), 1461(s), 1439 (s), 1376 (m), 1354 (m),
1288 (m), 1240 (s); 1H NMR (CDCl3, 200 MHz): d ˆ 7.08 ± 7.04 (m, 2H),
6.84 ± 6.73 (m, 2H), 5.68 (sym. m, 1H), 4.94 ± 4.83 (m, 2H), 3.71 (s, 3H),
3.01 (quint, J ˆ 7.2 1H), 2.05 ± 1.90 (m, 1H), 1.79 ± 1.67(m, 2H), 0.92 (d, J ˆ
7.1 Hz, 3H), 0.79 (d, J ˆ 6.5 Hz, 3H); 13C NMR (CDCl3, 75 MHz): d ˆ
156.9, 138.0, 135.2, 127.5, 126.6, 120.4, 115.0, 110.4, 55.2, 39.6, 37.3, 36.8, 16.3,
15.8. anti isomer: 157.0, 138.2, 135.4, 127.6, 126.5, 120.3, 55.3, 115.2, 110.44,
‡
MS (EI): m/z (%): 174 (60) [M ], 159 (48), 132 (100), 104 (46), 77 (14);
‡
HRMS calcd. for C12H14O: 174.1045, found :174.1044.
39.74, 37.4, 36.3, 16.4, 15.9; MS (EI): m/z (%): 205 (1) [M ‡H], 204 (9)
‡
[M ], 136 (12), 135 (100), 105 (19); elemental analysis (%) calcd for
trans-1-Methyl-2,3-dihydro-1H-indan-2-ol (30): 1-methyl-3H-indene (5c)
(1.3 g, 10 mmol) was hydroborated with (À)-IpcBH2 (0.7m in Et2O,
C14H20O: C 82.30, H 9.87, found: C 81.89, H 10.05.
14.3 mL, 1 equiv) at À308C for 48 h.
A white precipitate formed
anti-1-(1, 2-Dimethyl-4-pentenyl)-2-methoxybenzene (anti-19): Reaction
of Z-2-phenylbut-2-ene (Z-11) (0.350 g, 2.2 mmol) and 3-bromoprop-1-ene
(0.840 g, 6.9 mmol, 3.2 equiv) according to general procedure II afforded
anti-19 as a clear oil (0.210 g, 47% yield) with a syn ± anti ratio of 24:76.
After 3 h at room temperature, the boron ± zinc conversion was 79%; IR
(film): nÄ ˆ 3074 (s), 3029 (s), 2964 (s), 2930 (s), 2875 (s), 2836 (m), 1639 (s),
1599 (m), 1585 (m), 1492 (s), 1462 (m), 1439 (m), 1240 (vs); 1H NMR
(CDCl3, 200 MHz): d ˆ 7.08 ± 7.04 (m, 2H), 6.84 ± 6.73 (m, 2H), 5.68 (sym.
m, 1H), 4.94 ± 4.83 (m, 2H), 3.71 (s, 3H), 3.01 (quint, J ˆ 7.2 1H), 2.25 ± 2.19
(m, 1H), 1.79 ± 1.67(m, 2H), 1.13 (d, J ˆ 7.2 Hz, 3H), 0.67 (d, J ˆ 6.6 Hz,
3H); 13C NMR (CDCl3, 75 MHz): d ˆ 157.0, 137.8, 135.0, 127.7, 126.4, 120.3,
115.3, 110.4, 55.2, 38.0, 37.9, 36.8, 17.6, 17.4; anti isomer: 157.0, 138.2, 135.4,
127.6, 126.5, 120.3, 55.3, 115.2, 110.44, 39.74, 37.4, 36.3, 16.4, 15.9; MS (EI):
(indanoyl-IpcBH) from which the solvent was separated by double-ended
cannula. The crystals were washed with cold Et2O (À308C) to remove
residual starting olefin, weighed, and dissolved in Et2O (08C) in order to
get a 1m solution. An aliquot (ca. 2 mmoles) was directly oxidized with
aqueous 3m NaOH/30% H2O2 (2 mL of each) to afford alcohol 30 as a
white solid after purification. A second aliquot (ca. 2 mmoles) was first
heated with excess Et2BH (508C, 16 h). Then after pumping off excess
volatiles (258C, 2 h) and redissolution of the residual organylborane in
Et2O, this sample was also oxidized with aqueous NaOH/30% H2O2 to
afford alcohol 30. The enantiomeric ratio was determined by chiral HPLC
(Daicel Chemicals, Chiracel OD, heptane:iPrOH 95:5, flow: 0.6 mLminÀ1).
In both cases, the enantiomeric ratio of the alcohol 30 was 77:23. IR (film):
nÄ ˆ 3336 (b), 3069 (m), 3043 (m), 2957 (s), 1, 477 (s), 1460 (s), 1068 (s), 1019
(s), 743 (s); 1H NMR (CDCl3, 200 MHz): d ˆ 7.13 ± 7.07 (m, 4H), 4.07 (q,
J ˆ 6.3 Hz, 1H), 3.19 ± 2.69 (m, 2H), 2.95 (quint, J ˆ 6.7 Hz, 1H), 2.14 (bs,
1H), 1.22 (d, J ˆ 6.9 Hz, 3H); 13C NMR (50 MHz, CDCl3) d ˆ 146.0, 140.1,
‡
‡
m/z (%): 205 (1) [M ‡H], 204 (9) [M ‡H], 136 (7), 135 (100), 105 (19),
elemental analysis (%) calcd for C14H20O: C 82.30, H 9.87, found: C 82.15,
H 10.02.
syn-3-Methyl-4-phenylpentanal (20): 4-Methyl-5-phenylhex-1-ene 18
(syn:anti 78:22, 0.220 g, 1.3 mmol) was dissolved in CH2Cl2 (10 mL) and
ozonolyzed at À788C for 5 min. Dimethyl sulfide (2.1 g, 34 mmol) was
added and the solution warmed to 258C overnight. The solvents were
evaporated and the residue purified by flash chromatography (hexanes/
diethyl ether 95:5) to yield the aldehyde 20 (0.190 g, 86%) as a colorless oil,
syn:anti ratio of 77:23. The unstable product was directly submitted to the
following oxidation.
‡
127.3, 125.1, 124.1, 81.2, 48.3, 40.9, 17.6; MS (EI): m/z (%): 148 (54) [M ],
133 (26), 119 (100), 105 (33), 91 (41), 77 (14), 65 (10), 28 (3); elemental
analysis (%) calcd for C10H12O: C 81.04, H 8.16, found: C 80.69, H 8.14.
