Kinetic Resolution of α-Hydroxy-Substituted Oxime Ethers by Enantioselective Cu?H-Catalyzed Si?O Coupling

Article abstract of DOI:10.1002/anie.201802947

A catalyst-controlled enantioselective alcohol silylation by Cu?H-catalyzed dehydrogenative Si?O coupling of hydroxy groups α to an oxime ether and simple hydrosilanes is reported. The selectivity factors reached in this kinetic resolution are generally high (s≈50), and these reactions thereby provide reliable access to highly enantioenriched α-hydroxy-substituted oxime ethers. The synthetic usefulness of these compounds is also demonstrated.

Full text of DOI:10.1002/anie.201802947

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Accepted Article
Title: Kinetic Resolution of alpha-Hydroxy-Substituted Oxime Ethers by
Enantioselective Cu-H-Catalyzed Si-O Coupling
Authors: Xichang Dong, Yuji Kita, and Martin Oestreich
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201802947
Angew. Chem. 10.1002/ange.201802947
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Angewandte Chemie International Edition
10.1002/anie.201802947
COMMUNICATION
Kinetic Resolution of α-Hydroxy-Substituted Oxime Ethers by
Enantioselective Cu–H-Catalyzed Si–O Coupling
Xichang Dong, Yuji Kita, and Martin Oestreich*
Dedicated to Professor Larry E. Overman on the occasion of his 75th birthday
Abstract: A catalyst-controlled, enantioselective alcohol silylation by
Cu‒H-catalyzed dehydrogenative Si‒O coupling of hydroxy groups α
to an oxime ether and simple hydrosilanes is reported. The
selectivity factors reached in this kinetic resolution are generally high
(
s
≈
50), thereby providing
a
reliable access to highly
enantioenriched α-hydroxy-substituted oxime ethers. Their synthetic
usefulness is also demonstrated.
[1]
Methods for the kinetic resolution of alcohols by silylation have
[
2]
advanced tremendously in recent years. Based on an early
effort by Ishikawa and co-workers, several classes of largely
cyclic monools have been resolved with chlorosilanes using
chiral catalysts containing an imine-type nitrogen donor atom.
Also, imidazoles with chiral substituents that allow for the
Scheme 1. Cu‒H-catalyzed kinetic resolution of unbiased benzylic and allylic
alcohols. (R,R)-Ph-BPE = 1,2-bis((2R,5R)-2,5-diphenylphospholan-1-yl)ethane.
s = selectivity factor.
[
12]
[
3]
[
4]
preorganization of the alcohol through either hydrogen bonding
Oxime ethers 1 were chosen as model substrates (Table 1).
Our study commenced with oxime methyl ether 1a, and its E/Z
isomers were separated by flash column chromatograph on
silica gel. Considering the possibility of two-point binding of the
catalyst involving the oxime nitrogen atom of (E)-1a, we decided
to initially focus on (Z)-1a. We subjected (Z)-1a to our
[5]
or reversible covalent bonding have been employed in the
regioselective kinetic resolution of 1,2-diols. Our approach rests
on dehydrogenative coupling of hydrosilanes and alcohols
[6]
catalyzed by transition-metal hydrides, “Cu–H” in particular.
[7]
[8]
However, diastereo- as well as enantioselective variants
require an additional nitrogen atom in the proximity of the
hydroxy group to coordinate to the catalyst. This serious
limitation was recently overcome by the identification of
[9]
established
kinetic
resolution
recipe,
that
is
CuCl/NaOtBu/(R,R)-Ph-BPE and Bu
3
SiH (cf. Scheme 1). After
stirring for five days at room temperature in toluene, the reaction
had merely reached 33.9% conversion but afforded an
exceedingly high selectivity factor of 129 (not shown, see the
Supporting Information). To our delight, the reaction rate
3
Bu SiH/(R,R)-Ph-BPE as an excellent hydrosilane/ligand
combination for the enantioselective Cu–H-catalyzed Si–O
coupling of a broad range of benzylic and allylic monools
[9,10]
[11]
(
Scheme 1).
