Stereoselective nickel-catalyzed cycloisomerization of 1,6-dienes

Article abstract of DOI:10.1002/adsc.200800104

Highly stereoselective cycloisomerization of 1,6-dienes with a catalyst system based on [Ni-(allyl)(cod)][BARF] and Wilke's azaphospholene all-(R)-1 is described. Unprecedented high enantiomeric excesses of up to 91% were obtained for the formation of five-membered cyclic products from symmetrically substituted 1,6-dienes. High chemo- and regioselectivities were achieved also for unsymmetrically 1,6-dienes substituted in terminal position leading again to five-membered cyclic products in fair to very good yields. Cycloisomerization products were subjected to sequential hydroboration as well as hydrogenation of the exo-methylene functional group. Promising diastereoselectivities were achieved and these reaction sequences could be efficiently performed in a one-pot procedure.

Full text of DOI:10.1002/adsc.200800104

FULL PAPERS
DOI: 10.1002/adsc.200800104
Stereoselective Nickel-Catalyzed Cycloisomerization of
1,6-Dienes
Christian Bçing,a Julia Hahne,a Giancarlo Franciò,a and Walter Leitnera,b,*
a
Institut für Technische und Makromolekulare Chemie, RWTH Aachen, Worringer Weg 1, 52074 Aachen, Germany
Fax : (+49)-241-802-2177; e-mail: leitner@itmc.rwth-aachen.de
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany
b
Received: February 15, 2008; Published online: April 18, 2008
Dedicated to Professor Andreas Pfaltz on the occasion of his 60th birthday.
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: Highly stereoselective cycloisomerization very good yields. Cycloisomerization products were
of 1,6-dienes with a catalyst system based on [Ni- subjected to sequential hydroboration as well as hy-
ACHTREUNG(allyl)ACHTREUNG(cod)]ACHTREUNG[BARF] and Wilkeꢀs azaphospholene all- drogenation of the exo-methylene functional group.
(R)-1 is described. Unprecedented high enantiomeric Promising diastereoselectivities were achieved and
excesses of up to 91% were obtained for the forma- these reaction sequences could be efficiently per-
tion of five-membered cyclic products from symmet- formed in a one-pot procedure.
rically substituted 1,6-dienes. High chemo- and regio-
selectivities were achieved also for unsymmetrically
1,6-dienes substituted in terminal position leading Keywords: asymmetric catalysis; cyclization; nickel
again to five-membered cyclic products in fair to catalysis; olefin dimerization; tandem reactions
Introduction
Five-membered carbo- or heterocycles are widespread
structural motifs in natural products and other biolog-
ically active compounds. The transition metal-cata-
lyzed cycloisomerization of enynes or dienes provides
an atom-economic approach for accessing such cyclic
Scheme 1. Cycloisomerization of 1,6-dienes.
