Practical approach for asymmetric hydroxyamination of aldehydes with in situ generated nitrosocarbonyl compounds: Application to one-pot synthesis of chiral allylamines

Article abstract of DOI:10.1021/ol5000742

The highly regio- and enantioselective hydroxyamination of aldehydes with in situ generated nitrosocarbonyl compounds from a hydroxamic acid derivative was realized by simple and readily available chiral amine catalysts. The resulting hydroxyamination products were readily converted to the corresponding chiral 1,2-aminoalcohol or allylamine derivatives in one pot.

Full text of DOI:10.1021/ol5000742

Letter
pubs.acs.org/OrgLett
Practical Approach for Asymmetric Hydroxyamination of Aldehydes
with in Situ Generated Nitrosocarbonyl Compounds: Application to
One-Pot Synthesis of Chiral Allylamines
Taichi Kano, Fumitaka Shirozu, and Keiji Maruoka*
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
S
* Supporting Information
ABSTRACT: The highly regio- and enantioselective hydrox-
yamination of aldehydes with in situ generated nitrosocarbonyl
compounds from a hydroxamic acid derivative was realized by
simple and readily available chiral amine catalysts. The resulting
hydroxyamination products were readily converted to the
corresponding chiral 1,2-aminoalcohol or allylamine derivatives
in one pot.
Scheme 1. Previous Asymmetric Hydroxyamination with in
Situ Generated Nitrosocarbonyl Compounds
he electrophilic α-amination of carbonyl compounds is
Tone of the most straightforward methods for the synthesis
of α-amino carbonyl compounds including α-amino acids.1 In
the area of organocatalysis, enamines, which are in situ
generated from carbonyl compounds and chiral amine catalysts,
are known to react with electrophilic aminating agents, and a
number of chiral amine catalyzed α-aminations of aldehydes
and ketones have been reported to date.2 In such reactions,
azodicarboxylates are the most frequently used aminating
agents;3 however, transformation of the reaction products to N-
protected α-amino carbonyl compounds by the N−N bond
cleavage requires harsh conditions.4 In enamine catalysis,
nitrosoarenes such as nitrosobenzene have also served as
electrophilic aminating agents.5,6 However, the synthetic utility
of products bearing an aryl group on the nitrogen atom is quite
limited due to the difficulty in removal of the aromatic N-
substituent. On the other hand, nitrosocarbonyl compounds are
ideal aminating agents, giving α-amino carbonyl compounds
having easily removable N-substituents such as tert-butoxy-
carbonyl (Boc) and benzyloxycarbonyl (Cbz).7,8 In contrast to
relatively stable nitrosobenzene, nitrosocarbonyl compounds
are highly reactive and transient species, which are generated in
situ by oxidation of hydroxamic acids or N-hydroxycarbamates.
While groups of Read de Alaniz and Yamamoto independently
reported the first example of the Cu(II)-catalyzed α-amination
of β-ketoesters with in situ generated nitrosocarbonyl
compounds,9 their use in asymmetric amination was not
achieved. In this context, we have previously developed a metal-
free asymmetric hydroxyamination of aldehyde with nitroso-
carbonyl intermediates using the binaphthyl-based secondary
amine catalyst (S)-2 and a combination of benzoyl peroxide
(BPO) and TEMPO as oxidants (Scheme 1).10 Despite the
potential of this organocatalytic transformation, however, the
substrate scope of the present system is limited to the sterically
less hindered aldehydes, and replacement of the catalyst with a
readily available chiral amine and reduction of the amounts of
reagents and byproducts are required to improve the utility of
this methodology. Thus we investigated a chiral pyrrolidine-
catalyzed hydroxyamination of aldehydes with in situ generated
nitrosocarbonyl compounds by standard oxidants and the
application to the one-pot synthesis of chiral allylamine
derivatives.
In view of catalyst accessibility, we first chose the secondary
amine catalyst (R)-3,11 which is commercially available and also
readily prepared from L-proline, for the asymmetric hydrox-
yamination of aldehydes with in situ generated nitrosocarbonyl
compounds. In the presence of 10 mol % of (R)-3, various
oxidants were screened to generate a nitrosocarbonyl
intermediate in the reaction of 3-phenylpropanal with tert-
butyl N-hydroxycarbamate (1a) (Table 1). Use of PhI(OAc)2
afforded the desired hydroxyamination product 5a in low yield
albeit with high enantioselectivity (Table 1, entry 1). A slightly
Received: January 9, 2014
Published: February 19, 2014
© 2014 American Chemical Society
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Organic Letters
Letter
Table 1. Asymmetric Hydroxyamination of 3-
Phenylpropanal with 1a
Table 2. Asymmetric Hydroxyamination of Aldehydes with
1a
a
a
b
c
d
entry
R
yield (%)
5/6
ee (%)
b
c
1
Me
Bu
75
67
69
51
51
43
64
59
63
<5
>20/1
>20/1
>20/1
>20/1
>20/1
>20/1
>20/1
>20/1
>20/1
−
99
99
99
97
99
99
99
99
99
−
entry catalyst
oxidant
solvent
yield (%)
ee (%)
2
1
2
3
4
5
6
7
8
9
(R)-3
(R)-3
(R)-3
(R)-4
(R)-4
(R)-4
(R)-4
(R)-4
(R)-4
(R)-4
PhI(OAc)2
BPO, TEMPO
MnO2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
(CH2Cl)2
toluene
THF
5
95
93
90
97
99
99
98
98
99
−
d
3
Bn
30
52
5
4
Allyl
5
CH2Cy
(CH2)3OBn
i-Pr
PhI(OAc)2
BPO, TEMPO
MnO2
d
6
56
69
50
23
30
n.d.
7
8
Cy
MnO2
9
t-Bu
MnO2
10
Ph
MnO2
a
The reaction of an aldehyde (0.10 mmol) with 1a (0.20 mmol) was
carried out in the presence of MnO2 (0.20 mmol) and (R)-4 (0.010
mmol) in CH2Cl2 (2.0 mL) at 0 °C for 20 h. Isolated yield.
Determined by H NMR analysis. Enantiomeric excess of 5 was
10
MnO2
a
The reaction of 3-phenylpropanal (0.10 mmol) with 1a (0.20 mmol)
was carried out in the presence of an oxidant (0.20 mmol) and a
catalyst (0.010 mmol) in a solvent (2.0 mL) at 0 °C for 20 h. Isolated
yield of 5a. Aminoxylation product 6a was not observed.
Enantiomeric excess of 5a was determined by HPLC using a chiral
column. Use of BPO (0.10 mmol) and TEMPO (0.20 mmol).
b
c
d
1
b
determined by HPLC using a chiral column.
c
d
Scheme 2. Asymmetric Hydroxyamination Using 1b
improved yield was obtained by using the combination of BPO
and TEMPO, which generates the corresponding oxoammo-
nium salt (Table 1, entry 2).12 Finally, MnO2 was found to be
the optimal oxidant and the desired hydroxyamination product
was obtained in moderate yield with high enantioselectivity
(Table 1, entry 3).9a Under these conditions using MnO2 the
formation of organic wastes was significantly reduced. When
the readily accessible secondary amine catalyst (R)-413 having a
trityl group was used instead of (R)-3, both yield and
enantioselectivity were improved (Table 1, entry 6). Among
the solvents tested, dichloromethane provided the highest level
of yield (Table 1, entries 6−10). In all cases, the aminoxylation
product 6a was not detected.
With the optimized conditions in hand, we examined the
substrate scope, and the results are shown in Table 2. In the
presence of 10 mol % of (R)-4 and 2.0 equiv of MnO2, the
reactions of various aldehydes with 1a gave the corresponding
hydroxyamination products 5 in moderate to good yields with
excellent regio- and enantioselectivities. The reaction of
sterically hindered 3,3-dimethylbutanal, which did not give
the product under our previously reported conditions (10 mol
% of (S)-2, 2.0 equiv of TEMPO, 1.0 equiv of BPO), proceeded
smoothly to give the desired product (Table 2, entry 9). On the
other hand, only a trace amount of product was obtained in the
reaction of phenylacetaldehyde (Table 2, entry 10). Use of
benzyl N-hydroxycarbamate instead of tert-butyl N-hydroxy-
carbamate gave the Cbz-protected hydroxyamination product 7
with excellent enantioselectivity albeit in low yield (Scheme 2).
We then examined the one-pot synthesis of chiral allylamine
9 by the present asymmetric hydroxyamination and the
subsequent Wittig reaction. The in situ treatment of the
hydroxyamination products with (ethoxycarbonylmethylene)-
triphenylphosphorane (8) gave the corresponding (E)-allyl-
amines 9 in good yield with high regio- and stereoselectivity
(Table 3).
a
Table 3. One-Pot Synthesis of Allylamine 9
b
c
d
entry
R
yield (%)
E/Z
ee (%)
1
2
3
4
5
Me
Bn
70
78
68
71
68
18/1
11/1
14/1
15/1
10/1
99
98
99
98
99
(CH2)3OBn
i-Pr
t-Bu
a
The reaction of an aldehyde (0.16 mmol) with 1a (0.32 mmol) was
carried out in the presence of MnO2 (0.32 mmol) and (R)-4 (0.016
mmol) in CH2Cl2 (3.0 mL) at 0 °C for 20 h. The reaction mixture was
b
c
1
then treated with 8 (0.48 mmol). Isolated yield. Determined by H
d
NMR analysis. Determined by HPLC using a chiral column.
The obtained hydroxyamination product was a useful
intermediate in organic synthesis and readily converted to the
corresponding N-Boc-protected allylamine and γ-amino ester,
respectively (Scheme 3).14 When a solution of 9a in acetonitrile
and water was treated with Mo(CO)6 at 60 °C, N-Boc-
protected allylamine 10 was obtained with complete retention
of stereochemistry. On the other hand, reduction of 9a with
Pd/C under a hydrogen atmosphere at 60 °C gave the N-Boc-
protected γ-amino ester 11 in good yield without loss of optical
purity.
The absolute configuration of the products in the asymmetric
hydroxyamination catalyzed by (R)-4 was determined to be R
by comparison of the result of HPLC analysis with the
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Organic Letters
Letter
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literature data.10 Based on the observed stereochemistry, a
transition-state model can be proposed as shown in Figure 1.
The Si face of the enamine intermediate is effectively shielded
by the bulky trityl substituent of (R)-4, and consequently, the
reaction of an aldehyde with a nitrosocarbonyl compound
provides the R isomer predominantly.
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ez-Bengoa, E. Angew. Chem., Int. Ed.
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Figure 1. Plausible transition state model.
In summary, we have realized the highly regio- and
enantioselective hydroxyamination of aldehydes with in situ
generated nitrosocarbonyl compounds using readily available
pyrrolidine-based amine catalysts and MnO2 as the oxidant.
The resulting optically enriched hydroxyamination products are
useful chiral building blocks in the asymmetric synthesis of
chiral amines such as amino acid derivatives and an allylamine.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedure and spectral data for all new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
■
(9) (a) Baidya, M.; Griffin, K. A.; Yamamoto, H. J. Am. Chem. Soc.
2012, 134, 18566. (b) Sandoval, D.; Frazier, C. P.; Bugarin, A.; Read
de Alaniz, J. J. Am. Chem. Soc. 2012, 134, 18948.
(10) Kano, T.; Shirozu, F.; Maruoka, K. J. Am. Chem. Soc. 2013, 135,
18036.
(11) (a) Marigo, M.; Wabnitz, T. C.; Fielenbach, D.; Jørgensen, K. A.
Angew. Chem., Int. Ed. 2005, 44, 794. (b) Hayashi, Y.; Gotoh, H.;
Hayashi, T.; Shoji, M. Angew. Chem., Int. Ed. 2005, 44, 4212.
*E-mail: maruoka@kuchem.kyoto-u.ac.jp.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by a Grant-in-Aid for Scientific
Research from MEXT, Japan.
■
́
(c) Franzen, J.; Marigo, M.; Fielenbach, D.; Wabnitz, T. C.; Jørgensen,
K. A. J. Am. Chem. Soc. 2005, 127, 18926.
(12) Kano, T.; Mii, H.; Maruoka, K. Angew. Chem., Int. Ed. 2010, 49,
6638.
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amino alcohol, respectively (see ref 10).
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