A chiral borane catalyzed asymmetric hydrosilylation of imines

Article abstract of DOI:10.1039/c4ob02419b

An enantioselectiveusing a chiral borane catalyst generated by the in situ hydroboration of a binaphthyl-based chiral diene with Piers' borane HB(C₆F₅)₂ to furnish a variety of optically active amines in 70% to >99% yields

Full text of DOI:10.1039/c4ob02419b

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DOI: 10.1039/C4OB02419B
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ARTICLE TYPE
A Chiral Borane Catalyzed Asymmetric Hydrosilylation of Imines†
Xiaxia Zhu and Haifeng Du*a
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
asymmetric hydrogenation of imines, silyl enol ethers, and 2,3-
50 disubstituted quinoxalines.16 The borane catalysts
were
5
An enantioselective hydrosilylation of imines was successfully
achieved using a chiral borane catalyst generated by the in
situ hydroboration of a binaphthyl-based chiral diene with
Piers’ borane HB(C6F5)2 to furnish a variety of optically
active amines in 70->99% yields and 44-82% ee’s.
5
generated in situ by the hydroboration of binaphthyl-based chiral
dienes 4 with Piers’ borane (Scheme 2).17,18 Since the Si-H bond
activation is similar to H-H bond, we envisioned that boranes 5
would be also likely one class of effective catalysts for the
55 asymmetric hydrosilylation of imines. Herein, we reported our
efforts on this subject.
10 Catalytic hydrosilylation of unsaturated molecules represents a
very important and useful transformation in organic chemistry,
and numerous excellent metal or metal-free catalytic systems
have been well established.1-3 Among these methodologies, the
Piers type hydrosilylation has both synthetic and mechanistic
15 interest for chemists. In 1996, Piers and Parks reported a
B(C6F5)3-catalyzed hydrosilylation of carbonyl compounds, in
which the Lewis acid activated the silane instead of carbonyl
function.4 This Si-H bond activation by B(C6F5)3 was further
extended to the reduction of imines, the dehydrocoupling reaction,
20 the hydrosilylation of olefins, the deoxygenative hydrosilylation
of carbon dioxide, and the deoxygenation of carbohydrates.5
Interestingly, the Si-H bond activation in the hydrosilylation is
similar to the H-H bond activation in the latterly emerging
chemistry of frustrated Lewis pairs (FLPs).6,7 In 2010, Alcarazo
25 and co-workers described such a silane activation using the FLPs
of hexaphenylcarbodiphosphorane and B(C6F5)3.8 Recently, Erker
and co-workers also described a reversible heterolytic Si-H bond
activation by an intramolecular FLP.9 Despite these advances, the
first asymmetric version of this type of hydrosilylation was not
30 disclosed until 2008.10 Oestreich and co-workers reported a
B(C6F5)3-catalyzed hydrosilylation of acetophenone using a
chiral silane to afford the chiral alcohol with 38% ee.11 In a
later study, the combination of B(C6F5)3 and chiral silanes for
the reduction of imines gave racemic products.12 In 2012, the
35 authors also developed a novel borane 2a for the asymmetric
reduction of imines 1 using PhMe2SiH or chiral silanes to give
chiral amines with up to 62% ee (Scheme 1).13 Recently,
Klankermayer and co-workers employed the camphor derived
borane catalyst 2b for this asymmetric hydrosilylation of
40 imines. The borane 2b exhibited an extremely high catalytic
activity, but led a racemic product (Scheme 1).14 However,
the FLP catalysts 2c gave up to 87% ee (Scheme 1).14 The
Lewis base tri-tert-butylphosphine largely improved the
enantioselectivity but diminished the reactivity. However, the
45 development of highly reactive and enantioselective
hydrosilylation is still a challenge.