compounds from readily accessible starting materi-
als.[1,2] Since the first example of Trost et al. in 1989, a
number of efficient catalyst systems has been devel- cause control of the chemo- and regioselectivity is
oped for the enyne cyclization and a high level of even more challenging in the case of unsymmetrical
chiral induction can be achieved in many cases.[3,4] substrates.[9a,16d]
The alternative synthetic strategy starting from dienes
An early example of asymmetric diene cycloisome-
´
(A) would seem to hold interesting potential as sever- rization was reported by Bogdanovic already in the
al achiral catalyst systems based on Ni,[5] Pd,[6] Pt,[7] 1970s. A cationic nickel complex bearing a menthyl-
Rh,[8] Ru,[9] and Ti,[10] were described, forming 5-mem- modified Horner phosphine was found to catalyze the
bered ring products B–D with high levels of chemo- cycloisomerization of 1,6-heptadiene (X=CH2) and
and regioselectivity/-selectivities (Scheme 1). Recent- diallyl ether (X=O) with optical yields up to 37%.[12]
ly, diene cycloisomerization combined with a second In 1998 Heumann et al. described the asymmetric cy-
transformation were also reported.[1c,11]
cloisomerization of diethyl diallylmalonate [X=C-
(CO2Et)2] with catalyst system based on
However, only very few examples for asymmetric
N
a
diene cycloisomerization were reported up to now [(CH3CN)2PdCl2]/2AgBF4 and either (R,R)-4,4’-di-
and enantioselectivities were far from synthetically benzylbisoxazoline or (À)-sparteine. Enantiomeric
useful levels. Furthermore, the scope of the reaction excess (ee) values up to 60% were achieved, albeit at
has been largely limited to unsubstituted dienes be- low conversions and regioselectivities.[13]
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Based on the mechanistic analogy between the benchmark substrate diethyl diallylmalonate (3) was
diene cycloisomerization and the hydrovinylation of converted to the desired chiral type B cyclopentene 4
olefins,[14–16] we have recently turned our attention to under the described conditions with an average turn-
Ni-based catalysts involving Wilkeꢀs azaphospholene over frequency (TOFav) of 144 hÀ1, a regioselectivity
all-(R)-1[17] and Cl-QUINAPHOS phosphoramidites of 91%, and an ee of 72% (Table 1, entry 2). An even
2[18] as ligands. Indeed, we found that systems based higher activity was observed with dimethyl diallylmal-
onate (5) as substrate (Table 1, entry 1), obtaining
91% conversion within one hour (TOFav of 182 hÀ1).
The regioselectivity towards the chiral exo-methylene-
cyclopentane 6 was almost perfect (97%), whereas a
small drop in enantioselectivity (67%) was observed
in comparison to the cycloisomerization of the diethyl
ester 3. Using the sterically more demanding di-tert-
butyl diallylmalonate (7) as the substrate, a slower re-
action was observed and a conversion of 55% was
reached within one hour at a catalyst loading of 0.7
mol%, corresponding to a TOFav of 77 hÀ1 (Table 1,
on these ligands and [Ni
catalysts for the asymmetric cycloisomerization of di- range as 3, whereas the enantioselectivity increased to
(cod)]+ afforded active entry 3). The regioselectivity of 89% was in the same
ACHRTUNEG(allyl)ACHTREUGN
ethyl diallylmalonate [X=CACHTRE(UNG CO2Et)2] and N,N-di-al- a remarkable 88% ee. This short series shows that in-
lyltosylamide (X=N-Ts).[19] The corresponding exo- creasing the steric bulk of the ester residues in diallyl-
methylenecyclopentanes of type B were formed in up malonates leads to reduced reactivity in the cycloiso-
to 80% ee for X=C
ACHTRE(UNG CO2Et)2 and up to 54% ee for merization, but to a significant enhancement of the
X=N-Ts, providing currently the best values for enantioselectivity.
these transformations. Beside promising enantioselec-
Next, we focused on the variation of the functional
tivities, also high activities (TOFs up to 158 hÀ1) and group of the carbon backbone. The cycloisomeriza-
almost perfect chemo- and regioselectivities towards tion of 4,4-hydroxymethyl-1,6-heptadiene (9) proceed-
the chiral products of type B could be obtained.
ed with an enantiomeric excess of 91% accompanied
In the present paper, we extend the scope of the with perfect regioselectivity (>99%) albeit at the ex-
system Ni/all-(R)-1 for symmetrical 1,6-dienes show- pense of catalyst activity. After one hour reaction
ing that unprecedented high enantioselectivities of up time and a catalyst loading of 5 mol% Ni, 39% of the
to 90% can be achieved in several cases. Furthermore, substrate was converted, corresponding to an average
we demonstrate for the first time the highly chemo- TOFav of 8 hÀ1. The activity was regained by protect-
and regioselective cycloisomerization of unsymmetri- ing the hydroxy functionalities by acetylation. Full
cally substituted 1,6-dienes and bisallylamines with conversion was achieved with substrate 11 after one
this catalytic system. Finally, the possibility of tandem hour. This corresponds to a lower limit of the TOFav
sequences involving asymmetric cycloisomerization as of at least 20 hÀ1 (Table 1, entry 5). However, the en-
À
initial C C bond-forming step is elucidated.
antiomeric excess dropped to 71%, being in the same
range as of that achieved with diethyl diallylmalonate
(3). We were pleased to find that both high enantiose-
lectivity and activity were attained using acetone as
protecting agent for the hydroxy functionalities. Sub-
strate 13 was fully converted within 1 hour at a cata-
lyst loading of 5 mol% (TOFav ꢀ20) with an enantio-
Results and Discussion
Cycloisomerization ofSymmetrical 1,6-Dienes
The catalyst system used in the present study was con- selectivity of 86% ee combined with a good regiose-
veniently prepared in situ from [Ni
ACHRTUNEG(allyl)ACHTRENUG
A
N
ACHTREUNG
in a ratio of 2/1, which corresponds to a P/Ni-ratio of application of the system Ni/all-(R)-1 to the formation
1. Catalyst loadings between 0.5 mol% and 5 mol% of pyrrolidinic derivatives from symmetrical bis-allyla-
were applied and the reactions carried out at room mines proved limited. For bisallylamine derivatives
temperature unless otherwise noted. First, unsubsti- 16a–d, only the tosylamide 16d could be cyclized ef-
tuted symmetrical diallylmalonates bearing different fectively using the Ni-based system to yield up to
ester groups were subjected to cycloisomerization. 54% ee.[19b] The unsubstituted as well as benzyl- and
Table 1 shows representative results from this study. BOC-protected amines showed no conversion. At-
With the exception of diallyl malonitrile (15), all sub- tempts to temporarily block the free amine group of
[20]
strates provided good to excellent yields of the corre- 16a with CO2 also did not lead to significant con-
sponding exo-methylenecyclopentanes of type B. The version. Interestingly, the BOC-protected substrate
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Stereoselective Nickel-Catalyzed Cycloisomerization of 1,6-Dienes
FULL PAPERS
[BARF]/all-(R)-1.[a]
Table 1. Cycloisomerization of symmetrical 1,6-dienes with [NiACHTER(UNG allyl)ACHERT(UNG cod)]ACHTREUNG
Entry
Substrate
Product
Conv. [%]
TOF [hÀ1]
Sel.[b] [%]
97%
ee[c] [%]
67 (+)
1
5
6
91
182
2
3
4
72
144
91
89
>99
83
87
-
72 (+)
88 (+)
91 (+)
71 (+)
86 (+)
-
3[d]
4[e]
5[e]
6[e]
7
8
55
77
9
10
12
14
-
39
8
11
13
15
>99
ꢀ20
>99
ꢀ20
7
no reaction
no reaction
[a]
Reaction conditions: 0.5 mol% [Ni
A
ACHRTUNEG(cod)]ACHTRE[UNG BARF], 0.25 mol% all-(R)-1, t=1 h, CH2Cl2, T=208C.
[b]
[c]
The ee values were determined either by chiral HPLC or NMR-spectroscopy of the derivatized products (see Supporting
Information).
0.7 mol% [Ni
[d]
[e]
G
A
ACHTRE[UNG BARF], 0.35 mol% all-(R)-1.
5 mol% [Ni(allyl)
A
A
ACHTREUNG
16c was cyclized with high yields using the achiral cat-
alytic system [{Pd(allyl)Cl}2]/NaBARF/PPh3
AHCTREUNG
(Scheme 2). So far, attempts to conduct this reaction
enantioselectively using all-(R)-1 as ligand were un-
successful.
Cycloisomerization ofUnsymmetrical 1,6-Dienes
The cycloisomerization of unsymmetrically substitut-
ed 1,6-dienes imposes additional challenges on the se-
lectivity control for a catalytic system. As shown in
Scheme 3, the addition of a catalytically active metal
Scheme 2. Cycloisomerization of bisallylamine derivatives.
hydride can occur either to the terminal or to the in- (Z)-configured product. On the other hand, addition
ternal double bond, thus distinguishing already in the of the nickel-hydride species to the higher substituted
first step of the catalytic cycle which type of products double bond would generate a product with an exocy-
can be formed. Addition to the terminal olefinic clic methylene group (Scheme 3, pathway B). Isomeri-
group leads to a cyclic product with a trisubstituted zation of these primary products can lead to isomers
double bond (Scheme 3, pathway A). In this case b- with internal double bonds in analogy to type C and
hydride elimination can result either in an (E)- or D shown in Scheme 1.
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Scheme 3. Cycloisomerization of unsymmetrical 1,6-dienes.
Very few examples of cycloisomerization are out to be lower (65%) compared with that obtained
known for unsymmetrical dienes with an aromatic with 19 (Table 2, entry 2). In addition to the main
substituent at the terminal carbon of one allyl moiety. product 22, two not fully assigned isomers were de-
Using [PdCl2ACHTREUNG(cod)Me]/AgBF4, Oh et al. succeeded tected via GC-MS, each with a GC yield slightly
converting (E)-phenyl-substituted diethyl diallylmalo- below 20%. Substrate 23 carrying electron-withdraw-
nate 19 into exo-benzylidenecyclopentane 20 with ing CF3 substituents at the aromatic group proved less
92% yield (pathway A).[21] Interestingly, the product reactive for the cycloisomerization and 61% conver-
was formed with complete (Z)-selectivity. With sion was obtained after 24 h (Table 2, entry 3).[23]
ACHTREUNG[(t-BuCN)2PdCl2] as catalyst, Lloyd-Jones and co- However, the selectivity towards 24 was again very
workers obtained a mixture (approx. 1:1) of 20 and high at 91%. The nitrophenyl substituted 25 did not
the corresponding cyclopentene product of type C.[16d] react at all under our standard conditions. This lack
By selecting the electronic properties of the substitu- of reactivity may be explained at least partly with the
ents in para-position of the phenyl group, they were deactivating effect exerted by electron-withdrawing
able to control product distribution. The main prod- groups already noticed for substrate 24. In accordance
ucts were arising from pathway A and exhibited also with the results of Oh[21] and Lloyd-Jones,[16d] the
exclusively (Z)-configured double bonds. Despite double bond showed exclusively (Z)-configuration for
their usually excellent substrate scope, ruthenium- all isolated main products.
based catalyst systems do not seem to be able to con-
(E)-Diethyl allylcrotylmalonate (26), carrying a
vert substrates with aromatic substituents at the methyl instead of an aryl group, resulted in a non-se-
double bond.[9]
lective cycloisomerization with [Ni
ACHRTUNEG(allyl)ACHTREUNG(cod)]-
The Heck reaction provides a convenient access to
ACHTRE[UNG BARF]/all-(R)-1. Five isomeric products with m/z=
the unsymmetrically aryl substituted 1,6-dienes shown 254 were detected in similar amounts after a reaction
in Table 2 (see Supporting Information). The expect- time of 24 h. The major product 27, which is formed
ed (E)-configuration of the substituted double bond with 32% selectivity, contains a terminal vinylic
was confirmed by NMR spectroscopic data. We were group. The driving force for this rearrangement may
pleased to find that the catalytic system [Ni
ACHTRE(UNG allyl)- be the release of ring strain within the five-membered
A
ACHTREUNG
gioselective cyclizations for a range of substrates, fur- Hence, in contrast to aryl-substituted substrates, a ter-
ther substantiating the synthetic potential of this cata- minal methyl substituent does not seem to be suffi-
lytic system.[22]
cient for determining a clear preference between the
(E)-Phenyl-substituted substrate 19 underwent cy- reaction pathways for the diethylmalonate substrates.
cloisomerization smoothly with 5 mol% [Ni(allyl)- Given the limited success with symmetric bisallyla-
(cod)][BARF] and 2.5 mol% all-(R)-1 and led to 20 mine derivatives, we were pleased to find that the
AHCTREUNG
A
ACHTREUNG
with complete conversion and very high regioselectiv- phenyl-substituted unsymmetrical substrate 28 was cy-
ity of 95% (Table 2, entry 1). The major product was clized very effectively. Again good selectivity towards
identified as the five-membered ring with an exocyclic the Z-configured exocyclic double bond was achieved
trisubstituted double bond, indicating that Pathway A providing 29 in approximately 71% yield. The allyl-
(Scheme 3) is predominant. Substrate 21 bearing an crotyltosylamide 30 was cyclized more smoothly than
(E)-para-methoxyphenyl substituent was also convert- the corresponding malonate 26 and with a fair regio-
ed quantitatively (>99%), but the selectivity turned selectivity. In accordance to the work by Song et al.[24]
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Stereoselective Nickel-Catalyzed Cycloisomerization of 1,6-Dienes
FULL PAPERS
Table 2. Cycloisomerization of unsymmetrical 1,6-dienes with [NiACTHRE(UNG allyl)ACRTHEUN(G cod)]ACHTREUNG
Entry
Substrate
Product
Sel.[b] [%]
95
1
19
21
20
22
>99
>99
2
65
3
4
23
25
24
61
-
91
-
no reaction
5
6
26
28
30
27
29
31
>99
>99
>99
32
71
58
7
[a]
Reaction conditions: 5 mol% [Ni
ACHTRE(UNG allyl)AHCERT(UNG cod)]ACHTREU[GN BARF], 2.5 mol% all-(R)-1, t=24 h, CH2Cl2, T=208C.
[b]
Selectivity towards the stated product. Enantioselectivity not determined.[22]
and analogously to 27, the major product 31, which is
The cycloisomerization/hydrogenation sequence
formed with 58% selectivity, contains a terminal vi- was chosen as a first benchmark transformation. The
nylic group.
hydrogenation of the cycloisomerization product 4 oc-
curred smoothly with a homogeneous as well as a het-
erogeneous catalyst (Scheme 4). The use of Wilkin-
Diastereoselective Transformation of
Cycloisomerization Products
sonꢀs complex [RhClACHTRE(NUG PPh3)3] as the homogeneous cat-
alyst precursor led to full conversion within 1 h at 5
mol% catalyst loading and 40 bar hydrogen pressure.
The resulting double bond in cycloisomerization prod-
ucts opens the possibility for further functionalization.
As the stereogenic center formed during the cycliza-
tion process is in an a-position to the double bond,
diastereoselective induction might occur in such pro-
cesses. Currently, there are only a few examples for
two-step processes based on diene cycloisomerization
and no information on the stereochemical integrity of
the chiral center is available.
Scheme 4. Diastereoselective hydrogenation of 4.
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The major product was the cis-configured dimethylcy- that obtained with BH3·SMe2 (Table 3, entry 4 vs.
clopentane 32 with a diastereoselectivity of 69%. entry 1). Surprisingly, 9-BBN led to a sharp decrease
Using palladium on charcoal as heterogeneous cata- in cis-selectivity (57%) although it is of a comparable
lyst under similar conditions, both full conversion and sterical bulk as thexylborane (Table 3, entry 5). The
an almost identical diastereoselectivity of 70% cis ee of the chiral center formed in the cycloisomeriza-
were achieved. In both cases the enantiomeric excess tion step was unaffected in all reactions.
of the starting material (71% ee) was retained in
trans-32 throughout the overall process.
The overall sequence of asymmetric cycloisomeriza-
tion/hydroboration/oxidative work-up converts direct-
Non-catalytic hydroboration[25] was carried out ly 1,6-dienes into hydroxymethylene substituted meth-
using 4 with an ee of 70% as starting material. A con- ylcyclopentanes comprising two adjacent chiral cen-
version of 83% was observed at room temperature ters. The transformation can be conveniently achieved
and with BH3·SMe2 as hydroborating agent after 1 h as one-pot procedure avoiding intermediate work-up
(Scheme 5, Table 3, entry 1). A diastereoselectivity of and isolation steps. To demonstrate this principle, di-
ethyl diallylmalonate (3) was transformed to 4 in di-
chloromethane with 5 mol% [NiCAHTRE(UNG allyl)ACHRET(UNG cod)]ACHTREU[NG BARF]/
Table 3. Diastereoselective hydroboration of cycloisomeriza-
tion products.[a]
all-(R)-1 at room temperature. After a reaction time
of 2 h, an excess of BH3·SMe2 was added directly to
the reaction mixture. After another 16 h at room tem-
perature, standard oxidative workup led to the de-
sired cyclcoisomerization/hydroboration product 33 in
full conversion and with a diastereoselectivity of 63%
for the cis-configuration. Also in the one-pot proce-
dure the more bulky thexyl borane led to 77% diaste-
reoselectivity but only 23% conversion was observed
(Scheme 5). The enantiomeric excess was not influ-
enced by the hydroboration step and showed a value
of 71%.
Entry
Borane
R
Conv.
Z/E
1
BH3·SMe2
BH3·SMe2
BH3·SMe2
thexylborane
9-BBN
Et
Et
t-Bu
Et
Et
83%
69/31
68/32
79/21
77/23
57/43
2[b]
3
>99%
>99%
37%
4
5
>99%
[a]
Reaction conditions: THF, t=1 h, T=208C.
t=16 h, T=À158C.
Conclusions
[b]
Highly enantioselective cycloisomerization of sym-
69% towards the cis-configured product 33 was de- metrical 1,6-dienes can be achieved with a catalyst
duced from NOESY spectra, indicating a borane system based on the ionic nickel-complex [Ni(allyl)-
[BARF] and the chiral ligand all-(R)-1. For
diallylmalonates as substrates, reactivity increases
ACHTREUNG
attack from the opposite side with respect to the
methyl group. Full conversion could be obtained at
ACHRTUNEG(cod)]ACHTRENUG
AHCTREUNG
À158C after 16 h reaction time, but no increase in se- with decreasing steric bulk in the ester function. An
lectivity was found upon lowering the reaction tem- average turnover frequency of 182 hÀ1 was obtained
perature (Table 3, entry 2). Increasing the steric bulk for dimethyl diallylmalonate (5) comparable to what
of the substrate was found to be beneficial for the re- can be achieved with the most active achiral catalysts.
activity and the diastereoselectivity. Compound 8 On the other hand, high steric bulk in the ester func-
bearing tert-butyl groups in the ester backbone was tions led to increased enantioselectivities reaching up
quantitatively converted to corresponding primary al- to 88% in case of di-tert-butyl diallylmalonate (7).
cohols 34 with 79% cis-selectivity (Table 3, entry 3). Very high stereoselectivities were also obtained for
The use of bulky thexylborane in the hydroboration 4,4-hydroxymethyl-1,6-heptadiene derivatives and for
of 4 resulted also in higher cis-diastereoselectivity the first time ees value of more than 90% were
(77%), but in lower activity (conversion: 37%) than reached for this transformation in case of substrate 9.
Scheme 5. One-pot cycloisomerization/hydroboration of diethyl diallylmalonate.
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Stereoselective Nickel-Catalyzed Cycloisomerization of 1,6-Dienes
FULL PAPERS
Unsymmetrical aryl-substituted 1,6-dienes can be General Procedure for a Typical Diastereoselective
successfully cycloisomerized with this catalytic system Hydroboration Reaction
as well providing high chemo- and regioselectivity for
various substrates. Diethyl diallylmalonate derivatives
A solution of 4 or 8 (0.2 mmol) in THF (5 mL) and the de-
sired borane (0.2 mmol) were mixed under inert gas condi-
19, 21, and 23 resulted in the selective formation of
exo-benzylidene cyclopentanes 20, 22, and 24, respec-
tively. The products showed exclusively (Z)-configura-
tion. Also the unsymmetrical derivatives of N,N-dial-
lyltosylamide 28 and 30 underwent cyclization to pro-
vide good yields of the five-membered heterocycles.
In addition, the possibility to incorporate the cyclo-
isomerization in multistep reaction sequences was
demonstrated. The asymmetric induction achieved
during the cycloisomerization step is fully retained in
the subsequent hydrogenation and hydroboration
even under one-pot conditions. The result of this
study underlines the synthetic potential of the nickel-
catalyzed cycloisomerization and to complement
other cyclization strategies based on dienes as sub-
strates such as ruthenium-catalyzed cycloisomeriza-
tion or ring-closing metathesis.
tions. The reaction mixture was stirred for 16 h and 1 mL
3MNaOH (aq) as well as 0.1 mL H O2 (70%) were added.
2
The reaction mixture was stirred for further 2 h and then ex-
tracted with CH2Cl2. The organic phase was washed with
water (3”2 mL), dried over sodium sulfate, and analyzed by
GC, GC-MS and NMR.
General Procedure for a Typical One-Pot
Cycloisomerization/Hydroboration Reaction
A solution of all-(R)-1 (0.03 mmol) in CH2Cl2 (5 mL) was
added at room temperature to a solution of [Ni
ACHRTUNEG(allyl)ACHTREUNG(cod)]-
AHCTREUNG
ditions. After 15 min, 3 (0.3 mmol) was added via syringe to
the yellow catalyst solution. After stirring for 2 h, the mix-
ture was diluted with 15 mL THF and the desired borane
(0.3 mmol) was added. After another 16 h, 1 mL 3MNaOH
(aqueous) as well as 0.1 mL H2O2 (70%) were added. The
reaction mixture was stirred for further 2 h and then extract-
ed with CH2Cl2. The organic phase was washed with water
(3”2 mL), dried over sodium sulfate, and analyzed by GC,
GC-MS and NMR.
Experimental Section
General Procedure for a Typical Cycloisomerization
Reaction
Supporting Information
Full details of the experimental procedures and analytical
data are available as Supporting Information.
A solution of all-(R)-1 (0.03 mmol) in CH2Cl2 (5 mL) was
added at room temperature to a solution of [Ni
ACHRTUNEG(allyl)ACHTRE(UGN cod)]-
ACHTREUNG
ditions. After 15 min, the desired amount of substrate was
added via syringe to the yellow catalyst solution. The reac-
tion mixture was stirred for the desired reaction time and
then quenched by adding aqueous ammonia (1 mL). The or-
ganic phase was washed with water (3”2 mL), dried over
sodium sulfate, and analyzed by GC and GC-MS. Further
details and modifications of the conditions are given in
Table 1 and Table 2.
For ee determination by chiral HPLC, the chlorinated sol-
vent was replaced by n-heptane/2-propanol and the solution
filtered through a pad of silica gel (for product 4).[19a] For ee
determination via 13C NMR, the cycloisomerization products
were reduced to 10 with 6 equiv. LiAlH4. The resulting com-
pound 10 (20 mg) was dissolved in CDCl3, treated with
0.1 mL anhydrous pyridine and 0.05 mL (À)-menthoxyacetyl
chloride. The resulting mixture was filtered through Flourisil
and analyzed by quantitative dept 45 13C NM R
(150 MHz).[26,27]
Acknowledgements
We are grateful to the Deutsche Forschungsgemeinschaft
(SFB 380) for financial support. C. B. thanks the Fonds der
Chemischen Industrie for a predoctoral fellowship. We also
thank Dr. J. Klankermayer for helpful discussions and K.
Woike as well as M. Küppers for technical assistance.
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General Procedure for a Typical Diastereoselective
Hydrogenation Reaction
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1080
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Adv. Synth. Catal. 2008, 350, 1073 – 1080