Enantioselective oxidation of 1,2-diols with quinine-derived urea organocatalyst

Article abstract of DOI:10.1021/ol4032045

Quinine-derived urea has been identified as a highly efficient organocatalyst for the enantioselective oxidation of 1,2-diols using bromination reagents as the oxidant. This simple procedure utilizes readily available reagents and operates at ambient temperature to yield a wide range of α-hydroxy ketones in good yield (up to 94%) and excellent enantioselectivity (up to 95% ee).

Full text of DOI:10.1021/ol4032045

Letter
pubs.acs.org/OrgLett
Enantioselective Oxidation of 1,2-Diols with Quinine-Derived Urea
Organocatalyst
Zi-Qiang Rong, Hui-Jie Pan, Hai-Long Yan, and Yu Zhao*
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543
S
* Supporting Information
ABSTRACT: Quinine-derived urea has been identified as a
highly efficient organocatalyst for the enantioselective
oxidation of 1,2-diols using bromination reagents as the
oxidant. This simple procedure utilizes readily available
reagents and operates at ambient temperature to yield a
wide range of α-hydroxy ketones in good yield (up to 94%)
and excellent enantioselectivity (up to 95% ee).
enantioselective addition of allyltrichlorosilane to aldehydes
atalytic asymmetric transformations of alcohol substrates
Csuch as kinetic resolution of racemic alcohols or
desymmetrization of meso-diols have proven to be a powerful
approach to access valuable enantioenriched materials in
organic synthesis.1 Along these lines, enantioselective oxidation
of alcohols has been one of the most explored reaction types, in
addition to asymmetric group transfer reactions.2 Among the
different catalytic strategies developed for enantioselective
oxidation, almost all the efficient and highly stereoselective
systems were based on transition-metal catalysis, which mainly
includes asymmetric dehydrogenation catalyzed by Ru or Ir
complexes,3 Pd-,4 V-5 or Fe-catalyzed6 oxidation with O2,
aerobic oxidation catalyzed by Ru(salen) or Fe(salan)
complexes,7 and Mn(salen)8 or Cu-bisoxazoline-catalyzed9
oxidation with PhI(OAc)2 or NBS (N-bromosuccinimide) as
the oxidant. Organocatalytic method for enantioselective
oxidation of alcohols remains scarce, with only examples
reported that are catalyzed by chiral TEMPO derivatives10 or
with Shi’s oxazolidinone dioxiranes.11 We report here our
finding of highly stereoselective quinine urea-catalyzed
oxidation of 1,2-diols using bromination reagents as the
oxidant.
catalyzed by quinine amides such as 4b (Table 1).13 As another
a
Table 1. Validating the Role of Quinine-Derived Amide
2a
b
3a
b
c
entry Cu (mol %) 4 (mol %)
yield (%)
yield (%)
2a ee (%)
d
d
1
2
3
4
5
6
0
10
10
0
0
7
93
4a (10)
4b (10)
4a (10)
4b (10)
4c (10)
86
91
70
70
89
<5
<5
<5
<5
<5
48
33
70
60
73
0
0
a
Reaction conditions: 1a (0.10 mmol), NBS (2.0 equiv), 0 or 10 mol
% Cu(OTf)2, 0 or 10 mol % 4 in CHCl3 (1.0 mL) at 24 °C for 3 h.
b
c
d
Isolated yield. Determined by HPLC (Chiracel Daicel OJ-H). 3 h
reaction.
Our group has been interested in the use of modified
cinchona alkaloids as bidentate ligand or catalyst in
enantioselective catalysis (utilizing the highly basic quinuclidine
nitrogen and another Lewis basic group as illustrated by model
A in Scheme 1).12 Recently, we reported highly diastereo- and
proof-of-principle system for transition-metal catalysis, we
evaluated the performance of quinine amides 4a,b as potential
bidentate ligands for Cu-catalyzed oxidative desymmetrization
of meso-diols using NBS as the oxidant (Table 1).
As shown by data in entry 1, oxidation of 1a with NBS alone
proceeded smoothly to yield the overoxidized dione 3a as the
major product. Gratifyingly, addition of Cu(OTf)2 in
combination with 4a or 4b led to the formation of 2a in high
yield (with <5% 3a) with moderate level of enantioselectivity,
implying significant acceleration over the background reactivity
Scheme 1. Different Catalysis Modes by Quinine-Amide
Received: November 6, 2013
© XXXX American Chemical Society
A
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Organic Letters
Letter
by the Cu-quinine amide complex (entries 2 and 3).
Intriguingly, however, in the absence of Cu salt, oxidation
catalyzed by 4a alone produced 2a in improved enantiose-
lectivity of 70% (entry 4). Again the side product 3a was
produced in <5% yield, indicating that the catalytic process was
selective toward diol oxidation. Inspired by the work of peptide-
catalyzed asymmetric bromination reported from the Miller
group14 and asymmetric halolactonization15 reported from the
Borhan group,16 the Tang group,17 the Jacobsen group,18 and
the Yeung group,19 we surmised that the amide or the
quinuclidine nitrogen in the catalyst may be involved in the
bromonium formation leading to an enantioselective oxidation
(models B or C in Scheme 1). Furthermore, the results
obtained from catalysts 4b and 4c (entries 5 and 6) showed
that more electron-deficient amide moiety led to higher
efficiency and selectivity, implying the possibility of amide
serving as H-bond donor in the interaction with succinimide.
Following this promising lead, much experimentation was
carried out on the optimization of quinine amides that,
unfortunately, led to no further improvement in the reaction
outcome. We then moved on to screen quinine-derived
molecules incorporated with related Lewis basic groups or H-
bond donor units (Table 2). While quinine sulfonamide 4d or
chiral urea moiety or quinine (4k) led to the formation of
racemic product.
Further screening of solvents showed that chloroform was
the best choice for the reaction of 1a (see the Supporting
Information, Table 1). N-Bromophthalimide (NBP) was
identified as the optimal oxidant from the examination of
various halogenation reagents (NCS, NIS, DBDMH (1,3-
dibromo-5,5-dimethylhydantoin), etc.), the loading of which
had some effect on the enantioselectivity as well, with 3 equiv
providing optimal enantioselectivity. Under the optimized
conditions, 2a could be obtained in 94% yield with 95% ee
(entry 1, Table 3).
Table 3. Enantioselective Oxidative Desymmetrization of
a
meso-Diols Catalyzed by 4f
product 2
b
c
entry
R
product
time (h)
yield (%)
ee (%)
d
1
2
Ph
2a
2b
2c
2d
2e
2f
3
24
3
94
90
92
83
90
91
94
85
65
50
95
d
,e
2-ClC6H4
3-ClC6H4
4-FC6H4
81
66
84
74
86
91
82
83
54
3
a
Table 2. Catalyst Optimization for Oxidation of 1a
d
4
3.5
3
5
4-ClC6H4
4-BrC6H4
4-CH3C6H4
4-OMeC6H4
1-naphthyl
CH2OBn
6
2
7
2g
2h
2i
2
8
2.5
2
e
9
d
,f
10
2j
18
a
Reaction conditions: 1 (0.1 mmol), NBP (3.0 equiv), 10 mol % of 4f
in CHCl3/PhCl (10:1; 1.0 mL) at 24 °C unless noted otherwise.
b
c
d
e
Isolated yield. Determined by HPLC. CHCl3 (1.0 mL). 20 mol %
f
of 4f. 2.0 equiv of NBS instead of NBP was used.
The substrate scope of this catalytic system was then
explored. A mixed solvent system (10:1 CHCl3/PhCl) was
discovered to be beneficial for most substrates. As shown in
Table 3, a wide range of diaryl-substituted meso-1,2-diols could
be oxidized selectively to mono-oxidation product 2 with
excellent yield and good to excellent enantioselectivity.
Different para-, meta- and even ortho-substitution on the aryl
unit could be well-tolerated (entries 1−9). When we tried
dialkyl-substituted diols such as 1j, however, both the efficiency
and selectivity of the system dropped dramatically, with 2j
obtained in only 54% ee (entry 10).
While the low efficiency in the oxidation of dialkyl
substituted-diols represents the limitation of this catalytic
system, we demonstrate here that it serves well for the
resolution of racemic syn-diols. As illustrated in Scheme 2, both
chemo- and enantioselectivities are involved for the oxidation
of racemic diol 5 bearing different substituents. If both high
enantio- and chemoselectivity (i.e., oxidation of benzylic
alcohol only) can be achieved for this reaction; hydroxy ketone
6 will be the sole product, and this will result in the kinetic
resolution of racemic 5.20 In another related scenario where the
reaction shows no chemoselectivity, both 6 and ent-7 can be
obtained in high enantioselectivity, which will result in a
divergent reaction on a racemic mixture,21 according to the
nomenclature of Vedejs.1c
b
c
b
c
entry
4
yield (%) ee (%) entry
4
yield (%) ee (%)
1
2
3
4
4d
4e
4f
83
52
94
92
32
7
5
6
7
8
4h
4i
90
93
92
82
70
77
<2
<2
91
84
4j
d
4g
4k
a
Reaction conditions: 1a (0.10 mmol), NBS (2.0 equiv), 10 mol % of
4 in CHCl3 (1.0 mL) at 24 °C for 3 h. See Table 1. See Table 1. 16
b
c
d
h reaction.
quinine thiourea 4e led to poor enantioselectivities, the use of
quinine urea 4f interestingly produced 2a in 94% yield with
91% ee (entry 3 vs entries 1 and 2). The electronic property of
the urea moiety was examined next, which followed the same
trend as in the quinine amide series (entries 3−5).
Monomethylated urea catalyst 4i proved much less selective
(77% ee, entry 6). These data seem to support the hypothesis
that urea moiety is serving as the H-bond donor. Finally, the
importance of urea as well as the quinuclidine nitrogen was
supported by the fact that utilizing catalyst 4j bearing only a
B
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Letter
Scheme 2. Extension to Kinetic Resolution or Divergent
Reaction on Racemic Diol 5
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures and characterization of the products.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: zhaoyu@nus.edu.sg.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful for the generous financial support from the
Singapore National Research Foundation (NRF Fellowship)
and the National University of Singapore.
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