General procedure III: CuI-catalyzed reactions of optically enriched zinc
reagents 27 with electrophiles: A one-neck Schlenk flask was charged with
IpcBH2 (23, 4.3 mL, 3 mmol, 0.7m in diethyl ether), cooled to À358C and
the olefin (3 mmol, 1 equiv) in diethyl ether (1 mL) was added. The
2758
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
0947-6539/00/0615-2758 $ 17.50+.50/0
Chem. Eur. J. 2000, 6, No. 15

Configurationally Defined Dialkylzinc Compounds
2748±2761
reaction mixture was stirred at À358C for 48 h and the solvents were
carefully evaporated under reduced pressure. Et2BH (2.5 mL of a 7.3m
solution in Me2S, 18 mmol, 6 equiv) was added and the resulting solution
was stirred at 508C for 16 h. The solvents were evaporated under reduced
pressure (room temperature, 2 h). iPr2Zn (1.8 mL of a 5m solution in Et2O,
9 mmol, 3 equiv) was added over a 10 min period and the reaction mixture
was stirred at room temperature for 5 h. The volatiles were evaporated
under reduced pressure (08C to 258C, 30 min) and the resulting gray
residue was dissolved in THF (5 mL). A 1m solution of CuCN ´ 2LiCl
(3.0 mL, 3.0 mmol, 1.0 equiv) was added at À788C. The reaction mixture
was stirred 10 min at À788C and the electrophile (9 mmol, 3.0 equiv) was
added. The reaction mixture was stirred 1 h at À788C and the cooling bath
was removed allowing the reaction temperature to rise to room temperature.
The reaction mixture was quenched with aqueous sat. NH4Cl and extracted
with Et2O. After drying (MgSO4) and evaporating the solvents, the crude
residue obtained was purified by flash chromatography (hexanes). The
syn:anti ratio and enantioselectivity were determined by capillary GC
analysis on a chiral b-cyclodextrin column (CP-Chirasil-Dex CB, Chrom-
pack). A calibration was performed in each case with racemic material.
to general procedure III afforded 28h as a clear oil (0.279 g, 43% yield)
with a trans:cis ratio of 99:1 and 64 %ee; IR (film): nÄ ˆ 3070 (w), 3022 (w),
2959 (s), 2931 (s), 2871 (s), 1711 (s), 1477 (m), 1460 (m), 1375 (m), 745 (s);
1H NMR (300 MHz, CDCl3): d ˆ 7.15 ± 7.07 (m, 1H), 3.56 ± 3.32 (m, 1H),
3.15 ± 2.89 (m, 3H), 2.47 (t, J ˆ 7.5 Hz, 2H), 1.55 (quint, J ˆ 7.5 Hz, 3H),
1.28 (d, J ˆ 6.9 Hz, 3H), 1.27 (sext, J ˆ 7.5 Hz, 2H), 0.86 (t, J ˆ 7.5 Hz);
13C NMR (75 MHz, CDCl3): d ˆ 212.2, 147.0, 141.1, 127.2, 127.1,124.6, 123.6,
‡
60.9, 42.4, 42.0, 35.6, 26.2, 22.8, 19.9, 14.3; MS (EI): m/z (%): 216 (14) [M ],
201 (15), 159 (100), 131 (48), 115 (21), 91 (19), 85 (9), 57 (33), 41 (13), 29
(15); HRMS calcd. for C15H20O: 216.1514, found: 216.1517.
trans-(1S, 2S)-2-Allyl-1-methyl-1,2,3,4-tetrahydronaphthalene (28i): Re-
action of 1-methyl-3,4-dihydro-1-naphthalene (5d) and 3-bromoprop-1-
ene according to general procedure III afforded 28i as a clear oil (0.223 g,
40% yield) with a trans:cis ratio of 98:2 and 42 %ee; IR (film): nÄ ˆ 3075
(w), 3017 (w), 2961 (m), 2928 (s), 2870 (m), 1491 (m), 1447 (m), 910 (m), 756
(s), 733 (m); 1H NMR (300 MHz, CDCl3): d ˆ 7.17 ± 7.04 (m, 4H), 5.91 ±
5.76 (m, 1H), 5.11 ± 4.98 (m, 2H), 2.79 ± 2.63 (m, 3H), 2.26 ± 2.16 (m, 1H),
2.09 ± 1.91 (m, 2H), 1.69 ± 1.47 (m, 2H), 1.30 (d, J ˆ 7.0 Hz, 3H, trans-dia,
3H), 1.11. (d, J ˆ 7.0 Hz, cis-dia, 3H); 13C NMR (75 MHz, CDCl3): d ˆ
141.1, 137.2, 136.1, 128.9, 128.6, 125.5, 125.1, 115.7, 39.6, 37.9, 37.2, 26.7, 24.1,
trans-(1S, 2R)-1-Allyl-2-phenylcyclohexane (28d): Reaction of 1-phenyl-
cyclohex-1-ene (5a) and 3-bromoprop-1-ene according to general proce-
dure III afforded 28d as a clear oil (0.270 g, 45% yield) with a trans:cis ratio
of 97:3 and 20%ee; IR (film): nÄ ˆ 3074 (w), 3026 (m), 2924 (s) , 2853 (m),
1493 (m), 1447 (m), 909 (m), 755 (s); 1H NMR (CDCl3, 300 MHz): d ˆ
7.30 ± 7.14 (m, 5H), 5.72 ± 5.59 (m, 1H), 4.90 ± 4.80 (m, 2H), 2.20 (td, J ˆ
11.0 Hz, 3.0 Hz, 1H), 1.93 ± 1.00 (m, 11H); 13C NMR (75 MHz, CDCl3): d ˆ
146.6, 137.3, 128.5, 127.8, 126.0,115.7, 50.6, 44.8, 38.9, 36.3, 32.2, 27.1, 26.7;
‡
23.1; MS (EI): m/z (%): 186 (8) [M ], 171 (18), 157 (9), 144 (100), 129 (89),
117(45), 105 (11), 91 (35), 77 (10), 51 (5), 32 (9); elemental analysis (%)
calcd for C14H18 (186.29): C 90.26, H 9.74; found: C 90.24, H 10.03.
1-[(1S, 2S)-1,2-Dimethyl-4-pentenyl]benzene (anti-32a): Reaction of Z-2-
phenyl-2-butene (Z-9) and 3-bromoprop-1-ene according to general
procedure III afforded anti-32a as a clear oil (0.209 g, 40% yield) with a
anti:syn ratio of 92:8 and 74 %ee; IR (film): nÄ ˆ 3077 (m), 3063 (m), 2965
(s), 2928 (m), 1494 (m), 1452 (s), 910 (s), 701 (s); 1H NMR (300 MHz,
CDCl3): d ˆ 7.20 ± 7.06 (m, 5H), 5.85 ± 5.65 (m, 1H), 4.99 ± 4.89 (m, 2H),
2.53 (quint, J ˆ 7.0 Hz, 1H), 2.25 ± 2.10 (m, 1H), 1.83 ± 1.66 (m, 2H), 1.19 (d,
J ˆ 7.0 Hz, 3H, trans-dia), 1.15 (d, J ˆ 7.0 Hz, cis-dia, 3H), 0.80 (d, J ˆ 7 Hz,
cis-dia, 3H) 0.66 (d, J ˆ 7 Hz, trans-dia, 3H); 13C NMR (75 MHz, CDCl3):
d ˆ 147.0, 137.7, 128.1, 128.0, 127.9,127.7, 125.8, 115.6, 44.5, 39.5, 39.2, 17.6,
‡
MS (EI): m/z (%): 200 (4) [M ], 158 (49), 129 (9), 117 (22), 104 (30), 91
(100), 81 (13), 67 (10), 55 (7), 41 (12); elemental analysis (%) calcd for
C15H20 (200.32): C 89.94, H 10.06; found: C 89.71, H 10.14.
