Enantioselective 2-alkylation of 3-substituted indoles with dual chiral lewis acid/hydrogen-bond-mediated catalyst

Article abstract of DOI:10.1021/acs.orglett.6b03500

A chiral-at-metal bis-cyclometalated iridium complex combines electrophile activation via metal coordination with nucleophile activation through hydrogen bond formation. This new bifunctional chiral Lewis acid/hydrogenbond-mediated catalyst permits the challenging enantioselective 2-alkylation of 3-substituted indoles with α, β-unsaturated 2-acyl imidazoles in up to 99% yield and with up to 98% enantiomeric excess at a catalyst loading of 2 mol %. As an application, the straightforward synthesis of a chiral pyrrolo- [1, 2-a]indole is demonstrated.

Full text of DOI:10.1021/acs.orglett.6b03500

Letter
pubs.acs.org/OrgLett
Enantioselective 2‑Alkylation of 3‑Substituted Indoles with Dual
Chiral Lewis Acid/Hydrogen-Bond-Mediated Catalyst
Zijun Zhou,† Yanjun Li,† Lei Gong,*,† and Eric Meggers*,†,‡
†College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, P. R. China
‡Fachbereich Chemie, Philipps-Universitat Marburg, Hans-Meerwein-Strasse 4, 35043 Marburg, Germany
̈
S
* Supporting Information
ABSTRACT: A chiral-at-metal bis-cyclometalated iridium
complex combines electrophile activation via metal coordina-
tion with nucleophile activation through hydrogen bond
formation. This new bifunctional chiral Lewis acid/hydrogen-
bond-mediated catalyst permits the challenging enantioselec-
tive 2-alkylation of 3-substituted indoles with α,β-unsaturated
2-acyl imidazoles in up to 99% yield and with up to 98%
enantiomeric excess at a catalyst loading of 2 mol %. As an
application, the straightforward synthesis of a chiral pyrrolo-
[1,2-a]indole is demonstrated.
ubstituted indoles are a frequent structural element of
C2-alkylation of 3-methylindole 1a with the α,β-unsaturated
Sbioactive compounds. The synthesis of substituted indoles 2-acyl imidazole 2a, the conversion was very sluggish even at the
often exploits their high nucleophilicity at the 3-position,1,2
elevated temperature of 55 °C (Table 1, entry 1). Mechanisti-
cally, the catalyst functions as a chiral Lewis acid and activates the
whereas the electrophilic aromatic substitution of 3-substituted
indoles at the 2-position is more challenging and has been much
less investigated.3 For example, only a few studies deal with a
direct enantioselective Friedel−Crafts alkylation of indoles at the
2-position.4−8 In 2013, Chen, Xiao and co-workers reported a
highly enantioselective indole C2-alkylation/N-hemiacetaliza-
tion cascade catalyzed by a Cu(II)-bisoxazoline catalyst.4 Soon
thereafter, Feng et al. successfully applied their chiral N,N′-
dioxide−Ni(II) complexes to a Friedel−Crafts C2-alkylation of
indoles with β,γ-unsaturated α-ketoesters.5 Hu and Zhao
reported a chiral Brønsted acid catalyzed C2-alkylation of
C3-substituted indoles with β,γ-unsaturated α-ketimino esters.6
Very recently, Jia’s group reported an enantioselective Friedel−
Crafts C2-alkylation of 3-substituted indoles with α,β-unsatu-
rated esters and nitroalkenes using Cu(II) or Zn(II) bisoxazoline
Lewis acid catalysts.7 Mechanistically distinct, the You group
developed very elegant transition-metal catalyzed asymmetric
dearomatization reactions to access, among others, five-
membered spiroindolenines which can readily undergo an acid-
catalyzed stereospecific rearrangement to chiral tetrahydro-1H-
carbazoles.8−10 Here, we introduce our progress toward the
challenging enantioselective, catalytic Friedel−Crafts C2-alkyla-
tion of 3-substituted indoles with α,β-unsaturated 2-acyl
imidazoles using a novel dual chiral Lewis acid/hydrogen-
bond-mediated catalyst.
a
Table 1. Catalyst Development
b
c
entry
catalyst
counterion
solvent
conv (%)
ee (%)
1
2
3
4
Λ-Ir1
Λ-Ir1
Λ-Ir2
Δ-Ir3
PF6
THF
21
24
14
89
92 (R)
95 (R)
88 (R)
98 (S)
BArF
BArF
BArF
toluene
toluene
toluene
a
Reaction conditions: A solution of α,β-unsaturated acyl imidazole 2a
(0.075 mmol) and the catalyst (0.0015 mmol) in freshly distilled
toluene (75 μL) was stirred in a brown glass vial for 20 min at 55 °C.
Then 3-methylindole 1a (0.300 mmol) was added. The reaction
b
Previously, we reported bis-cyclometalated chiral-at-metal11
iridium(III) and rhodium(III) complexes as versatile chiral Lewis
acid catalysts for a variety of transformations,12 such as the
Friedel−Crafts C3-alkylation of indoles with α,β-unsaturated
2-acyl imidazoles.12a,13 When we tried to apply the catalyst
Λ-Ir1 (PF6 counterion) to the more challenging Friedel−Crafts
mixture was stirred under air at 55 °C for 12 h. Conversion deter-
c
1
mined by H NMR analysis. Ee value determined by HPLC analysis
on a chiral stationary phase.
Received: November 23, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b03500
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
α,β-unsaturated 2-acyl imidazole by two-point binding, thus
improving its electrophilicity. However, this activation by iridium
coordination is apparently not sufficient to smoothly promote
the desired C2-alkylation of 3-substituted indoles, which dis-
play a much reduced HOMO electron density at C2 compared
to C3.8
S-configured reaction product when using a Δ-configured
catalyst.
To probe the proposed hydrogen bond interaction between
the catalyst and indole substrate, several control experiments
were carried out as shown in Table 2. Accordingly, N-methyl
Inspired by bifunctional catalysis14,15 and our previous work
on bifunctional metal-templated hydrogen-bond-mediated
catalysis for enantioselective Friedel−Crafts alkylations,16 we
wondered if an additional activation of the indole nucleo-
phile through hydrogen bond formation would sufficiently
improve the catalytic activity.17 To achieve this, we synthesized
the catalyst Λ-Ir2, in which the two tert-butyl groups are replaced
with two N-phthalimides. Furthermore, we replaced the
hexafluorophosphate counterion with the hydrophobic tetrakis-
[3,5-di(trifluoromethyl)phenyl]borate (BArF) in order to
render the catalyst more soluble in hydrogen-bond-promoting
unpolar solvents. Unfortunately, no improvement in yields and
enantioselectivity were observed (compare entries 2 and 3 of
Table 1). We attributed this to the very modest hydrogen bond
acceptor cababilities of the imide carbonyl groups and there-
fore next replaced the N-phthalimides with N-methyl uracil
moieties, since uracil is an established and natural hydrogen bond
acceptor.18 For purely synthetic purposes, we additionally
introduced a tert-butyl group into the phenyl moieties of the
cyclometalating ligands (see Supporting Information). To our
delight, Δ-Ir3 exhibited significantly improved activity by
affording the desired product 3a with 89% conversion after
12 h at 55 °C and with an excellent enantioselectivity of 98% ee
(entry 4). The need for an elevated temperature can be attributed
to the reduced nucleophilicity of indoles at the 2-position.
The proposed mechanism is shown in Figure 1 and is based on
a cocrystal structure of Δ-Ir3 coordinated to an α,β-unsaturated
Table 2. Control Experiments To Probe the Hydrogen Bond
Interaction during the Catalysis
a
b
c
entry
indole
additive
yield (%)
ee (%)
d
1
1a
1a′
1a
1a
none
none
89
15
51
14
98
91
97
93
2
3
4
ethylene glycol (4 equiv)
DMF (4 equiv)
a
Reaction conditions: A solution of α,β-unsaturated acyl imidazole 2a
(0.075 mmol) and the iridium catalyst (0.0015 mmol) in the freshly
distilled toluene (75 μL) was stirred in a brown glass vial for 20 min
at 55 °C. Then 1a or 1a′ (0.300 mmol) and the indicated additive
(0.300 mmol) were added. The reaction mixture was stirred at 55 °C
b
c
for 12 h under air. Isolated yield. Ee value determined by HPLC
d
analysis on a chiral stationary phase. Taken from entry 4 of Table 1.
protected 3-methylindole (1a′), which is unable to donate a
hydrogen bond to the uracil moiety of iridium catalyst Δ-Ir3, was
tested in the reaction with α,β-unsaturated 2-acyl imidazole 2a.
As expected, with 2 mol % of Δ-Ir3 under our optimized reaction
conditions, the 2-alkylated product was only afforded with a yield
of 15% within 12 h, compared to 89% using 3-methylindole
(entries 1 and 2 of Table 2). However, the reaction still proceeds
with satisfactory enantioselectivity (91% ee), thereby revealing
that steric effects play an important role for the asymmetric
induction (see Figure 1).
The role of the proposed hydrogen bond is also supported by
experiments in the presence of competing H-bond donors/
acceptors which lead to a decrease in reaction rate and enan-
tioselectivity (Table 2, entries 3 and 4). These experiments
strongly support the importance of a hydrogen bond between
one of the uracil moieties and the indole substrate which not only
increases the reaction rate by rendering the indole substrate more
nucleophilic but also provides improved enantioselectivity.
Next, we evaluated the substrate scope with respect to
α,β-unsaturated 2-acyl imidazoles. As shown for 12 different
α,β-unsaturated 2-acyl imidazoles in Scheme 1, in the presence of
2 mol % of Δ-Ir3 in toluene at 55 °C, α,β-unsaturated 2-acyl
imidazoles containing different substituents at the imidizole
nitrogen (products 3b and 3c), substituted aromatic moieties
(products 3d−j), a thiophene (product 3k), or a methyl group
(product 3l) at the β-position are formed in yields of 55−99%
yield and 92−98% ee. With respect to 3-substituted indoles,
Scheme 2 reveals that 3-methylindoles with an additional methyl
group at position 4 to 7 (products 3m−p) or a methoxy group
in position 4 or 5 (products 3q and 3r) are well tolerated.
The methyl group in the 3-position can also be replaced by a
larger aliphatic or aromatic moiety (products 3t and 3u). How-
ever, electron-withdrawing substituents in the indole moiety
fail to provide the desired 2-substituted products as shown for
Figure 1. Proposed transition state. 3-Methylindole was positioned
into a cocrystal structure of the catalyst Δ-Ir3 coordinated to an
α,β-unsaturated 2-acyl imidazole substrate (CCDC 1496421).
acyl imidazole substrate (bromo-derivatized substrate 2h) in a
bidentate fashion, upon release of the two labile acetonitrile
ligands. 3-Methylindole was modeled into the structure for-
ming a hydrogen bond with a carbonyl oxygen atom of one
uracil moiety which places the 2-position of the indole in a
perfect position for a Si-face attack at the electrophilic β-position
of the coordinated α,β-unsaturated 2-acyl imidazole substrate.
The second uracil moiety is blocking the Re-face of the pro-
chiral alkene. This mechanism is consistent with an observed
B
DOI: 10.1021/acs.orglett.6b03500
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
the presence of 4 Å molecular sieves for 2 h, followed by reacting
with triethylamine for 30 min, led to the formation of chiral
pyrrolo[1,2-a]indol-3(2H)-one 4 in almost quantitative yield
and with almost complete retention of the stereochemical infor-
mation (97% ee) (Scheme 3). A subsequent reduction of the
Scheme 1. Scope with Respect to α,β-Unsaturated 2-Acyl
Imidazoles
Scheme 3. Follow-up Chemistry with a 2-Alkylated Reaction
Product
lactam resulted in the formation of pyrrolo[1,2-a]indole 5 in 64%
yield and with 96% ee. Such chiral dihydropyrroloindoles are
core skeletons for a variety of bioactive compounds, for example
the commerically available PKC inhibitor L-888,607.19
In conclusion, we developed a bis-cyclometalated iridium
catalyst which combines substrate activation by metal coordina-
tion and hydrogen bond formation. This new bifunctional chiral
Lewis acid/hydrogen-bond-mediated catalyst was applied to the
challenging enantioselective 2-alkylation of 3-substituted indoles
with α,β-unsaturated 2-acyl imidazoles in up to 99% yield and
with up to 98% enantiomeric excess at a catalyst loading of only
2 mol %. X-ray crystallography together with control experiments
supports a mechanistic picture in which the α,β-unsaturated
2-acyl imidazole electrophile is activated by bidentate coordina-
tion to the iridium, whereas the 3-substituted indole donates a
hydrogen bond to one of the uracil moieties, thereby improving
the nucleophilicity of the C2-position and increasing the
asymmetric induction. Thus, in this system, a single hydrogen
bond to the natural hydrogen bond acceptor uracil plays a crucial
role in the rate and enantioselectivity of the asymmetric catal-
ysis. Applications to other challenging transformations and the
synthesis of the related rhodium catalyst are underway in our
laboratory.
Scheme 2. Scope with Respect to 3-Substituted Indoles
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.6b03500.
Experimental procedures, full characterization data of all
new compounds, X-ray crystallographic data, and chiral
HPLC traces (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: gongl@xmu.edu.cn.
*E-mail: meggers@chemie.uni-marburg.de.
ORCID
Eric Meggers: 0000-0002-8851-7623
Notes
The authors declare no competing financial interest.
5-bromo-3-methylindole. Instead, an N-alkylated side product
can be isolated.
The Friedel−Crafts C2-alkylation adducts are valuable chiral
building blocks. This is demonstrated for the synthesis of opti-
cally active fused tricyclic indoles. Accordingly, treatment of
product 3a (98% ee) with methyl trifluoromethanesulfonate in
ACKNOWLEDGMENTS
■
We gratefully acknowledge funding from the National Natural
Science Foundation of P. R. China (Grant Nos. 21272192,
21472154, and 21572184), the Fundamental Research Funds for
the Central Universities (Grant No. 20720160027) and the
C
DOI: 10.1021/acs.orglett.6b03500
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Gong, L.; Meggers, E. Chem. Sci. 2015, 6, 1094. (c) Shen, X.; Huo, H.;
Wang, C.; Zhang, B.; Harms, K.; Meggers, E. Chem. - Eur. J. 2015, 21,
9720. (d) Tan, Y.; Yuan, W.; Gong, L.; Meggers, E. Angew. Chem., Int. Ed.
2015, 54, 13045. (e) Huang, Y.; Song, L.; Gong, L.; Meggers, E. Chem. -
Asian J. 2015, 10, 2738. (f) Tian, C.; Gong, L.; Meggers, E. Chem.
Commun. 2016, 52, 4207. (g) Song, L.; Gong, L.; Meggers, E. Chem.
Commun. 2016, 52, 7699. (h) Zheng, Y.; Harms, K.; Zhang, L.; Meggers,
E. Chem. - Eur. J. 2016, 22, 11977. (i) Ma, J.; Shen, X.; Harms, K.;
Meggers, E. Dalton Trans. 2016, 45, 8320.
(13) For catalytic enantioselective indole alkylations with α,β-
unsaturated 2-acyl imidazoles, see: (a) Evans, D. A.; Fandrick, K. R.;
Song, H.-J. J. Am. Chem. Soc. 2005, 127, 8942. (b) Evans, D. A.; Fandrick,
K. R.; Song, H.-J.; Scheidt, K. A.; Xu, R. J. Am. Chem. Soc. 2007, 129,
10029.
(14) For the concept of bi- or multifunctional catalysis, see:
(a) Sawamura, M.; Ito, Y. Chem. Rev. 1992, 92, 857. (b) Steinhagen,
H.; Helmchen, G. Angew. Chem., Int. Ed. Engl. 1996, 35, 2339.
(c) Shibasaki, M.; Yoshikawa, N. Chem. Rev. 2002, 102, 2187. (d) Ma, J.-
A.; Cahard, D. Angew. Chem., Int. Ed. 2004, 43, 4566. (e) Yamamoto, H.;
Futatsugi, K. Angew. Chem., Int. Ed. 2005, 44, 1924. (f) Li, P.; Yamamoto,
H. Top. Organomet. Chem. 2011, 37, 161. (g) Kumagai, N.; Shibasaki, M.
Angew. Chem., Int. Ed. 2013, 52, 223.
(15) For reviews on bifunctional hydrogen-bond-mediated organo-
catalysis, see: (a) Takemoto, Y. Org. Biomol. Chem. 2005, 3, 4299.
(b) Bhadury, P.; Li, H. Synlett 2012, 23, 1108. (c) Serdyuk, O.; Heckel,
C.; Tsogoeva, S. Org. Biomol. Chem. 2013, 11, 7051.
National Thousand Talents Program of P. R. China, and the 985
Program of the Chemistry and Chemical Engineering disciplines
of Xiamen University.
REFERENCES
■
(1) For reviews on catalytic asymmetric Friedel−Crafts alkylations of
indoles, see: (a) Bandini, M.; Melloni, A.; Umani-Ronchi, A. Angew.
Chem., Int. Ed. 2004, 43, 550. (b) Poulsen, T. B.; Jørgensen, K. A. Chem.
Rev. 2008, 108, 2903. (c) You, S.-L.; Cai, Q.; Zeng, M. Chem. Soc. Rev.
2009, 38, 2190. (d) Zeng, M.; You, S.-L. Synlett 2010, 1289.
(e) Terrasson, V.; de Figueiredo, R. M.; Campagne, J. M. Eur. J. Org.
Chem. 2010, 2010, 2635. (f) Bartoli, G.; Bencivenni, G.; Dalpozzo, R.
Chem. Soc. Rev. 2010, 39, 4449. (g) Dalpozzo, R. Chem. Soc. Rev. 2015,
44, 742.
(2) For selected recent examples of asymmetric Friedel−Crafts
3-alkylations of indoles, see: (a) Wu, L.; Liu, R.-R.; Zhang, G.; Wang, D.-
J.; Wu, H.; Gao, J.; Jia, Y.-X. Adv. Synth. Catal. 2015, 357, 709. (b) Fang,
F.; Hua, G.; Shi, F.; Li, P. Org. Biomol. Chem. 2015, 13, 4395. (c) Frías,
M.; Padron
S.; Aylward, M.; Keogh-Hansen, C.; Fitzpatrick, B.; McManus, H. A.;
Muller-Bunz, H.; Guiry, P. J. J. Org. Chem. 2015, 80, 10177. (e) Ranjbar,
́ ́
, J. M.; Aleman, J. Chem. - Eur. J. 2015, 21, 8237. (d) O’Reilly,
̈
̀
S.; Riente, P.; Rodríguez-Escrich, C.; Yadav, J.; Ramineni, K.; Pericas, M.
A. Org. Lett. 2016, 18, 1602. (f) Garcia-Garcia, C.; Ortiz-Rojano, L.;
Alvarez, S.; Alvarez, R.; Ribagorda, M.; Carreno, M. C. Org. Lett. 2016,
18, 2224. (g) Ge, C.; Liu, R.-R.; Gao, J.-R.; Jia, Y.-X. Org. Lett. 2016, 18,
3122. (h) Mendez, I.; Rodriguez, R.; Polo, V.; Passarelli, V.; Lahoz, F. J.;
Garcia-Orduna, P.; Carmona, D. Chem. - Eur. J. 2016, 22, 11064.
(i) Tsuchida, K.; Senda, Y.; Nakajima, K.; Nishibayashi, Y. Angew. Chem.,
Int. Ed. 2016, 55, 9728.
(16) For examples of metal-templated hydrogen-bond-mediated
catalysis developed by our group, see: (a) Chen, L.-A.; Xu, W.;
Huang, B.; Ma, J.; Wang, L.; Xi, J.; Harms, K.; Gong, L.; Meggers, E. J.
Am. Chem. Soc. 2013, 135, 10598. (b) Chen, L.-A.; Tang, X.; Xi, J.; Xu,
W.; Gong, L.; Meggers, E. Angew. Chem., Int. Ed. 2013, 52, 14021.
(c) Ma, J.; Ding, X.; Hu, Y.; Huang, Y.; Gong, L.; Meggers, E. Nat.
(3) 4,7-Dihydroindoles undergo a regioselective Friedel−Crafts
alkylation at the 2-position and, after oxidation, afford 2-substituted
Commun. 2014, 5, 5531. (d) Xu, W.; Arieno, M.; Low, H.; Huang, K.;
̈
indoles. For this strategy, see: C
2005, 61, 2401.
̆
̧avdar, H.; Saraco̧ glu, N. Tetrahedron
Xie, X.; Cruchter, T.; Ma, Q.; Xi, J.; Huang, B.; Wiest, O.; Gong, L.;
Meggers, E. J. Am. Chem. Soc. 2016, 138, 8774.
(4) Cheng, H.-G.; Lu, L.-Q.; Wang, T.; Yang, Q.-Q; Liu, X.-P.; Li, Y.;
Deng, Q.-H.; Chen, J.-R.; Xiao, W.-J. Angew. Chem., Int. Ed. 2013, 52,
3250.
(5) Zhang, Y.; Liu, X.; Zhao, X.; Zhang, J.; Zhou, L.; Lin, L.; Feng, X.
Chem. Commun. 2013, 49, 11311.
(6) Bi, B.; Lou, Q.-X.; Ding, Y.-Y.; Chen, S.-W.; Zhang, S.-S.; Hu, W.-
H.; Zhao, J.-L. Org. Lett. 2015, 17, 540.
(7) Weng, J.-Q.; Fan, R.-J.; Deng, Q.-M.; Liu, R.-R.; Gao, J.-R.; Jia, Y.-X.
J. Org. Chem. 2016, 81, 3023.
(8) Zhuo, C.-X.; Zheng, C.; You, S.-L. Acc. Chem. Res. 2014, 47, 2558.
(9) (a) Wu, Q.-F.; Zheng, C.; You, S.-L. Angew. Chem., Int. Ed. 2012,
51, 1680. (b) Zheng, C.; Wu, Q.-F.; You, S.-L. J. Org. Chem. 2013, 78,
4357. (c) Zhuo, C.-X.; Wu, Q.-F.; Zhao, Q.; Xu, Q.-L.; You, S.-L. J. Am.
Chem. Soc. 2013, 135, 8169. (d) Wu, Q.-F.; Zheng, C.; Zhuo, C.-X.; You,
S.-L. Chem. Sci. 2016, 7, 4453.
(10) Another catalytic asymmetric approach to 2-functionalized
indoles which exploits functional groups at the 3-substituent is based
on the Pictet−Spengler reaction. See, for example: (a) Taylor, M. S.;
Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 10558. (b) Seayad, J.;
Seayad, A. M.; List, B. J. Am. Chem. Soc. 2006, 128, 1086. (c) Raheem, I.
T.; Thiara, P. S.; Peterson, E. A.; Jacobsen, E. N. J. Am. Chem. Soc. 2007,
129, 13404. (d) Muratore, M. E.; Holloway, C. A.; Pilling, A. W.; Storer,
R. I.; Trevitt, G.; Dixon, D. J. J. Am. Chem. Soc. 2009, 131, 10796. (e) Cai,
Q.; Liang, X.-W.; Wang, S.-G.; Zhang, J.-W.; Zhang, X.; You, S.-L. Org.
Lett. 2012, 14, 5022.
(17) For recent examples combining metal activation with hydrogen
bond formation in a single catalyst, see: (a) Tan, F.; Bian, Q.; Chen, J.-R.;
Xiao, W.-J. Chem. - Eur. J. 2014, 20, 3415. (b) Dong, X.-Q.; Zhao, Q.; Li,
P.; Chen, C.; Zhang, X. Org. Chem. Front. 2015, 2, 1425. (c) Tan, F.; Lu,
L.-Q.; Arai, T.; Ogawa, H.; Awata, A.; Sato, M.; Watabe, M.; Yamanaka,
M. Angew. Chem., Int. Ed. 2015, 54, 1595. (d) Yang, Q.-Q.; Guo, W.;
Arai, T.; Tsuchiya, K.; Matsumura, E. Org. Lett. 2015, 17, 2416.
(e) Zhao, J.-Q.; Wu, Z.-J.; Zhou, M.-Q.; Xu, X.-Y.; Zhang, X.-M.; Yuan,
W.-C. Org. Lett. 2015, 17, 5020. (f) Liu, H.-C.; Liu, K.; Xue, Z.-Y.; He,
Z.-L.; Wang, C.-J. Org. Lett. 2015, 17, 5440. (g) Zhu, D.-Y.; Xu, M.-H.;
Tu, Y.-Q.; Zhang, F.-M.; Wang, S.-H. Chem. - Eur. J. 2015, 21, 15502.
(h) Liu, H.-C.; Tao, H.-Y.; Cong, H.; Wang, C.-J. J. Org. Chem. 2016, 81,
3752. (i) Wen, J.; Jiang, J.; Zhang, X. Org. Lett. 2016, 18, 4451.
(18) For examples of uracil serving as a hydrogen bond acceptor, see:
(a) Llanes-Pallas, A.; Yoosaf, K.; Traboulsi, H.; Mohanraj, J.; Seldrum,
T.; Dumont, J.; Minoia, A.; Lazzaroni, R.; Armaroli, N.; Bonifazi, D. J.
Am. Chem. Soc. 2011, 133, 15412. (b) Maggini, L.; Marangoni, T.;
Georges, B.; Malicka, J. M.; Yoosaf, K.; Minoia, A.; Lazzaroni, R.;
Armaroli, N.; Bonifazi, D. Nanoscale 2013, 5, 634. (c) Diez-Martinez, A.;
Kim, E.; Krishnamurthy, R. J. Org. Chem. 2015, 80, 7066. (d) Đorđevic,
́
L.; Marangoni, T.; Miletic, T.; Rubio-Magnieto, J.; Mohanraj, J.;
Amenitsch, H.; Pasini, D.; Liaros, N.; Couris, S.; Armaroli, N.; Surin, M.;
Bonifazi, D. J. Am. Chem. Soc. 2015, 137, 8150. (e) Sigalov, M. V.;
Pylaeva, S. A.; Tolstoy, P. M. J. Phys. Chem. A 2016, 120, 2737.
(19) For selected examples, see: (a) Fernandez, L. S.; Buchanan, M. S.;
Carroll, A. R.; Feng, Y. J.; Quinn, R. J.; Avery, V. M. Org. Lett. 2009, 11,
329. (b) Schrader, T. O.; Johnson, B. R.; Lopez, L.; Kasem, M.;
Gharbaoui, T.; Sengupta, D.; Buzard, D.; Basmadjian, C.; Jones, R. M.
Org. Lett. 2012, 14, 6306. (c) Ding, Z.; Yoshikai, N. Angew. Chem., Int.
Ed. 2013, 52, 8574.
(11) For reviews covering chiral-at-metal complexes in catalysis, see:
(a) Brunner, H. Angew. Chem., Int. Ed. 1999, 38, 1194. (b) Knight, P. D.;
Scott, P. Coord. Chem. Rev. 2003, 242, 125. (c) Fontecave, M.; Hamelin,
́
O.; Menage, S. Top. Organomet. Chem. 2005, 15, 271. (d) Bauer, E. B.
Chem. Soc. Rev. 2012, 41, 3153. (e) Gong, L.; Chen, L.-A.; Meggers, E.
Angew. Chem., Int. Ed. 2014, 53, 10868. (f) Cao, Z.-Y.; Brittain, W. D. G.;
Fossey, J. S.; Zhou, F. Catal. Sci. Technol. 2015, 5, 3441.
(12) For chiral-at-metal Lewis acid catalysts developed by our group,
see: (a) Huo, H.; Fu, C.; Harms, K.; Meggers, E. J. Am. Chem. Soc. 2014,
136, 2990. (b) Wang, C.; Chen, L.-A.; Huo, H.; Shen, X.; Harms, K.;
D
DOI: 10.1021/acs.orglett.6b03500
Org. Lett. XXXX, XXX, XXX−XXX