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
&
4
&
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
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