Amide groups switch selectivity: C-H trifluoromethylation of α,β-unsaturated amides and subsequent asymmetric transformation

Article abstract of DOI:10.1021/ol503067g

The first direct C-H β-trifluoromethylation of unsubstituted or α-alkyl-substituted α,β-unsaturated carbonyl compounds under metal-free conditions was realized with excellent regio- and stereoselectivity as well as a very broad substrate scope. Both olefi

Full text of DOI:10.1021/ol503067g

Letter
pubs.acs.org/OrgLett
Amide Groups Switch Selectivity: C−H Trifluoromethylation of α,β-
Unsaturated Amides and Subsequent Asymmetric Transformation
Lei Li,† Jing-Yao Guo,† Xing-Guo Liu,‡ Su Chen,† Yong Wang,§ Bin Tan,*,† and Xin-Yuan Liu*,†
†Department of Chemistry, South University of Science and Technology of China, Shenzhen, 518055, P. R. China
‡School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, P. R. China
§College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, P. R. China
S
* Supporting Information
ABSTRACT: The first direct C−H β-trifluoromethylation of
unsubstituted or α-alkyl-substituted α,β-unsaturated carbonyl
compounds under metal-free conditions was realized with
excellent regio- and stereoselectivity as well as a very broad
substrate scope. Both olefinic and allylic trifluoromethylation
products are accessible with high selectivities by altering the
substrate substitutions. The resultant olefinic products, namely (E)-β-trifluoromethyl (CF3) α,β-unsaturated hydroxamic acid
derivatives, served as acceptors in organocatalytic asymmetric Michael addition reactions to give hydroxamic acid derivatives
bearing a chiral CF3-substituted stereocenter with high enantioselectivities.
ydroxamic acid derivatives with functional substituents are
structural motifs found in a number of interesting
In this regard, Loh8a and Besset8b have independently
developed a Cu-catalyzed or -mediated elegant C−H β-
trifluoromethylation of α-substituted acrylamides to furnish
preferably the Z isomers via the possible involvement of the
directing group in the formation of the C−CF3 bond (Scheme
2a). In contrast, Bi et al. has successfully demonstrated Cu-
H
pharmaceuticals and biologically active molecules.1 The stereo-
selective introduction of trifluoromethyl groups in these
therapeutically important organic motifs at a specific site may
give rise to significant changes in the chemical and physical
properties of a potential drug candidate owing to improved
solubility and lipophilicity properties.2,3 However, the stereo-
selective synthesis of chiral trifluoromethylated hydroxamic acids
has been much less explored and remains a very important and
extremely challenging task for practitioners of chemical and
pharmaceutical synthesis. To address this demand and as part of
our continued interest in the area of trifluoromethylation4 and
asymmetric catalysis,5 we envisaged that a two-step sequential
synthetic strategy comprising the direct C−H β-trifluoromethy-
lation of α,β-unsaturated hydroxamic acid derivatives with a CF3
source and enantioselective organocatalytic Michael addition of
nucleophiles to the resulting β-trifluoromethylated compounds
could yield the desired chiral trifluoromethylated hydroxamic
acid scaffold in a stereocontrolled manner (Scheme 1).
Scheme 2. Direct C−H Trifluoromethylation of Electron-
Deficient Alkenes
catalyzed C−H α-trifluoromethylation of β-substituted α,β-
unsaturated carbonyl compounds (Scheme 2b).9 While these
reports stand out as pioneering efforts, limitations such as the
required substitution at the α- or β-position of a double bond to
efficiently control α- or β-site selectivity and E/Z selectivity and
the need for a metal catalyst or mediator have left great potential
for further development. For example, the direct C−H
trifluoromethylation of unsubstituted α,β-unsaturated carbonyl
compounds has no report and remains an unmet challenge due to
the selectivity issues including the regioselectivity (α- or β-site)
and stereoselectivity (E/Z isomers) based on the previously
reported methods.8,9 An additional disadvantage of the reported
methods is the difficulty in controlling the reaction pattern in the
Scheme 1. Our Strategy for the Synthesis of Desired Chiral
Trifluoromethylated Hydroxamic Acid Scaffold
Despite the recent great advances in the direct C−H
trifluoromethylation of various types of organic molecules,2,6
the C−H trifluoromethylation of electron-deficient alkenes has
been proven as an attractive but underexploited strategy for
providing easy access to trifluoromethylated α,β-unsaturated
carbonyls.6b,7
Received: October 20, 2014
Published: November 10, 2014
© 2014 American Chemical Society
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Letter
direct C−H β-trifluoromethylation of α-alkyl-substituted α,β-
unsaturated carbonyl compounds, thereby affording both an
olefinic and allylic trifluoromethylation product with low
selectivity.8 Therefore, the development of a promising and
mechanistically distinct strategy for the direct C−H β-
trifluoromethylation of unsubstituted or α-alkyl-substituted
α,β-unsaturated carbonyl compounds with high selectivity
especially under metal-free conditions would be highly
interesting (Scheme 2c) not only from the viewpoint of the
synthetic versatility of such trifluoromethylated products10 but
also from the mechanistic point of view. We herein present the
details of our studies. Significantly, E isomers of β-trifluor-
omethylation are accessed with high selectivities under metal-
free conditions, which provide a useful alternative to the known
transition metal catalyzed methods.8,9 Furthermore, the judicious
choice of the amide groups of α-alkyl substituted acrylamides can
completely switch the reaction pattern from an olefinic to allylic
trifluoromethylation product with high efficiency (Scheme 2c).
Our investigation commenced with the reaction between 1a
and Togni’s reagent11 2 in the presence of catalytic or
substoichiometric amounts of different copper salts CuI, CuBr,
or CuCl with various organic solvents, based on recent reports on
the direct C−H β-trifluoromethylation of α,β-unsaturated
carbonyls.8,9 Not surprisingly, all of the reactions gave a complex
result under these conditions, presumably due to low reactivity
and the difficulty in controlling both regioselectivity and E/Z
selectivity (Table S1, entries 1 and 2). Inspired by recent work
concerning the direct trifluoromethylation reactions with
nBu4NI as an initiator,12 we chose nBu4NI (10 mol %) as the
catalyst in the presence of NaHCO3 (2 equiv) in CH3CN to
activate this reaction, and we found that the expected β-
trifluoromethylation E isomer could be obtained in 14% yield
with high selectivity (Table S1, entry 3). Encouraged by this
result, we then screened different amounts of nBu4NI as an
initiator revealing 1.5 equiv of nBu4NI as being optimal to give 3a
in 71% yield (Table S1, entry 8). Among the different organic
solvents examined, CH3CN gave the best results (Table S1,
entries 8−11). We then investigated the effect of different
additives and found that the yield of the reaction marginally
improved to 83% with high regioselectivity and up to almost
complete stereoselectivity with the use of NaOAc (2 equiv) as
the base (Table S1, entry 12).
Scheme 3. C−H β-Trifluoromethylation of α,β-Unsaturated
a
Hydroxamic Acid Derivatives
a
Conditions: 1 (0.2 mmol), 2 (0.4 mmol), nBu4Nl (0.3 mmol),
NaOAc (0.4 mmol), MeCN (3 mL). b NaHCO3 was used as the base.
next turned our attention to expand the substrate scope to
acrylamides (Scheme 4). Under the standard conditions, the
Scheme 4. C−H β-Trifluoromethylation of Acrylamides
With the optimized reaction conditions in hand, various
unsubstituted α,β-unsaturated hydroxamic acid derivatives 1b−
1h were reacted with 2 to examine the generality of this protocol
(Scheme 3). By switching the cyclopentyl substituent bound to
the N atom (R1 group in the substrate) to the cyclohexyl (1b),
linear aliphatic (1c−1e), branched aliphatic (1f and 1g), and
phenethyl (1h) group, the reaction also proceeded smoothly to
give the corresponding desired products 3b−3h in good yields in
excellent regio- and stereoselectivity. To further investigate the
scope of application, we tested the use of more challenging α-
methyl α,β-unsaturated hydroxamic acid derivatives as sub-
strates, since the mixtures of Z-selective-olefinic and allylic
trifluoromethylation products were observed in previous Cu-
catalyzed β-trifluoromethylations of α-alkyl acrylamides.8 We are
delighted to find that, under the standard conditions, various α-
methyl α,β-unsaturated hydroxamic acids with different aliphatic
substituents on the N atom could be exclusively transformed into
the corresponding olefinic β-trifluoromethylation 3i−3l as a
single thermodynamical E isomer in good yields.
expected E-isomer 3m was obtained in 57% yield with high
selectivity when unsubstituted N,N-diisopropylacrylamide 1m
was used as the substrate. In addition, reactions of 2 with different
types of acrylamides were also carried out. The α- or β-
substituted acrylamides, including those having a methyl group at
the α- or β position, gave the corresponding products 3n and 3o
in 70% and 53% yields, respectively. This contrasts with the
formation of similar β-trifluoromethylation products in relatively
lower yields (especially in 19% yield for α-alkyl derivative) in the
presence of 1.1 equiv of CuI with excess amounts of TFA
(trifluoroacetic acid) and N-methylforamide as the additives at
120 °C.8b It should be noted that this process has also been
applied to the use of substituted α, β-unsaturated imides as a
viable substrate. For example, different types of unsubstituted, α-
or β-substituted imides including pyrrolidinone (1p, 1q, and 1t),
oxazolidinone (1r), and acyclic imide (1s) were well-tolerated,
giving the corresponding products 3p−3t as single geometrical
isomers in moderate to good yields. It is encouraging to note that
the present process is a rather general reaction that can be
extended to a wide range of synthetically important functional
groups. The structure of 3r was determined by X-ray
Encouraged by the aforementioned C−H β-trifluoromethyla-
tion reaction of α,β-unsaturated hydroxamic acid derivatives, we
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Organic Letters
Letter
crystallographic analysis, and the configuration of other products
was determined in reference to 3r.
It is interesting to note that the current protocol could be
extended to sterically bulky acrylamides as a viable substrate with
a complete switch of the reaction pattern while under the
reaction conditions identical to those of C−H β-trifluoromethy-
lation detailed above (Scheme 5). Thus, the reaction of 2 with 1u
we explored the organocatalytic asymmetric Michael additions13
of nitromethane to (E)-β-trifluoromethyl α,β-unsaturated
hydroxamic acid derivatives in the presence of a bifunctional
organocatalyst, although no example of such a scenario has been
reported to date presumably due to their inherent low
electrophilicity. Inspired by the recent reports14,15 that a
pyrrolidinone, oxazolidinone, or pyrazole moiety of α,β-
unsaturated imides is demonstrated in the thiourea-catalyzed
Michael reaction via multiple H-bonding interactions, we
envisioned that hydroxamic acid derivatives might have a similar
interaction with such a catalyst for suitable reactivity and
stereoinduction. After optimization of the reaction conditions
with several bifunctional organocatalysts, the reaction proceeded
smoothly with cinchona-alkaloid-thiourea (I)16 and provided the
corresponding products 4a−4e in good yields with excellent
enantioselectivity albeit with long reaction times (5 days)
(Scheme 7). The absolute configuration of the products 4a−4e
Scheme 5. Allylic Trifluoromethylation
Scheme 7. Enantioselectivie Michael Addition of
Nucleophiles to Trifluoromethylatated Acrylamides
a
or 1v in the presence of nBu4NI (1.5 equiv) under the standard
conditions proceeded selectively and afforded only the allylic
trifluoromethylation products 3u and 3v in 85% and 87% yields,
respectively (Scheme 5). Most importantly, the product yields
did not have a significant influence when the amount of nBu4NI
was reduced from 1.5 to 0.3 equiv. Furthermore, changing the
substituent of the double bond in 1w from a methyl to butyl
group gave 3w in 68% yield. These results indicate that
substituents on acrylamide can switch the reaction pattern and
that a more bulky amide group makes the allylic trifluoromethy-
lation more favorable due to their extremely sterically and
electronically distinct inherent properties as compared to general
amide groups as shown in Scheme 4.
a
Reaction conditions: 3 (0.1 mmol), CH3NO2 (0.5 mmol),
b
malononitrile (0.3 mmol), toluene (0.2 mL). Microwave (MV)
assisted at 40 °C for 12 h. c MV assisted at 100 °C for 1 h. d 10 mol %
of catalyst at 0 °C for 2 d.
Based on the above experimental results and the mechanistic
investigation on aryltrifluoromethylation of activated alkenes
with nBu4NI as the initiator previously reported by Nevado et
al.,12a a plausible mechanism for our methodology is depicted in
Scheme 6, which involves the generation of the highly
was determined to be R by chiroptical methods and X-ray
crystallographic analysis (Figures S1 and S2, Supporting
Information). To shorten the reaction times, we subjected the
organocatalytic reaction to microwave irradiation.18 For product
4a, the chemical yield can be increased to 78% without significant
loss of the enantioselectivity within only 12 h. In contrast, the
disappointing results for product 4c suggested that the
temperature and the substrate might have a significant influence
on the optical purity. Furthermore, the reaction of an (E)-β-
trifluoromethyl α,β-unsaturated pyrrolidinone with nitrome-
thane or malononitrile with I or Takemoto’s catalyst19 (II) gave
the desired product 4f or 4g in excellent yields with good
enantioselectivity.17 This is interestingly in contrast with the
moderate enantioselectivity in the asymmetric reaction with an
(E)-β-trifluoromethyl α,β-unsaturated oxazolidinone.15b
In summary, we have successfully developed the first direct C−
H β-trifluoromethylation of unsubstituted or α-alkyl-substituted
α,β-unsaturated carbonyl compounds with excellent regio- and
stereoselectivity as well as a very broad substrate scope under
metal-free conditions. Interestingly, both olefinic and allylic
trifluoromethylation products are accessed with high selectivities
by altering the amide groups of α-alkyl substituted acrylamides.
Moreover, it is the first example involving (E)-β-trifluoromethyl
α,β-unsaturated hydroxamic acid derivatives as acceptors in
organocatalytic asymmetric Michael addition reactions. Mecha-
nistic studies and further synthetic applications of this reaction
are under investigation in our laboratory.
Scheme 6. Proposed Mechanism
electrophilic species A from the reaction of nBu4NI with Togni’s
reagent 2, followed by addition of activated alkene 1 and
elimination to give intermediate B, with subsequent deprotona-
tion of the resulting carbocation B, which leads to the desired
product 3. However, an alternative mechanism involving the CF3
radical intermediate cannot be ruled out at the present stage.12b
The high stereoselectivity of this olefinic trifluoromethylation
may arise from the steric interaction between the CF3 and amide
group, in which the CF3 substituent is directed away from the
amide group to give the single thermodynamical E isomer.
To further demonstrate the synthetic utility of the method-
ology and considering the fact that chiral trifluoromethyl
hydroxamic acid derivatives are pharmaceutically important,2
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(4) (a) Lin, J.-S.; Xiong, Y.-P.; Ma, C.-L.; Zhao, L.-J.; Tan, B.; Liu, X.-Y.
Chem.Eur. J. 2014, 20, 1332. (b) Li, L.; Deng, M.; Zheng, S.-C.; Xiong,
Y.-P.; Tan, B.; Liu, X.-Y. Org. Lett. 2014, 16, 504. (c) Xiong, Y.-P.; Wu,
M.-Y.; Zhang, X.-Y.; Ma, C.-L.; Huang, L.; Zhao, L.-J.; Tan, B.; Liu, X.-Y.
Org. Lett. 2014, 16, 1000. (d) Zhu, X.-L.; Xu, J.-H.; Cheng, D.-J.; Zhao,
L.-J.; Liu, X.-Y.; Tan, B. Org. Lett. 2014, 16, 2192.
(5) Cheng, D.-J.; Yan, L.; Tian, S.-K.; Wu, M.-Y.; Wang, L.-X.; Fan, Z.-
L.; Zheng, S.-C.; Liu, X.-Y.; Tan, B. Angew. Chem., Int. Ed. 2014, 53,
3684.
(6) For recent examples on direct C−H trifluoromethylation, see:
(a) Kieltsch, I.; Eisenberger, P.; Togni, A. Angew. Chem., Int. Ed. 2007,
46, 754. (b) Ball, N. D.; Kampf, J. W.; Sanford, M. S. J. Am. Chem. Soc.
2010, 132, 2878. (c) Wang, X.; Ye, Y.; Zhang, S.; Feng, J.; Xu, Y.; Zhang,
Y.; Wang, J. J. Am. Chem. Soc. 2011, 133, 16410. (d) Parsons, A. T.;
Buchwald, S. L. Angew. Chem., Int. Ed. 2011, 50, 9120. (e) Nagib, D. A.;
MacMillan, D. W. C. Nature 2011, 480, 224. (f) Herrmann, A. T.; Smith,
L. L.; Zakarian, A. J. Am. Chem. Soc. 2012, 134, 6976. (g) Feng, C.; Loh,
T. P. Chem. Sci. 2012, 3, 3458. (h) Zhang, X.-G.; Dai, H.-X.; Wasa, M.;
Yu, J.-Q. J. Am. Chem. Soc. 2012, 134, 11948. (i) Chu, L.; Qing, F.-L. J.
Am. Chem. Soc. 2012, 134, 1298. (j) Fujiwara, Y.; Dixon, J. A.; O’Hara,
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental procedures, characterization of all new com-
pounds, Table S1, Figures S1 and S2. This material is available
free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: tanb@sustc.edu.cn.
*E-mail: liuxy3@sustc.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are thankful for the financial support from the National
Natural Science Foundation of China (Nos. 21302088,
21302087), Shenzhen special funds for the development of
biomedicine, Internet, new energy, and new material industries
(JCYJ20130401144532131, JCYJ20130401144532137), and
South University of Science and Technology of China (Talent
Development Starting Fund from Shenzhen Government). We
are grateful to Prof. Dr. Tao Wang at Peking University Shenzhen
Graduate School for crystallographic analysis and Dr. Bei Zhao at
Soochow University for helpful discussions.
́
F.; Funder, E. D.; Dixon, D. D.; Rodriguez, R. A.; Baxter, R. D.; Herle, B.;
Sach, N.; Collins, M. R.; Ishihara, Y.; Baran, P. S. Nature 2012, 492, 95.
(k) Pair, E.; Monteiro, N.; Bouyssi, D.; Baudoin, O. Angew. Chem., Int.
Ed. 2013, 52, 5346. (l) Aiguabella, N.; del Pozo, C.; Verdaguer, X.;
Fustero, S.; Riera, A. Angew. Chem., Int. Ed. 2013, 52, 5355.
(7) (a) Uraguchi, D.; Yamamoto, K.; Ohtsuka, Y.; Tokuhisa, K.;
Yamakawa, T. Appl. Catal., A 2008, 342, 137. (b) Wang, X.; Ye, Y.; Ji, G.;
Xu, Y.; Zhang, S.; Feng, J.; Zhang, Y.; Wang, J. Org. Lett. 2013, 15, 3730.
(c) Ilchenko, N. O.; Janson, P. G.; Szabo, K. J. Chem. Commun. 2013, 49,
́
6614.
(8) (a) Feng, C.; Loh, T. P. Angew. Chem., Int. Ed. 2013, 52, 12414.
(b) Besset, T.; Cahard, D.; Pannecoucke, X. J. Org. Chem. 2014, 79, 413.
(9) Fang, Z.; Ning, Y.; Mi, P.; Liao, P.; Bi, X. Org. Lett. 2014, 16, 1522.
(10) Hayashi, T.; Yamasaki, K. Chem. Rev. 2003, 103, 2829.
(11) For selected examples on trifluoromethylation with the Togni’s
reagent, see: (a) Eisenberger, P.; Gischig, S.; Togni, A. Chem.Eur. J.
2006, 12, 2579. (b) Koller, R.; Stanek, K.; Stolz, D.; Aardoom, R.;
Niedermann, K.; Togni, A. Angew. Chem., Int. Ed. 2009, 48, 4332.
(c) Wiehn, M. S.; Vinogradova, E. V.; Togni, A. J. Fluorine Chem. 2010,
131, 951.
REFERENCES
■
(1) (a) Summers, J. B.; Kim, K. H.; Mazdiyasni, H.; Holms, J. H.;
Ratajczyk, J. D.; Stewart, A. O.; Dyer, R. D.; Carter, G. W. J. Med. Chem.
1990, 33, 992. (b) Banks, T. M.; Bonin, A. M.; Glover, S. A.; Prakash, A.
S. Org. Biomol. Chem. 2003, 13, 2238. (c) Li, X.; Wu, Y.-D.; Yang, D. Acc.
Chem. Res. 2008, 41, 1428.
(2) For selected reviews on trifluoromethylation of organic
compounds, see: (a) Purser, S.; Moore, P. R.; Swallow, S.;
Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320. (b) Nie, J.; Guo, H.-C.;
Cahard, D.; Ma, J.-A. Chem. Rev. 2011, 111, 455. (c) Tomashenko, O. A.;
Grushin, V. V. Chem. Rev. 2011, 111, 4475. (d) Ye, Y.; Sanford, M. S.
Synlett 2012, 23, 2005. (e) Furuya, T.; Kamlet, A. S.; Ritter, T. Nature
2011, 473, 470. (f) Wu, X.-F.; Neumann, H.; Beller, M. Chem.Asian J.
2012, 7, 1744. (g) Studer, A. Angew. Chem., Int. Ed. 2012, 51, 8950.
(3) Selected examples of methods for the asymmetric construction of a
chiral carbon center containing a CF3 group: (a) Kawai, H.; Kusuda, A.;
Nakamura, S.; Shiro, M.; Shibata, N. Angew. Chem., Int. Ed. 2009, 48,
6324. (b) Nagib, D. A.; Scott, M. E.; MacMillan, D. W. C. J. Am. Chem.
(12) For examples on trifluoromethylation reactions with nBu4NI as
initiator, see: (a) Kong, W.; Casimiro, M.; Fuentes, N.; Merino, E.;
Nevado, C. Angew. Chem., Int. Ed. 2013, 52, 13086. (b) Zhang, B.; Muck-
̈
Lichtenfeld, C.; Daniliuc, C. G.; Studer, A. Angew. Chem., Int. Ed. 2013,
52, 10792. (c) Zhang, B.; Studer, A. Org. Lett. 2014, 16, 1216.
(13) For selected reviews, see: (a) Fagnou, K.; Lautens, M. Chem. Rev.
2003, 103, 169. (b) Poulsen, T. B.; Jørgensen, K. A. Chem. Rev. 2008,
108, 2903. (c) Bandini, M.; Eichholzer, A. Angew. Chem., Int. Ed. 2009,
48, 9608.
́ ́
Soc. 2009, 131, 10875. (c) Blay, G.; Fernandez, I.; Monleon, A.; Pedro, J.
(14) For selected examples, see: (a) Hoashi, Y.; Okino, T.; Takemoto,
Y. Angew. Chem., Int. Ed. 2005, 44, 4032. (b) Zu, L.; Wang, J.; Li, H.; Xie,
H.; Jiang, W.; Wang, W. J. Am. Chem. Soc. 2007, 129, 1036. (c) Sibi, M.;
Itoh, K. J. Am. Chem. Soc. 2007, 129, 8064.
(15) For selected examples on organocatalytic Michael addition to β-
trifluoromethylated acylamides, see: (a) Zhang, W.; Tan, D.; Lee, R.;
Tong, G.; Chen, W.; Qi, B.; Huang, K. W.; Tan, C.-H.; Jiang, Z. Angew.
Chem., Int. Ed. 2012, 51, 10069. (b) Wen, L.; Yin, L.; Shen, Q.; Lu, L.
ACS Catal. 2013, 3, 502.
R.; Vila, C. Org. Lett. 2009, 11, 441. (d) Ogawa, S.; Iida, N.; Tokunaga,
E.; Shiro, M.; Shibata, N. Chem.Eur. J. 2010, 16, 7090. (e) Huang, Y.;
Tokunaga, E.; Suzuki, S.; Shiro, M.; Shibata, N. Org. Lett. 2010, 12, 1136.
(f) Matoba, K.; Kawai, H.; Furukawa, T.; Kusuda, A.; Tokunaga, E.;
Nakamura, S.; Shiro, M.; Shibata, N. Angew. Chem., Int. Ed. 2010, 49,
5762. (g) Allen, A. E.; MacMillan, D. W. C. J. Am. Chem. Soc. 2010, 132,
4986. (h) Matousek, V.; Togni, A.; Bizet, V.; Cahard, D. Org. Lett. 2011,
13, 5762. (i) Li, Y.; Liang, F.; Li, Q.; Xu, Y.-C.; Wang, Q.-R.; Jiang, L.
Org. Lett. 2011, 13, 6082. (j) Shibatomi, K.; Kobayashi, F.; Narayama, A.;
Fujisawa, I.; Iwasa, S. Chem. Commun. 2012, 48, 413. (k) Herrmann, A.
T.; Smith, L. L.; Zakarian, A. J. Am. Chem. Soc. 2012, 134, 6976.
(l) Zhang, F.-G.; Ma, H.; Nie, J.; Zheng, Y.; Gao, Q.; Ma, J.-A. Adv. Synth.
Catal. 2012, 354, 1422. (m) Bizet, V.; Pannecoucke, X.; Revaud, J.;
Cahard, D. Angew. Chem., Int. Ed. 2012, 51, 6467. (n) Deng, Q.-H.;
Wadepohl, H.; Gade, L. H. J. Am. Chem. Soc. 2012, 134, 10769. (o) Gao,
J.-R.; Wu, H.; Xiang, B.; Yu, W.-B.; Han, L.; Jia, Y.-X. J. Am. Chem. Soc.
2013, 135, 2983. (p) Kawai, H.; Yuan, Z.; Kitayama, T.; Tokunaga, E.;
Shibata, N. Angew. Chem., Int. Ed. 2013, 52, 5575. (q) Kawai, H.; Okusu,
S.; Yuan, Z.; Tokunaga, E.; Yamano, A.; Shiro, M.; Shibata, N. Angew.
Chem., Int. Ed. 2013, 52, 2221.
(16) Vakulya, B.; Varga, S.; Csam
1967.
́ ́
pai, A.; Soos, T. Org. Lett. 2005, 7,
(17) The absolute configuration of 4f and 4g was determined by
comparison with similar products with Takemoto’s catalyst (II)
reported by Shen’s work (see ref 15b).
(18) We appreciate the reviewer’s helpful suggestion for conducting
the reaction under microwave-assisted conditions to shorten the
reaction times.
(19) Tomotaka, O.; Hoashi, Y.; Takemoto, Y. J. Am. Chem. Soc. 2003,
125, 12672.
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