Chiral hetero- and carbocyclic compounds from the asymmetric hydrogenation of cyclic alkenes

Article abstract of DOI:10.1002/chem.201104073

Several types of chiral hetero- and carbocyclic compounds have been synthesized by using the asymmetric hydrogenation of cyclic alkenes. N,P-Ligated iridium catalysts reduced six-membered cyclic alkenes with various substituents and heterofunctionality in good to excellent enantioselectivity, whereas the reduction of five-membered cyclic alkenes was generally less selective, giving modest enantiomeric excesses. The stereoselectivity of the hydrogenation depended more strongly on the substrate structure for the five- rather than the six-membered cyclic alkenes. The major enantiomer formed in the reduction of six-membered alkenes could be predicted from a selectivity model and isomeric alkenes had complementary enantioselectivity, giving opposite optical isomers upon hydrogenation. The utility of the reaction was demonstrated by using it as a key step in the preparation of chiral 1,3-cis-cyclohexane carboxylates. Copyright

Full text of DOI:10.1002/chem.201104073

FULL PAPER
DOI: 10.1002/chem.201104073
Chiral Hetero- and Carbocyclic Compounds from the Asymmetric
Hydrogenation of Cyclic Alkenes
J. Johan Verendel,[a] Jia-Qi Li,[a] Xu Quan,[a] Byron Peters,[a] Taigang Zhou,[a]
Odd R. Gautun,[b] Thavendran Govender,[c] and Pher G. Andersson*[a, c]
Abstract: Several types of chiral
hetero- and carbocyclic compounds
have been synthesized by using the
asymmetric hydrogenation of cyclic al-
kenes. N,P-Ligated iridium catalysts re-
duced six-membered cyclic alkenes
with various substituents and hetero-
functionality in good to excellent enan-
tioselectivity, whereas the reduction of
five-membered cyclic alkenes was gen-
erally less selective, giving modest
enantiomeric excesses. The stereoselec-
tivity of the hydrogenation depended
more strongly on the substrate struc-
ture for the five- rather than the six-
membered cyclic alkenes. The major
enantiomer formed in the reduction of
six-membered alkenes could be pre-
dicted from a selectivity model and iso-
meric alkenes had complementary
enantioselectivity, giving opposite opti-
cal isomers upon hydrogenation. The
utility of the reaction was demonstrat-
ed by using it as a key step in the prep-
aration of chiral 1,3-cis-cyclohexane
carboxylates.
Keywords: asymmetric synthesis ·
heterocyclic compounds · homoge-
neous catalysis · hydrogenation · iri-
dium
Introduction
give access to a broad spectrum of chiral cyclic building
blocks if appropriate catalysts were available (Scheme 1).
Chiral hetero- and carbocycles are used in almost every
field of chemistry. They are frequently encountered in, for
example, pharmaceuticals,[1] natural products,[2] fragrances,[3]
and molecular switches,[4] as well as in catalysts[5] and chiral
auxiliaries[6] for organic synthesis. Thus, methods for their
enantioselective synthesis are valuable tools for organic
chemists. However, the wide range of structural motifs pres-
ent in chiral hetero- and carbocycles complicates the devel-
opment of general synthetic methods for their production.
The asymmetric hydrogenation by using hydrogen gas and
a chiral homogeneous catalyst is a powerful tool in organic
synthesis[7] and has potential in the enantioselective synthe-
sis of cyclic molecules, because it is among the most general,
atom-efficient, and selective methods for producing chiral
compounds.[8] Therefore, asymmetric hydrogenation could
Scheme 1. General scheme to access chiral heterocycles through the
asymmetric hydrogenation of cyclic alkenes.
