Catalytic enantioselective synthesis of α-aminooxy and α-hydroxy ketone using nitrosobenzene

Article abstract of DOI:10.1021/ja0298702

The highly enantioselective and O-selective nitroso aldol reaction of tin enolates 2 and nitrosobenzene (1) has been developed with the use of (R)-BINAP-silver complexes as a catalyst. After the various silver salts were surveyed, the AgOTf and the AgClO₄ complex were found to be optimal in the O-selective nitroso aldol reaction in both asymmetric induction (up to 97% ee) and regioselection (O/N = >99/1), affording aminooxy ketone 3. The product 3 can be transformed to α-hydroxy ketone 5 without any loss of enantioselectivity. Thus, the method provides an efficient approach to the catalytic enantioselective introduction of oxygen α- to the carbonyl group. Copyright

Full text of DOI:10.1021/ja0298702

Published on Web 04/25/2003
Catalytic Enantioselective Synthesis of r-Aminooxy and r-Hydroxy Ketone
Using Nitrosobenzene
Norie Momiyama and Hisashi Yamamoto*
Department of Chemistry, UniVersity of Chicago, 5735 South Ellis AVenue, Chicago, Illinois 60637
Received December 21, 2002; E-mail: yamamoto@uchicago.edu
Table 1. (R)-BINAP-Silver Complex-Catalyzed Nitroso Aldol
Reaction of Tin Enolate 2a with Nitrosobenzenea
The stereoselective synthesis of R-hydroxy carbonyl compounds
is a topic of interest as these structures are found in numerous
important natural products; the importance has motivated the
investigation of a wide variety of reactions to diastereoselective
and enantioselective synthesis.1 The asymmetric R-hydroxylation
of enolates and enol derivatives is one of the simplest and most
frequently used methods.2 Despite considerable research,3 the
ultimate goal of developing a practical and highly effective catalytic
system for enantioselective hydroxylation has remained elusive.
Here we describe the catalytic enantioselective introduction of an
oxy group at the R-position of ketone enolates using nitrosobenzene4
and the synthesis of chiral R-hydroxy ketone in up to 97% ee
(Scheme 1).
b
c
entry
AgX
yield, %
3a/4a
ee, %
1
2
3
4
5
6
7
AgOTf
AgClO4
AgBF4
AgNTf2
AgSbF6
AgPF6
88
95
64
78
85
86
82
>99/1
>99/1
>99/1
88/12
81/19
80/20
72/28
3a: 91
3a: 95
3a: 54
3a: 63
3a: 87
3a: 76
3a: 87
4a: n.d.d
4a: n.d.
4a: n.d.
4a: 3
4a: <1
4a: <1
4a: 23
AgOAc
Scheme 1
a Reactions were conducted with 10 mol % (R)-BINAP‚AgX, 1.0 equiv
of nitrosobenzene, and 1.0 equiv of 2a in THF at -78 °C for 2 h. b Isolated
yield of two isomers. c Determined by HPLC (Supporting Information).
d n.d. ) not determined.
In an effort to expand the scope of the reaction, the tin enolates10
of various carbonyl compounds were next investigated. Both the
O-regioselectivity and the enantioselectivity were maintained for
a range of alkyl- and phenyl-substituted tin enolates (Table 2, entries
7-13). The reaction took place equally well with any variation in
cyclic tin enolate (Table 2, entries 1-6, 15-17). Although the tin
enolate exists in the O-Sn form and/or C-Sn form, the O-Sn form
was found to be much more reactive for this process. As compared
to trimethyl tin enolates, tributyl tin enolates proved to have slightly
increased N-selectivity under these conditions. To evaluate the
relative reactivity of trimethyl tin substrate with tributyl tin substrate,
1 equiv of nitrosobenzene and a 1:1 mixture of these two alkyl tin
enolates (2a and 2d) were subjected to a competitive experiment
in the absence of catalyst (eq 2). Tributyl tin enolates provided
N-adduct in 78-79% yield, while trimethyl tin enolates afforded
only 21-22% of N-adduct. This could explain the significant
amount of uncatalyzed process that proceeds with tributyl tin
enolate, which increases the N selectivities as compared to that
with trimethyl tin enolate (entries 11,12 and 15,16).
The transformation of R-aminooxy ketone to R-hydroxy ketone
is smooth and facile. Thus, the cleavage of the N-O bond in
aminooxy ketone 3a with a catalytic amount of copper sulfate
afforded the R-hydroxy ketone 5a in 94% yield without loss of
enantioselectivity. As a more efficient procedure, after addition of
2a to nitrosobenzene 1, followed by treatment with a catalytic
amount of copper sulfate and excess MeOH, R-hydroxy ketone 5a
was isolated as a single enantiomer in 93% yield and 97%
enantiomeric excess (eq 3).
The present study sprang from our own earlier findings involving
the reaction of nitrosobenzene (1) and silyl enolate which provided
the aminooxy ketone 3,5 while the reaction of nitrosobenzene and
silyl or tin enolate 2 without any Lewis acid catalyst led to the
sole production of the hydroxyamino ketone 4 (eq 1).6 From this
starting point, a highly enantioselective reaction of tin enolate 2
and nitrosobenzene has been developed in the presence of BINAP
and AgOTf7 (10 mol %, -78 °C, in THF) to furnish the amino-
oxy ketone 3a in 91% ee and with high O-selectivity8 (Table 1,
9
entry 1). The (R)-BINAP‚Pd(ClO4)2 -catalyzed reaction also
generally afforded O-adduct, giving a highly regioselective reaction
with an even slightly higher enantioselectivity. Of the various silver
salts surveyed, the AgOTf and the AgClO4 complex provided
superior levels in both asymmetric induction and regioselection,
affording 3a (Table 1, entry 2), while the AgSbF6 and AgOAc were
more reactive and had comparable enantioselectivity, but less
regioselectivity in comparison. The other metal catalysts including
copper complexes were not catalytically active in providing
O-adduct.
In conclusion, we have developed a highly catalytic, enantiose-
lective process for the synthesis of R-aminooxy and R-hydroxy
ketone. This study expands the scope of the enantioselective addition
9
6038
J. AM. CHEM. SOC. 2003, 125, 6038-6039
10.1021/ja0298702 CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Nitroso Aldol Reaction Using Various Tin Enolates
2a-2ha
Acknowledgment. Support for this research was provided by
the SORST project of the Japan Science and Technology Corp.
(JST).
Supporting Information Available: Representative experimental
procedure and spectral data for 3a-h (PDF). This material is available
free of charge via the Internet at http://pubs.acs.org.
References
(1) Reviews for hydroxylation: (a) Davis, F. A.; Chen, B. C. In Houben-
Weyl: Methods of Organic Chemistry; Helmchen, G., Hoffmann, R. W.,
Mulzer, J., Schaumann, E., Eds.; Georg Thieme Verlag: Stuttgart, 1995;
Vol. E 21, p 4497. (b) Zhou, P.; Chen, B. C.; Davis, F. A. In Asymmetric
Oxidation Reactions; Katsuki, T., Ed.; Oxford University Press: Oxford,
2001; p 128.
(2) Davis, F. A.; Chen, B. C. Chem. ReV. 1992, 92, 919.
(3) (a) Davis, F. A.; Haque, M. S. J. Org. Chem. 1986, 51, 4083. (b) Chen,
B. C.; Weismiller, M. C.; Davis, F. A.; Boschelli, D.; Empfield, J. R.;
Smith, A. B. Tetrahedron 1991, 47, 173. (c) Davis, F. A.; Kumar, A. J.
Org. Chem. 1992, 57, 3337. (d) Davis, F. A.; Weismiller, M. C.; Murphy,
C. K.; Reddy, R. T.; Chen, B. C. J. Org. Chem. 1992, 57, 7274. (e) Davis,
F. A.; Kumar, A.; Reddy, R. T.; Rajarathnam, E.; Chen, B. C.; Wade, P.
A.; Shah, S. W. J. Org. Chem. 1993, 58, 7591. (f) Davis, F. A.; Clark,
C.; Kumar, A.; Chen, B. C. J. Org. Chem. 1994, 59, 1184.
(4) Reviews of nitroso compounds, see: (a) Zuman, P.; Shah, P. Chem. ReV.
1994, 94, 1621. (b) Vogt, P. F.; Miller, M. J. Tetrahedron 1998, 54, 1317.
(c) Joghyuk, L.; Li, C.; Ann, H. W.; George, B. R. Chem. ReV. 2002,
102, 1019.
a Reactions were conducted with 10 mol % catalyst, 1.0 equiv of nitroso-
benzene, and 1.0 equiv of tin enolate in THF at -78 °C for 2 h. b O-Sn/
C-Sn ) >99/1. c O-Sn/C-Sn ) 53/47. d O-Sn/C-Sn ) 19/81, E/Z ) 16/84.
e Reactions were conducted with 10 mol % (R)-BINAP‚AgOTf, 1.0 equiv
of nitrosobenzene, and 2.0 equiv of tin enolate in THF at -78 °C for 2 h.
f Reactions were conducted with 10 mol % (R)-BINAP‚AgOTf, 1.0 equiv
of nitrosobenzene, and 5.0 equiv of tin enolate in THF at -78 °C for 2 h.
g Tin enolates were prepared from 1 equiv of acetate and 1 equiv of tin
methoxide and distilled. h Tin enolates were generated in situ from 1.0 equiv
of trichloro acetate and 1.2 equiv of tin methoxide. i Catalyst A: (R)-
BINAP‚AgClO4. Catalyst B: (R)-TolBINAP‚AgOTf. Catalyst C: (R)-
TolBINAP‚AgClO4. j Isolated yield of two isomers. k Determined by HPLC
(Supporting Information).
(5) Momiyama, N.; Yamamoto, H. Angew. Chem., Int. Ed. 2002, 41, 2986,
3313.
(6) (a) Sasaki, T.; Ishibashi, Y.; Ohno, M. Chem. Lett. 1983, 863. (b) Sasaki,
T.; Mori, K.; Ohno, M. Synthesis 1985, 279. (c) Sasaki, T.; Mori, K.;
Ohno, M. Synthesis 1985, 280. (d) Momiyama, N.; Yamamoto, H. Org.
Lett. 2002, 4, 3579.
(7) (a) Yanagisawa, A.; Nakashima, H.; Ishiba, A.; Yamamoto, H. J. Am.
Chem. Soc. 1996, 118, 4723. (b) Yanagisawa, A.; Matsumoto, Y.;
Nakashima, H.; Asakawa, K.; Yamamoto, H. J. Am. Chem. Soc. 1997,
119, 9319. (c) Yanagisawa, A.; Matsumoto, Y.; Asakawa, K.; Yamamoto,
H. J. Am. Chem. Soc. 1999, 121, 892. (d) Yanagisawa, A.; Nakashima,
H.; Nakatsuka, Y.; Ishiba, A.; Yamamoto, H. Bull. Chem. Soc. Jpn. 2001,
74, 1129. (e) Yanagisawa, A.; Matsumoto, Y.; Nakashima, H.; Asakawa,
K.; Yamamoto, H. Tetrahedron 2002, 58, 8331.
(8) The reaction of nitrosobenzene and enolsilane with (R)-TolBINAP‚AgOTf
did not afford aminooxy ketone.
(9) Ferraris, D.; Young, B.; Dudding, T.; Lectka, T. J. Am. Chem. Soc. 1998,
120, 4548.
to the NdO bond catalyzed by Lewis acid. The enantioselective,
O-selective nitroso aldol process provides direct access to chiral
R-hydroxy ketone. Further investigations into the mechanism and
catalytic enantioselective variants of this process are currently
underway, and results will be reported in due course.
(10) (a) Preyre, M.; Bellegarde, B.; Mendelsohn, J.; Valade, J. J. Organomet.
Chem. 1968, 11, 97. (b) Yanagisawa, A.; Matsumoto, Y.; Asakawa, K.;
Yamamoto, H. J. Am. Chem. Soc. 1999, 121, 892.
JA0298702
9
J. AM. CHEM. SOC. VOL. 125, NO. 20, 2003 6039