R2
R1
R2
R1
N
catalyst 2
HN
PhMe2SiH
*
Ar
Ar
1
3
H
B(C6F5)2
B(C6F5)2
THF
B
Ar'
tBu3PH
C6F5
Ar' = 2-Np or Ph
2a
2b
2c
M. Oestreich
J. Klankermayer
reaction time
17-120 h
2 h
96 h
up to 87 % ee
< 2% ee
ee up to 62% ee
Scheme 1 Representative asymmetric hydrosilylation of imines
60
Ar
Ar
previous work
asymmetric
hydrogenation
HB(C6F5)2
B(C6F5)2
B(C6F5)2
in situ
asymmetric
hydrosilylation
this work
Ar
Ar
5
4
Scheme 2 Chiral borane catalyst for asymmetric reactions
The asymmetric hydrosilylation of imine 1a with PhMe2SiH
was initially examined using 1 mol % of chiral dienes 4a-g and 2
65 mol % of Piers’ borane (Scheme 3). It was found that all these
reactions can proceed efficiently at 0 °C to give the desired amine
2a in quantitative conversions. Chiral dienes 4a-d bearing less
bulky substituents gave very low ee’s. The more bulky chiral
dienes 4e-g gave 51-58% ee’s. In sharp contrast to borane 2b
70 reported by Klankermayer and co-workers (Scheme 1),12 boranes
5 generated in situ from chiral dienes 4 gave a promising
enantioselectivity instead of racemic products, and additional
Lewis bases were unnecessary in the current catalytic system.
The reaction conditions including concentration, solvents,
75 temperature, and catalyst loading were carefully optimized to
further improve the enantioselectivities. It was found that the
As our interest in developing novel borane catalysts for the
FLP-catalyzed hydrogenation,15 very recently, we reported the
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reaction concentration had an obvious impact on the 35 conditions. As shown in Table 2, a wide range of imines 1 can be
enantioselectivities when chiral diene 4g was used, and 67% ee
was obtained at the concentration of 0.5 M (Table 1, entries 1-3).
However, for chiral diene 4f, such an improvement was not
observed. Solvents were found to affect the enantioseletivities
efficiently reduced to furnish the desired amines 3a-r in 70->99%
yields with 44-82% ee’s. Both electron-donaDtiOngI: 1a0n.d10w39it/hCd4rOawB0i2n4g19B
substituents on the para and/or meta positions of phenyl group
were well tolerant for this reaction (Table 2, entries 2-12). Imines
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5
obviously but have little influence on the reactivities, and C6H5F 40 derived from 1-(nathphthalen-2-yl)ethanones were suitable
proved to be a better solvent (Table 1, entries 4-9). Decreasing
the reaction temperature to -20 °C did not improve the
enantioselectivity (Table 1, entry 10). The catalyst loading can be
substrates (Table 2, entries 13 and 14). The reaction of imines
derived from phenylpropanones gave relatively lower ee’s (Table
2, entries 15 and 16). In particular, the asymmetric
hydrosilylation can be extended to the challenging
10 reduced to 0.5 mol % without loss of enantioselectivity, but a
longer reaction time was required (Table 1, entry 11). In fact, the 45 dialkylketoimine substrates to give reasonable yields and ee’s
asymmetric hydrosilylation of imine 1a using 1 mol % of borane
4g and Piers’ borane can be completed in 6.5 h (Table 1, entry
12). Moreover, silanes Ph3SiH and Ph2MeSiH were examined,
15 but no reaction was observed under the current conditions. The
substituents on the nitrogen atom of imines were also evaluated.
Electron-deficient groups such as 4-chlorophenyl and 4-
bromophenyl gave a very low reactivity (<10% conversion).
Several electron-rich groups (4-isopropoxylphenyl, 4-piperidin-1-
20 ylphenyl, and cyclohexanyl) gave a similar reactivity with the
PMP group but an obviously lower enantioselectivity (31-57%
ee’s).
(Table 2, entries 17 and 18).
Table 2 Chiral borane catalyzed asymmetric hydrosilylation of iminesa
Entry
Product (3)
Yield (%)b
Ee (%)c,d
PMP
HN
R
1
2
3a: R = H
3b: R = 4-Me
>99
99
99
>99
97
97
>99
96
>99
90
67
61
65
61
59
68
72
68
71
78
82
3
4
3c: R = 4-OMe
3d: R = 4-Ph
5
3e: R = 4-Br
6
3f: R = 3-Me
PMP
PMP
HB(C6F5)2 (2 mol %)
chiral diene 4 (1 mol %)
HN
Ph
N
7
8
3g: R = 3-OMe
3h: R = 3-Br
Ph
PhMe2SiH (1.1 equiv)
C6H5F, 0 °C, 15 h
3a
9
10
11
3i: R = 3,4-Me2
3j: R = 3,4-(OMe)2
3k: R = 3,4,5-(OMe)3
1a
R
96
4a: R = 4-Et
>99% conv, 23% ee
>99% conv, 22% ee
PMP
4b: R = 4-iPrO
HN
>99% conv, 20% ee
>99% conv, 22% ee
4c: 3,3'-(2-Np)2
4d: R = 2-OMe-5-iPr
O
O
4e: R = 3,5-tBu2
>99% conv, 51% ee
12
3l
>99
59
4f: R = 3,5-(TMS)2C6H3 >99% conv, 58% ee
4g: R = 3,5-tBu2C6H3
>99% conv, 54% ee
PMP
HN
R
Scheme 3 Evaluation of chiral dienes for asymmetric hydrosilylations
25 Table 1 Optimization of reaction conditionsa
Conc. (M)
R
13
14
3m: R = H
3n: R = OMe
>99
>99
71
74
Entry Solvent
Time (h) Conv (%)b Ee (%)c
PMP
HN
1
2
C6H5F
C6H5F
C6H5F
C6H5Cl
C6H5Br
Toluene
CH2Cl2
Et2O
0.25
0.5
1.0
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
15
15
15
15
15
15
15
15
15
24
21
6.5
>99
>99
>99
>99
>99
>99
>99
91
54
67
62
63
58
56
58
30
14
68
67
67
R
3
15
16
3o: R = H
3p: R = Me
>99
90
50
55
4
5
PMP
HN
6
7
8
9
Pentane
C6H5F
C6H5F
C6H5F
>99
87
17
3q
86
70
44
60
10 d
11e
12
PMP
HN
>99
>99
18e
3r
a All the reactions were carried out with imine 1a (0.50 mmol), PhMe2SiH
(0.55 mmol), chiral diene 4g (0.005 mmol), and Piers’ borane (0.010
a
All the reactions were carried out with imine 1 (0.50 mmol), PhMe2SiH
b
mmol) at 0 °C unless otherwise noted. The conversion was determined
(0.55 mmol), chiral diene 4g (0.005 mmol) and Piers’ borane (0.010
1
c
by crude H NMR. The ee was determined by chiral HPLC (Chiralcel
30 OD-H column). d At -20 °C. e 0.5 mol % of chiral diene 4g and 1.0 mol %
of Piers’ borane were used.
50 mmol) in C6H5F (1.0 mL) at 0 °C for 8 h unless otherwise noted. b Isolated
c
d
yield based on imine 1. The ee was determined by chiral HPLC. The
absolute configuration was determined as R except for entries 12,14, 16
and 18 by comparing the optical rotation or the retention time in HPLC
with the reported one. 2.5 mol % of chiral diene 4g and 5.0 mol % of
55 Piers’ borane were used, and the reaction time was 24 h.
e
The asymmetric hydrosilylation of imines
1 was next
investigated using chiral diene 4g under the optimal reaction
2 | Journal Name, [year], [vol], 00–00
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Organic & Biomolecular Chemistry
10 For a recent review, see: X. Feng and H. Du, Tetrehedron Lett., 2014,
55, 6959.
11 S. Rendler and M. Oestreich, Angew. Chem. Int. Ed., 2V0i0ew8,A4rt7ic,le59O9n7li.ne
DOI: 10.1039/C4OB02419B
Conclusions
65
70
75
80
85
90
In summary, a simple chiral borane catalyst generated in situ by
the hydroboration of a chiral diene 4g with Piers’ borane was
highly effective for the asymmetric hydrosilylation of imines to
furnish the desired optically active amines in 70->99% yields and
44-82% ee’s. It is noteworthy that the usage of highly reactive
chiral borane as a catalyst without addition of any other Lewis
bases can give promising enantioselectivies. Further efforts to
improve the enantioselectivity and expand the substrate type are
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5
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10 underway in our laboratory.
Acknowledgements
This work was supported by the National Science Foundation of
China (20802079, 21222207), the National Basic Research
Program of China (2011CB808600).
15 Notes and references
a
Beijing National Laboratory of Molecular Sciences, CAS Key
Laboratory of Molecular Recognition and Function, Institute of
Chemistry, Chinese Academy of Sciences, Beijing 100190, China. Fax:
0086-10-62554449;
18 (a) D. J. Parks, R. E. von H. Spence and W. E. Piers, Angew. Chem.
Int. Ed. Engl., 1995, 34, 809; (b) D. J. Parks, W. E. Piers and G. P.
A. Yap, Organometallics, 1998, 17, 5492.
Tel:
0086-10-62652117;
E-mail:
20 haifengdu@iccas.ac.cn
† Electronic Supplementary Information (ESI) available: The procedure
for the asymmetric hydrosilylation and the characterization and data for
the determination of enantiomeric excess of amine products along with
the NMR spectra. See DOI: 10.1039/b000000x/
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