Several catalytic systems for the asymmetric hydrogena-
tion of functionalized cyclic alkenes have been reported. For
example, the hydrogenation of 1-aza-2-cycloalkene carboxy-
lates with rhodium and ruthenium catalysts has yielded
chiral 1- or 2-substituted piperidines and piperazines highly
selectively.[9] Zhang and co-workers have reported the asym-
metric hydrogenation of b-acetylamino acrylonitriles[10] and
the group of Szçllçsi has performed enantioselective hydro-
genation of carboxylate-substituted 3,4-dehydropiperi-
dines[11] and 5,6-dihydro-2H-pyrans.[12] Non- or weakly func-
tionalized cyclic alkenes, however, have been much less ex-
[a] J. J. Verendel, J.-Q. Li, X. Quan, B. Peters, T. Zhou,
Prof. P. G. Andersson
Department of Biochemistry and Organic Chemistry
Uppsala University
Box 576, S-75123, Uppsala (Sweden)
Fax : (+46)18-471-3705
plored. N,P-Ligated iridium complexes of the form [Ir
ACHTUNGTRENNUNG(cod)
(N\P)]+A[BArF]ꢀ (cod=1,5-cyclooctadiene, [BArF]ꢀ =[(3,5-
CTHUNGTRENNUNG
(F3C)2-C6H3)4B]ꢀ), originally developed and investigated as
asymmetric hydrogenation catalysts by Pfaltz and co-work-
ers,[13] are especially promising for this purpose, because
they can selectively and efficiently add dihydrogen to un-
functionalized double bonds[14] without relying on a vicinal
metal-coordinating group to direct the stereochemistry.[15]
Zhou and co-workers used iridium complexes of spiro phos-
phoramidite to hydrogenate cyclic N-alkyl enamines in high
selectivity;[16] however, only five-membered a-substituted
E-mail: pher.andersson@biorg.uu.se
[b] Dr. O. R. Gautun
Department of Chemistry
Norwegian University of Science and Technology (NTNU)
NO-7491, Trondheim (Norway)
[c] Prof. T. Govender, Prof. P. G. Andersson
School of Chemistry, University of KwaZulu-Natal
Durban, (South Africa)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201104073.
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enamides were used. Takaya and co-workers discovered that
Ru–BINAP (BINAP=2,2’-bis(diphenylphosphino)-1,1’-bi-
naphthalene) reduced 2-methyl-3,4-dihydrofuran in good se-
lectivity while studying the hydrogenation of alkenes bear-
ing adjacent oxygen functionalities.[17]
In an initial study, we reported the iridium-catalyzed
asymmetric hydrogenation of cyclic alkenes containing
tosyl-protected amines.[18] These were easily obtained from
ring-closing metathesis and hydrogenation by using N,P-li-
gated iridium catalysts and selectively yielded tosyl-protect-
ed chiral pyrrolidines, piperidines, and azepanes, typically in
greater than 90% ee (Scheme 2). Our report was the first on
Scheme 2. The iridium-catalyzed hydrogenation of five-, six-, and seven-
membered cyclic alkenes containing an N-Ts heterofunctionality.[18]
Figure 1. The ligands and the corresponding catalysts used in this study.
the asymmetric hydrogenation of cyclic alkenes of this type
and the methodology allowed easy access to azacycles with
chiral centers distal to the N atom (Scheme 2).
fluorides.[23] The ligands in catalyst class 2, with bicyclic
We have now expanded this study to the asymmetric hy-
drogenation of a broader range of prochiral cyclic alkenes
to better understand which substrates can be hydrogenated
to optically active compounds in high selectivity and with
which catalysts. We have been striving towards revealing the
substrate tolerance, mechanistic considerations, and synthet-
ic utility of the reaction. Several types of prochiral alkenes,
of which the majority has not previously been used in asym-
metric hydrogenation, including dihydropyrans, cyclic malo-
nate esters, and unsaturated lactones, have been reduced
highly selectively. Based on the results of this study and a se-
lectivity model,[19] we also propose a mnemonic device that
correctly predicts the absolute configuration of the resulting
chiral heteroalkane. The synthesis methodology was also ap-
plied in the preparation of 1,3-cis-cyclohexane carboxylates.
backbones and PACHTNGUTERNNU(G o-tol)2 P donors, are more sterically de-
manding than the ligands of class 1. These catalysts derive
their chirality from amino acids and have been applied to
the iridium-catalyzed asymmetric hydrogenations of
imines,[24] enamines,[25] and vinyl boronates.[26]
3,4-Unsaturated cyclic alkenes: Our initial study showed
that several 3-substituted-3,4-dehydropiperidines could be
reduced very effectively and stereoselectively, though the
optimal catalyst varied with the alkene substituent (Table 1,
entries 1a–g).[18] Alkenes bearing aromatic substituents (en-
tries 1a–d) were most effectively reduced by using the less
bulky, open-backbone ligands of class 1. Notably, the cata-
lyst based on electron-rich ligand 1C gave better yields and
ee values than 1A for the reduction of alkenes with elec-
tron-withdrawing aryl substituents, whereas the opposite
was true for 3,4-unsaturated azacycles bearing electron-rich
aryl groups. Alkenes with non-aryl substituents (Table 1, en-
tries 1e–j) were reduced faster and more selectively by cata-
lysts of which the ligands had bicyclic backbones (class 2).
The same reactivity pattern that was observed for 3-substi-
tuted-3,4-dehydropiperidines also applied to 3-substituted
5,6-dihydro-2H-pyrans (Table 1, entry 2). The 5,6-dihydro-3-
phenyl-2H-pyran was hydrogenated in excellent conversion
and enantioselectivity by using the catalyst with ligand 1A
(Table 1, entry 2a). Although this catalyst was also effective
in the hydrogenation of the 3-benzyl and 3-hydroxymethyl
analogues, these substrates were hydrogenated more selec-
tively when the catalyst was based on ligand 2C. 3,4-Unsatu-
rated carbocycles were also tested in asymmetric hydrogena-
tion. Malonates (entry 3), spirocyclic ketals (entry 4), and
ethers (entry 5) were enantioselectively reduced by using
catalysts based on ligands 1A and 1B (compare entries 1a
Results and Discussion
The substrates studied here, which include carbo-, aza-, and
oxacycles, possess a range of electronic and steric properties,
and we therefore examined an array of iridium-based hydro-
genation catalysts (Figure 1). Catalyst class 1 consists of the
sterically similar ligands A–D. Ligands 1A and 1B, in which
the coordinating N atom is part of a thiazole moiety, have
been used for the asymmetric hydrogenation of unfunction-
alized olefins, including sterically demanding substrates,
such as trisubstituted 1,1-diarylolefins,[20] vinyl phospho-
nates,[21] and vinyl silanes.[22] In ligands 1C and 1D, the coor-
dinating N atom is part of an imidazole ring and thus, is
more electron-rich than the thiazole nitrogen, producing
more electron-rich, less acidic catalysts that are suitable for
acid-sensitive substrates, such as allylic alcohols and vinyl
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Asymmetric Hydrogenation of Cyclic Alkenes
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Table 1. Iridium-catalyzed asymmetric hydrogenation of 3,4-unsaturated six-mem-
bered hetero- and carbocycles.
their higher ring strain and lower steric demands. A
similar trend of decrease in selectivity when going
from six- to five-membered rings has been observed
by Pfaltz and co-workers when performing asym-
metric hydrogenations of tetrasubstituted cyclic ole-
fins.[28] The excellent selectivities observed for cyclic
malonates (Table 2, entries 3a and b), which con-
tain the sterically more demanding carbocycle
moiety, suggest that the size of the heterofunction-
ality significantly affects the selectivity in the asym-
metric hydrogenation of five-membered 3,4-unsatu-
rated cyclic compounds.
Entry
R
Ligand
Conv.[a] [%]
ee[b] [%]
a[d]
b[d]
c[d]
d[d]
Ph
1A
1A
1C
1C
2A
1B
2A
2A
2C
2C
2B
1A
2C
2C
1A
1B
>99
>99
94
74
99
97
97
>99
80
96
>99 (+)
99 (+)
98 (+)
96 (+)
4-MeOC6H4
4-ClC6H4
4-F3CC6H4
97 (ꢀ) (S)
e[d]
Me
1[c]
70 (+) (R)
92 (ꢀ) (R)
97 (ꢀ) (S)
87 (ꢀ)
f[d]
g[d]
h
Bn
CH2OH
CH2OAc
iPr
OP(O)
Ph
CH2OH
Bn
Ph
To further investigate this hypothesis, a dihydro-
i
66 (ꢀ)
pyrrole with
a bulky diphenylacetyl protecting
j[e]
a
(OEt)2
94
98 (+)
group (entry 4) instead of a tosyl group (entry 1b)
was prepared. Although no significant improvement
was observed when using the catalyst containing
ligand 2C, the one based on ligand 1B gave the re-
duced alkene in 80% ee, as compared to 21% ee
for the N-tosyl derivative.
Overall, the nature of the heterofunctionality had
little effect on the asymmetric hydrogenation of six-
membered cyclic olefins, because excellent enantio-
selectivities were obtained for most of these sub-
strates. However, the presence of very sterically de-
manding alkene substituents, such as iPr, decreased
selectivity (Table 1, entry 1i). The heterofunctionali-
ty had a greater impact on the asymmetric hydroge-
nation of olefins in five-membered rings; the bulky
dimethylmalonate functionality gave the best re-
sults. This group likely inhibited inverted substrate
coordination, thereby favoring stereoselectivity.
>99
>99
99
48
98
>99 (+)
96 (ꢀ) (R)
92 (+)
2[c]
b
c
a
b
>99 (ꢀ)
3[f,g]
Me
98 (ꢀ)
a
b
Ph
Me
1A
1B
>99
86
>99 (+)
96 (ꢀ)
4[f]
a
b
Ph
Me
1A
1B
>99
>99
>99 (+)
94 (ꢀ)
5[f]
Reaction conditions: substrate (0.25m) in CH2Cl2, 15 h, RT. [a] Determined by
1H NMR spectroscopy; see the Supporting Information for details. [b] Determined by
chiral chromatography; see the Supporting Information for details. [c] Catalyst
(0.5 mol%), H2 (50 bar). [d] See ref. [18] [e] Catalyst (5 mol%), H2 (50 bar). [f] Cata-
lyst (1 mol%), H2 (100 bar). [g] E=COOMe.
and 1e). Catalysts based on ligands from class 2 were less
active for the hydrogenation of these alkenes and generally
gave lower selectivity.
Chiral cyclic 3-substituted malonates give access to 3-sub-
stituted cyclohexane esters in high cis selectivity after decar-
boxylation and subsequent thermodynamic equilibration
(Scheme 3). Krapcho and Weimaster reported that 3-meth-
Table 2. The iridium-catalyzed hydrogenation of five-membered 3,4-un-
saturated hetero- and carbocycles.
Entry
1[c]
R
Ligand
Conv.[a] [%]
ee[b] [%]
a
b
c
Ph
Me
Bn
1B
2C
2C
99
>99
>99
85 (ꢀ)
44 (+)
54 (+)
2[c]
Ph
1B
>99
65 (+)
Scheme 3. Preparation of cis-3-substituted cyclohexane carboxylates from
a
b
Ph
Me
1B
1B
99
99
99 (ꢀ)
93 (ꢀ)
chiral cyclic malonates.[27]
3[c]
ylcyclohexane methylcarboxylate could be obtained in 83%
cis and 17% trans form after thermodynamic equilibration
with a base.[27] By using their protocol, we obtained 98% of
the cis diastereomer for the 3-phenyl analogue.
The asymmetric hydrogenation of five-membered 3,4-un-
saturated hetero- and carbocycles was also tested. Generally,
these alkenes were reduced faster, but less selectively than
their six-membered counterparts (Table 2), likely owing to
2C
1B
69
40
47 (ꢀ)
80 (+)
4[d]
Me
Reaction conditions: substrate (0.25m) in CH2Cl2, H2 (50 bar), 15 h, RT.
[a] Determined by 1H NMR spectroscopy; see the Supporting Informa-
tion for details. [b] Determined by chiral chromatography; see the Sup-
porting Information for details. [c] Catalyst (0.5 mol%). [d] Catalyst
(1 mol%).
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P. G. Andersson et al.
2,3-Unsaturated cyclic alkenes: Next, we evaluated the hy-
drogenation of cyclic alkenes with a heteroatom or a substi-
tuted carbon atom bound directly to the olefin. These sub-
strates proved more difficult to reduce than their 3,4-unsatu-
rated counterparts and often had to be reduced under harsh-
er conditions. Two phenyl-substituted olefins, N-tosyl-3-
phenyl-2,3-dehydropiperidine and 5-phenyl-3,4-dihydro-2H-
pyran (Table 3, entries 1a and 2), were reduced in low enan-
have developed a rhodium-based system that yields 3-substi-
tuted cyclic ketones in moderate to good selectivity,[31] but
iridium catalysts have not proven efficient in this reaction.
We obtained the targeted 3-substituted ketones and lactones
in high selectivity by using catalysts bearing the electron-
rich ligand 1D (Table 3, entries 4 and 5). In the reduction of
3-phenylcyclohex-2-enone, the reaction did not proceed
cleanly when performed in CH2Cl2. Using simple alcohols
(MeOH, EtOH, and iPrOH) as solvents gave very low con-
version (<10%) of the starting material. However, when
the more acidic alcohol 2,2,2-trifluoroethanol was used as
solvent, the reaction proceeded satisfactorily, yielding only
the desired 3-phenylcyclohex-1-one, fast and in high enan-
tioselectivity (Table 3, entry 4a). For the methyl and butyl
derivatives, however, the reaction was slower and less selec-
tive when performed in 2,2,2-trifluoroethanol compared to
CH2Cl2.
Table 3. The iridium-catalyzed hydrogenation of six-membered, 2,3-unsa-
turated hetero- and carbocycles.
Entry
1[c]
R
Ligand Conv.[a] [%] ee[b] [%]
1A
2A
2A
20
21
90
rac.
64 (+)
89 (+) (R)
a
Ph
b
c
Me
OP(O)
Finally, we attempted the hydrogenation of cyclic five-
membered 2,3-unsaturated hetero- and carbocycles
(Table 4). Good selectivities were obtained for the phenyl-
N
decomposition
1A
1B
39
29
64 (ꢀ)
81 (ꢀ)
2[c]
Ph
3[d]
Ph
1D
40
66 (ꢀ) (S)
Table 4. The iridium-catalyzed hydrogenation of five-membered, 2,3-un-
saturated hetero- and carbocycles.
a[e] Ph
b[f] Me
c[f] Bu
1D
1D
1D
>99
>99
47
94 (ꢀ) (S)
92 (ꢀ) (S)
88 (ꢀ) (S)
4
Entry
1[c]
R
Ligand
Conv.[a] [%]
ee[b] [%]
90 (ꢀ)
a
b
Ph
Me
1D
1D
15
99
93 (+) (S)
79 (ꢀ) (S)
5[g]
Ph
1C
>99
Reaction conditions: substrate (0.25m) in solvent, RT. [a] Determined by
1H NMR spectroscopy; see the Supporting Information for details.
[b] Determined by chiral chromatography; see the Supporting Informa-
tion for details. [c] CH2Cl2, catalyst (0.5 mol%), 15 h, H2 (50 bar).
[d] CH2Cl2, catalyst (1 mol%), 15 h, H2 (50 bar). [e] 2,2,2-trifluoroetha-
nol, catalyst (1 mol%), 24 h, H2 (100 bar). [f] CH2Cl2, catalyst (1 mol%),
24 h, H2 (50 bar). [g] CH2Cl2, catalyst (1 mol%), 24 h, H2 (100 bar).
a
b
Ph
Me
2B
2C
20
24
92 (ꢀ) (R)
85 (ꢀ) (S)
2[d]
1
Conditions: substrate (0.25m) in CH2Cl2, RT. [a] Determined by H NMR
spectroscopy; see the Supporting Information for details. [b] Determined
by chiral chromatography; see the Supporting Information for details.
[c] Catalyst (1 mol%), 15 h, H2 (50 bar). [d] Catalyst (1 mol%), 24 h, H2
(100 bar).
tioselectivity by the catalyst containing ligand 1A, which
had performed well for the phenyl-substituted 3,4-unsaturat-
ed hetero- and carbocycles. Better selectivities were ob-
tained by using ligands 2A and 1B, although the ee values
remained modest. The 3-methyl derivative (entry 1b) was
reduced in 89% ee. We also attempted the hydrogenation of
substituted furan (entry 1) and unsaturated lactones
(entry 2), although the later were reduced very slowly. Five-
membered cyclic enones were essentially inert to these reac-
tion conditions.
a
phosphate enol ether (entry 1c; compare Table 1,
entry 1j), but when this leaving group was present on the
alkene, N-tosylpiperidine was obtained as the only reaction
product.
Origin of enantioselectivity: The reduction of a 3-substituted
3,4-unsaturated six-membered heterocycle gives the oppo-
site enantiomer than the reduction of the isomeric 2,3-unsa-
turated heterocycle. For instance, the asymmetric hydroge-
nation of N-tosyl-3-methyl-3,4-dehydropiperidine (Table 1,
entry 1e) by using the catalyst deriving from ligand 2A
gives the chiral product in the (S) configuration, whereas N-
tosyl-3-methyl-2,3-dehydropiperidine (Table 3, entry 1b)
yields the same product, but in the (R) configuration. This
complementary reaction pattern is especially useful, because
the iridium catalyst containing ligand 2A derives its chirality
from tert-leucine, therefore, one catalyst enantiomer is con-
siderably cheaper to produce than the other. Thus, it is for-
The asymmetric hydrogenation of one a-substituted en-
amide (Table 3, entry 3) was also tested, but the conversion
and selectivity of this reaction were as disappointing as
those obtained for the b-substituted enamides. The hydroge-
nations of a,b-unsaturated cyclic ketones and lactones were
also performed. Although high enantioselectivities have
been obtained in the transfer hydrogenation of this type of
alkenes,[29] their direct catalytic hydrogenation is less effi-
cient and the few examples reported to date have shown
modest selectivity.[30] Scheuermann nꢁe Taylor and Jaekel
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Asymmetric Hydrogenation of Cyclic Alkenes
FULL PAPER
tunate that both enantiomers of the product can be obtained
from the same catalyst by using isomeric alkene substrates.
This is likely owing to the substrate coordination modes
shown in Figure 2. Several groups have suggested that the
catalyst–alkene complex that exists prior to the enantiode-
termining migratory insertion has the structure shown in
Figure 2a (drawn for simplicity with ethene as the al-
because it is occupied by the R group of the ligand hetero-
cycle (see Figure 1). The ligand also contributes some steric
bulk to quadrant ii, whereas quadrants i and vi are largely
unhindered. The bicyclic ligands present in catalyst class 2
have a different shape and therefore, produce a different
chiral environment (Figure 2b, right) than those in catalyst
class 1. Here, quadrant i is occupied by the R group of the
A
heterocycle and consequently most hindered; the PACHTUNGTRENNUNG(o-tol)2
op a selectivity model that predicts the absolute configura-
tion of an alkane produced by these hydrogenation catalysts
and this model is based on the optimal coordination of a tri-
substituted alkene to the catalytic pocket.[19] In the model
shown in Figure 2b, the coordination of a trisubstituted
alkene is most favorable when the hydrogen of the alkene is
positioned in the most encumbered quadrant. In the case of
ligand class 1 (Figure 2b, left), quadrant iii is most hindered,
group contributes some bulk to quadrant iv. As a result,
these two catalysts generate the opposite heterocycloalkane
enantiomer upon alkene hydrogenation (Figure 2c). This is
clear, for example, from the reductions of N-tosyl-3-methyl-
3,4-dehydropiperidine (Table 1, entry 1e) and N-diphenyl-
AHCTUNGTREGaNNUN cetyl-3-methyl-2,5-dihydropyrrole (Table 2, entry 4). The
ꢀ ꢀ
sign of the quasi-dihedral angle q between the N Ir P
plane and the R group of the ligand (measured from the po-
sition of the incoming alkene;
Figure 2b) can be used to deter-
mine the absolute configuration
of the reaction product. This
has been demonstrated for the
hydrogenation of various trisub-
stituted alkenes by using a large
number of N,P-ligated iridium-
catalysts.[19a] Hence, the reduc-
tion of a 3,4-unsaturated cyclic
alkene by a catalyst deriving
from ligand 1A (q<0) produ-
ces one enantiomer of an
alkane and the reduction by
a catalyst deriving from ligand
2B (q>0) gives the other. This
model can be used as a mne-
monic device to predict the ab-
solute configuration of alkanes
produced from the asymmetric
hydrogenation of six-membered
heterocyclic
ure 2c).
alkenes
(Fig-
Unfortunately, low selectivity
and a lack of relevant configu-
ration data in the literature pre-
clude the evaluation of this
model in the asymmetric hydro-
genation of unsaturated five-
membered heterocycles. None-
theless, it is clear that 3-phenyl-
2,5-dihydrofuran
(Table 2,
entry 2) and 4-phenyl-2,3-dihy-
drofuran (Table 4, entry 1) give
opposite enantiomers upon
asymmetric hydrogenation.
Figure 2. Model explaining the selectivity of the heterocycle hydrogenation. Z=H2 or solvent. a) Catalyst–
alkene complex prior to migratory insertion, b) structure of the open coordination site on the catalyst, as
viewed from the perspective of the incoming alkene (some hydrogen atoms have been omitted for clarity),
and c) selectivity model for the asymmetric hydrogenation of six-membered heterocyclic alkenes.
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P. G. Andersson et al.
Penne, Chiral Auxiliaries and Ligands in Asymmetric Synthesis,
Wiley, New York, 1995.
Conclusion
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Experimental Section
General procedure for the asymmetric hydrogenation of olefins: A vial
was charged with a magnetic stirrer bar, substrate (0.25m), iridium cata-
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apparatus and the system was purged three times with Ar and then filled
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1H NMR spectroscopy. The crude product was filtered through a short
plug of silica gel and the ee value was determined by using chiral GC or
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Asymmetric Hydrogenation of Cyclic Alkenes
FULL PAPER
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Received: December 30, 2011
Published online: && &&, 0000
Chem. Eur. J. 2012, 00, 0 – 0
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www.chemeurj.org
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These are not the final page numbers!

P. G. Andersson et al.
Several types of chiral hetero- and car-
bocyclic compounds have been synthe-
sized by asymmetric hydrogenation of
cyclic alkenes by using N,P-ligated iri-
dium catalysts (see scheme). Six-mem-
bered cyclic alkenes were reduced in
good to excellent selectivity, whereas
the reduction of five-membered cyclic
alkenes was generally less selective.
The major enantiomer formed could
be predicted from a selectivity model
and isomeric alkenes gave complemen-
tary enantioselectivity.
Asymmetric Hydrogenation
J. J. Verendel, J.-Q. Li, X. Quan,
B. Peters, T. Zhou, O. R. Gautun,
T. Govender,
P. G. Andersson* ............. &&&& — &&&&
Chiral Hetero- and Carbocyclic
Compounds from the Asymmetric
Hydrogenation of Cyclic Alkenes
&
8
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www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!