trans-(1S, 2R)-1-Allyl-2-phenylcyclopentane (28e): Reaction of 1-phenyl-
cyclopent-1-ene (5b) and 3-bromoprop-1-ene according to general proce-
dure III afforded 28e as a clear oil (0.262 g, 47% yield) with a trans:cis ratio
of 97:3 and 94 %ee; IR (film): nÄ ˆ 3076 (w), 3026 (w), 2952 (s), 2908 (m),
1492 (m), 1451 (m), 993 (m), 910 (m), 755 (m), 699 (s); 1H NMR (300 MHz,
CDCl3): d ˆ 7.31 ± 7.17 (m, 5H), 5.77 ± 5.68 (m, 1H), 4.98 ± 4.88 (m, 2H),
2.59 ± 2.50 (q, J ˆ 9.0 Hz, 1H), 2.23 ± 1.64 (m, 8H), 1.43 ± 1.31 (m, 1H);
13C NMR (75 MHz, CDCl3): d ˆ 145.5, 137.8, 128.3, 127.6, 125.9,115.0, 52.3,
‡
16.1; MS (EI): m/z (%): 174 (1) [M ], 132 (21), 118 (4), 105 (100), 91 (24),
77 (7), 65(2), 55 (4), 41 (9), 39 (4); elemental analysis (%) calcd for C13H18
(174.28): C 89.59, H 10.41; found: C 89.97, H 10.25.
Ethyl 2-[(2S, 3S)-2-methyl-3-phenylbutyl]acrylate (anti-32b): Reaction of
Z-2-phenyl-2-butene (Z-9) and ethyl 2-(bromomethyl)acrylate according
to general procedure III afforded anti-32b as a clear oil (0.281 g, 38%
yield) with a anti:syn ratio of 90:10 and 74 %ee; IR (film): nÄ ˆ 3084 (w),
3061 (w), 3027 (w), 2959 (s), 2928 (s), 2872 (s), 1721 (ss), 1219 (s), 1198 (s),
1159 (s), 702 (m); 1H NMR (300 MHz, CDCl3): d ˆ 7.30 ± 7.15 (m, 5H), 6.16
(s, 1H), 6.10 (s, cis ± dia), 5.46 (s, 1H), 5.43 (s, cis-dia), 4.19 (q, J ˆ 7.0 Hz,
2H), 2.72 ± 2.56 (m, 2H), 1.32 (t, J ˆ 7.0 Hz, 3H), 1.27 (d, J ˆ 7.0 Hz, 3H),
0.83 (d, J ˆ 6.5 Hz, cis-dia), 0.69 (d, J ˆ 6 Hz, 3H, trans-dia); 13C NMR
(75 MHz, CDCl3): d ˆ 167.6, 146.1, 140.2, 128.3, 128.1,127.9, 126.0, 125.9,
60.7, 45.5, 45.1 (cis-dia), 38.3, 38.0 ( cis-dia) , 37.2, 19.0, 17.5 (cis-dia), 16.9,
‡
47.7, 38.3, 35.4, 31.8, 24.1; MS (EI): m/z (%): 186 (3) [M ], 157 (5), 144
(100), 129 (21), 117 (26), 104 (48), 91 (72), 77 (9), 67 (20), 41 (13); elemental
analysis (%) calcd for C14H18 (186,.29): C 90.26, H 9.74; found: C 90.11, H
9.54.
trans-1-[(1R, 2S)-2'-Allylcyclopentyl]-2-methoxybenzene (28 f): Reaction
of o-methoxyphenyl-cyclopentene (5 f) and 3-bromoprop-1-ene according
to general procedure III afforded 28 f as a clear oil (0.500 g, 77% yield)
with a trans:cis ratio of 98:2 and 84 %ee; IR (film): nÄ ˆ 2952 (s), 2870 (s),
1
1493 (s), 1465 (s), 1242 (s), 1033 (s), 910 (s), 752 (s); H NMR (300 MHz,
‡
CDCl3): d ˆ 7.21 ± 6.83 (m, 4H), 5.86 ± 5.63 (m, 1H), 4.98 ± 4.86 (m, 2H),
3.80 (s, 3H), 3.14 ± 3.01 (q, J ˆ 8.9 Hz, 1H), 2.29 ± 1.19 (m, 9H); 13C NMR
(75 MHz, CDCl3): d ˆ 159.8, 140.4, 135.7, 129.6, 128.7,122.8, 116.9, 112.7,
15.8 (cis-dia), 15.4 (cis-dia), 14.4; MS (EI): m/z (%): 246 (10) [M ], 200 (3),
183 (3), 141 (32), 132 (10), 113 (37), 105 (100), 95 (18), 91 (32), 77 (10), 55
(6), 28 (4), elemental analysis (%) calcd for C16H22O2 (246.34): C 78.01, H
9.00; found: C 77.88, H 9.22.
‡
57.5, 48.3, 46.7, 40.7, 36.0, 33.9, 26.2; MS (EI): m/z (%): 216 (34) [M ], 185
(5), 174 (100), 159 (11), 147 (28), 134 (28), 121 (98), 115 (15), 108 (13), 91
(77), 77 (15), 65 (12), 41 (15), 28 (17); elemental analysis (%) calcd for
C15H20O (216.32): C 83.29, H 9.32; found: C 83.17, H 9.40.
Trimethyl-[(3R, 4S)-3-methyl-4-phenyl-1-pentynyl]silane (anti-32c): Re-
action of Z-2-phenyl-2-butene (Z-9) and 2-bromo-1-trimethylsilylacetylene
according to general procedure III afforded anti-32c as a clear oil (0.283 g,
41% yield) with a anti:syn ratio of 94:6 and 82 %ee; IR (film): nÄ ˆ 2964 (s),
trans-(1S, 2R)-2-Allyl-1-methyl-2,3-dihydro-1H-indene (28g): Reaction of
1-methyl-3H-ind-1-ene (5c) and 3-bromoprop-1-ene according to general
procedure III afforded 28g as a clear oil (0.207 g, 40% yield) with a
trans:cis ratio of 97:3 and 66 %ee; IR (film): nÄ ˆ 3076 (s), 3045 (m), 3022
(s), 2958 (vs), 2902 (vs), 2869 (vs), 2840 (vs), 1642 (s), 1478 (vs), 1461 (s),
996 (s), 911 (vs), 770 (vs), 743 (vs): 1H NMR (300 MHz, CDCl3): d ˆ 7.23 ±
7.09 (m, 4H), 5.94 ± 5.81 (m, 1H), 5.12 ± 5.00 (m, 2H), 3.06 ± 2.99 (m, 1H),
2.82 (quint, J ˆ 7.0 Hz, 1H), 2.61 ± 2.53 (m, 1H), 2.49 ± 2.40 (m, 1H), 2.07 ±
1.98 (m, 1H), 1.30 (d, 7.2 Hz, 3H), 1.10 (d, J ˆ 7.2 Hz, cis-dia); 13C NMR
(75 MHz, CDCl3): d ˆ 148.0, 142.5, 137.4, 126.1, 126.0, 124.1, 123.0, 115.4,
1
2166 (s), 1454 (s), 1249 (s), 842 (s), 760 (s); H NMR (300 MHz, CDCl3):
d ˆ 7.19 ± 7.05 (m, 5H), 2.61 ± 2.45 (m, 2H), 1.28 (d, J ˆ 6.5 Hz, 3H), 0.92 (d,
J ˆ 6.5 Hz, 3H), 0.0 (s, 9H); 13C NMR (75 MHz, CDCl3): d ˆ 145.0, 128.0,
127.3, 126.1, 110.5, 85.6, 45.2, 34.0, 19.5, 19.2, 0.0; MS (EI): m/z (%): 230 (1)
‡
[M ], 215 (3), 156 (9), 135 (2), 105 (100), 97 (5), 73 (14), 59 (3); elemental
analysis (%) calcd for C15H22Si (230.42): C 78.19, H 9.62; found: C 77.81, H
9.58.
(2S, 3R)-3-Methyl-2-phenyloctan-4-one (anti-32d): Reaction of Z-2-phe-
nyl-2-butene (Z-9) and pentanoyl chloride according to general procedure
III afforded anti-32d as a clear oil (0.269 g, 41% yield) with a anti:syn ratio
of 97:3 and 56 %ee; IR (film): nÄ ˆ 3061 (w), 3028 (m), 2962 (s) , 2933 (s),
2874 (m), 1711 (s), 1454 (s), 1376 (m), 760 (m), 701 (s); 1H NMR (300 MHz,
CDCl3): d ˆ 7.32 ± 7.15 (m, 5H), 2.92 (q, J ˆ 6.7 Hz, 1H), 2.72 (q, J ˆ 6.9 Hz,
1H), 2.58 ± 2.36 (m, 2H), 1.68 (quint, J ˆ 7.5 Hz, 2H), 1.34 (sext, J ˆ 7.3 Hz,
2H), 1.17 (d, J ˆ 6.7 Hz, 3H), 0.92 (t, J ˆ 7.3 Hz, 3H), 0.82 (d, J ˆ 6.9 Hz,
‡
48.2, 44.6, 38.3, 37.5, 18.4; MS (EI): m/z (%): 172 (2) [M ], 157 (2), 143 (17),
130 (100), 115 (24), 91 (15), 77 (5), 65 (3), 51 (3), 41 (5), 28 (3); elemental
analysis (%) calcd for C13H16 (172.27): C 90.70, H 9.30; found: C 90.83, H
9.52.
trans-1-[(1S, 2R)-1'-Methyl-2',3'-dihydro-1H-indenyl]-1-pentanone (28h):
Reaction of 1-methyl-3H-ind-1-ene (5c) and pentanoyl chloride according
Chem. Eur. J. 2000, 6, No. 15
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
0947-6539/00/0615-2759 $ 17.50+.50/0
2759

P. Knochel et al.
FULL PAPER
3H); 13C NMR (75 MHz, CDCl3): d ˆ 215.0, 145.0, 128.6, 127.7, 127.5, 126.5,
reaction mixture was quenched with aqueous sat. NH4Cl and extracted with
Et2O. After drying (MgSO4) and evaporating the solvents, the crude
residue obtained was purified by flash chromatography (hexanes). The
syn:anti ratio and enantioselectivity were determined by capillary GC
analysis on a chiral b-cyclodextrin column (CP-Chirasil-Dex CB, Chrom-
pack).
53.2, 42.9, 42.7, 25.8, 22.5, 20.7, 18.4, 16.4, 14.0; MS (EI): m/z (%): 218 (8)
‡
[M ], 161 (12), 133 (27), 117 (4), 105 (100), 91 (42), 85 (49), 77 (12), 57 (52),
41 (11), 29 (12); elemental analysis (%) calcd for C15H22O (218.33): C 82.52,
H 10.16; found: C 82.66, H 10.51.
1-[(1R, 2R)-1,2-Dimethyl-4-pentenyl]benzene (syn-32a): Reaction of E-2-
phenyl-2-butene (E-9) and 3-bromo-prop-1-ene according to general
procedure III afforded syn-32a as a clear oil (0.220 g, 42% yield) with a
anti:syn ratio of 6:94 and 46 %ee; IR (film) 3076 (m), 3063 (m), 2966 (s),
2928 (m), 1493 (m), 1452 (s), 908 (s), 701 (s); 1H NMR (300 MHz, CDCl3):
d ˆ 7.40 ± 7.10 (m, 5H), 5.80 ± 5.65 (m, 1H), 5.10 ± 4.90 (m, 2H), 2.60 (quint,
J ˆ 7.0 Hz, 1H), 2.05 (quint, J ˆ 7.0 Hz, 1H), 1.80 ± 1.66 (m, 2H), 1.28 (d,
J ˆ 7.0 Hz, trans-dia), 1.22 (d, J ˆ 7.0 Hz, 3H), 0.74 (d, J ˆ 7 Hz, 3H) 0.76 (d,
J ˆ 7 Hz, trans-dia); 13C NMR (75 MHz, CDCl3): d ˆ 144.3, 13.6, 126.3,
126.1, 126.0,125.7, 125.1, 123.9, 113.9, 44.7, 37.2, 36.6, 17.0, 15.3; MS (EI): m/z
trans-(1S, 2S)-2-((E)-1-Hexenyl)-1-methyl-2,3-dihydro-1H-indene (33a):
Reaction of 1-methyl-3H-ind-1-ene (5c) and trans-1-iodohex-1-ene accord-
ing to general procedure IVafforded 33a as a clear oil (0.187 g, 35% yield)
with a trans:cis ratio of 99:1 and 56 %ee; IR (film): nÄ ˆ 3069 (w), 3021 (m),
2957 (s) , 2928 (s), 2872 (s), 1476 (s), 1458 (s), 760 (s), 743 (s); 1H NMR
(300 MHz, CDCl3): d ˆ 7.23 ± 7.10 (m, 4H), 5.59 ± 5.46 (m, 2H), 3.02 ± 2.68
(m, 2H), 2.84 (quint, J ˆ 6.9 Hz, 1H), 2.50 ± 2.43 (m, 1H), 2.08 ± 2.00 (m,
2H), 1.42 ± 1.28 (m, 4H), 1.28 (d, J ˆ 6.9 Hz), 0.91 (t, J ˆ 6.8 Hz); 13C NMR
(75 MHz, CDCl3): d ˆ 148.0, 142.9, 132.7, 131.4, 126.3, 124.2, 123.8, 123.1,
‡
‡
(%): 174 (1) [M ], 132 (13), 117 (3), 105 (100), 91 (24), 77 (10), 6 (4), 55 (4),
54.5, 45.3, 38.9, 32.4, 31.9, 22.3, 17.0, 14.1; MS (EI): m/z (%): 214 (20) [M ],
41 (7), 39 (3); elemental analysis (%) calcd for C13H18 (174.28): C 89.59, H
10.41; found: C 89.93, H 10.33.
199 (4), 157 (22), 143 (58), 130 (100), 117 (53), 105 (5), 91 (20), 77 (5), 55
(15), 41 (18); HRMS calcd. for C16H22: 214.1721, found: 214.1717.
Ethyl 2-[(2R, 3R)-2-methyl-3-phenylbutyl]acrylate (syn-32b): Reaction of
E-2-phenyl-2-butene (E-9) ethyl 2-(bromomethyl)acrylate according to
general procedure III afforded syn-32b as a clear oil (0.259 g, 35% yield)
with a anti:syn ratio of 2:98 and 44 %ee; IR (film): nÄ ˆ 3084 (w), 3061 (w),
3027 (w), 2967 (m), 1717 (ss), 1453 (m), 1194 (m), 1175 (s), 1157 (s), 702 (s);
1H NMR (300 MHz, CDCl3): d ˆ 7.24 ± 7.08 (m, 5H), 6.07 (s, 1H), 5.35 (s,
1H), 4.10 (q, J ˆ 7.0 Hz, 2H), 2.53 (quint, J ˆ 7.0 Hz, 1H), 2.35 ± 2.31 (m,
1H), 1.21 (t, J ˆ 7.0 Hz, 3H), 1.17 (d, J ˆ 7.0 Hz, 3H), 0.78 (d, J ˆ 6.0 Hz,
3H), 0.61 (d, J ˆ 6 Hz, trans-dia); 13C NMR (75 MHz, CDCl3): d ˆ 167.5,
146.6, 140.2, 128.2, 127.8, 125.9, 125.8, 60.6, 45.1, 38.2, 38.0, 17.5, 15.8, 14.3;
trans-(1S, 2S)-2-((E)-1-Hexenyl)-1-methyl-1,2,3,4-tetrahydro-naphthalene
(33b): Reaction of 1-methyl-3H-ind-1-ene (5c) trans-1-iodohex-1-ene
according to general procedure IV afforded 33b as a clear oil (0.234 g,
41% yield) with a trans:cis ratio of 99:1 and 52 %ee; IR (film): nÄ ˆ 3061
(m), 3017 (m), 2959 (s), 2928 (s), 2872 (m), 1491 (m), 970 (m), 908 (s), 758
(m), 734 (s); 1H NMR (300 MHz, CDCl3): d ˆ 7.17 ± 6.96 (m, 4H), 5.45 ±
5.27 (m, 2H), 2.70 (t, J ˆ 6.5 Hz, 2H), 2.56 (quint, J ˆ 7.0 Hz, 1H), 2.08 ±
1.78 (m, 4H), 1.58 ± 1.46 (m, 1), 1.36 ± 1.24 (m, 4H), 1.22 (d, J ˆ 7.0 Hz), 0,82
(t, J ˆ 7.0 Hz); 13C NMR (75 MHz, CDCl3): d ˆ 141.4, 136.7, 134.5, 130.6,
128.8, 128.2, 125.8, 125.4, 45.4, 38.0, 32.4, 31.9, 28.7, 28.4, 22.3, 21.4, 14.0; MS
‡
‡
MS (EI): m/z (%): 246 (25) [M ], 200 (7), 183 (11), 141 (57), 133 (27), 113
(EI): m/z (%): 228 (26) [M ], 157 (18), 143 (85), 129 (55), 118 (100), 103
(56), 105 (100), 95 (34), 91 (57), 77 (35), 55 (24), 29 (25); elemental analysis
(%) calcd for C16H22O2 (246.34): C 78.01, H 9.00; found: C 77.86, H 9.25.
(64), 91 (18), 55 (20), 41 (16), 28 (11); HRMS calcd. for C17H24: 228.1878,
found: 228.1871.
Trimethyl-[(3S, 4R)-3-methyl-4-phenyl-1-pentynyl]silane (syn-32c): Reac-
tion of E-2-phenyl-2-butene (E-9) and 2-bromo-1-trimethylsilylacetylene
according to general procedure III afforded syn-32c as a clear oil (0.242 g,
35% yield) with a anti:syn ratio of 11:89 and 46 %ee; IR (film): nÄ ˆ 2962
(s), 2166 (s), 1453 (s), 1250 (s), 842 (s), 758 (s); 1H NMR (300 MHz, CDCl3):
d ˆ 7.19 ± 7.07 (m, 5H), 2.74 ± 2.55 (m, 2H), 1.18 (d, J ˆ 7 Hz, 3H), 0.93 (d,
J ˆ 7 Hz, 3H), 0.0 (s, 9H); 13C NMR (75 MHz, CDCl3): d ˆ 143.8, 128.1,
127.7, 127.4, 162.2, 110.4, 86.0, 44.0, 33.7, 18.2, 18.1, 0.0; MS (EI): m/z (%):
trans-1-((1S,
2S)-2-((E)-1-Hexenyl)cyclopentyl-methyl)-2-methoxyben-
zene (33c): Reaction of 1-methyl-3H-ind-1-ene (5c) and trans-1-iodohex-
1-ene according to general procedure IVafforded 33c as a clear oil (0.258 g,
40% yield) with a trans:cis ratio of 98:2 and 83 %ee; IR (film): nÄ ˆ 3065
(w), 3027 (w), 2955 (vs), 2932 (vs), 2872 (s), 1493 (s), 1242 (vs), 908 (s), 753
1
(m), 735 (vs); H NMR (300 MHz, CDCl3): d ˆ 7.15 ± 6.80 (m, 4H), 5.40 ±
5.20 (m, 2H), 3.80 (s, 3H), 3.10 (q, J ˆ 9.7 Hz, 1H), 2.67 ± 2.52 (m, 1H),
2.20 ± 1.48 (m, 8H), 1.40 ± 1.10 (m, 4H), 0.85 (t, J ˆ 6.7 Hz); 13C NMR
(75 MHz, CDCl3): d ˆ 156.7, 133.1, 133.0, 129.3, 127.3, 126.3, 120.3, 110.3,
55.2, 49.2, 45.2, 33.3, 33.0, 32.8, 32.0, 31.5, 23.7, 21.8, 13.7; MS (EI): m/z (%):
‡
230 (1) [M ], 215 (4), 156 (13), 135 (2), 105 (100), 97 (4), 73 (20), 59 (3);
elemental analysis (%) calcd for C15H22Si (230.42): C 78.19, H 9.62; found:
C 78.32, H 9.59.
‡
258 (54) [M ], 201 (18), 187 (39), 174 (58), 160 (22), 159 (34), 147 (85), 121
(100), 91 (82), 67 (43), 41 (50), 28 (22); HRMS calcd. for C18H26O: 258.1984,
found: 258.1980.
(2R, 3S)-3-Methyl-2-phenyloctan-4-one (syn-32d): Reaction of E-2-phe-
nyl-2-butene (E-9) and pentanoyl chloride according to general procedure
III afforded syn-32d as a clear oil (0.249 g, 38% yield) with a anti:syn ratio
of 5:95 and 56 %ee; IR (film): nÄ ˆ 3061 (w), 3028 (m), 2962 (s) , 2933 (s),
2874 (m), 1711 (s), 1454 (s), 1376 (m), 760 (m), 701 (s); 1H NMR (300 MHz,
CDCl3): d ˆ 7.28 ± 7.10 (m, 5H), 2.93 (quint, J ˆ 7.2 Hz , 1H), 2.69 (quint,
J ˆ 6.9 Hz, 1H), 2.18 ± 1.85 (m, 2H); 13C NMR (75 MHz, CDCl3): d ˆ 214.5,
145.5, 128.4, 127.4, 126.3, 53.2, 42.3, 42.0, 25.3, 22.1, 18.0, 14.1, 13.7; MS (EI):
General procedure V: Pd0-catalyzed acylations of enantiomerically
enriched zinc reagents 27 with acid chlorides: A Schlenk flask was charged
with IpcBH2 (23, 3.1 mL, 2.5 mmol, 0.8m) in diethyl ether, cooled to À358C
and the olefin (2.5 mmol, 1 equiv) in diethyl ether (1 mL) was added. The
reaction mixture was stirred at À358C for 48 h and then the solvent was
carefully evaporated under reduced pressure. Et2BH (2.1 mL of a 7.3m
solution in Me2S, 15 mmol, 6 equiv) was added and the resulting solution
was stirred at 508C for 16 h. Excess volatiles were evaporated under
reduced pressure (room temperature, 2 h). iPr2Zn (2.5 mL of a 3m solution
in Et2O, 7.5 mmol, 3 equiv) was added over a 10 min period and the
reaction mixture was stirred at room temperature for 5 h. The volatiles
were evaporated under reduced pressure (08C to 258C, 30 min) and the
resulting gray residue was dissolved in dioxane (5 mL). The mixture was
filtered under inert gas and cooled to 08C. A previously prepared mixture
of [Pd(dba)2] (29 mg, 2 mol%) and P(o-tolyl)3 (30 mg, 4 mol%) and the
acid chloride (7.5 mmol, 3 equiv) in dioxane (3 mL) was added . The
reaction mixture was allowed to warm slowly to 258C. After 12 h the
reaction mixture was quenched with aqueous 30% NH3 and stirred for
15 min. Then aqueous 2m HCl was added and the mixture was extracted
with Et2O. After drying (MgSO4) and evaporating the solvents, the crude
residue obtained was purified by chromatography (hexanes:Et2O). The
syn:anti ratio and enantioselectivity were determined by capillary GC
analysis on a chiral b-cyclodextrin column (CP-Chirasil-Dex CB, Chrom-
pack).
‡
m/z (%): 218 (21) [M ], 161 (13), 133 (21), 122 (18), 114 (21), 105 (100), 91
(54), 85 (50), 72 (15), 57 (45), 41 (16), 29 (24); HRMS calcd. for C15H22O:
218.1671, found: 218.1670.
General procedure IV: Pd0-catalyzed cross-couplings of enantiomerically
enriched zinc reagents 27 with E-1-iodohex-1-ene: A Schlenk flask was
charged with IpcBH2 (23, 2.5 mL, 2.5 mmol, 1.0m) in diethyl ether, cooled
to À358C and the olefin (2.5 mmol, 1 equiv) in diethyl ether (1 mL) was
added. The reaction mixture was stirred at À358C for 48 h and then the
solvent was carefully evaporated under reduced pressure. Et2BH (2.1 mL
of a 7.3m solution in Me2S, 15 mmol, 6 equiv) was added and the resulting
solution was stirred at 508C for 16 h. Excess volatiles were evaporated
under reduced pressure (room temperature, 2 h). iPr2Zn (2.5 mL of a 3m
solution in Et2O, 7.5 mmol, 3 equiv) was added over a 10 min period and the
reaction mixture was stirred at room temperature for 5 h. The volatiles
were evaporated under reduced pressure (08C to 258C, 30 min) and the
resulting gray residue was dissolved in THF (5 mL). The mixture was
filtered under inert gas and cooled to 08C. A previously prepared mixture
of [Pd(dba)2] (29 mg, 2 mol%) and P(o-tolyl)3 (30 mg, 4 mol%) and E-1-
iodohex-1-ene (1.575 g, 7.5 mmol, 3 equiv) in THF (3 mL) was added. The
reaction mixture was allowed to warm slowly to 258C. After 12 h the
trans-1-[(1S,
2R)-1'-Methyl-2',3'-dihydro-1H-2'-indenyl]-1-pentanone
(33d): Reaction of 1-methyl-3H-ind-1-ene (5c) and pentanoyl chloride
2760
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
0947-6539/00/0615-2760 $ 17.50+.50/0
Chem. Eur. J. 2000, 6, No. 15

Configurationally Defined Dialkylzinc Compounds
2748±2761
according to general procedure Vafforded 33d as a clear oil (0.211 g, 39%
yield) with a trans:cis ratio of 92:8 and 64 %ee; IR (film): nÄ ˆ 3070 (w),
3022 (w), 2959 (s), 2931 (s), 2871 (s), 1711 (s), 1477 (m), 1460 (m), 1375 (m),
745 (s); 1H NMR (300 MHz, CDCl3): d ˆ 7.23 ± 7.05 (m, 4H), 3.45 (quint,
J ˆ 7.0 Hz, 1H), 3.18 ± 2.86 (m, 3H), 2.50 ± 2.42 (td, J ˆ 7.0 Hz, 2.0 Hz, 2H),
1.54 (quint, J ˆ 7.0 Hz, 2H), 1.34 ± 1.18 (m, 2H), 1.27 (d, J ˆ 7.0 Hz, 3H),
0.85 (t, J ˆ 7.0 Hz); 13C NMR (75 MHz, CDCl3): d ˆ 211.5, 146.4, 140.6,
126.6, 126.5,124.0, 123.4, 60.3, 55.6, 41.9, 41.5, 35.0, 25.7, 22.3, 19.3, 13.9; MS
4399 ± 4402; e) R. J. Linderman, A. Ghannam, J. Am. Chem. Soc.
