Journal of the American Chemical Society
Communication
byproduct. Under the same conditions using quinoline-based
La·FeCl2 as a precatalyst instead of pyridine-based OIP·FeCl2,
the alkene could be fully converted to 2a with 88% ee (entry
2). The use of more sterically hindered 2,6-diisopropyl imine
(Lb) improved the enantioselectivity to 99% ee (entry 3).
Further increasing the steric hindrance on imine (Lc) did
inhibit the reaction (entry 4). When the group on the
oxazoline was changed to an isopropyl group (Le), the reaction
went smoothly to afford 2a with >99% conversion and 99% ee
(entries 5 and 6). Without acetonitrile, the reaction could go
smoothly; however, 35% of the isomerization product was
observed, which indicated that acetonitrile could inhibit the
isomerization side-reaction (entry 7).10 Besides, the solid 3-
methoxybenzonitrile could play the same role as acetonitrile
(Table S1, in the Supporting Information). Without hydro-
silane, the reaction did not occur (entry 8). Without
hydrosilane and acetonitrile, the reaction could occur to access
2a in 27% yield and 99% ee with 27% yield of the isomerization
product (entry 9).11 Without hydrogen, the reaction could
occur with low conversion (entry 10), which demonstrated
that hydrosilane could promote the hydrogenation reaction
however with less efficiency. The use of methyl lithium instead
of NaBHEt3 as an activator could promote the reaction
smoothly to give 2a with >99% conversion and 99% ee (entry
11). The standard conditions were identified as entry 6.
With the optimized reaction conditions in hand, the
substrate scope of alkenes was shown in Scheme 3. All the
reactions could complete in 12 h. Both electron-rich and
electron-poor substituents on the phenyl ring, such as ether,
silyl ether, alkyl, amino, Bpin,12 thiol ether, and halides, could
be tolerated to deliver 2a−2m with excellent enantioselectiv-
eties (>92% ee). Due to the steric effect, this reaction of the
alkene with the ortho-methoxyphenyl group could occur
smoothly in the presence of 10 mol % of the catalyst to afford
2n with a slightly lower ee. The polycycles and heterocycles,
such as naphthyl (1o), indole (1p), and pyridine (1q), could
be also tolerated. The alkenes bearing linear and branched
purely aliphatic side chains (1r−1x) and phenyl (1y) were
easily converted to the corresponding products with 88−98%
ee. Moreover, the reactions of alkenes with the functional
groups such as amino (1z) and acetal (1aa, 1ab) on the alkyl
chain exclusively provided 2z−2ab with 96−97% ee.
Asymmetric hydrogenation of exocyclic alkene could give
2ac with 90% ee. The reactions of substrates bearing menthol,
borneol, adamantane, geraniol, and terpineol moieties
proceeded well to give 2ad−2ah with 95−97% ee which
indicated that this protocol could be potentially employed on
late-stage functionalization of alkenes containing the cores of
natural products and drug molecules. The highly enantiose-
lective hydrogenation of nonaryl 1,1-disubstituted alkenes is
still a big challenge in asymmetric alkene hydrogenation. The
iron-catalyzed asymmetric hydrogenation of a nonaryl
substrate could be converted to the nonaryl chiral alkane 2ai
with 42% conversion and 54% ee. This primary result would
encourage us to further develop more efficient chiral ligands to
solve this problem.
Scheme 2. Design and Synthesis of Chiral Quinoline-Based
Ligand and Its Iron Complex
hydrosilane. Additionally, acetonitrile has been known as an
efficient additive for improving the selectivity in iron-catalyzed
reductive reactions.10 By using OIP·FeCl2 as a precatalyst and
NaBHEt3 as an activator,11 the iron-catalyzed hydrogenation of
1,1-disubstituted alkene 1a under 1 atm of hydrogen gas in a
solution of toluene at room temperature afforded the
hydrogenation product 2a in 25% yield and 58% ee (entry 1,
Table 1), with 24% of isomerized trisubstituted alkene as a
a
Table 1. Optimization of the Reaction Conditions
yield of 2a/1a/3a
ee of 2a
b
b
entry catalyst
other changes
(%)
(%)
1
OIP·
FeCl2
25/51/24
58
2
3
4
5
6
7
8
9
La·FeCl2
Lb·FeCl2
Lc·FeCl2
Ld·FeCl2
Le·FeCl2
Le·FeCl2 no CH3CN
Le·FeCl2 no hydrosilane
Le·FeCl2 no CH3CN and
>99/0/0
98/0/2
2/98/0
88
99
98/0/2
97
99
96
>99/0/0
65/0/35
0/>99/0
27/46/27
99
hydrosilane
10
11
Le·FeCl2 no H2
10/89/1
>99/0/0
91
99
Le·FeCl2 MeLi instead of
NaBHEt3
To showcase the utility of this transformation, a gram-scale
reaction in the presence of 3 mol % of the iron complex could
be carried out smoothly to afford 2a with 98% yield and 98% ee
(Scheme 4a). By using the steric bulky catalyst Lb·FeCl2, the
reaction of 1aj containing two different carbon−carbon double
bonds afforded the 2aj in 95% yield and 93% ee in which a
trisubstituted alkene still remained (Scheme 4b). This unique
a
The reactions were conducted using alkene (0.5 mmol), H2 balloon,
hydrosilane (20 mol %), CH3CN (20 mol %), iron cat. (5 mol %),
b
NaBHEt3 (15 mol %), and toluene (1 mL) at rt for 12 h. The
conversions and recoveries were determined by 1H NMR using
TMSPh as an internal standard; ee values were determined by GC
using chiral column.
B
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX