Tuning the Basicity of a Metal-Templated Br?nsted Base to Facilitate the Enantioselective Sulfa-Michael Addition of Aliphatic Thiols to α,β-Unsaturated N-Acylpyrazoles

Article abstract of DOI:10.1002/ejoc.201501494

The enantioselective addition of aliphatic thiols to α,β-unsaturated N-acylpyrazoles catalyzed by a bis-cyclometalated iridium(III) complex with fine-tuned Br?nsted basicity was investigated. Good to excellent yields (71-99 %) and enantioselectivities (86-98 % ee) were achieved at catalyst loadings of 0.2-2.5 mol-%. In this metal-templated catalyst design, the metal serves as a structural center and the catalysis is executed by the organic ligand sphere through a combination of proton transfer, hydrogen-bond formation, and electrostatic interactions.

Full text of DOI:10.1002/ejoc.201501494

DOI: 10.1002/ejoc.201501494
Communication
Asymmetric Catalysis
Tuning the Basicity of a Metal-Templated Brønsted Base to
Facilitate the Enantioselective Sulfa-Michael Addition of
Aliphatic Thiols to α,ꢀ-Unsaturated N-Acylpyrazoles
Xiaobing Ding,[a] Cheng Tian,[a] Ying Hu,[a] Lei Gong,*[a] and Eric Meggers*[a,b]
Abstract: The enantioselective addition of aliphatic thiols to 0.2–2.5 mol-%. In this metal-templated catalyst design, the
α,ꢀ-unsaturated N-acylpyrazoles catalyzed by a bis-cyclometal- metal serves as a structural center and the catalysis is executed
ated iridium(III) complex with fine-tuned Brønsted basicity was by the organic ligand sphere through a combination of proton
investigated. Good to excellent yields (71–99 %) and enantio- transfer, hydrogen-bond formation, and electrostatic interac-
selectivities (86–98 % ee) were achieved at catalyst loadings of tions.
Introduction
ployed metal-templated Brønsted base catalyst. Herein, we re-
port our successful efforts to expand the scope of this sulfa-
Michael addition to aliphatic thiols by tuning the basicity of the
metal-templated Brønsted base (Figure 1).
The stereoselective addition of sulfur-based nucleophiles to
electron-acceptor-substituted alkenes, named the sulfa-Michael
addition, constitutes an attractive method for the formation of
chiral, nonracemic compounds containing C–S bonds.[1,2] In this
respect, chiral Brønsted bases are particularly popular catalysts
for asymmetric sulfa-Michael additions owing to the significant
acidity of thiols in combination with a strong increase in their
nucleophilicity upon deprotonation. Recently, we introduced a
novel class of metal-templated chiral Brønsted base catalysts
based on substitutionally and configurationally inert bis-cyclo-
metalated iridium(III) complexes.[3–7] In our design, the iridium
atom serves as a key structural center by constituting the exclu-
sive source of chirality (metal-centered chirality[8]) and by pro-
viding a sophisticated handle to arrange functional groups in
the ligands sphere that are then responsible for mediating the
catalysis. We demonstrated the excellent performance of this
class of asymmetric Brønsted base catalysts for asymmetric aza-
Henry reactions and sulfa-Michael additions.[3–5] With respect to
sulfa-Michael additions, α,ꢀ-unsaturated N-acylpyrazoles[3] and
α,ꢀ-unsaturated 2-acylimidazoles[5] served as the Michael ac-
ceptors, and they provided the sulfa-Michael addition products
with high enantioselectivity at very low catalyst loadings. Unfor-
tunately, this methodology is more or less limited to aromatic
thiols, which we attribute to the insufficient basicity of the em-
Figure 1. Previous work and this study regarding the catalytic enantioselect-
ive sulfa-Michael addition of thiols to α,ꢀ-unsaturated N-acylpyrazoles.
Results and Discussion
We initiated our study by modifying our previously developed
metal-templated Brønsted base catalyst Λ-IrBB1 (Figure 1). Λ-
IrBB1 contains two cyclometalating 2-phenylbenzoxazole li-
gands that are coordinated in a propeller-like fashion, which
thereby creates the necessary chirality. The hydroxymethyl sub-
stituents can contribute to hydrogen-bonding interactions with
a substrate, whereas the additional 3,5-nHex2Ph moieties facili-
tate high solubility in apolar solvents even at low temperatures.
Finally, the third bidentate ligand, a deprotonated pyrazolylpyr-
idine, serves as the actual Brønsted base. The NHPh substituent
constitutes a hydrogen-bond donor and at the same time con-
[a] Key Laboratory for Chemical Biology of Fujian Province and Department
of Chemical Biology, College of Chemistry and Chemical Engineering,
Xiamen University,
Xiamen 361005, People's Republic of China
E-mail: gongl@xmu.edu.cn
http://www.meggers-gong.cn
[b] Fachbereich Chemie, Philipps-Universität Marburg,
Hans-Meerwein-Strasse 4, 35043 Marburg, Germany
E-mail: meggers@chemie.uni-marburg.de
http://www.uni-marburg.de/fb15/ag-meggers
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejoc.201501494.
Eur. J. Org. Chem. 2016, 887–890
887
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
tributes to the basicity of the iridium-coordinated pyrazolato selectivity. Moreover, as can be seen from entries 5–8, molecular
ligand with an approximate pKa = 16 for the conjugate acid [Λ- sieves and low temperatures were beneficial in achieving high
IrBB1+H]+ in MeCN. This is sufficient for efficient deprotonation enantioselectivity.
of aromatic thiols (PhSH: pKa = 10.3 in DMSO) but borderline
for aliphatic thiols (nBuSH: pKa = 17.0 in DMSO).[9] We envi-
sioned that modifying Λ-IrBB1 by introducing a secondary
amine at the 5-position of the pyridyl moiety would raise the
basicity owing to conjugation with the metalated pyrazole
moiety.[10] The new complex Λ-IrBB2 was synthesized in an en-
antiopure fashion by following our developed auxiliary-medi-
ated procedure (see the Supporting Information).[11] Subse-
quent NMR titration experiments indeed revealed that replac-
ing a hydrogen atom at the 5-position of the pyridine ring (Λ-
IrBB1) with a pyrrolidine substituent (Λ-IrBB2) increased the pKa
value of the corresponding conjugate Brønsted acid by around
3 pKa units (for pKa determination, see the Supporting Informa-
tion).
With Λ-IrBB2 in hand, we undertook a survey of the sub-
strate scope for this reaction. As shown in Table 2, a variety of
aliphatic thiols were applicable to this reaction and provided
the corresponding sulfa-Michael addition products in good to
excellent yields (85–99 %) with ee values of 87–96 %. For steri-
cally more hindered thiols, such as 2-methylpropane-1-thiol
(Table 2, entry 9) and cyclopentanethiol (Table 2, entry 10),
higher catalyst loadings of 1.0 and 2.5 mol-%, respectively, were
required to obtain satisfactory results. Notably, in contrast to
Λ-IrBB2, Λ-IrBB1 did not provide satisfactory results for thiols
that were less acidic than phenylmethanethiol, such as ethane-
thiol, for which Λ-IrBB1 at a loading of 1.0 mol-% provided the
sulfa-Michael addition product with a conversion of merely
12 % after 40 h at –78 °C with a reduced enantioselectivity of
We next compared the performance of our previous catalyst 89 % ee. Finally, with respect to the α,ꢀ-unsaturated N-acyl-
Λ-IrBB1 with that of the new more Brønsted basic catalyst Λ- pyrazoles, aliphatic as well as aromatic substituents were toler-
IrBB2 and used the reaction of α,ꢀ-unsaturated N-acylpyrazole ated at the ꢀ position to afford the sulfa-Michael addition pro-
1a with phenylmethanethiol (2a) as our initial test reaction. As ducts in yields of 71–99 % with 93–98 % ee at a loading of 0.5–
shown in Table 1 (entry 1), under optimized conditions in the 1.0 mol-% Λ-IrBB2 (Table 3).
presence of 4 Å molecular sieves, Λ-IrBB1 provided sulfa-
Michael addition product 3a with good enantioselectivity
Table 2. Scope with respect to aliphatic thiols.[a]
(94 % ee) but only with a sluggish conversion of 65 % after 90 h
at –78 °C, a temperature that was necessary to suppress any
uncatalyzed background reaction. To our delight, Λ-IrBB2 was
significantly more active, and it provided product 3a with 98 %
conversion after only 40 h at –78 °C and with an improved
enantioselectivity of 96 % ee (Table 1, entry 2). The catalyst
loading could even be reduced to 0.5 mol-% (Table 1, entry 3)
and 0.2 mol-% (Table 1, entry 4) without affecting the enantio-
Entry
R (2)
Catalyst loading
[mol-%]
t
[h]
Yield[b]
[%]
ee[c]
[%]
1
2
3
4
Bn (2a)
0.5
0.5
0.5
1.0
0.5
0.5
0.2
0.5
1.0
2.5
0.5
0.5
72
84
71
82
72
72
80
80
82
82
71
45
90
91
89
99
85
90
99[e]
85
91
96
86
99
96
96
96
96
96
95
94
96
95
96
90
87
4-MeBn (2b)
4-FBn (2c)
4-MeOBn (2d)
Ph(CH2)2 (2e)
Et (2f)
Et (2f)
nBu (2g)
iBu (2h)
Table 1. Optimization of the asymmetric sulfa-Michael addition of phenyl-
5
methanethiol (2a) to α,ꢀ-unsaturated N-acylpyrazole 1a.[a]
6[d]
7
8
9
10
11[f]
12
cyclopentyl (2i)
HS(CH2)2 (2j)
MeO2CCH2 (2k)
[a] Reaction conditions: A mixture of aliphatic thiol 2a–k (0.084–0.90 mmol,
1.05–3.0 equiv.), Λ-IrBB2 (0.2–2.5 mol-%), and molecular sieves (4 Å, powder,
100 mg per mmol of 1a) in dry CH2Cl2 (0.020–0.15 mL) was cooled to –78 °C
and stirred for 5 min. A solution of α,ꢀ-unsaturated N-acylpyrazole 1a (0.080–
0.12 mmol) in CH2Cl2 (0.020 mL) was added dropwise over 1 min under an
argon atmosphere. The resulting suspension was stirred at –78 °C for the
indicated time. [b] Yield of isolated product. [c] Determined by HPLC analysis
on a chiral stationary phase. [d] For comparison, the use of the Λ-IrBB1 cata-
lyst at 1.0 mol-% provided only 12 % conversion with 89 % ee after 40 h.
[e] Conversion as determined by 1H NMR spectroscopy. [f] Executed at a
threefold reduced concentration.
Entry
Catalyst Catalyst loading Conditions
[mol-%]
t
[h]
Conv.[b] ee[c]
[%]
[%]
1
2
3
4
5
6
7
8
Λ-IrBB1 1.0
Λ-IrBB2 1.0
Λ-IrBB2 0.5
Λ-IrBB2 0.2
Λ-IrBB2 1.0
Λ-IrBB2 1.0
Λ-IrBB2 1.0
Λ-IrBB2 1.0
4 Å MS, –78 °C
90
40
72
91
40
24
10
4
65
98
99
85
98
97
95
99
94
96
96
96
94
94
91
74
4 Å MS, –78 °C
4 Å MS, –78 °C
4 Å MS, –78 °C
no MS, –78 °C
4 Å MS, –50 °C
4 Å MS, –20 °C
4 Å MS, 0 °C
[a] Reaction conditions: A mixture of phenylmethanethiol (2a; 0.144 mmol,
1.2 equiv.), Λ-IrBB1 (1.0 mol-%) or Λ-IrBB2 (0.2–1.0 mol-%), and molecular
sieves (4 Å, powder, 100 mg per 1 mmol 1a, except for entry 5) in dry CH2Cl2
(0.020 mL) was cooled to the indicated temperature and stirred for 5 min.
Thereafter, a solution of α,ꢀ-unsaturated N-acylpyrazole 1a (0.12 mmol) in
CH2Cl2 (0.020 mL) was added dropwise over 1 min under an atmosphere of
argon, and the resulting suspension was stirred at the temperature for the
indicated time. [b] Conversion as determined by 1H NMR spectroscopy. [c] De-
termined by HPLC analysis on a chiral stationary phase.
The obtained sulfa-Michael addition products are useful chi-
ral thioether building blocks in which the N-acylpyrazole can
be converted into a variety of functional groups under mild
reaction conditions.[12] For example, the reaction of 3a (96 % ee)
with NaBH4 at room temperature afforded corresponding alco-
hol (R)-4[13] in 94 % yield with 96 % ee (Scheme 1). The absolute
configuration of 3a was accordingly inferred as R. Treatment of
Eur. J. Org. Chem. 2016, 887–890
www.eurjoc.org
888
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
Table 3. Scope with respect to α,ꢀ-unsaturated N-acylpyrazoles.[a]
metric induction, as shown in Figure 2. This mechanism is con-
sistent with the observation that a Λ configuration at the irid-
ium center leads to an R configuration in the sulfa-Michael addi-
tion product.
Entry
R
Catalyst loading
[mol-%]
t
[h]
Yield[b]
[%]
ee[c]
[%]
1
2
3
4
5
nPr (1b)
iPr (1c)
Me(CH2)6 (1d)
TBSO(CH2)4 (1e)
0.5
0.5
0.5
1.0
0.5
72
71
72
84
84
93
99
90
75
71
96
93
93
86
98
[d]
Ph (1f)
[a] Reaction conditions:
A mixture of phenylmethanethiol (2a; 0.14–
0.30 mmol, 1.2 equiv.), Λ-IrBB2 (0.5 or 1.0 mol-%), and molecular sieves (4 Å,
powder, 100 mg per mmol of α,ꢀ-unsaturated N-acylpyrazole) in dry CH2Cl2
(0.020–0.13 mL) was cooled to –78 °C and stirred for 5 min. Afterwards, a
solution of 1b–f (0.12–0.25 mmol) in CH2Cl2 (0.020–0.13 mL) was added drop-
wise over 1 min under an atmosphere of argon. The resulting suspension
was stirred at –78 °C for the indicated time. [b] Yield of isolated product.
[c] Determined by HPLC analysis on a chiral stationary phase. [d] TBS = tert-
butyldimethylsilyl.
Figure 2. Proposed mechanism for the asymmetric sulfa-Michael addition cat-
alyzed by Λ-IrBB2.
Conclusions
3a with MeMgBr in Et2O at –40 °C for 10 h provided ketone 5
in 92 % yield with 96 % ee. Moreover, 3a could be converted
into ester 6 and amide 7 in good yields and with retention of
enantiomeric excess by substitution of the pyrazole with
In summary, we herein reported the expansion of our previ-
ously developed catalytic, enantioselective sulfa-Michael addi-
tion with α,ꢀ-unsaturated N-acylpyrazoles from aromatic thiols
to less-acidic aliphatic thiols.[3,4] This was simply accomplished
by increasing the basicity of the metal-templated Brønsted base
through modification of one coordinating ligand. This work
demonstrates the merit of our metal-templated asymmetric cat-
alysts in which catalyst tuning is accomplished in a straightfor-
ward fashion by ligand modification. The obtained nonracemic
thioethers are useful building blocks, as N-acylpyrazoles can be
readily converted into many other functional groups.
methoxide and L-phenylalanine methyl ester, respectively.
Experimental Section
Representative Catalysis: A mixture of phenylmethanethiol (2a;
29.7 μL, 0.25 mmol), catalyst Λ-IrBB2 (1.5 mg, 1.0 μmol, 0.5 mol-%),
and molecular sieves (4 Å, powder, 20.8 mg) in CH2Cl2 (34.6 μL) was
cooled to –78 °C and stirred for 5 min. Then, a solution of (2E)-
1-(pyrazol-1-yl)but-2-en-1-one (1a, 28.6 mg, 0.21 mmol) in CH2Cl2
(34.6 μL) was added dropwise over 1 min under an argon atmos-
phere. The resulting suspension was stirred at –78 °C for 72 h,
quenched with AcOH (50 μL, 1.0 % v/v in n-hexane), and purified
by flash chromatography (silica gel, n-hexane/diethyl ether = 30:1)
to afford product 3a as a colorless oil (48.6 mg, 0.19 mmol, 90 %).
The enantiomeric excess was established by HPLC analysis by using
a Chiralpak OJ column, ee = 96 %. HPLC (Daicel OJ column, UV
absorption monitored at λ = 230 nm, n-hexane/2-propanol = 95:5,
flow rate = 1 mL min–1, 25 °C): tR = 33.5 (major), 19.2 min (minor).
[α]D20 = +52.7 (c = 1.0, CHCl3). The analytical data of 3a are consistent
with the literature.[3]
Scheme 1. Transformation of N-acylpyrazole 3a into corresponding deriva-
tives without loss of chiral information; DMAP = 4-(dimethylamino)pyridine.
The proposed mechanism for this sulfa-Michael addition in-
cludes initial proton transfer from the aliphatic thiol (pKa = 17.0
in DMSO for nBuSH)[9] to a pyrazole nitrogen atom of Λ-IrBB2
(pKa ca. 19 for the conjugate acid [Λ-IrBB2+H]+ in MeCN), which
results in a double-hydrogen-bond-supported ion pair between
the protonated Brønsted base and the thiolate anion (Figure 2).
We furthermore propose that the α,ꢀ-unsaturated N-acylpyr-
azole electrophile forms a three-centered hydrogen bond with
the hydroxymethyl substituent of the benzoxazole moiety,
Acknowledgments
which thereby establishes a ternary complex through hydrogen The authors gratefully acknowledge funding from the National
bonds and electrostatic attraction that allows the Michael addi- Natural Science Foundation (NSFC) of P. R. China (grant num-
tion to proceed with a high rate of acceleration and high asym- bers 21272192, 21472154, and 21572184), the Program for
Eur. J. Org. Chem. 2016, 887–890
www.eurjoc.org
889
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
Liu, X. Feng, Angew. Chem. Int. Ed. 2010, 49, 4290–4293; Angew. Chem.
2010, 122, 4386–4389.
[3] J. Ma, X. Ding, Y. Hu, Y. Huang, L. Gong, E. Meggers, Nat. Commun. 2014,
5, 4531.
[4] Y. Hu, Z. Zhou, L. Gong, E. Meggers, Org. Chem. Front. 2015, 2, 968–972.
[5] X. Ding, H. Lin, L. Gong, E. Meggers, Asian J. Org. Chem. 2015, 4, 434–
437.
Changjiang Scholars and Innovative Research Team (PCSIRT) of
P. R. China, the National Thousand Talents Program of P. R.
China, and the Xiamen University (985 Program of the Chemis-
try and Chemical Engineering disciplines).
[6] For related metal-templated catalysts from our group, see: a) L.-A. Chen,
W. Xu, B. Huang, J. Ma, L. Wang, J. Xi, K. Harms, L. Gong, E. Meggers, J.
Am. Chem. Soc. 2013, 135, 10598–10601; b) L.-A. Chen, X. Tang, J. Xi, W.
Xu, L. Gong, E. Meggers, Angew. Chem. Int. Ed. 2013, 52, 14021–14025;
Angew. Chem. 2013, 125, 14271–14275; c) H. Huo, C. Fu, C. Wang, K.
Harms, E. Meggers, Chem. Commun. 2014, 50, 10409–10411; d) J. Liu, L.
Gong, E. Meggers, Tetrahedron Lett. 2015, 56, 4653–4656.
[7] For a recent review on metal-templated asymmetric catalysis by using
octahedral metal complexes, see: L. Gong, L.-A. Chen, E. Meggers, Angew.
Chem. Int. Ed. 2014, 53, 10868–10874; Angew. Chem. 2014, 126, 11046–
11053.
Keywords: Michael addition · Brønsted bases · Chirality ·
Iridium · Sulfur
[1] For comprehensive reviews on asymmetric sulfa-Michael addition, see:
a) P. Chauhan, S. Mahajan, D. Enders, Chem. Rev. 2014, 114, 8807–8864;
b) D. Enders, K. Lüttgen, A. Narine, Synthesis 2007, 959–980.
[2] For recent examples of asymmetric sulfa-Michael additions, see: a) A. C.
Breman, S. E. M. Telderman, R. P. M. van Santen, J. I. Scott, J. H. van Maar-
seveen, S. Ingemann, H. Hiemstra, J. Org. Chem. 2015, 80, 10561–10574;
b) R. Wang, J. Liu, J. Xu, Adv. Synth. Catal. 2015, 357, 159–167; c) Y.-F.
Wang, S. Wu, P. G. Karmaker, M. Sohail, Q. Wang, F.-X. Chen, Synthesis
2015, 47, 1147–1153; d) J. Chen, S. Meng, L. Wang, H. Tang, Y. Huang,
Chem. Sci. 2015, 6, 4184–4189; e) S. Shaw, J. D. White, Org. Lett. 2015,
17, 4564–4567; f) N. Fu, L. Zhang, S. Luo, J.-P. Cheng, Org. Lett. 2014, 16,
4626–4629; g) Y.-H. Li, B.-L. Zhao, Y. Gao, D.-M. Du, Tetrahedron: Asymme-
try 2014, 25, 1513–1519; h) B.-L. Zhao, L. Liu, D.-M. Du, Eur. J. Org. Chem.
2014, 7850–7858; i) J. D. White, S. Shaw, Chem. Sci. 2014, 5, 2200–2204;
j) X. Fang, X.-Q. Dong, Y.-Y. Liu, C.-J. Wang, Tetrahedron Lett. 2013, 54,
4509–4511; k) S. Diosdado, J. Etxabe, J. Izquierdo, A. Landa, A. Mielgo, I.
Olaizola, R. López, C. Palomo, Angew. Chem. Int. Ed. 2013, 52, 11846–
11851; Angew. Chem. 2013, 125, 12062–12067; l) L. Yao, K. Liu, H.-Y. Tao,
G.-F. Qiu, X. Zhou, C.-J. Wang, Chem. Commun. 2013, 49, 6078–6080; m)
X. Fang, J. Li, C.-J. Wang, Org. Lett. 2013, 15, 3448–3451; n) W. Yang, Y.
Yang, D.-M. Du, Org. Lett. 2013, 15, 1190–1193; o) X.-Q. Dong, X. Fang,
H.-Y. Tao, X. Zhou, C.-J. Wang, Adv. Synth. Catal. 2012, 354, 1141–1147;
p) X.-Q. Dong, X. Fang, H.-Y. Tao, X. Zhou, C.-J. Wang, Chem. Commun.
2012, 48, 7238–7240; q) Z.-C. Geng, N. Li, J. Chen, X.-F. Huang, B. Wu, G.-
G. Liu, X.-W. Wang, Chem. Commun. 2012, 48, 4713–4715; r) T. Ogawa,
N. Kumagai, M. Shibasaki, Angew. Chem. Int. Ed. 2012, 51, 8551–8554;
Angew. Chem. 2012, 124, 8679–8682; s) D. Uraguchi, N. Kinoshita, D. Na-
kashima, T. Ooi, Chem. Sci. 2012, 3, 3161–3164; t) L. Dai, H. Yang, F. Chen,
Eur. J. Org. Chem. 2011, 5071–5076; u) X.-Q. Dong, X. Fang, C.-J. Wang,
Org. Lett. 2011, 13, 4426–4429; v) X. Tian, C. Cassani, Y. Liu, A. Moran, A.
Urakawa, P. Galzerano, E. Arceo, P. Melchiorre, J. Am. Chem. Soc. 2011,
133, 17934–17941; w) M. Ueno, T. Kitanosono, M. Sakai, S. Kobayashi,
Org. Biomol. Chem. 2011, 9, 3619–3621; x) F. Zhao, W. Zhang, Y. Yang, Y.
Pan, W. Chen, H. Liu, L. Yan, C.-H. Tan, Z. Jiang, Adv. Synth. Catal. 2011,
353, 2624–2630; y) C. Yu, Y. Zhang, A. Song, Y. Ji, W. Wang, Chem. Eur. J.
2011, 17, 770–774; z) Y. Hui, J. Jiang, W. Wang, W. Chen, Y. Cai, L. Lin, X.
[8] For different aspects of metal-centered chirality, see: a) U. Knof, A.
von Zelewsky, Angew. Chem. Int. Ed. 1999, 38, 302–322; Angew. Chem.
1999, 111, 312–333; b) H. Brunner, Angew. Chem. Int. Ed. 1999, 38, 1194–
1208; Angew. Chem. 1999, 111, 1248–1263; c) P. D. Knight, P. Scott, Coord.
Chem. Rev. 2003, 242, 125–143; d) M. Fontecave, O. Hamelin, S. Ménage,
Top. Organomet. Chem. 2005, 15, 271–288; e) H. Amouri, M. Gruselle,
Chirality in Transition Metal Chemistry, Wiley, Chichester, UK, 2008; f) J.
Crassous, Chem. Soc. Rev. 2009, 38, 830–845; g) E. Meggers, Eur. J. Inorg.
Chem. 2011, 2911–2926; h) J. Crassous, Chem. Commun. 2012, 48, 9684–
9692; i) E. C. Constable, Chem. Soc. Rev. 2013, 42, 1637–1651; j) Z.-Z. Li,
S.-Y. Yao, J.-J. Wu, B.-H. Ye, Chem. Commun. 2014, 50, 5644–5647; k) Z.-Z.
Li, S.-Y. Yao, B.-H. Ye, ChemPlusChem 2015, 80, 141–150; l) Z.-Z. Li, A.-H.
Wen, S.-Y. Yao, B.-H. Ye, Inorg. Chem. 2015, 54, 2726–2733.
[9] F. G. Bordwell, D. L. Hughes, J. Org. Chem. 1982, 47, 3224–3232.
[10] The basicity of pyridine is enhanced by 5.4 pKa units by introduction of
an electron-donating dimethylamino group into the para position
(DMAP). See, for example: I. Kaljurand, A. Kutt, L. Soovali, T. Rodima, V.
Maemets, I. Leito, I. A. Koppel, J. Org. Chem. 2005, 70, 1019–1028.
[11] For our synthetic method to synthesize nonracemic iridium(III) com-
plexes with two cyclometalated ligands, see: a) M. Helms, Z. Lin, L. Gong,
K. Harms, E. Meggers, Eur. J. Inorg. Chem. 2013, 4164–4172; for a related
strategy, see also: b) L. Gong, M. Wenzel, E. Meggers, Acc. Chem. Res.
2013, 46, 2635–2644; c) E. Meggers, Chem. Eur. J. 2010, 16, 752–758.
[12] a) D. Uraguchi, K. Yamada, T. Ooi, Angew. Chem. Int. Ed. 2015, 54, 9954–
9957; Angew. Chem. 2015, 127, 10092–10095; b) Q. Yao, Z. Wang, Y.
Zhang, X. Liu, L. Lin, X. Feng, J. Org. Chem. 2015, 80, 5704–5712.
[13] M. Marigo, T. Schulte, J. Franzén, K. A. Jørgensen, J. Am. Chem. Soc. 2005,
127, 15710–15711.
Received: November 27, 2015
Published Online: January 22, 2016
Eur. J. Org. Chem. 2016, 887–890
www.eurjoc.org
890
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim