Asymmetric catalysis with an inert chiral-at-metal iridium complex

Article abstract of DOI:10.1021/ja403777k

The development of a chiral-at-metal iridium(III) complex for the highly efficient catalytic asymmetric transfer hydrogenation of β,β′- disubstituted nitroalkenes is reported. Catalysis by this inert, rigid metal complex does not involve any direct metal coordination but operates exclusively through weak interactions with functional groups properly arranged in the ligand sphere of the iridium complex. Although the iridium complex relies only on the formation of three hydrogen bonds, it exceeds the performance of most organocatalysts with respect to enantiomeric excess (up to 99% ee) and catalyst loading (down to 0.1 mol %). This work hints at an advantage of structurally complicated rigid scaffolds for non-covalent catalysis, which especially relies on conformationally constrained cooperative interactions between the catalyst and substrates.

Full text of DOI:10.1021/ja403777k

Subscriber access provided by George Mason University Libraries & VIVA (Virtual Library of Virginia)
Communication
Asymmetric Catalysis with Inert Chiral-At-Metal Iridium Complex
Liang-An Chen, Weici Xu, Biao Huang, JiaJia Ma, Lun
Wang, Jianwei Xi, Klaus Harms, Lei Gong, and Eric Meggers
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 14 May 2013
Downloaded from http://pubs.acs.org on May 15, 2013
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Journal of the American Chemical Society is published by the American Chemical
Society. 1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 5
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
Asymmetric Catalysis with Inert Chiral-At-Metal Iridium Com-
plex
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Liang–An Chen,† Weici Xu,† Biao Huang,† Jiajia Ma,† Lun Wang,† Jianwei Xi,† Klaus Harms,‡ Lei
Gong,*,† and Eric Meggers*,†,‡
†
Fujian Provincial Key Laboratory of Chemical Biology, Department of Chemical Biology, College of Chemistry and
Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, People’s Republic of China
‡Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse, 35043 Marburg, Germany
more simplify the design of defined globular and rigid
ABSTRACT: The development of a chiral-at-metal iridi-
structures because molecular geometries are basically
um(III) complex for the highly efficient catalytic asym-
constructed from a common center with chelating ligands
metric transfer hydrogenation of β,β’-disubstituted ni-
troalkenes is reported. Catalysis by this inert, rigid metal
limiting the degree of conformational flexibility.13 We
here now demonstrate how this sophisticated octahedral
complex does not involve any direct metal coordination
stereochemistry can be exploited for the tailored design of
but operates exclusively through cooperative, weak inter-
a highly efficient low-loading asymmetric noncovalent
actions with functional groups properly arranged in the
catalyst.7
ligand sphere of the iridium complex. Although the iridi-
um complex only relies on the formation of three hydro-
gen bonds, it exceeds the performance of most organocat-
alysts with respect to enantiomeric excess (up to 99% ee)
and catalyst loading (down to 0.1 mol%). This work hints
towards an advantage of structurally complicated, rigid
scaffolds for non-covalent catalysis which especially relies
on conformationally constrained, cooperative interactions
between catalyst and substrates.
The growing impact of asymmetric catalysis in chemis-
try is driven by an increasing demand for the economical
synthesis of enantiomerically pure chiral compounds to
Figure 1. Bifunctional hydrogen bonding asymmetric or-
be used as drugs, agricultural chemicals, flavors, fragranc-
ganocatalysis as inspiration for a chiral-at-metal iridium
es and components of materials.1,2 Over the past decade,
catalyst. Stereogenic centers are indicated with asterisks.
organocatalysis has emerged as a new branch of enanti-
oselective synthesis.3 In one general mode of activation,
Inspired by bifunctional double H-bond donor asym-
substrate binding and activation is solely achieved via
metric organocatalysts such as the thiourea shown in Fig-
multiple, concerted noncovalent interactions, such as
ure 1, in which the thiourea activates an electrophile while
an additional functional group serves as a hydrogen bond
hydrogen bonds.4 Despite the attractivity of this concept,
the catalytic rate acceleration for such reactions is often
acceptor for activating an incoming nucleophile, we chose
only modest, thus requiring high catalyst loadings, which
the substitutionally inert bis-cyclometalated iridium(III)
can be traced back to the fact that attractive noncovalent
interactions are considerably weaker than coordinative or
covalent bonds and thus are more affected by dynamic
and entropic effects. The performance of such noncova-
lent catalysts therefore crucially relies on the proper rela-
a benzoxazole ligand serves as a hydrogen bond acceptor
tive and absolute arrangement of key activating function-
al groups in the three-dimensional space and we envi-
sioned that octahedral metal complexes may serve as
complex Λ-Ir1 (Figure 2) as the starting point for our
study.14,15 In this design, a coordinated 5-amino-3-(2-
pyridyl)-1H-pyrazole provides two donor-hydrogen bonds
to a nitroalkene, whereas a hydroxymethyl substituent at
for the incoming nucleophile.16
Encouragingly, we found that Λ-Ir1 catalyzes the
asymmetric reduction of the β,β’-disubstituted nitroal-
kene 1a with the Hantzsch ester 2 (1.1 eq) to afford the
nitroalkane (R)-3a, albeit with modest enantiomeric ex-
powerful structural templates for the design of such non-
covalent “organocatalysts”.5-12 Octahedral stereocenters
permit the straightforward generation of compounds with
cess of 63% at 20 mol% catalyst loading (entry 1, Table
1).17-19 However, when we modified the exocyclic primary
high shape and stereochemical complexity and further-
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 5
1). Reducing the catalyst loading to 1 mol% still afforded
amine with n-butyl (Λ-Ir2), phenyl (Λ-Ir3) or a trifluoroa-
cetyl group (Λ-Ir4), the ee values increased to 70%, 84%
and 90%, respectively (entries 2-4, Table 1). The introduc-
tion of the trifluoroacetyl group also significantly acceler-
ated the catalysis, presumably due to an increase in the
acidity of the amide NH-group (entry 4, Table 1). In the
next round of catalyst optimization, we attempted to in-
fluence the binding of the nitroalkene substrate by intro-
ducing steric constraints. To our delight, Λ-Ir5, in com-
parison to Λ-Ir4 just bearing an additional phenyl sub-
stituent, provided a significant increase in enantiomeric
excess (99% ee) and
1
2
3
4
5
6
7
8
the nitroalkane in 98% ee within 20 hours at room tem-
perature. Finally, the catalytic efficiency could be further
improved by modifying the phenyl moiety with two me-
thyl groups (Λ-Ir6) (entry 6, Table 1). With a loading of 1
mol%, Λ-Ir6 catalyzes the conversion 1a→(R)-3a with
99% ee within 14 hours at room temperature (entry 7,
Table 1). To summarize this part, the modularity of the
metal complex scaffold allowed us a rapid, stepwise opti-
mization of the catalysis performance.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Next, we tested the scope of catalyst Λ-Ir6. Table 2 re-
veals that a selection of eight β,β’-disubstituted nitroal-
kenes 1a-h provide reduced nitroalkane products (R)-3a-h
with high yields and excellent enantioselectivities (93-
99% ee) with a catalyst loading of just 1 mol% and reac-
tion times of ≤ 24 h at room temperature (entries 1-8, Ta-
ble 2). Interesting for practical purposes, the catalyst
loading can be reduced even below 1 mol% without much
affecting the reached enantioselectivities and yields. For
example, at a catalyst loading of just 0.3 mol% of Λ-Ir6, 1a
is converted to (R)-3a with a yield of 95% and 97% ee at
room temperature within 3 days. Astonishingly, even at a
catalyst loading of 0.1 mol%, satisfactory yields of 89%
and 94% ee are reached. A survey of the literature reveals
that with this combination out of high enantioselectivity
and low catalyst loading, Λ-Ir6 appears to match or even
surpass the best published metal-,20 bio-,21 or organo-
catalysts19b,d for the asymmetric reduction of β,β’-
disubstituted nitroalkenes.
Cat
R1
R2
H
R3
Λ-Ir1 CH2OH
Λ-Ir2 CH2OH nBu
Λ-Ir3 CH2OH Ph
H
H
H
H
Λ-Ir4 CH2OH COCF3
Λ-Ir5 CH2OH COCF3 Ph
Λ-Ir6 CH2OH COCF3 3,5-Me2C6H3
Λ-Ir7
H
Ph
H
Figure 2. Chiral-at-metal iridium complexes investigated for
asymmetric H-bonding catalysis. See Supporting information
for the synthesis of the enantiopure iridium complexes.
BArF24- = tetrakis[(3,5-di-trifluoromethyl)phenyl]borate.
Table 1. Development of inert chiral-at-metal Ir(III) com-
plexes for the asymmetric transfer hydrogenation with
Hantzsch estera
Table 2. Scope of the asymmetric transfer hydrogenation
with Λ-Ir6.a
entry catalyst amount cat. t (h)
conv.
(%)b
ee
(%)c
entry substrate (R1, R2)
t (h) yield (%)b ee (%)c
Λ-Ir6
1
20 mol%
20 mol%
20 mol%
20 mol%
20 mol%
1 mol%
22
24
20
7
92
63
70
84
90
99
98
99
0
Λ-Ir1
Λ-Ir2
Λ-Ir3
Λ-Ir4
Λ-Ir5
Λ-Ir5
Λ-Ir6
Λ-Ir7
1
nHex, Ph (1a)
nPr, Ph (1b)
iPr, Ph (1c)
Me, Ph (1d)
1 mol%
1 mol%
1 mol%
1 mol%
18
94
96
92
91
99
98
96
95
95
94
93
2
3
4
5
6
7
8
82
2d
24
24
22
24
24
24
94
96
100
96
94
<20
3
4
5
6
7
1
Me, p-MePh (1e) 1 mol%
95
93
91
20
14
20
Me, p-ClPh (1f)
Me, m-ClPh (1g)
1 mol%
1 mol%
1 mol%
20 mol%
Me, 2-Naphthyl
(1h)
8
9
1 mol%
24
96
96
a
Reaction conditions: Nitroalkene 1a (0.10 mmol),
Hantzsch ester 2 (0.11 mmol) and Λ-Ir1-7 (1-20 mol%) in
nHex, Ph (1a)
nHex, Ph (1a)
0.3 mol% 72
0.1 mol% 96
95
89
97
94
toluene (0.10 mL, 1.0 M) were stirred at room temp. (ca. 18-
b
1
10
20 °C) under argon. Conversion determined by H-NMR.
c Determined by chiral HPLC analysis.
a
Reaction conditions: Nitroalkenes 1a-h (0.10 mmol),
Hantzsch ester 2 (0.11 mmol for entries 1-8, 0.15 mmol for
entries 9 and 10) and Λ-Ir6 (0.1-1.0 mol%) in toluene (0.10
reaction rate (complete conversion within 1 h at room
temperature at 20 mol% catalyst loading) (entry 5, Table
ACS Paragon Plus Environment

Page 3 of 5
Journal of the American Chemical Society
mL, 1.0 M) were stirred at room temp. (ca. 18-20 °C) under
b
c
1
2
argon. Isolated yields. Determined by chiral HPLC analy-
d
sis. The reaction is scalable to 1.0 mmol substrate, provid-
3
ing (R)-3b with 97% yield and 97.4% ee after 24 h at room
temp. (ca. 27 °C).
4
5
6
7
8
The performance of the bis-cyclometalated iridium(III)
complex Λ-Ir6 demonstrates that inert octahedral chiral-
at-metal complexes are not merely a laboratory curiosity
but show high promise for the design of asymmetric cata-
lysts. Since these iridium complexes are substitutionally
inert, the observed catalysis must be mediated through
the ligand sphere.22 Interestingly, in our optimized cata-
lyst Λ-Ir6, all three bidentate ligands appear to contribute
to an efficient catalysis in a cooperative fashion. A model
of the ternary complex leading to the transition state is
presented in Figure 3 and is consistent with the observed
preference for the formation of the R-configured nitroal-
kanes catalyzed by the Λ-configured iridium complexes.
Based on related previous work on the activation of ni-
troalkenes by thiourea,15,16,19 in addition to mechanistic
investigations regarding the role of the OH group in bi-
functional thiourea organocatalysts by Paradies et al.,19d it
can be assumed that the amidopyrazole moiety is respon-
sible for activating the nitroalkene by double hydrogen
bonding and thus increasing the electrophilicity of the
nitroalkene, while one of the two cyclometalated
phenybenzoxazole ligands places an OH-group in a prop-
er position for activating the hydride donor ability of the
Hantzsch ester by forming a hydrogen bond between the
NH-group of the Hantzsch ester and a lone pair of the
OH-group. In fact, complex Λ-Ir7, derived from Λ-Ir3 by
removing the OH-group, does not show any asymmetric
induction (entry 8, Table 1), thus confirming the im-
portance of the OH-group for the observed enantioselec-
tivities. Furthermore, the second cyclometalated phe-
nylbenzoxazole orients an aryl substituent in a position
which apparently is also important for the catalysis. It is
noteworthy that the 3,5-dimethylphenyl substituent in Λ-
Ir6 does not only improve the asymmetric induction
compared to the analogous complex devoid of this sub-
stituent (Λ-Ir4) but also speeds up the catalysis by around
an order of magnitude. It is curious that a steric group
accelerates catalysis and we hypothesize that this might
be due to a stabilization of the proper hydrogen bonding
of the nitroalkene substrate, preventing a dynamic mo-
tion perpendicular to the two formed hydrogen bonds.
However, attractive van der Waals interactions between
the 3,5-dimethylphenyl substituent of the catalyst and the
nitroalkene substrate which would stabilize the major
transition state may also play an important role.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 3. Proposed hydrogen bonded ternary complex out of
catalyst Λ-Ir6 (wheat), nitroalkene 1d (yellow) and Hantzsch
ester 2 (green) leading to the transitions state. Represented
with the PyMOL Molecular Graphics System, Version 1.3
Schrödinger, LLC.
In conclusion, we here reported a highly efficient
asymmetric catalyst solely relying on octahedral chirality-
at-metal.23 We estimate that the inert iridium complex Λ-
Ir6 accelerates the rate of the asymmetric transfer hydro-
genation reaction by around 10,000-fold.24 One can specu-
late that the rigidity of the octahedral metal complex, in
which conformational freedom is limited by chelate ef-
fects, might provide an advantage over the typical more
flexible organocatalysts, since the preorganization of the
ternary complex must play an important contribution
towards lowering the entropic penalty to be paid for the
highly organized transition state. We believe that these
results demonstrate that the here disclosed design based
on rigid and inert chiral-at-metal octahedral metal com-
plexes, a class of compounds that has previously been
more or less neglected for the design of asymmetric cata-
lysts, will serve as attractive scaffolds for the design of an
entire family of highly efficient metal-based non-bonding
asymmetric catalysts.
ASSOCIATED CONTENT
Supporting Information. Experimental details, chiral HPLC
traces, CD spectra, and crystallographic data. This material is
available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
meggers@chemie.uni-marburg.de, meggers@xmu.edu.cn,
gongl@xmu.edu.cn
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We gratefully acknowledge funding from the National Natu-
ral Science Foundation of P. R. China (21272192, 21201143), the
Program for Changjiang Scholars and Innovative Research
Team of the University (PCSIRT), the National Thousand
Plan Foundation of P. R. China, and the 985 Program of the
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 5
Hildebrand, J. P.; Raabe, G. Angew. Chem. Int. Ed. 2001, 40, 1488.
Chemistry and Chemical Engineering disciplines of Xiamen
University.
1
2
3
4
5
6
(g) Gibson, S. E.; Ibrahim, H. Chem. Commun. 2002, 2465. (h)
Özçubukçu, S.; Schmidt, F.; Bolm, C. Org. Lett. 2005, 7, 1407. (i)
Fu, G. C. Acc. Chem. Res. 2006, 39, 853. (j) Huang, H.; Peters, R.
Angew. Chem. Int. Ed. 2009, 48, 604. (k) Kanbayashi, N.; Onit-
suka, K. J. Am. Chem. Soc. 2010, 132, 1206. (l) Ogasawara, M.; Wu,
W.-Y.; Arae, S.; Watanabe, S.; Morita, T.; Takahashi, T.; Kamika-
wa, K. Angew. Chem. Int. Ed. 2012, 51, 2951.
REFERENCES
(1) Halpern, J.; Trost, B. M. Proc. Nat. Acad. Sci. USA 2004, 101,
5347.
(2) Walsh, P. J.; Kozlowski, M. C. Fundamentals of Asymmetric
Catalysis, University Science Books, 2009.
7
8
9
(13) For the same reasons, octahedral metal complexes have
been exploited successfully as powerful structural scaffolds for
the design of enzyme inhibitors. See, for example: Feng, L.; Geis-
selbrecht, Y.; Blanck, S.; Wilbuer, A.; Atilla-Gokcumen, G. E.;
Filippakopoulos, P.; Kräling, K.; Celik, M. A.; Harms, K.; Maksi-
moska, J.; Marmorstein, R.; Frenking, G.; Knapp, S.; Essen, L.-O.;
Meggers, E. J. Am. Chem. Soc. 2011, 133, 5976.
(14) For pioneering work on the generic use of asymmetric H-
bonding catalysis, see: (a) Vachal, P.; Jacobsen, E. N. J. Am.
Chem. Soc. 2002, 124, 10012. (b) Wenzel, A. G.; Jacobsen, E. N. J.
Am. Chem. Soc. 2002, 124, 12964.
(15) For an early example of the asymmetric activation of ni-
troalkenes with a bifunctional thiourea catalyst, see: Okino, T.;
Hoashi, Y.; Takemoto; Y. J. Am. Chem. Soc. 2003, 125, 12672.
(16) For asymmetric double H-bond donor organocatalysts
with an additional hydroxyl group, see: (a) Herrera, R. P.; Sgar-
zani, V.; Bernardi, L.; Ricci, A. Angew. Chem. Int. Ed. 2005, 44,
6576. (b) Sibi, M. P.; Itoh, K. J. Am. Chem. Soc. 2007, 129, 8064.
(c) Herrera, R. P.; Monge, D.; Martín-Zamora, E.; Fernández, R.;
Lassaletta, J. M. Org. Lett. 2007, 9, 3303.
(3) (a) List, B.; Yang, J. W. Science 2006, 313, 1584. (b) MacMil-
lan, D. W. C. Nature 2008, 455, 304.
(4) (a) Schreiner, P. R. Chem. Soc. Rev. 2003, 32, 289. (b)
Takemoto, Y. Org. Biomol. Chem. 2005, 3, 4299. (c) Taylor, M. S.;
Jacobsen, E. N. Angew. Chem. Int. Ed. 2006, 45, 1520. (d) Connon,
S. J. Chem. Eur. J. 2006, 12, 5418. (e) Doyle, A. G.; Jacobsen, E. N.
Chem. Rev. 2007, 107, 5713. (f) Yu, X.; Wang, W. Chem. Asian J.
2008, 3, 516. (g) Zhang, Z.; Schreiner, P. R. Chem. Soc. Rev. 2009,
38, 1187. (h) Knowles, R. R.; Jacobsen, E. N. Proc. Natl. Acad. Sci.
USA 2010, 107, 20678.
(5) For reviews on hydrogen bonding interactions involving
metal coordinated ligands, see: (a) Loeb, S. J.; Mercer, D. J.
Chem. Soc. Rev. 2010, 39, 3612. (b) Reedijk, J. Chem. Soc. Rev.
2013, 42, 1776.
(6) For reviews on chiral-at-metal complexes and their appli-
cations, see: (a) Pierre, J.-L. Coord. Chem. Rev. 1998, 178-180, 1183.
(b) Knof, U.; von Zelewsky, A. Angew. Chem. Int. Ed. 1999, 38,
302. (c) Brunner, H. Angew. Chem. Int. Ed. 1999, 38, 1194. (d)
Knight P. D.; Scott, P. Coord. Chem. Rev. 2003, 242, 125. (e)
Ganter, C. Chem. Soc. Rev. 2003, 32, 130. (f) Lacour, J.; Hebbe-
Viton, V. Chem. Soc. Rev. 2003, 32, 373. (g) Fontecave, M.;
Hamelin, O.; Ménage, S. Top. Organomet. Chem. 2005, 15, 271.
(h) Meggers, E. Eur. J. Inorg. Chem. 2011, 2911. (i) Bauer, E. B.
Chem. Soc. Rev. 2012, 41, 3153. (j) Crassous, J. Chem. Commun.
2012, 48, 9684. (k) Constable, E. C. Chem. Soc. Rev. 2013, 42, 1427.
(7) In pioneering precedence it was reported that the octahe-
dral complex ꢀ-[Co(1,2-ethylenediamine)3]{B(ArF24)4}3 catalyzes
the Michael addition of dimethyl malonate to 2-cyclopenten-1-
one enantioselectively, albeit with modest 33% ee. See:
Ganzmann, C.; Gladysz, J. A. Chem. Eur. J. 2008, 14, 5397.
(8) For an octahedral chiral-at-metal ruthenium complex as a
metalloligand for asymmetric catalysis, see: Hamelin, O.; Rim-
boud, M.; Pécaut, J.; Fontecave, M. Inorg. Chem. 2007, 46, 5354.
(9) For an octahedral chiral-at-metal ruthenium complex as
reactive, asymmetric oxidation catalyst, see: Chavarot, M.; Mé-
nage S.; Hamelin, O.; Charnay, F.; Pécaut, J.; Fontecave, M. In-
org. Chem. 2003, 42, 4810.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(17) You, S.-L. Chem. Asian J. 2007, 2, 820.
(18) For an early example of organocatalytic asymmetric trans-
fer hydrogenation with Hantzsch ester, see: Yang, J. W.; Hecha-
varria Fonseca, M. T.; List, B. Angew. Chem. Int. Ed. 2004, 43,
6660.
(19) For racemic and enantioselective organocatalytic transfer
hydrogenation of nitroalkenes, see: (a) Zhang, Z. G.; Schreiner, P.
R. Synthesis 2007, 2559. (b) Martin, N. J. A.; Ozores, L.; List, B. J.
Am. Chem. Soc. 2007, 129, 8976. (c) Martin, N. J. A.; Cheng, X.;
List, B. J. Am. Chem. Soc. 2008, 130, 13862. (d) Schneider, J. F.;
Lauber, M. B.; Muhr, V.; Kratzer, D.; Paradies, J. Org. Biomol.
Chem. 2011, 9, 4323.
(20) For metal-catalyzed asymmetric conjugate reduction of
nitroalkenes, see: (a) Czekelius, C.; Carreira, E. M. Angew. Chem.
Int. Ed. 2003, 42, 4293. (b) Czekelius, C.; Carreira, E. M. Org.
Lett. 2004, 6, 4575. (c) Czekelius, C.; Carreira, E. M. Org. Process
Res. Dev. 2007, 11 633. (d) Soltani, O.; Ariger, M. A.; Carreira, E.
M. Org. Lett. 2009, 11, 4196. (e) Tang, Y.; Xiang, J.; Cun, L.; Wang,
Y.; Zhu, J.; Liao, J.; Deng, J. Tetrahedron: Asymmetry 2010, 21,
1900. (f) Li, S.; Huang, K.; Cao, B.; Zhang, J.; Wu, W.; Zhang, X.
Angew. Chem. Int. Ed. 2012, 51, 8573.
(21) For the asymmetric conjugate bioreduction of nitroal-
kenes, see for example: (a) Ohta, H.; Kobayashi, N.; Ozaki, K. J.
Org. Chem. 1989, 54, 1802. (b) Hall, M.; Stueckler, C.; Kroutil, W.;
Macheroux, P.; Faber, K. Angew. Chem. Int. Ed. 2007, 46, 3934.
(c) Toogood, H. S.; Fryszkowska, A.; Hare, V.; Fisher, K.; Rouje-
inikova, A.; Leys, D.; Gardiner, J. M.; Stephens, G. M.; Scrutton,
N. S. Adv. Synth. Catal. 2008, 350, 2789. (d) Oberdorfer, G.;
Gruber, K.; Faber, K.; Hall, M. Synlett 2012, 23, 1857.
(10) For the induction of asymmetric autocatalysis by chiral
octahedral cobalt complexes, see: Sato, I.; Kadowaki, K.; Ohgo,
Y.; Soai, K.; Ogino, H. Chem. Commun. 2001, 1022.
(11) For representative examples of tetrahedral chiral-at-metal
complexes as part of asymmetric catalysts, see: (a) Brunner, H.;
Wachter, J.; Schmidbauer, J.; Sheldrick, G. M.; Jones, P. G. Or-
ganometallics 1986, 5, 2212. (b) Zwick, B. D.; Arif, A. M.; Patton,
A. T.; Gladysz, J. A. Angew. Chem. Int. Ed. Engl. 1987, 26, 910. (c)
Kromm, K.; Zwick, B. D.; Meyer, O.; Hampel, F.; Gladysz, J. A.
Chem. Eur. J. 2001, 7, 2015. (d) Kromm, K.; Osburn, P. L.;
Gladysz, J. A. Organometallics 2002, 21, 4275. (e) Seidel, F.
Gladysz, J. A. Synlett 2007, 986.
(12) For representative examples of planar chiral-at-metal
complexes as inert templates for asymmetric catalysts, see: (a)
Hayashi, T.; Kumada, M. Acc. Chem. Res. 1982, 15, 395. (b) Togni,
A.; Breutel, C.; Schnyder, A.; Spindler, F.; Landert, H.; Tijani, A. J.
Am. Chem. Soc. 1994, 116, 4062. (c) Kudis, S.; Helmchen, G.
Angew. Chem. Int. Ed. 1998, 37, 3047. (d) Ireland, T.;
Grossheimann, G.; Wieser-Jeunesse, C.; Knochel, P. Angew.
Chem. Int. Ed. 1999, 38, 3212. (e) Fu, G. C. Acc. Chem. Res. 2000,
33, 412. (f) Bolm, C.; Kesselgruber, M.; Hermanns, N.;
(22) Catalysis experiments were routinely performed in brown
glass vials under reduced light as a precaution to exclude poten-
tial interferences from photoactivation of the iridium complexes.
(23) For a recent review on low-loading asymmetric organoca-
talysis, see: Giacalone, F.; Gruttadauria, M.; Agrigento, P.; Noto,
R. Chem. Soc. Rev. 2012, 41, 2406.
(24) Calculated from the transfer hydrogenation reaction with
0.1 mol% catalyst loading (entry 10 of Table 2) under the assump-
tion that the formation of the minor enantiomer is attributed to
the uncatalyzed background reaction.
ACS Paragon Plus Environment

Page 5 of 5
Journal of the American Chemical Society
1
2
3
4
5
TOC graphic:
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACS Paragon Plus Environment