1990, 112, 2392 ± 2398; f) J. M. Chong, E. K. Mar, Tetrahedron Lett.
1990, 31, 1981 ± 1984; g) J. M. Chong, S. B. Park, J. Org. Chem. 1992,
57, 2220 ± 2222; h) W. H. Pearson , A. C. Lindbeck, J. Am. Chem. Soc.
1991, 113, 8546 ± 8548; i) H. J. Reich, M. A. Medina, M. D. Bowe, J.
Am. Chem. Soc. 1992, 114, 11003 ± 11004; j) D. Hoppe, O. Zschage,
Angew. Chem. 1989, 101, 67 ± 69; Angew. Chem. Int. Ed. Engl. 1989,
28, 65 ± 67; k) O. Zschage, J.-R. Schwark, D. Hoppe, Angew. Chem.
1990, 102, 336 ± 337; Angew. Chem. Int. Ed. Engl. 1990, 29, 296; l) O.
Zschage, D. Hoppe, Tetrahedron 1992, 48, 5657 ± 5666; m) H. Paulsen,
D. Hoppe, Tetrahedron 1992, 48, 5667 ± 5670; n) D. Hoppe, F. Hintze,
P. Tebben, M. Paetow, H. Ahrens, J. Schwerdtfeger, P. Sommerfeld, J.
Haller, W. Guarnieri, S. Kolczewski, T. Hense, I. Hoppe, Pure Appl.
Chem. 1994, 66, 1479 ± 1486; o) S. T. Kerrick, P. Beak, J. Am. Chem.
Soc. 1991, 113, 9708 ± 9710; p) S. Thayumanavan, S. Lee, C. Liu, P.
Beak, J. Am. Chem. Soc. 1994, 116, 9755 ± 9756; q) N. Voyer, J. Roby,
Tetrahedron Lett. 1995, 36, 6627 ± 6630; r) R. W. Hoffmann, W. Klute,
Chem. Eur. J. 1996, 2, 694 ± 700.
‡
(EI): m/z (%): 216 (15) [M ], 201 (23), 159 (100), 130 (65), 115 (18), 91 (27),
85 (13), 57 (25), 43 (4), 29 (12); HRMS calcd. for C15H20O: 216.1514, found:
216.1519.
trans-1-[(1S,
2R)-1-Methyl-1,2,3,4-tetrahydronaphthanyl]-1-pentanone
(33e): Reaction of 1-methyl-3,4-dihydro-1-naphthalene (5d) and pentano-
yl chloride according to general procedure V afforded 33e as a clear oil
(0.247 g, 43% yield) with a trans:cis ratio of 92:8 and 60 %ee; IR (film):
nÄ ˆ 3061 (w), 3018 (w), 2958 (s), 2932 (s), 2872 (m), 1710 (s), 1491 (m), 1459
(m), 1378 (m), 758 (m); 1H NMR (300 MHz, CDCl3): d ˆ 7.21 ± 6.96 (m,
4H), 3.22 (quint, J ˆ 7.0 Hz, 1H), 2.78 ± 2.64 (m, 2H), 2.58 ± 2.32 (m, 3H),
2.00 ± 1.62 (m, 2H), 2.53 (quint, J ˆ 7.5 Hz, 2H), 1.23 (sext, J ˆ 7.3 Hz,), 1.17
(d, J ˆ 7.0 Hz, 3H), 0.82 (t, J ˆ 7.3 Hz); 13C NMR (75 MHz, CDCl3): d ˆ
213.4, 140.5, 135.7, 128.6, 127.5, 126.1, 125.5, 55.2, 41.7, 33.5, 29.2, 25.8, 25.4,
[2] a) G. M. Whitesides, M. Witanowski, J. D. Roberts, J. Am. Chem. Soc.
1965, 87, 2854 ± 2862; b) M. Witanowski, J. D. Roberts, J. Am. Chem.
Soc. 1966, 88, 737 ± 741; c) W. H. Glaze, C. M. Selman, A. L. Ball, Jr.,
L. E. Bray, J. Org. Chem. 1969, 34, 641 ± 644; d) E. Pechhold, D. G.
Adams, G. Fraenkel, J. Org. Chem. 1971, 36, 1368 ± 1374; e) G.
Fraenkel, C. E. Cottrell, D. T. Dix, J. Am. Chem. Soc. 1971, 93, 1704 ±
1708.
‡
22.4, 21.3, 13.9; MS (EI): m/z (%): 230 (29) [M ], 215 (44), 173 (100), 145
(85), 130 (66), 91 (28), 85 (75), 57 (94), 41 (63), 28 (91); elemental analysis
(%) calcd for C16H22O (230.17): C 83.43, H 9.63; found: C 83.51, H 9.63.
trans-1-[(1R, 2S)-2-(2-Methoxybenzyl)cyclopentyl]-1-pentanone (33 f):
Reaction of o-methoxy-phenyl-cyclopent-1-ene (5 f) and pentanoyl chlor-
ide according to general procedure V afforded 33 f as a clear oil (0.377 g,
58% yield) with a trans:cis ratio of 99:1 and 81 %ee; IR (film): nÄ ˆ 2956 (s),
2870 (m), 1708 (s), 1492 (s), 1463 (s), 1243 (s), 1030 (m), 753 (s); 1H NMR
(300 MHz, CDCl3): d ˆ 7.12 ± 7.06 (m, 4H), 3.70 (s, 3H), 3.53 ± 3.44 (q, J ˆ
8.0 Hz, 1H), 3.04 ± 2.95 (q, J ˆ 8.0 Hz, 1H), 2.22 ± 2.16 (td, J ˆ 7.5 Hz,
3.5 Hz, 2H), 2.04 ± 1.64 (m, 6H), 1.42 ± 1.33 (quint, J ˆ 7.5 Hz, 2H), 1.19 ±
1.05 (sext, J ˆ 7.5 Hz, 2H), 0.71 (t, J ˆ 7.5 Hz); 13C NMR (75 MHz, CDCl3):
d ˆ 231.3, 157.3, 132.8, 127.6, 1127.2, 120.7, 110.6, 63.4, 57.6, 55.2, 43.2, 42.1,
[3] a) R. Duddu, M. Eckhardt, M. Furlong, H. P. Knoess, S. Berger, P.
Knochel, Tetrahedron 1994, 50, 2415 ± 2432; b) S. Klein, I. Marek, J.-F.
Normant, J. Org. Chem. 1994, 59, 2925 ± 2926; c) S. Sakami, T.
Houkawa, M. Asaoka, H. Takei, J. Chem. Soc. Perkin Trans. I 1995,
285 ± 286; d) T. Houkawa, T. Ueda, S. Sakami, M. Asaoka, H. Takei,
Tetrahedron Lett. 1996, 37, 1045 ± 1048.
[4] a) L. Micouin, M. Oestreich, P. Knochel, Angew. Chem. 1997, 109,
274 ± 276; Angew. Chem. Int. Ed. Engl. 1989, 28, 69 ± 71. b) C. Darcel,
F. Flachsmann, J. Chem. Soc. Chem. Commun. 1998, 2, 205 ± 206.
[5] F. Langer, L. Schwink, A. Devasagayaraj, P.-Y. Chavant, P. Knochel, J.
Org. Chem. 1996, 61, 8229 ± 8243.
[6] M. W. Rathke, H. Yu, J. Org. Chem. 1972, 37, 1732 ± 1734.
[7] R. Köster, G. Grisanov, W. Larbig, P. Binger, Liebigs Ann. Chem.
1964, 672, 1 ± 34.
[8] We have observed that the addition of magnesium salts increases also
the rate of the iodine ± zinc exchange reaction, however this reaction is
not stereoselective and not applicable to the stereoselective gener-
ation of diorganozinc compounds: L. Micouin, P. Knochel, Synlett
1997, 327 ± 328.
[9] a) P. Knochel, M. C. P. Yeh, S. C. Berk, J. Talbert, J. Org. Chem. 1988,
53, 2390 ± 2392; b) P. Knochel, R. Singer, Chem. Rev. 1993, 93, 2117 ±
2188.
[10] M. C. P. Yeh, P. Knochel, Tetrahedron Lett. 1989, 30, 4799 ± 4802.
[11] A. B. Smith III, T. L. Leenay, J. Am. Chem. Soc. 1989, 111, 5761 ± 5768.
[12] For leading reviews about the preparation and use of chiral organo-
boranes in organic synthesis see: aH. C. Brown, B. Singaram, Acc.
Chem. Res. 1988, 21, 287 ± 293; bD. S. Matteson, Synthesis 1986, 973 ±
985, and references therein.
[13] H. C. Brown, A. K. Mandal, N. M. Yoon, B. Singaram, J. R. Schwier,
P. K. Jadhav, J. Org. Chem. 1982, 47, 5069 ± 5074.
[14] W. C. Still; M. Kahn; A. Mitra, J. Org. Chem. 1978, 43, 2923 ± 2925.
[15] A. Boudier, F. Flachsmann, P. Knochel, Synlett 1998, 1438 ± 1446.
[16] A. Boudier, P. Knochel, Tetrahedron Lett. 1999, 40, 687 ± 690.
‡
33.8, 30.0, 25.7, 22.4, 13.9; MS (EI): m/z (%): 260 (55) [M ], 203 (67), 175
(72), 148 (57), 121 (100), 108 (83), 91 (52), 85 (59), 57 (68), 41 (67), 29 (59);
HRMS calcd. for C17H24O2: 260.1776, found: 260.1774.
trans (2S, 3R)-3-Methyl-2-phenyloctan-4-one (33g): Reaction of Z-2-
phenyl-2-butene (Z-9) and pentanoyl chloride according to general
procedure Vafforded 33g as a clear oil (0.245 g, 45% yield) with a syn:anti
ratio of 10:90 and 88 %ee; IR (film): nÄ ˆ 3061 (w), 3028 (m), 2962 (s), 2933
(s), 2874 (m), 1711 (s), 1454 (s), 1376 (m), 760 (m), 701 (s); 1H NMR
(300 MHz, CDCl3): d ˆ 7.24 ± 7.08 (m, 5H), 2.85 (qd, J ˆ 10.0 Hz, 6.5 Hz,
1H), 2.64 (qd, J ˆ 10.0 Hz, 6.9 Hz, 1H), 2.50 ± 2.29 (m, 2H), 1.50 (quint, J ˆ
7.2 Hz, 2H), 1.25 (sext, J ˆ 7.2 Hz, 2H), 1.09 (d, J ˆ 6.5 Hz, 3H), 0.85 (t, J ˆ
7.2 Hz, 3H), 0.76 (t, J ˆ 6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3): d ˆ 214.6,
144.7, 135.7, 128.2, 128.1,127.3, 126.1, 52.9, 42.6, 42.1, 25.4, 22.1, 20.4, 16.0,
‡
13.6; MS (EI): m/z (%): 218 (16) [M ], 161 (14), 133 (24), 114 (18), 105
(100), 91 (47), 85 (62), 72 (12), 57 (41), 41 (11), 29 (14); HRMS calcd. for
C15H22O: 218.1671, found: 218.1673.
trans-(1S, 2R)-1-Methyl-2,3-dihydro-1H-2-indenyl-phenylketone (33h):
Reaction of 1-methyl-3H-ind-1-ene (5c) and benzoyl chloride according
to general procedure Vafforded 33h as a clear oil (0.242 g, 41% yield) with
a trans:cis ratio of 95:5 and 60 %ee; IR (film): nÄ ˆ 3067 (w), 3023 (w), 2959
(w), 1680 (s), 1448 (m), 1252 (m), 1217 (m), 758 (m), 745 (m); 1H NMR
(300 MHz, CDCl3): d ˆ 8.10 ± 7.94 (m, 2H), 7.62 ± 7.34 (m, 7H), 3.89 (q, J ˆ
8.5 Hz, 1H), 3.79 (q, J ˆ 6.7 Hz, 1H), 1.37 (d, J ˆ 6.7 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d ˆ 201.2, 146.7, 140.8, 137.1, 133.0,128.5, 126.8, 123.3,
Â
[17] J. Villieras, M. Rambaud, Synthesis 1982, 924 ± 926.
‡
55.6, 42.2, 36.7, 19.3; MS (EI): m/z (%): 236 (33) [M ], 221 (45), 130 (65),
[18] Organikum, Autorenkollektiv, 16th ed., VEB Leipzig 1986, p. 228.
[19] M. Adamczyk, D. S. Watt, D. A. Netzel, J. Org. Chem. 1984, 49, 4226 ±
4237.
107 (43), 105 (92), 77 (100), 51 (17), 28 (4); elemental analysis (%) calcd for
C17H16O: C 86.41, H 6.82; found: C 86.33, H 6.68.
[20] M. Bianchi, U. Matteoli, P. Frediani, G. Menchi, F. Piacenti, J.
Organomet. Chem. 1983, 252, 317 ± 325.
[21] E. L. Allred, J. Sonnenberg, S. Winstein, J. Org. Chem. 1960, 25, 26 ±
29.
[22] A. D. Buss, N. Greeves, R. Mason, S. Warren, J. Chem. Soc. Perkin
Trans. I 1987, 2569 ± 2577.
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Chem. Soc. Perkin Trans. I 1989, 1529 ± 1535; c) J. M. Chong, E. K.
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Tripathy, A. Sarkar, K. M. Sadhu, J. Am. Chem. Soc. 1989, 111,
Received: November 22, 1999 [F2151]
Chem. Eur. J. 2000, 6, No. 15
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