We report here that the same chiral ligand
3
increased significantly with less bulky Et SiH (2a) while
together with several simple hydrosilanes enables the kinetic
resolution of α-hydroxy-substituted oxime ethers. As
demonstrated for selected examples, these are useful synthetic
building blocks.
maintaining an excellent selectivity factor of 52.8 (Table 1, entry
1). We moved on to examine the effect of the oxime ether group
employing Et
2‒5). As a general trend, the bulkier the protective group was
Bn, Ph, tBu, and TIPS), the higher the selectivity factor and the
lower the reactivity were. Oxime ethers (Z)-1b, (Z)-1d, and (Z)-
e afforded the corresponding silyl ethers (S,Z)-3 with high
enantiomeric excesses at low to acceptable conversions (entries
, 4, and 5), and (Z)-1c did not react (entry 3). (Z)-1e with a
3
SiH (2a) as the silylating reagent (Table 1, entries
(
1
2
cleavable TIPS group combines superb selectivity and
synthetically useful reactivity (entry 5).
Table 1: Identification of the oxime ether group.
[
*]
X. Dong, Y. Kita, Prof. Dr. M. Oestreich
Institut für Chemie, Technische Universität Berlin
Strasse des 17. Juni 115, 10623 Berlin (Germany)
E-mail: martin.oestreich@tu-berlin.de
Homepage: http://www.organometallics.tu-berlin.de
Supporting information for this article is given via a link at the end of
the document.
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Angewandte Chemie International Edition
10.1002/anie.201802947
COMMUNICATION
OTIPS
OH
TIPSO
[d]
N
N
Entry
R
ee of silyl ether
ee of alcohol
(R,Z)-1 [%]
Conv. of
[c]
(Z)-1 [%]
s
[a]
[b]
(
S,Z)-3 [%]
OH
Me
Me
(E)-1e
1
2
3
4
5
Me
Bn
88.0, (S,Z)-3aa
97.8, (S,Z)-3ba
—, (S,Z)-3ca
93.0, (R,Z)-1a
27.4, (R,Z)-1b
—, (R,Z)-1c
51.4 (10 h)
21.9 (18 h)
n.r. (18 h)
8.4 (18 h)
43.4 (18 h)
52.8
113
—
(
Z)-1e
with Et3SiH (2a, 0.55 equiv)
Z)-1e (S,Z)-3ea/(R,Z)-1e
3.4% conversion (18 h)
S,Z)-3ea: 96.0% ee
with Et3SiH (2a, 0.55 equiv)
(E)-1e (S,E)-3ea/(R,E)-1e
52.9% conversion (18 h)
(S,E)-3ea: 88.6% ee
(R,E)-1e: 99.6% ee
s = 101
(
4
Ph
(
(
R,Z)-1e: 73.6% ee
s = 108
tBu
TIPS
97.2, (S,Z)-3da
96.0, (S,Z)-3ea
9.0, (R,Z)-1d
73.6, (R,Z)-1e
>50
108
with Bu3SiH (2b, 0.55 equiv)
Z)-1e (S,Z)-3eb/(R,Z)-1e
6.6% conversion (18 h)
S,Z)-3eb: 97.4% ee
with Bu3SiH (2b, 0.55 equiv)
(
(E)-1e
(S,E)-3eb/(R,E)-1e
3
35.2% conversion (18 h)
(S,E)-3eb: 98.2% ee
(R,E)-1e: 53.4% ee
s = 200
(
(
[
a] Determined by HPLC analysis on chiral stationary phases after cleavage of
the silyl ether. [b] Determined by HPLC analysis on chiral stationary phases.
c] Monitored by GLC analysis using tetracosane as an internal standard and
calculated by the following equation: conversion
ether+eeunreacted alcohol). [d] Calculated from s = ln[(1–C)(1–ee)]/ln[(1–C)(1+ee)]
R,Z)-1e: 56.2% ee
s = 131
[
=
eeunreacted alcohol/(eesilyl
with Me2PhSiH (2c, 0.55 equiv)
Z)-1e (S,Z)-3ec/(R,Z)-1e
53.8% conversion (18 h)
S,Z)-3ec: 85.2% ee
with Me2PhSiH (2c, 0.55 equiv)
(
(E)-1e
(S,E)-3ec/(R,E)-1e
[
12]
51.1% conversion (18 h)
(S,E)-3ec: 93.6% ee
(R,E)-1e: 97.6% ee
s = 129
where ee = ee/100 and C = conversion/100. TIPS = triisopropylsilyl. n.r. =
no reaction.
(
(R,Z)-1e: 99.2% ee
s = 67.4
with Et2PhSiH (2d, 0.55 equiv)
Z)-1e (S,Z)-3ed/(R,Z)-1e
with Et2PhSiH (2d, 0.55 equiv)
(
(E)-1e
(S,E)-3ed/(R,E)-1e
1
8.4% conversion (18 h)
(S,Z)-3ed: 97.4% ee
50.4% conversion (18 h)
(S,E)-3ed: 91.4% ee
(R,E)-1e: 92.8% ee
s = 74.5
We continued with probing the oxime ether geometry of 1e
with four hydrosilanes 2a‒d (Table 2). For comparison, these
reactions were conducted under exactly the same setup. As
expected, differing reactivities were found for (Z)-1e and (E)-1e
but s values were essentially in the same order of magnitude
(
R,Z)-1e: 22.0% ee
s = 100
[
7b,9,13]
Given the close-to-optimal substrate/reagent pair of (E)-1e
and Me PhSiH (2c) (s = 129 at 51.1% conversion), we started to
ranging from 67.4 to 200. As pointed out earlier,
precise
2
calculation of selectivity factors greater than 50 is thwarted by
the inaccuracy of the analytical techniques used to determine
enantiomeric excess and conversion. Hence, the obtained s
values must not be overinterpreted. What we extract from the
results collected in Table 2 is that (1) the steric bulk of the
hydrosilane does influence the reactivity, being highest for both
explore the scope of this kinetic resolution with α-hydroxy oxime
silyl ethers having E configuration (Table 3). Electronically
modified (E)-1e with various substituents in the para position
reacted smoothly with consistently high selectivity factors and
reactivity [(E)-4e‒12e]. A similar result was obtained with a 2-
furyl instead of the phenyl group but the E/Z isomers could not
be separated on a preparative scale (14e). The minor isomer
2
isomers with least hindered Me PhSiH (2c) and (2) the role of
the oxime ether geometry is marginal. We therefore believe that
the oxime nitrogen atom in the E isomer is not acting as a ligand
for the copper catalyst, i.e., two-point binding is not a key feature
of this enantioselective process. The reaction outcome with
(
E)-14e was more reactive than (Z)-14e but this difference was
too small for their resolution. Variation of the alkyl group at the
carbinol carbon atom entailed the same problem, and 16e‒20e
had to be used a isomeric mixtures. Fortunately, baseline
separation of the four α-hydroxy oxime stereoisomers (R,Z),
2
Et PhSiH (2d) stands out though: high conversion for (E)-1e but
low conversion for (Z)-1e. We attribute this dramatic reactivity
difference to the steric situation rather than an interfering
nitrogen donor in the more reactive E isomer. — It is worth
mentioning that here and elsewhere neither N‒O bond cleavage
(
S,Z), (R,E), and (S,E) was achieved by HPLC analysis on chiral
stationary phases. By this, the full set of data became available
for both the slow-reacting alcohol isomers and the silyl ethers
[9]
[14]
after deprotection. In agreement with our previous study, an
increasing size of the alkyl substituent was detrimental to
enantiomer discrimination of both isomers [Me (1e) < Et (16e) <
Pent (18e)]; branching was not tolerated, and the selectivity
factor collapsed [iPr (20e)]. The reactivity remained unaffected,
giving conversions of approximately 50% throughout. Cognate
cyclic systems (E)-22e and (E)-24e worked equally well but each
or C=N reduction were detected.
Table 2: Screening of hydrosilanes and influence of the oxime ether geometry.
required another hydrosilane, Bu
Et SiH (2a) for (E)-24e, to secure high selectivity [conversion
was low in the latter case; see also footnote [f] in Table 3 for the
result with routinely used Me PhSiH (2c)]. A moderate s value
3
SiH (2b) for (E)-22e and
3
2
was obtained with cyclic (E)-26e, and a hydrosilane screening
did not lead to any selectivity improvement (see the Supporting
Information). No kinetic resolution of (E)-28e with aryl groups in
these positions was reached, and hardly any conversion was
3
seen with more bulky Et SiH (2a).
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Angewandte Chemie International Edition
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COMMUNICATION
Table 3: Substrate scope of the kinetic resolution of α-hydroxy-substituted oxime silyl ethers.
CuCl (5.0 mol%)
NaOtBu (5.0 mol%)
(R,R)-Ph-BPE (6.0 mol%)
OH Me2PhSiH (2c, 0.55 equiv)
TIPSO
TIPSO
TIPSO
N
N
N
R
R
R
OSiMe2Ph
OH
+
toluene
RT
n
n
n
12 h
TIPSO
TIPSO
TIPSO
O
OTIPS
OH
TIPSO
N
N
N
N
N
OH
Me
OH
Me
OH
Me
and
OH
O
Me
MeO
Z:E = 67:33[b]
n
(E)-22e (n = 0)[d]
(S,E)-23eb/(R,E)-22e
(
E)-1e
(S,E)-3ec/(R,E)-1e
(E)-4e[a,b]
(S,E)-5ec/(R,E)-4e
(Z)-14e
x
(E)-14e
(S,E)-15ec/(R,E)-14e
56.1% conversion
38.5% (S,E)-15ec: 74.6% ee
(
E)-22e
(
E)-1e
(E)-4e
(Z)-14e
(S,Z)-15ec/(R,Z)-14e x (E)-14e
36.7% conversion
(S,Z)-15ec: 91.4% ee
(R,Z)-14e: 53.0% ee
s = 37.9
52.0% conversion
48.5% conversion
49.7% conversion
(S,E)-5ec: 38.9%, 94.4% ee
(R,E)-4e: 47.3%, 93.2% ee
s = 117
x
(
(
S,E)-23eb: 44.1%, 87.4% ee
R,E)-22e: 42.7%, 94.6% ee
(
S,E)-3ec: 46.4%, 95.4% ee
R,E)-1e: 47.0%, 90.0% ee
(
46.5%
x
(R,E)-14e: 95.2% ee
s = 53.6
s = 136
s = 25.0
(
E)-24e (n = 1)[e,f]
(S,E)-25ea/(R,E)-24e
15.9% conversion
(
E)-24e
TIPSO
N
TIPSO
N
TIPSO
N
OTIPS
N
(
(
S,E)-25ea: 13.1%, 97.6% ee
R,E)-24e: 79.1%, 18.4% ee
OH
OH
OH
R
OH
and
s = 99.2
Me
Me
Me
R
Br
TIPSO
N
E:Z = 59:41[b]
OH
(
E)-6e
(S,E)-7ec/(R,E)-6e
(E)-8e
(S,E)-9ec/(R,E)-8e
(E)-16e (R = Et)
(S,E)-17ec/(R,E)-16e x (Z)-16e
54.5% conversion
(S,E)-17ec: 82.8% ee
(R,E)-16e: 99.0% ee
s = 54.8
x
(Z)-16e (R = Et)
(
E)-6e
(E)-8e
(E)-16e
(S,Z)-17ec/(R,Z)-16e
54.4% conversion
(S,Z)-17ec: 81.6% ee
(R,Z)-16e: 97.2% ee
s = 41.0
48.0% conversion
50.2% conversion
(S,E)-9ec: 47.5%, 87.6% ee
(R,E)-8e: 46.5%, 88.2% ee
s = 43.7
x
(E)-26e
(S,E)-27ec/(R,E)-26e
44.7% conversion
S,E)-27ec: 41.9%, 79.4% ee
(
S,E)-7ec: 42.9%, 90.0% ee
R,E)-6e: 45.1%, 83.0% ee
s = 48.8
4
4
8.1%
2.5%
x
(E)-26e
(
(
E:Z = 86:14[b,c]
(R,E)-26e: 48.9%, 64.2% ee
s = 16.8
(
E)-18e (R = Pent)
(S,E)-19ec/(R,E)-18e x (Z)-18e
x
(Z)-18e (R = Pent)
TIPSO
N
TIPSO
N
(E)-18e
(S,Z)-19ec/(R,Z)-18e
54.3% conversion
(S,Z)-19ec: 82.2% ee
(R,Z)-18e: 97.8% ee
s = 45.6
TIPSO
N
56.7% conversion
x
OH
OH
(
S,E)-19ec: 74.4% ee 50.3%
(R,E)-18e: 97.4% ee
s = 28.6
OH
Me
Me
41.5%
x
Cl
F3C
E:Z = 79:21[b]
(
E)-10e
(E)-12e
(E)-20e (R = iPr)
x
(Z)-20e (R = iPr)
(S,Z)-21ec/(R,Z)-20e (E)-28e
57.6% conversion
(S,Z)-21ec: 63.8% ee
(R,Z)-20e: 86.6% ee
s = 12.3
(E)-28e
(S,E)-29ec/(R,E)-28e
51.3% conversion
(
E)-10e
(S,E)-11ec/(R,E)-10e (E)-12e
0.9% conversion
S,E)-11ec: 48.5%, 90.4% ee
R,E)-10e: 46.2%, 93.8% ee
(S,E)-13ec/(R,E)-12e (E)-20e
51.8% conversion
(S,E)-13ec: 43.9%, 87.6% ee
(R,E)-12e: 46.0%, 94.0% ee
s = 52.7
(S,E)-21ec/(R,E)-20e x (Z)-20e
48.4% conversion
(S,E)-21ec: 76.8% ee 43.6%
5
x
(
(
(S,E)-29ec: 38.2%, 15.4% ee
(R,E)-28e: 44.3%, 16.2% ee
s = 1.57
(R,E)-20e: 72.2% ee
40.0%
x
s = 70.3
s = 16.4
[
a] E:Z = 90:10; only the E isomer analyzed. [b] Isomeric oxime ethers not separable by flash chromatography on silica gel on a preparative scale. [c] 0.60 equiv
2
of Me PhSiH (2c) used. [d] Bu
3 2
SiH (2b) used instead of Me PhSiH (2c). [e] Et
3 2 2
SiH (2a) used instead of Me PhSiH (2c). [f] With Me PhSiH (2c), 53.5%
conversion, (S,E)-25ec, 79.2% ee, (R,E)-24e, 91.2% ee, and s = 27.6 obtained.
[
16]
As noted at the outset, enantioenriched α-hydroxy-
substituted oxime ethers are valuable as these can be converted
into other important compounds without or little erosion of the
enantiomeric purity (Scheme 2). To illustrate this, a gram-scale
kinetic resolution of (E)-1e (1.61 g) was performed to produce
acidic
medium
delivered
the
β-hydroxy-substituted
hydroxylamine 31 with poor diastereoselectivity; both (S,R)-31
and (R,R)-31 formed with >99% ee. Exhaustive reduction of
(R,E)-1e by Pd/C-catalyzed hydrogenation
deprotection with TBAF afforded the β-amino alcohol (S,R)-32
with good diastereoselectivity. Beckmann-type ring
enlargement mediated by DIBAL-H converted (R,E)-22e into
tetrahydroquinoline (R)-33 with complete preservation of
enantiopurity (Scheme 2, bottom).
[17]
subsequent to
(
R,E)-1e with >99% ee and in 39% isolated yield (see the
Supporting Information). Deoximation was achieved by acid-
catalyzed oxime exchange between (R,E)-1e and
formaldehyde, furnishing the α-hydroxy ketone (R)-30 with
98% ee and in good yield. The absolute configuration of 30
A
[15]
[18]
>
was assigned as R by comparison with the literature-known
optical rotation. The chemoselective reduction of the oxime C=N
bond without cleavage of the fragile N‒O bond by NaCNBH in
3
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Angewandte Chemie International Edition
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COMMUNICATION
TIPSO
N
[2]
a) L.-W. Xu, Y. Chen, Y. Lu, Angew. Chem. Int. Ed. 2015, 54, 9456–
9466; Angew. Chem. 2015, 127, 9590–9601; b) A. Weickgenannt, M.
OH
Mewald, M. Oestreich, Org. Biomol. Chem. 2010, 8, 1497–1504; c) S.
Rendler, M. Oestreich, Angew. Chem. Int. Ed. 2008, 47, 248–250;
Angew. Chem. 2008, 120, 254–257.
exhaustive
oxime
reduction
Me
deoximation
Conditions A)
7
4%
84%
(
(R,E)-1e: >99% ee
prepared on gram scale)
(
(Conditions C)
[
[
3]
4]
a) T. Isobe, K. Fukuda, Y. Araki, T. Ishikawa, Chem. Commun. 2001,
243–244; b) C. I. Sheppard, J. L. Taylor, S. L. Wiskur, Org. Lett. 2011,
oxime
reduction
Conditions B)
59%
13, 3794–3797; c) R. W. Clark, T. M. Deaton, Y. Zhang, M. I. Moore, S.
(
L. Wiskur, Org. Lett. 2013, 15, 6132–6135; d) L. Wang, R. K. Akhani, S.
L. Wiskur, Org. Lett. 2015, 17, 2408–2411; e) S. Yoshimatsu, A.
Yamada, K. Nakata, J. Org. Chem. 2018, 83, 452–458.
HO
O
NH
NH2 • HCl
OH
OH
OH
a) Y. Zhao, A. W. Mitra, A. H. Hoveyda, M. L. Snapper, Angew. Chem.
Int. Ed. 2007, 46, 8471–8474; Angew. Chem. 2007, 119, 8623–8626; b)
J. M. Rodrigo, Y. Zhao, A. H. Hoveyda, M. L. Snapper, Org. Lett. 2011,
13, 3778–3781.
Me
R)-30: >98% ee
Me
Me
(
(S,R)-31: >99% ee (S,R)-32: >99% ee
and
d.r. = 90:10
(
R,R)-31: >99% ee
d.r. = 66:34
[
[
5]
6]
a) A. D. Worthy, X. Sun, K. L. Tan, J. Am. Chem. Soc. 2012, 134,
7321–7324; b) X. Sun, A. D. Worthy, K. L. Tan, J. Org. Chem. 2013, 78,
TIPSO
reductive
ring expansion
Conditions D)
10494–10499.
N
H
N
a) C. Lorenz, U. Schubert, Chem. Ber. 1995, 128, 1267–1269; for
reviews of Cu–H catalysis, see: b) C. Deutsch, N. Krause, B. H.
Lipshutz, Chem. Rev. 2008, 108, 2916–2927; c) S. Rendler, M.
Oestreich, Angew. Chem. Int. Ed. 2007, 46, 498–504; Angew. Chem.
(
OH
R,E)-22e: 95% ee
4
1%
OH
(R)-33: 95% ee
(
2
007, 119, 504–510.
a) S. Rendler, G. Auer, M. Oestreich, Angew. Chem. Int. Ed. 2005, 44,
620–7624; Angew. Chem. 2005, 117, 7793–7797; b) H. F. T. Klare, M.
[
7]
Scheme 2. α-Hydroxy-substituted oxime ethers as versatile building blocks.
7
Conditions A: aq. HCHO (37%), aq. HCl (1M), THF, RT, 4 h. Conditions B: 1.
TBAF (2 equiv), THF, RT, 2 h; 2. NaCNBH
0
3
(4 equiv), aq. HCl (2M), MeOH,
°C to RT, 4 h. Conditions C: 1. TBAF (2 equiv), THF, RT, 2 h; 2. Pd/C (10%),
(1 bar), HCl in MeOH (3%), RT, 24 h. 3. HCl (gas), CH Cl /Et O, RT.
Cl
tetrabutylammonium fluoride. DIBAL-H
Oestreich, Angew. Chem. Int. Ed. 2007, 46, 9335–9338; Angew. Chem.
2007, 119, 9496–9499; c) B. Karatas, S. Rendler, R. Fröhlich, M.
Oestreich, Org. Biomol. Chem. 2008, 6, 1435–1440; d) S. Rendler, O.
Plefka, B. Karatas, G. Auer, R. Fröhlich, C. Mück-Lichtenfeld, S.
Grimme, M. Oestreich, Chem. Eur. J. 2008, 14, 11512–11528; e) A.
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a) A. Weickgenannt, M. Mewald, T. W. T. Muesmann, M. Oestreich,
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2012, 68, 3468–3479.
H
2
2
2
2
Conditions D: 1. TBAF (2 equiv), THF, RT, 2 h; 2. DIBAL-H (9 equiv), CH
°C to RT, 12 h. TBAF
diisobutylaluminum hydride.
2
2
,
=
0
=
[
[
8]
9]
To summarize, we have reported here a robust procedure
for the catalyst-controlled kinetic resolution of α-hydroxy-
substituted oxime ethers by dehydrogenative Si‒O coupling.
While the commercially available catalyst system was disclosed
X. Dong, A. Weickgenannt, M. Oestreich, Nat. Commun. 2017, 8,
1
5547.
[10] It must be mentioned in its own right that Song and co-workers
developed unique catalyst system that also enables the kinetic
[9]
by us recently, its application to this new structural motif is still
a
a rare example of an enantioselective Cu‒H-catalyzed alcohol
resolution of monools using HMDS (1,1,1,3,3,3-hexamethyldisilazane):
S. Y. Park, J.-W. Lee, C. E. Song, Nat. Commun. 2015, 6, 7512. For a
related approach, see: K. Hyodo, S. Gandhi, M. van Gemmeren, B. List,
Synlett 2015, 26, 1093–1095.
[
19]
silylation.
The selectivity factors are high across a broad
range of substrates, and the highly enantioenriched alcohols can
be further processed to other synthetically useful compounds
with no racemization.
[11] For selected examples, see: a) E. Ascic, S. L. Buchwald, J. Am. Chem.
Soc. 2015, 137, 4666‒4669; b) M. T. Pirnot, Y.-M. Wang, S. L.
Buchwald, Angew. Chem. Int. Ed. 2016, 55, 48‒57; Angew. Chem.
2
016, 128, 48‒57; c) Y. Yang, I. B. Perry, G. Lu, P. Liu, S. L. Buchwald,
Acknowledgements
Science 2016, 353, 144‒150.
[
[
[
12] H. B. Kagan, J. C. Fiaud in Topics in Stereochemistry, Vol. 18 (Eds.: E.
L. Eliel, S. H.Wilen), Wiley, New York, 1988, pp. 249–330.
13] J. M. Goodman, A. K. Köhler, S. C. M. Alderton, Tetrahedron Lett. 1999,
This
research
was
supported
by
the
Deutsche
Forschungsgemeinschaft (Oe 249/14-1) and the China
Scholarship Council (predoctoral fellowship to X.D., 2014−2018).
Y.K. (on leave from Osaka University) thanks JSPS KAKENHI
40, 8715–8718.
14] For Cu–H-catalyzed hydrosilylation of imines, see: B. H. Lipshutz, H.
Shimizu, Angew. Chem. Int. Ed. 2004, 43, 2228–2230; Angew. Chem.
(No. JP15H05848) for financial support. M.O. is indebted to the
2
004, 116, 2278–2280.
15] J. Y. Lee, Y.-T. Hong, S. Kim, Angew. Chem. Int. Ed. 2006, 45, 6182–
186; Angew. Chem. 2006, 118, 6328–6332.
16] R. Sivappa, N. M. Hernandez, H. He, C. J. Lovely, Org. Lett. 2007, 9,
861–3864.
Einstein Foundation (Berlin) for an endowed professorship.
[
[
6
Keywords: asymmetric catalysis • copper • dehydrogenative
3
coupling • kinetic resolution • silicon
[
[
17] K. Harada, S. Shiono, Bull. Chem. Soc. Jpn. 1984, 57, 1040–1045.
18] H. Cho, Y. Iwama, K. Sugimoto, S. Mori, H. Tokuyama, J. Org. Chem.
[
1]
E. Vedejs, M. Jure, Angew. Chem. Int. Ed. 2005, 44, 3974–4001;
Angew. Chem. 2005, 117, 4040–4069.
2010, 75, 627–636.
[
19] For an early attempt, see: J. T. Issenhuth, S. Dagorne, S. Bellemin-
Laponnaz, J. Mol. Cat. A: Chem. 2008, 286, 6–10.
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Kinetic Resolution of α-Hydroxy-
Substituted Oxime Ethers by
Enantioselective Cu–H-Catalyzed Si–
O Coupling
Cinderella. The commerically available catalyst system CuCl/NaOtBu/(R,R)-Ph-
BPE together with several simple hydrosilanes as resolving reagents enables the
kinetic resolution of alcohols with an oxime ether group in the α position. This
enantioselective alcohol silylation is highly efficient, reliably affording highly
enantioenriched, synthetically useful building blocks (see scheme).
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