Enantioselective nitroso aldol reaction catalyzed by quinoxp *silver(I) complex and tin methoxide

Article abstract of DOI:10.1021/ja910588w

A catalytic enantioselective O-nitroso aldol reaction of alkenyl trichloroacetates with nitrosoarenes was achieved using the (R,R)-t-Bu- QuinoxP*AgOAc complex as the chiral catalyst and Bu₂Sn(OMe) ₂ as the achiral cocatalyst in the presence of methanol. Optically active ?-aminooxy ketones with up to 99% ee were regioselectively obtained in high yields from various alkenyl trichloroacetates of cyclic ketones.

Full text of DOI:10.1021/ja910588w

Published on Web 03/25/2010
Enantioselective Nitroso Aldol Reaction Catalyzed by QuinoxP*· Silver(I)
Complex and Tin Methoxide
Akira Yanagisawa,* Satoshi Takeshita, Youhei Izumi, and Kazuhiro Yoshida
Department of Chemistry, Graduate School of Science, Chiba UniVersity, Chiba 263-8522, Japan
Received December 16, 2009; E-mail: ayanagi@faculty.chiba-u.jp
Table 1. Optimization of Catalytic Asymmetric Nitroso Aldol
The asymmetric nitroso aldol reaction is a convenient method for
the preparation of nonracemic R-aminooxy and/or R-hydroxyamino
carbonyl compounds.1-3 We have recently found that dibutyltin
dimethoxide catalyzes the N-nitroso aldol reaction between alkenyl
trichloroacetates and nitrosobenzene in the presence of methanol.4 The
reaction proceeds via a tin enolate, and the tin methoxide is regenerated
with the assistance of MeOH. We envisaged that if an appropriate
chiral Lewis acid could activate the nitrosoarene without disturbing
the tin-promoted catalysis, the asymmetric version of the nitroso aldol
reaction would be achieved. We report here a novel example of the
enantioselective nitroso aldol reaction using QuinoxP* ·silver(I) com-
plex as the chiral catalyst (eq 1).
Reaction of Alkenyl Trichloroacetatesa
ee, %
(O-adduct)c
entry
phosphine ligand
a
b
solvent yield, %b
O/N
d
(S,S)-CHIRAPHOS
(S)-BINAP
(S)-Tol-BINAP
(R)-MOP
10 20 toluene
10 20 toluene
10 20 toluene
10 20 toluene
10 20 toluene
55
73
68
29
68
70
45
68
68
64
65
26
72/28
87/13
90/10
39/61
79/21
91/9
78/22
88/12
73/27
92/8
<1
1
2
3
4
d
85 (R)
92 (R)
22 (S)
93 (R)
98 (S)
96 (S)
98 (S)
94 (S)
95 (S)
99 (S)
98 (S)
d
d
(S)-SEGPHOS
5
6
7
8
9
(R,R)-t-Bu-QuinoxP* 10 20 toluene
(R,R)-t-Bu-QuinoxP* 10 20 CH2Cl2
(R,R)-t-Bu-QuinoxP* 10 20 Et2O
(R,R)-t-Bu-QuinoxP* 10 20 THF
First, we tested the catalytic activity of BINAP ·AgX complexes
that have been shown by Momiyama and Yamamoto5 to be efficient
chiral catalysts for asymmetric nitroso aldol reactions. When a 1:2
mixture of nitrosobenzene and 1-trichloroacetoxycyclohexene was
treated with (S)-BINAP ·AgOAc (10 mol %) and Bu2Sn(OMe)2 (20
mol %) in the presence of MeOH (30 equiv) in toluene at -78 °C
for 3 h, an 87:13 mixture of the R-aminooxy ketone (O-adduct)
and R-hydroxyamino ketone (N-adduct) was obtained in 73%
combined yield (Table 1, entry 2). The O-adduct had 85% ee (R).
Next, we further examined the catalytic activity of chiral phosphines
other than BINAP and found that t-Bu-QuinoxP* was the chiral
ligand of choice (entry 6 vs entries 1-5).6 The enantioselectivity
of the reaction reached 98% ee (entry 6). In order to get better
results, we attempted to optimize the reaction conditions. Among
the solvents investigated, toluene gave the highest yield and ee
(entry 6 vs entries 7-10). Reducing the amounts of t-Bu-
QuinoxP* ·AgOAc and Bu2Sn(OMe)2 to 5 and 10 mol %, respec-
tively, did not affect the chemical yield, the O/N ratio, or the
enantioselectivity (entry 11).
10 (R,R)-t-Bu-QuinoxP* 10 20 MeOH
11 (R,R)-t-Bu-QuinoxP*
12 (R,R)-t-Bu-QuinoxP*
5
2
10 toluene
toluene
89/11
79/21
4
a Unless otherwise specified, the reaction was carried out using chiral
phosphine (2-10 mol %), silver acetate (2-10 mol %), dibutyltin
dimethoxide (4-20 mol %), alkenyl trichloroacetate (2 equiv),
nitrosobenzene (1 equiv), and methanol (30 equiv) in the specified
solvent at -78 °C for 3 h. b Isolated yield. c The value is for the
O-adduct and was determined by HPLC analysis. The absolute
configuration of the O-adduct is shown in parentheses. d The reaction
time was 2 h.
Table 2. Catalytic Asymmetric O-Nitroso Aldol Reaction of Diverse
Nitrosoarenesa
With the optimized reaction conditions in hand, we studied the
catalytic asymmetric O-nitroso aldol reaction employing substituted
nitrosobenzenes (Table 2). An obvious decrease in the ee as well
as the yield and the O/N ratio was observed for a substrate that
had an electron-withdrawing group at the para position (entry 2).
In contrast, the introduction of a methyl group at the ortho or para
position promoted the reaction, affording the O-adduct with 99%
ee without significant loss of reactivity or regioselectivity (entries
3 and 4). However, use of 1-methoxy-4-nitrosobenzene resulted in
no yield of adducts because of their instability.
entry
R1
R2
yield, %b
O/N
ee, % (O-adduct)c
1
2
3
4
H
H
H
H
Me
65
28
40
67
89/11
63/37
90/10
76/24
99 (S)d
90
99
Br
Me
H
99
a Unless otherwise specified, the reaction was carried out using
(R,R)-t-Bu-QuinoxP* (5 mol %), silver acetate (5 mol %), dibutyltin
dimethoxide (10 mol %), alkenyl trichloroacetate (2 equiv), nitrosoarene
(1 equiv), and methanol (30 equiv) in toluene at -78 °C for 3 h.
b Isolated yield. c The value is for the O-adduct and was determined by
HPLC analysis. d The absolute configuration is shown in parentheses.
The aforementioned results further encouraged us to use various
alkenyl trichloroacetates of cyclic ketones in the asymmetric
R-aminooxylation, as shown in Table 3. Both cyclopentanone and
9
5328 J. AM. CHEM. SOC. 2010, 132, 5328–5329
10.1021/ja910588w  2010 American Chemical Society

C O M M U N I C A T I O N S
cycloheptanone derivatives gave high optical purities similar to that
of the cyclohexanone derivative (entries 1-3). In regard to
1-tetralone derivatives, nearly exclusive O-selectivity in addition
to excellent enantioselectivity was observed, although the 2-methyl-
1-tetralone derivative afforded a low yield because of steric
bulkiness (entries 4-6). The existence of two methyl groups at
either the 4- or 6-position of the cyclohexanone-derived alkenyl
trichloroacetate effectively improved the O/N ratio (entries 7 and
8). In the case of acyclic alkenyl trichloroacetates, a significant
amount of N-adduct was formed (entries 9 and 10).
Table 3. Catalytic Asymmetric O-Nitroso Aldol Reaction of Various
Alkenyl Trichloroacetatesa
Figure 1. Plausible catalytic cycle for the asymmetric O-nitroso aldol
reaction.
Figure 2. Proposed transition states for the asymmetric O-nitroso aldol
reaction.
Acknowledgment. We gratefully acknowledge the generous
gifts of (R,R)-t-Bu-QuinoxP* from Nippon Chemical Industrial Co.,
Ltd. and (S)-SEGPHOS from Takasago International Corporation.
We also thank Professor Takayoshi Arai at Chiba University for
helpful discussions.
a Unless otherwise specified, the reaction was carried out using
(R,R)-t-Bu-QuinoxP* (5 mol %), silver acetate (5 mol %), dibutyltin
dimethoxide (10 mol %), alkenyl trichloroacetate (2 equiv), nitrosobenzene
(1 equiv), and methanol (30 equiv) in toluene at -78 °C for 3 h. b Isolated
yield. c The value is for the O-adduct and was determined by HPLC
analysis. d The absolute configuration is shown in parentheses. e The
reaction was performed at -40 °C. f The value is for the N-adduct.
Supporting Information Available: Experimental procedures and
spectral data for the products in Tables 1-3. This material is available
free of charge via the Internet at http://pubs.acs.org.
References
(1) For reviews, see: (a) Merino, P.; Tejero, T. Angew. Chem., Int. Ed. 2004,
43, 2995. (b) Janey, J. M. Angew. Chem., Int. Ed. 2005, 44, 4292. (c)
Yamamoto, H.; Momiyama, N. Chem. Commun. 2005, 3514. (d) Yamamoto,
H.; Kawasaki, M. Bull. Chem. Soc. Jpn. 2007, 80, 595.
(2) For recent notable examples of N-nitroso aldol reactions promoted by
organocatalysts, see: (a) Momiyama, N.; Yamamoto, H. J. Am. Chem. Soc.
2005, 127, 1080. (b) Kano, T.; Ueda, M.; Takai, J.; Maruoka, K. J. Am.
Chem. Soc. 2006, 128, 6046. (c) Palomo, C.; Vera, S.; Velilla, I.; Mielgo,
A.; Go´mez-Bengoa, E. Angew. Chem., Int. Ed. 2007, 46, 8054.
A plausible catalytic cycle is shown in Figure 1. First of all,
Bu2Sn(OMe)2 reacts with alkenyl trichloroacetate 1 to yield tin
enolate 2 accompanied by methyl trichloroacetate. Next, enolate 2
is allowed to add to nitrosobenzene enantioselectively in the
presence of the chiral phosphine ·silver(I) complex, affording the
tin amide of R-aminooxy ketone 3. Finally, protonation of tin amide
3 with MeOH results in the formation of optically active R-ami-
nooxy ketone 4 and the regeneration of Bu2Sn(OMe)2. The rapid
methanolysis of tin amide 3 promotes the catalytic cycle.
The proposed transition state structures of this O-nitroso aldol
reaction are shown in Figure 2. Initially, the silver atom of the
(R,R)-t-Bu-QuinoxP* ·AgOAc complex coordinates to the nitrogen
atom of nitrosobenzene. A tin enolate then approaches the oxygen
atom of nitrosobenzene while avoiding steric repulsion from a tert-
butyl group of the chiral phosphine ligand. Thus, aminooxylation
occurs selectively at the Si face of the tin enolate to afford the
(S)-R-aminooxy ketone.
(3) For recent notable examples of O-nitroso aldol reactions promoted by
organocatalysts, see: (a) Zhong, G. Angew. Chem., Int. Ed. 2003, 42, 4247.
(b) Brown, S. P.; Brochu, M. P.; Sinz, C. J.; MacMillan, D. W. C. J. Am.
Chem. Soc. 2003, 125, 10808. (c) Bøgevig, A.; Sunde´n, H.; Co´rdova, A.
Angew. Chem., Int. Ed. 2004, 43, 1109. (d) Hayashi, Y.; Yamaguchi, J.;
Sumiya, T.; Shoji, M. Angew. Chem., Int. Ed. 2004, 43, 1112. (e) Lu, M.;
Zhu, D.; Lu, Y.; Hou, Y.; Tan, B.; Zhong, G. Angew. Chem., Int. Ed. 2008,
47, 10187. (f) Lu, M.; Zhu, D.; Lu, Y.; Zeng, X.; Tan, B.; Xu, Z.; Zhong,
G. J. Am. Chem. Soc. 2009, 131, 4562. (g) Kano, T.; Yamamoto, A.; Shirozu,
F.; Maruoka, K. Synlett 2009, 1557. (h) Jiao, P.; Kawasaki, M.; Yamamoto,
H. Angew. Chem., Int. Ed. 2009, 48, 3333. Also see ref 2a.
(4) Yanagisawa, A.; Izumi, Y.; Takeshita, S. Synlett 2009, 716.
(5) (a) Momiyama, N.; Yamamoto, H. J. Am. Chem. Soc. 2003, 125, 6038.
Momiyama, N.; Yamamoto, H. J. Am. Chem. Soc. 2004, 126, 6498
(correction). (b) Momiyama, N.; Yamamoto, H. J. Am. Chem. Soc. 2004,
126, 5360. (c) Yamamoto, Y.; Momiyama, N.; Yamamoto, H. J. Am. Chem.
Soc. 2004, 126, 5962. Also see: (d) Kawasaki, M.; Li, P.; Yamamoto, H.
Angew. Chem., Int. Ed. 2008, 47, 3795.
In conclusion, we have developed a novel catalytic asymmetric
aminooxylation system. The use of the t-Bu-QuinoxP* ·AgOAc
complex as the chiral catalyst and Bu2Sn(OMe)2 as the achiral
cocatalyst allows the synthesis of various nonracemic R-aminooxy
ketones with enantioselectivities of up to 99% ee.
(6) (a) Imamoto, T.; Sugita, K.; Yoshida, K. J. Am. Chem. Soc. 2005, 127, 11934.
(b) Imamoto, T.; Itoh, T.; Yamanoi, Y.; Narui, R.; Yoshida, K. Tetrahedron:
Asymmetry 2006, 17, 560. (c) Imamoto, T.; Nishimura, M.; Koide, A.;
Yoshida, K. J. Org. Chem. 2007, 72, 7413.
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