Urea/transition-metal cooperative catalyst for anti-selective asymmetric nitroaldol reactions

Article abstract of DOI:10.1002/anie.201107785

A cooperative catalyst that features urea H-bonding and a cobalt center was developed for anti-selective asymmetric Henry reactions (see scheme). The H-bonds of urea play a crucial role in the improvement in yield (from 30 % to 84 %), enantioselectivity (

Full text of DOI:10.1002/anie.201107785

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DOI: 10.1002/anie.201107785
Cooperative Catalysis
Urea/Transition-Metal Cooperative Catalyst for anti-Selective
Asymmetric Nitroaldol Reactions**
Kai Lang, Jongwoo Park, and Sukwon Hong*
Dedicated to Professor Eun Lee on the occasion of his 65th birthday
Simultaneous activation of two reaction partners in a well-
defined spatial arrangement is a common theme in enzyme
catalysis. This nature-inspired concept of cooperative activa-
tion has emerged as a new trend in the design of highly
efficient asymmetric catalysts.[1] A number of bimetallic
catalysts,[2] bifunctional organocatalysts,[3] and bifunctional
metal catalysts[4] that demonstrate excellent performance
have been developed. Among them, bifunctional catalysts
often feature an acidic site (Lewis acid or H-bond-donor
unit), which is tethered to a base. Nonetheless, examples of an
alternative design in which a Lewis acid and an H-bond donor
are tethered are quite rare.[5]
Henry reaction,[10] either by bimetallic dual activation or by
H-bond/metal bifunctional activation (Scheme 1). Herein we
report highly enantio- and anti-diastereoselective Henry
reactions that are catalyzed by the [(bisurea–salen)Co]
catalysts 1·X. The cooperative activation by H-bonds of
urea and the Lewis acidic metal center is suggested by
preliminary studies.
Asymmetric nitroaldol (Henry) reactions[6–8,9a,b,10] have
ꢀ
drawn much attention as important carbon carbon bond-
forming reactions. Several bimetallic and bifunctional cata-
lysts exhibited high enantioselectivity in Henry reactions with
nitromethane. However, asymmetric Henry reactions with
nitroalkanes other than nitromethane proved to be more
challenging,[7,8] and often suffered from slow reaction rates
and poor diastereoselectivity. Particularly, anti diastereose-
lectivity is difficult to achieve,[8] which could be attributed to
the fact that a metal-chelation transition state would favor a
syn diastereomer.[8g] Thus, an open antiparallel transition
state was strategically pursued for anti-selective Henry
reactions.[8a–c] Recently, the research groups of Ooi and
Shibasaki have independently reported highly anti-selective
catalysts that enable an antiparallel transition geometry by
double H-bonding[8d,e] and a heterobimetallic scaffold,[8f,g]
respectively.
Scheme 1. a) Bimetallic (self-assembled) and b) monometallic (bifunc-
tional) activation by [(bisurea–salen)Co] catalysts.
With the aim to design dual activation catalysts, we
previously developed base-tethered copper catalysts[9a] and
self-assembled dinuclear cobalt catalysts through aminopyr-
idine/pyridone H-bonding interactions.[9b] Recently, we
devised second-generation self-assembled catalysts that fea-
ture urea–urea H-bonding, and such [(bisurea–salen)Co]
catalysts showed significant rate acceleration in bimetallic
transformations.[9c] During the course of the study, we were
intrigued by the possibility that the [(bisurea–salen)Co]
catalyst might enable the antiparallel transition state for the
[(Bisurea–salen)Co] catalysts (1·X) were optimized with
the diastereoselective Henry reaction with nitroethane (3a)
at ꢀ708C (Table 1). The metal oxidation state proved to be
pivotal, and a CoIII-based catalyst (X = OTs) significantly
improved the reaction yield, the anti/syn diastereomeric ratio,
and the enantioselectivity (Table 1, entry 1 versus entry 2).
The reaction conditions were then further optimized with
regard to solvent, base, and counterion. Higher anti selectivity
was observed with methyl tert-butyl ether (MTBE) as solvent
and N-ethylpiperidine (EtPip) as base. Although both
toluene-p-sulfonate (OTs) and 3,5-bis(trifluoromethyl)ben-
zoate (OBzF) gave excellent stereoselectivity with 2a
(Table 1, entries 7 and 8), OBzF was selected from further
screening with 4-fluorobenzaldehyde (2b).[11] Note that an
excellent anti diastereoselectivity (48:1) and enantioselectiv-
ity (96% ee) were achieved under the optimized conditions
(Table 1, entry 8).
[*] K. Lang, J. Park, Prof. S. Hong
Department of Chemistry, University of Florida
Gainesville, FL 32611-7200 (USA)
E-mail: sukwon@ufl.edu
[**] This work was supported by the U.S. National Science Foundation
(Grant CHE-0957643).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201107785.
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Table 1: Optimization of reaction conditions.[a]
(Table 2, entry 12) and linear aliphatic aldehydes (Table 2,
entries 13 and 14).
Catalyst 1·OBzF generally gave excellent enantioselectiv-
ities (90–98% ee for anti product) and good yields (80–94%)
in the Henry reactions with nitroethane (3a; Table 3).
Table 3: Scope of diastereoselective Henry reactions.[a]
Entry
Xꢀ
Base
Solvent
Yield [%][b]
d.r.[c]
4:1
8:1
11:1
13:1
18:1
24:1
>50:1
48:1
ee [%][d]
Entry
R
t [h] Yield [%][b]
d.r.[c] ee [%][d]
1
2
3
4
5
6
7
8
–
DIPEA
DIPEA
DIPEA
Et3N
CH2Cl2
CH2Cl2
MTBE
CH2Cl2
MTBE
CH2Cl2
MTBE
MTBE
49
71
68
88
82
83
81
84
53/18
92/59
87/58
90/59
93/73
95/82
93/n.d.
96/n.d.
OTs
OTs
OTs
OTs
OTs
OTs
OBzF
1
2
3
4
2-MeO-C6H4 (2a)
2-BnO-C6H4(2o)
2-Cl-C6H4(2c)
2-F-C6H4 (2d)
3-F-C6H4 (2 f)
3-MeO-C6H4(2p)
4-F-C6H4 (2b)
4-Ph-C6H4 (2h)
C6H5 (2k)
24
24
20
24
24
24
18
24
48
24
30
84
85
89
90
82
95
87
86
94
89
80
82
48:1 96/nd
11:1 96/76
10:1 90/74
8:1 94/82
1.8:1 95/85
2.0:1 99/87
2.5:1 98/85
2.4:1 97/86
1.6:1 97/82
1.1:1 96/90
9:1 98/65
4:1 97/90
Et3N
EtPip
EtPip
EtPip
5
6[e]
7
8
9
10
11
12
[a] All reactions were performed on a 0.25 mmol scale of aldehyde with
1·X (5 mol%) and nitroethane (10 equiv) in solvent (0.1 mL) at ꢀ708C.
[b] Yields of isolated products. [c] Determined by 1H NMR spectroscopy.
[d] ee values of anti/syn diastereomers determined by HPLC analysis on a
chiral stationary phase. DIPEA=N,N-diisopropylethylamine, n.d.=not
determined. The entry in bold marks the optimized reaction conditions.
BnOCH2CH2 (2m)
Me2C CH (2q)
(E)-Ph(Me)C CH (2r) 36
=
=
[a] Reactions were performed on a 0.25 mmol scale of aldehyde with
1·OBzF (5 mol%) and nitroethane (10 equiv) in MTBE (0.1 mL) at
ꢀ708C. [b] Yields of isolated products. [c] Ratio of anti:syn determined by
1H NMR spectroscopy. [d] ee values of anti/syn diastereomers, deter-
mined by HPLC analysis on a chiral stationary phase. [e] Reaction was
run at ꢀ508C.
The optimized catalyst 1·OBzF was first applied to
enantioselective Henry reactions with nitromethane
(Table 2). Excellent enantioselectivities (94–97% ee) and
good yields (82–99%) were observed with variously substi-
tuted benzaldehydes (Table 2, entries 1–11). Furthermore,
high enantioselectivities (91–92% ee) and good yields (88–
90%) were also observed with an a,b-unsaturated aldehyde
However, the anti diastereoselectivity varies with the sub-
strate. While high anti selectivities were obtained with
benzaldehydes with an ortho substituent (Table 3, entries 1–
4), anti selectivity significantly decreased with benzaldehydes
that lack ortho substitution (d.r. ꢁ 2:1; Table 3, entries 5–9).
Interestingly, a similar “ortho effect” was observed with non-
aromatic aldehydes (Table 3, entries 11 and 12 versus
entry 10).
Table 2: Enantioselective Henry reactions with nitromethane.[a]
High anti selectivities as well as excellent enantioselectiv-
ities were observed for di- or trisubstituted benzaldehydes
that bear an ortho-alkoxy substituent (Table 4). Additional
substitution at the C-3 (Table 4, entry 1), C-4 (entries 2 and 3),
and C-5 positions (entries 4–7) seems to be well tolerated if an
ortho-alkoxy group is present. Furthermore, it is possible to
use other nitroalkanes, such as TBSOCH2CH2NO2 (3b;
Table 4, entries 8–10) and nitropropane (3c; entry 11). To
the best of our knowledge, examples of highly anti-selective
asymmetric nitroaldol reactions with such 2-alkoxy-contain-
ing benzaldehydes are very rare.[12]
The synthetic utility of anti-selective nitroaldol reactions
of 2-alkoxy-containing benzaldehydes is demonstrated by the
short stereoselective synthesis of (1R,2S)-methoxamine hy-
drochloride, an a1-adrenergic receptor agonist[13] (Scheme 2).
While previous stereoselective syntheses of methoxami-
ne·HCl typically involved diastereoselective reduction of a
chiral a-aminoketone,[14] the current method allows the
introduction of both stereocenters in a single step with
Entry
R
t [h]
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
2-MeO-C6H4 (2a)
2-Cl-C6H4 (2c)
2-F-C6H4(2d)
20
24
24
24
24
24
24
18
30
24
24
30
24
18
99
94
99
99
88
85
87
95
82
86
85
88
90
89
97
95
96
97
95
94
95
96
94
95
97
92
92
91
1-naphthyl (2e)
3-F-C6H4 (2 f)
4-F-C6H4 (2b)
4-Cl-C6H4 (2g)
4-Ph-C6H4 (2h)
4-MeO-C6H4 (2i)
4-benzodioxole (2j)
C6H5(2k)
9[d]
10
11
12
13
14[d]
=
(E)-Ph-CH CH (2l)
BnOCH2CH2(2m)
PhCH2CH2 (2n)
[a] Reactions were performed on a 0.25 mmol scale of aldehyde with
1·OBzF (5 mol%) and nitromethane (10 equiv) in CH2Cl2 (0.3 mL) at
ꢀ708C. [b] Yields of isolated products. [c] Determined by HPLC analysis
on a chiral stationary phase. [d] Reaction was run at ꢀ508C. Bn=benzyl.
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Table 4: Henry reactions of substituted benzaldehydes that bear an ortho- Table 5: Control experiments.
alkoxy group.[a]
Entry Product
1
t [h] Yield [%][b] d.r.[c]
ee [%][d]
96/80
4ja
24
96
8:1
4sa
2
3
(R2 =Br)
4ta
24
72
94
81
15:1 95/96
>50:1 90/n.d.
Entry
Catalyst
Additive
Yield [%][a]
d.r.[b]
ee [%][c]
(R2 =OMe)
4ua
1
2
3
6·OBzF
6·OBzF
6·OBzF
–
–
30
75
85
85
14
84
3:1
5:1
5:1
3:1
4:1
78/81
62/65
62/64
0/0
85/82
96/n.d.
8 (10 mol%)
8 (50 mol%)
8 (10 mol%)
–
–
4
(R3 =F)
4va
24
16
92
99
26:1 96/86
24:1 96/76
5[e]
4[d]
5
(R3 =OMe)
7·OBzF
1·OBzF
6
48:1
6
4wa
4xa
24
36
96
95
9:1 94/n.d.
17:1 97/n.d.
[a] Yields of isolated products. [b] Ratio of anti/syn determined by
1H NMR spectroscopy. [c] ee values of anti/syn diastereomers, deter-
mined by HPLC analysis on a chiral stationary phase. [d] The reaction
does not proceed with N-ethylpiperidine alone at ꢀ708C.
7[e]
methyl-functionalized catalyst 7·OBzF gave nitroaldol prod-
uct 4aa in much lower yield and stereoselectivity (Table 5,
entries 1 and 5), compared to urea-functionalized catalyst
1·OBzF (Table 5, entry 6). Furthermore, control experiments
with varying amounts of exogenous urea additive[15] 8 show
that the reaction is significantly accelerated by the additive
(Table 5, entries 1–3). Note that 8 alone (without the Co
catalyst) can catalyze the diastereoselective Henry reaction to
give the product in 85% yield and 3:1 d.r. (Table 5, entry 4),
thus suggesting that urea 8 is capable to activate the
reactants.[16]
Secondly, when the relationship between the enantiomer-
ic purity of the [(salen)Co] catalysts and that of the Henry
reaction product 5a was investigated, an interesting trend was
observed (Figure 1). A positive nonlinear effect[17] was
observed for both CoII catalysts (6 and 1), thus suggesting a
nonmonomeric active species (Figure 1a and c), whereas a
linear relationship was observed for the corresponding CoIII
catalysts (6·OBzF and 1·OBzF; Figure 1b and d). Furthermore,
while the rate of the reaction 2a!5a was second order with
respect to [catalyst] for the unfunctionalized CoII catalyst 6
(rate = k[6]2),[9b] the corresponding CoIII catalyst 6·OBzF
showed first-order kinetics (rate = k[6·OBzF]).[18,19] These
results suggest that a monometallic pathway is favored in
[(salen)CoIII]-catalyzed Henry reactions. Our initial attempts
to determine the association constant between urea 8 and
nitroalkane from 1H NMR experiments were unsuccessful,[11]
presumably because of the weak urea/nitroalkane interac-
tion.[20] In sharp contrast, when the pregenerated 2-nitro-
propanate anion and urea 8 were used in the 1H NMR
titration experiment, a sufficiently high association constant
(Ka = 510mꢀ1) was observed in [D6]-DMSO at 258C, which is
in good agreement with previous reports.[21] Note that the
NMR titration results support the idea that the urea group
can interact/activate anionic nitronate nucleophiles. All of
4ab
(R4 =H)
4ub
8[f]
48
42
60
88
99
97
>50:1 94/n.d.
8:1 93/75
9[f]
(R4 =F)
4vb
10[f]
7:1 91/76
(R4 =OMe)
11
4ac
36
67
6:1 85/88
[a] Reactions were performed on a 0.25 mmol scale of aldehyde with
1·OBzF (5 mol%) and nitroethane (10 equiv) in MTBE (0.1 mL) at ꢀ708C.
[b] Yields of isolated products. [c] Ratio of anti:syn determined by 1H NMR
spectroscopy. [d] ee values of anti/syn diastereomers, determined by
HPLC analysis on a chiral stationary phase. [e] Reaction was run at
ꢀ508C. [f] Reaction was run at ꢀ508C with 3b (5 equiv) in MTBE
(0.5 mL). TBS=tert-butyldimethylsilyl.
Scheme 2. Asymmetric synthesis of (1R,2S)-methoxamine·HCl.
excellent stereocontrol (anti:syn = 24:1, 94% ee for anti) by
using 5 mol% of the antipode catalyst (S,S)-1·OBzF.
To elucidate the mechanism of the [(bisurea–salen)Co]
catalyzed reaction, a series of experimental studies were
performed. Firstly, the NH moiety of urea proved to be crucial
for both the reaction rate and stereoselectivity (Table 5). The
unfunctionalized [(salen)CoIII] catalyst 6·OBzF and the N-
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c) S. Handa, V. Gnanadesikan, S. Matsunaga, M. Shibasaki, J.
Am. Chem. Soc. 2010, 132, 4925; d) K. Endo, M. Ogawa, T.
Shibata, Angew. Chem. 2010, 122, 2460; Angew. Chem. Int. Ed.
2010, 49, 2410.
[3] For reviews on bifunctional organocatalysts, see: a) M. S. Taylor,
E. N. Jacobsen, Angew. Chem. 2006, 118, 1550; Angew. Chem.
Int. Ed. 2006, 45, 1520; b) S. J. Connon, Chem. Commun. 2008,
2499; c) A. Dondoni, A. Massi, Angew. Chem. 2008, 120, 4716;
Angew. Chem. Int. Ed. 2008, 47, 4638; d) C. Palomo, M.
Oiarbide, R. Lꢀpez, Chem. Soc. Rev. 2009, 38, 632.
[4] For selected examples of bifunctional metal/tethered amine
catalysts, see: a) E. F. DiMauro, M. C. Kozlowski, J. Am. Chem.
Soc. 2002, 124, 12668; b) S. France, M. H. Shah, A. Weatherwax,
H. Wack, J. P. Roth, T. Lectka, J. Am. Chem. Soc. 2005, 127,
1206; c) Y.-M. Lin, J. Boucau, Z. Li, V. Casarotto, J. Lin, A. N.
Nguyen, J. Ehrmantraut, Org. Lett. 2007, 9, 567; d) F. Yang, D.
Zhao, J. Lan, P. Xi, L. Yang, S. Xiang, J. You, Angew. Chem.
2008, 120, 5728; Angew. Chem. Int. Ed. 2008, 47, 5646; e) T. Kull,
J. Cabrera, R. Peters, Chem. Eur. J. 2010, 16, 9132.
[5] For a recent example of cooperative catalysis that comprises a
Lewis acid and an amine – urea organocatalyst, see: T. Yang, A.
Ferrali, F. Sladojevich, L. Campbell, D. J. Dixon, J. Am. Chem.
Soc. 2009, 131, 9140.
Figure 1. Studies on the (non)linear effect of the reaction of 2a to 5a
with [(salen)Co] catalysts by varying the metal oxidation state and the
presence of the bisurea functionality. Reactions with a) unfunctional-
ized CoII catalyst, b) unfunctionalized CoIII catalyst, c) bisurea-function-
alized CoII catalyst, and d) bisurea-functionalized CoIII catalyst.
[6] For recent reviews, see: a) C. Palomo, M. Oiarbide, A. Laso, Eur.
J. Org. Chem. 2007, 2561; for selected examples, see: b) H. Sasai,
T. Suzuki, S. Arai, T. Arai, M. Shibasaki, J. Am. Chem. Soc. 1992,
114, 4418; c) C. Christensen, K. Juhl, R. G. Hazell, K. A.
Jørgensen, J. Org. Chem. 2002, 67, 4875; d) B. M. Trost, V. S. C.
Yeh, Angew. Chem. 2002, 114, 889; Angew. Chem. Int. Ed. 2002,
41, 861; e) D. A. Evans, D. Seidel, M. Rueping, H. W. Lam, J. T.
Shaw, C. W. Downey, J. Am. Chem. Soc. 2003, 125, 12692; f) C.
Palomo, M. Oiarbide, A. Laso, Angew. Chem. 2005, 117, 3949;
Angew. Chem. Int. Ed. 2005, 44, 3881.
[7] For syn-selective asymmetric Henry reactions, see: a) H. Sasai,
T. Tokunaga, S. Watanabe, T. Suzuki, N. Itoh, M. Shibasaki, J.
Org. Chem. 1995, 60, 7388; b) Y. Sohtome, Y. Hashimoto, K.
Nagasawa, Eur. J. Org. Chem. 2006, 2894; c) Y. Sohtome, Y.
Kato, S. Handa, N. Aoyama, K. Nagawa, S. Matsunaga, M.
Shibasaki, Org. Lett. 2008, 10, 2231; d) L. Cheng, J. Dong, J. You,
G. Gao, J. Lan, Chem. Eur. J. 2010, 16, 6761; e) T. Arai, R.
Takashita, Y. Endo, M. Watanabe, A. Yanagisawa, J. Org. Chem.
2008, 73, 4903; f) Y. Zhou, J. Dong, F. Zhang, Y. Gong, J. Org.
Chem. 2011, 76, 588.
[8] a) D. Seebach, A. K. Beck, F. Lehr, T. Weller, E. Colvin, Angew.
Chem. 1981, 93, 422; Angew. Chem. Int. Ed. Engl. 1981, 20, 397;
for anti-selective asymmetric Henry reactions using silyl nitro-
nates, see: b) T. Risgaard, K. V. Gothelf, K. A. Jørgensen, Org.
Biomol. Chem. 2003, 1, 153; c) T. Ooi, K. Doda, K. Maruoka, J.
Am. Chem. Soc. 2003, 125, 2054; for anti-selective Henry
reactions using nitroalkanes directly, see: d) D. Uraguchi, S.
Sakaki, T. Ooi, J. Am. Chem. Soc. 2007, 129, 12392; e) D.
Uraguchi, S. Nakamura, T. Ooi, Angew. Chem. 2010, 122, 7724;
Angew. Chem. Int. Ed. 2010, 49, 7562; f) S. Handa, K. Nagawa, Y.
Sohtome, S. Matsunaga, M. Shibasaki, Angew. Chem. 2008, 120,
3274; Angew. Chem. Int. Ed. 2008, 47, 3230; g) T. Nitabaru, A.
Nojiri, M. Kobayashi, N. Kumagai, M. Shibasaki, J. Am. Chem.
Soc. 2009, 131, 13860; h) G. Blay, L. R. Domingo, V. Hernꢁndez-
Olmos, J. R. Pedro, Chem. Eur. J. 2008, 14, 4725; i) G. Blay, V.
Hernꢁndez-Olmos, J. R. Pedro, Org. Lett. 2010, 12, 3058.
[9] a) K. Lang, J. Park, S. Hong, J. Org. Chem. 2010, 75, 6424; b) J.
Park, K. Lang, K. A. Abboud, S. Hong, J. Am. Chem. Soc. 2008,
130, 16484; c) J. Park, K. Lang, K. A. Abboud, S. Hong, Chem.
Eur. J. 2011, 17, 2236.
those observations collectively suggest that the monometallic,
bifunctional mechanism is operative for the [(bisurea–sale-
n)CoIII] catalyzed nitroaldol reactions in which the coopera-
tive activation is provided by H-bonds of urea[22,23,24] and the
Lewis acidic metal center (Scheme 1b).
In conclusion, a new type of cooperative catalyst that
features urea H-bonding and a cobalt center has been
developed for anti-selective asymmetric nitroaldol reactions.
The urea H-bonds play a crucial role in the dramatic
improvement in reaction yield, enantioselectivity, and anti-
diastereoselectivity. The use of the urea–cobalt bifunctional
catalyst successfully extends the substrate scope of anti-
selective Henry reactions to previously unexplored aldehydes,
and the synthetic utility is demonstrated by the concise
asymmetric synthesis of (1R,2S)-methoxamine hydrochloride.
Further application of this novel concept as well as more
detailed mechanistic studies are currently under way in our
research group.
Received: November 4, 2011
Published online: January 4, 2012
Keywords: asymmetric catalysis · cobalt · cooperative effects ·
.
hydrogen bonds · ureas
[1] Reviews: a) J.-A. Ma, D. Cahard, Angew. Chem. 2004, 116, 4666;
Angew. Chem. Int. Ed. 2004, 43, 4566; b) D. H. Paull, C. J.
Abraham, M. T. Scerba, E. Alden-Danforth, T. Lectka, Acc.
Chem. Res. 2008, 41, 655; c) M. Shibasaki, M. Kanai, S.
Matsunaga, N. Kumagai, Acc. Chem. Res. 2009, 42, 1117.
[2] For selected recent examples, see: a) B. M. Trost, J. Hitce, J. Am.
Chem. Soc. 2009, 131, 4572; b) C. Mazet, E. N. Jacobsen, Angew.
Chem. 2008, 120, 1786; Angew. Chem. Int. Ed. 2008, 47, 1762;
[10] For [(salen)metal]-catalyzed Henry reactions, see: a) Y. Kogami,
T. Nakajima, T. Ikeno, T. Yamada, Synthesis 2004, 1947; b) R.
Kowalczyk, Ł. Sidorowicz, J. Skarz
˙ewski, Tetrahedron: Asym-
metry 2007, 18, 2581; c) R. Kowalczyk, P. Kwiatkowski, J.
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Skarz˙ewski, J. Jurczak, J. Org. Chem. 2009, 74, 753; d) A. Zulauf,
M. Mellah, E. Schulz, J. Org. Chem. 2009, 74, 2242; also see
ref. [9b].
cannot distinguish between the two mechanisms (Scheme 1a
versus b), as the first-order kinetics is expected from the
covalently tethered bimetallic catalysts or strongly self-associat-
ing systems. For relevant discussions, see: a) J. M. Ready, E. N.
Jacobsen, J. Am. Chem. Soc. 2001, 123, 2687; b) D. G. Black-
mond, Adv. Synth. Catal. 2002, 344, 156; c) Ref [9c].
[11] See the Supporting Information for details.
[12] To the best of our knowledge, there is only one report that shows
significant anti selectivity for 2-alkoxy-containing benzalde-
hydes. Pedro and co-workers reported the Cu-catalyzed anti-
selective Henry reaction between 2a and nitroethane (3a) to
afford 4aa in 95% yield, anti:syn = 82:18, and 95%/94% ee
(anti/syn). See Ref. [8h].
[13] a) P. N. Patil, A. Tye, J. B. LaPidus, J. Pharmacol. Exp. Ther.
1967, 156, 445; b) R. Baltzly, N. B. Mehta, J. Med. Chem. 1968,
11, 833; c) R. M. DeMarinis, W. M. Bryan, D. H. Shah, J. P.
Hieble, R. G. Pendleton, J. Med. Chem. 1981, 24, 1432; d) O. M.
Jones, J. M. Thompson, A. F. Brading, N. J. M. Mortensen, Br. J.
Surg. 2003, 90, 872.
[14] M. Fujita, T. Hiyama, J. Org. Chem. 1988, 53, 5415.
[15] For a recent example showing the synergy between a chiral Co
catalyst and a thiourea additive, see: H. Y. Kim, K. Oh, Org.
Lett. 2011, 13, 1306.
[16] In contrast, urea additives decreased the rate of the [(salen)-
CoIII]-catalyzed hydrolytic kinetic resolution of epoxides. See
Ref. [9c].
[20] The interaction between (thio)ureas and neutral nitro com-
pounds is generally weak, see: a) T. R. Kelly, M. H. Kim, J. Am.
Chem. Soc. 1994, 116, 7072; b) J. Bu, N. D. Lilienthal, J. E.
Woods, C. E. Nohrden, K. T. Hoang, D. Truong, D. K. Smith, J.
Am. Chem. Soc. 2005, 127, 6423.
[21] Hamilton
determined
the
Ka
(120mꢀ1
)
between
Bu4N+NO2CHCH3ꢀ and 1,3-dimethylthiourea in [D6]-DMSO.
It was found that the negative charge on the nitronate is crucial
for a strong association with thiourea, see: B. R. Linton, M. S.
Goodman, A. D. Hamilton, Chem. Eur. J. 2000, 6, 2449.
[22] For anion recognition by (thio)urea, see: C. Caltagirone, P. A.
Gale, Chem. Soc. Rev. 2009, 38, 520.
[23] For reviews on H-bond-donor catalysis, see: a) A. G. Doyle,
E. N. Jacobsen, Chem. Rev. 2007, 107, 5713; b) Z. Zhang, P. R.
Schreiner, Chem. Soc. Rev. 2009, 38, 1187.
[24] For reviews on catalysis involving (thio)urea/nitro-
(nate)interactions, see: a) Y. Takemoto, Chem. Pharm. Bull.
2010, 58, 593; for selected examples, see: b) T. P. Yoon, E. N.
Jacobsen, Angew. Chem. 2005, 117, 470; Angew. Chem. Int. Ed.
2005, 44, 466; c) T. Okino, Y. Hoashi, T. Furukawa, X. Xu, Y.
Takemoto, J. Am. Chem. Soc. 2005, 127, 119; d) C. Rabalakos,
W. D. Wulff, J. Am. Chem. Soc. 2008, 130, 13524; e) W. J. Nodes,
D. R. Nutt, A. M. Chippindale, A. J. A. Cobb, J. Am. Chem. Soc.
2009, 131, 16016.
[17] T. Satyanarayana, S. Abraham, H. B. Kagan, Angew. Chem.
2009, 121, 464; Angew. Chem. Int. Ed. 2009, 48, 456.
[18] Increased Lewis acidity of CoIII versus CoII might be a plausible
reason for this mechanism change.
[19] First-order kinetics are observed for both bisurea-containing
CoII catalyst 1 and CoIII catalyst 1·OBzF (see the Supporting
Information for details). However, first-order kinetics alone
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