NaClO-Promoted Atroposelective Couplings of 3-Substituted Indoles with Amino Acid Derivatives

Article abstract of DOI:10.1021/acs.orglett.9b01638

A new class of C-N axial chirality based on N-indole sulfonamides has been disclosed. This new axially chiral N-indole sulfonamides were constructed by NaClO-promoted couplings of 3-substituted indoles with chiral amino acid-based sulfonamides. A series of structurally diverse N-indole sulfonamide-based atropisomers were prepared using this established method. The stability of these structurally interesting atropisomers highly relied on the C3-substituents of indoles and side chains of amino acid derivatives.

Full text of DOI:10.1021/acs.orglett.9b01638

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
NaClO-Promoted Atroposelective Couplings of 3‑Substituted
Indoles with Amino Acid Derivatives
Zhaojie Li, Hao Zhang, and Shouyun Yu*
State Key Laboratory of Analytical Chemistry for Life Science, Jiangsu Key Laboratory of Advanced Organic Materials, School of
Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China
S
* Supporting Information
ABSTRACT: A new class of C−N axial chirality based on N-
indole sulfonamides has been disclosed. This new axially chiral
N-indole sulfonamides were constructed by NaClO-promoted
couplings of 3-substituted indoles with chiral amino acid-
based sulfonamides. A series of structurally diverse N-indole
sulfonamide-based atropisomers were prepared using this
established method. The stability of these structurally
interesting atropisomers highly relied on the C3-substituents of indoles and side chains of amino acid derivatives.
tropisomerism is a property exhibited by molecules where
bond rotation is restricted.1 Progress in this area saw a
efforts on the investigation of atropisomeric phenomenon with
an N-indole chiral axis (Figure 1b).
A
steep increase after the advent of biaryl-based atropisomeric
catalysts and the discovery of natural products with biaryl
atropisomeric skeletons.2 Along with biaryls, several other
classes of compounds display atropisomerism.3 As one of the
most important classes of nonbiaryl axially chiral compounds,
atropisomers around the C−N chiral axis have received much
attention recently as novel chiral molecules.4 These C−N
axially chiral compounds have widespread appearance in
naturally occurring compounds5 and also play a significant
role in acting as chiral ligands or organocatalysts.6 These C−N
axially chiral compounds have also been found to be useful in
molecular devices.7 As such, their stereoselective syntheses are
the focus of recent studies.8 After the pioneering works on
atropisometric anilides by Curran and co-workers,9 syntheses
of compounds with C−N axial chirality were reported by
several other groups10 (Figure 1a), most of which are amide-
Indoles are one of the most important heteroarenes, which
widely exist in natural products and pharmaceuticals, and they
have been of intensive research interest in synthetic and
medicinal chemistry.14 Recently, we are engaged in amidation
of indole derivatives with sulfonamides.15 Inspired by these
works, we are interested in couplings of indole derivatives with
amino acid derivatives. Our initial investigation started by the
coupling of 1,3-dimethylindole (1a) with N-triflyl-(L)-valine
tert-butyl ester (2a) promoted by NaClO aqueous solution at
room temperature (Figure 2). Interestingly, two products 3a
and 3a′ were isolated with a 7.7:1 ratio in 41% combined yield.
These two compounds, in which structures and stereo-
chemistry were established unambiguously by single crystal
X-ray diffraction analysis,16 were assigned as two diaster-
eoisomers with an N-indole chiral axis. This type of N-indole
axial chirality has not hitherto been disclosed.
Figure 1. C−N chiral axis.
type compounds, such as naphthamides, carbamates, imides,
oxoamides, and ureas. As pioneered by Uemura11 and others,12
aromatic heterocyclic frameworks, such as indoles and pyrroles,
could also be involved in axial chirality. The Caryl−N chiral axis
of atropisomers aforementioned are all based on N-phenyl
motifs. N-Heteroaryl atropisomers with a C−N chiral axis were
rarely reported to date.13 Herein, we would like to report our
Figure 2. Coupling of 3-methylindole with valine derivative.
Received: May 8, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b01638
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
It is known that the indole-based atropisomers are expected
to have less steric congestion and relatively lower rotation
barriers than the corresponding benzene derivatives.17 In order
to investigate the stereochemical stability of this N-indole
atropisomer, the half-lives and free energy barriers for
racemization of 3a in toluene at three different temperatures
were measured (Table 1, see the Supporting Information for
improvement in the results was obtained (entries 7−9). When
the reaction time was prolonged from 30 min to 12 h, the
isolated yield was improved to 87% without affecting the
stereoselectivity (entry 10). Nitrogen protection was not
necessary, and when the reaction performed under an air
atmosphere, the same reaction outcome was observed (entry
10).
After establishing the optimized conditions of this
atroposelective coupling, we next diversified this N-indole
axial chirality. First, a series of structurally diverse substituted
indole derivatives coupled with the (L)-valine derivative 2a
(Figure 3). The substituents at the N1 position were explored.
Table 1. Rate, Half-Life, and Free Energy Barrier for the
Racemization of 3a in Toluene
τ1/2rac
(h)
ΔG⧧kf
ΔG⧧kb
T
(kcal/mol)
(kcal/mol)
Keq
313.15 K (40 °C)
333.15 K (60 °C)
353.15 K (80 °C)
122.68
9.21
1.22
27.66
27.75
28.04
26.80
26.84
27.07
0.25
0.25
details). It was found that the half-life of 3a was more than 5
days (122.68 h) at 313.15 K (40 °C), while the half-life was
about 1.2 h at 353.15 K (80 °C). The energy barrier for
racemization of 3a was 28.04 kcal/mol (ΔG⧧kf) and 27.07
kcal/mol (ΔG⧧kb) at 353.15 K (80 °C).
In order to improve the efficiency and stereoselectivity of
this NaClO-promoted atroposelective coupling further, the
optimization of the reaction conditions was conducted using
indole 1b and (L)-valine derivative 2a as the model coupling
partners (Table 2). When a solution of 1b, 2a, and NaClO
a
Table 2. Reaction Conditions Optimization
Figure 3. Scope of indole derivatives. Reaction conditions: a solution
of 1 (0.2 mmol), 2a (0.1 mmol), and NaClO (0.3 mmol) in PhCF3 (2
mL) for 12 h under air. The yields were isolated yields, and the dr
a
values were determined by 19F NMR. The reaction was run at the 3
mmol scale (2a).
b
c
entry
1b/2a/NaClO
solvent
PhCH3
PhOCH3
DMF
1,4-dioxane
CH3CN
PhCF3
PhCF3
PhCF3
PhCF3
PhCF3
yield/%
dr
1
2
3
4
5
6
7
8
9
2:1:3
2:1:3
2:1:3
2:1:3
2:1:3
2:1:3
1:2:3
1.5:1:3
1.5:1:1.5
2:1:3
51
15
trace
12
12
74
60
67
69
87
13:1
13:1
13:1
13:1
13:1
13:1
13:1
13:1
13:1
13:1
N1 substituents could be aryl groups with different
functionalities, and good yields and stereoselectivities could
be achieved (3b, 3c, and 3e, 52−87% yields and >10:1 dr).
When the N1 position was alkylated, the coupling was less
efficient in terms of yields and dr values (41% yield and 7.7:1
dr for 3a, 46% yield and 9.6:1 dr for 3d, respectively). When
the substituent at the C3 position was changed from methyl to
benzyl group, the coupling product 3f was delivered with
12.6:1 dr but moderate yield (35%). 3-Chloro and 3-
bromoindole derivatives could also go through this reaction
with good yields and dr values (88% yield and 7.6:1 dr for 3g
and 77% yield and 5:1 dr for 3h, respectively). Subsequently,
indoles bearing various substituents at the C4−C7 positions
were coupled with 2a to give the corresponding products 3i−
3p with satisfactory to excellent yields (62−94%) and good dr
values (10.5:1−15.0:1). Not only electron-withdrawing groups,
such as 5-CF3 (3l) and 5-NO2 (3m), but also electron-
donating groups, such as 4-OBn (3i) and 5-OMe (3j),
tolerated well in this transformation. To demonstrate the
practicability of this method, we subsequently conducted this
reaction on the gram scale. When 1.42 g of 1b was subjected to
the standard conditions, a comparative isolated yield of 3b
d
10
a
Reaction conditions: a solution of 1b, 2a (0.1 mmol), and NaClO in
b
the indicated solvent (2 mL) for 30 min under N2. Combined yields
c
of two atropisomers. The dr values were determined by 19F NMR.
d
12 h under air. PMP = 4-methoxyphenyl.
with a ratio of 2:1:3 in toluene for 30 min at room
temperature, the coupling product 3b could be isolated with
51% yield and 13:1 dr (entry 1). It was found that the solvent
effect had significant influence on the efficiency of this
coupling but did not affect the stereoselectivity (entries 2−
6). PhCF3 proved to be the optimal solvent (74% yield, entry
6). The ratio of 1b/2a/NaClO was then tested and no
B
DOI: 10.1021/acs.orglett.9b01638
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(1.39 g, 86% yield) was achieved with the same stereo-
selectivity (13.0:1 dr).
We next sought to establish the scope of the amino acid
derivatives using indole 1b as the coupling partner (Figure 4).
Figure 5. Control experiments.
HOAc into the reaction mixture of 1b and NaClO gave 3-
chloroindolinone 5 and indolinone 6 in significantly improved
yields (55% and 35%, respectively, Figure 5c). Given the
acidity of sulfonamides,19 amino acid-derived sulfonamide 2a
acts not only as an amine source but also as an acid to promote
the chlorine transfer from NaClO in this reaction.
Based on the aforementioned experimental observations and
related literature,20 a possible reaction pathway is proposed for
this transformation (Figure 6). Indole 1b undergoes electro-
Figure 4. Scope of sulfonamides. Reaction conditions: a solution of
1b (0.2 mmol), 2 (0.1 mmol), and NaClO (0.3 mmol) in PhCF3 (2
mL) for 12 h under air. The yields were based on two isolated
a
atropisomers. The dr values were determined by 19F NMR. The dr
1
value was determined by H NMR.
4-Nitrobenzenesulfonyl (Ns) could be used as the protecting
group of amino group instead of triflyl group to give the
atropisomer 3q with the identical stereoselectivity and slightly
low yield (65%). When the t-butyl ester was changed to ethyl
ester, the stereoselectivity of the coupling was affected
negatively (3r, 11.0:1 dr) but with slightly better yield
(90%). A variety of natural amino acid derivatives, such as
phenylalanine (Phe, 3s), leucine (Leu, 3t), threonine (Thr,
3u), isoleucine (Ile, 3v), and serine (Ser, 3w), were coupled
with indole 1b, and the corresponding products 3s−3w were
isolated in 51−94% yields and good dr values (5.4:1−7.1:1).
Steric bulky side chains of amino acid derivatives have a
positive influence on the stereoselectivity. It is not surprising
that alanine derivative could go through this reaction but
without stereoselectivity (not shown). The cyclohexyl (Cy)-
based non-natural amino acid derivative could also undergo
this reaction to give the product 3x with high yield and dr
value (89% yield and 12.0:1 dr). A chiral amino alcohol
derivative was also explored, and a moderate yield and
stereoselectivity were observed (50% yield and 5.1:1 dr for 3y).
To better understand the mechanism of this reaction, a
series of control experiments were conducted, as show in
Figure 5. Treatment of sulfonamide 2a with NaClO could not
give the N-chlorosulfonamide 4, which was the potential
chlorinating reagent in our previous work (Figure 5a).15c
Therefore, it was proposed that NaClO directly served as the
chlorinating reagents in this reaction. Indole 1b reacting with
NaClO could give 3-chloroindolinone 5 and indolinone 6 but
in low yields (10% and 8%, respectively) (Figure 5b). It is
known that chlorine transfer may be assisted by acid when
NaClO is the chlorinating reagent.18 The introduction of
Figure 6. Plausible reaction mechanism.
philic chlorination with NaClO with the help of sulfonamide
2a to give the iminium ion 7. Subsequently, the iminium ion 7
is attacked by amino acid-based sulfonamide 2a. After losing
HCl assisted by a base, the desired product 3b is given. As
observed, the iminium ion 7 can also be attacked by water to
afford 9. Intermediate 9 can either be oxidized to furnish the
byproduct 3-chloroindolinone 5 or lose HCl to give indolinone
6.
In summary, we have disclosed a new class of C−N axial
chirality based on N-indole sulfonamides. This new axially
chiral N-indole sulfonamides were constructed by NaClO-
promoted couplings of 3-substituted indoles with chiral amino
acid-based sulfonamides. The stability of these structurally
interesting atropisomers highly relied on the C3-substituents of
indoles and side chains of amino acid derivatives. Further
improvement of the diastereoselectivity and investigation of
the application of this novel axially chiral indoles are underway
in our laboratory.
C
DOI: 10.1021/acs.orglett.9b01638
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Murakami, Y.; Aoyama, T. Synlett 2003, 2047−2051. (f) Dai, W.-M.;
Yeung, K. K. Y.; Wang, Y. Tetrahedron 2004, 60, 4425−4430.
(g) Pesch, J.; Harms, K.; Bach, T. Eur. J. Org. Chem. 2004, 2004,
2025−2035. (h) Brandes, S.; Niess, B.; Bella, M.; Prieto, A.;
Overgaard, J.; Jørgensen, K. A. Chem. - Eur. J. 2006, 12, 6039−
6052. (i) Dai, W.-M.; Li, Y.; Zhang, Y.; Yue, C.; Wu, J. Chem. - Eur. J.
2008, 14, 5538−5554. (j) Wang, F.; Li, S.; Qu, M.; Zhao, M.-X.; Liu,
L.-J.; Shi, M. Chem. Commun. 2011, 47, 12813−12815. (k) Mino, T.;
Ishikawa, M.; Nishikawa, K.; Wakui, K.; Sakamoto, M. Tetrahedron:
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b01638.
■
S
Experimental details, NMR spectra, and details of the
experiments (PDF)
́
́
Asymmetry 2013, 24, 499−504. (l) Faigl, F.; Erdelyi, Z.; Deak, S.;
Accession Codes
́
̈
Nyerges, M.; Matravolgyi, B. Tetrahedron Lett. 2014, 55, 6891−6894.
(m) Bai, X.-F.; Song, T.; Xu, Z.; Xia, C.-G.; Huang, W.-S.; Xu, L.-W.
Angew. Chem., Int. Ed. 2015, 54, 5255−5259.
CCDC 1909079−1909080 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
(7) (a) Iwamura, H.; Mislow, K. Acc. Chem. Res. 1988, 21, 175−182.
(b) Rebek, J.; Marshall, L.; Wolak, R.; McManis, J. J. Am. Chem. Soc.
1984, 106, 1170−1171. (c) Rebek, J.; Marshall, L.; Wolak, R.; Parris,
K.; Killoran, M.; Askew, B.; Nemeth, D.; Islam, N. J. Am. Chem. Soc.
1985, 107, 7476−7481. (d) Rebek, J. Angew. Chem., Int. Ed. Engl.
1990, 29, 245−255. (e) Choi, D.-S.; Chong, Y. S.; Whitehead, D.;
Shimizu, K. D. Org. Lett. 2001, 3, 3757−3760. (f) Degenhardt, C. F.;
Lavin, J. M.; Smith, M. D.; Shimizu, K. D. Org. Lett. 2005, 7, 4079−
4081. (g) Rasberry, R. D.; Shimizu, K. D. Org. Biomol. Chem. 2009, 7,
3899−3905. (h) Chong, Y. S.; Dial, B. E.; Burns, W. G.; Shimizu, K.
D. Chem. Commun. 2012, 48, 1296−1298. (i) Dial, B. E.; Pellechia, P.
J.; Smith, M. D.; Shimizu, K. D. J. Am. Chem. Soc. 2012, 134, 3675−
3678.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: yushouyun@nju.edu.cn.
ORCID
Shouyun Yu: 0000-0003-4292-4714
Notes
(8) For selected examples, see (a) Kitagawa, O.; Kohriyama, M.;
Taguchi, T. J. Org. Chem. 2002, 67, 8682−8484. (b) Kitagawa, O.;
Takahashi, M.; Yoshikawa, M.; Taguchi, T. J. Am. Chem. Soc. 2005,
127, 3676−3677. (c) Kitagawa, O.; Yoshikawa, M.; Tanabe, H.;
Morita, T.; Takahashi, M.; Dobashi, Y.; Taguchi, T. J. Am. Chem. Soc.
2006, 128, 12923−12931. (d) Takahashi, M.; Kitagawa, O. Yuki Gosei
Kagaku Kyokaishi 2011, 69, 985−993. (e) Shirakawa, S.; Liu, K.;
Maruoka, K. J. Am. Chem. Soc. 2012, 134, 916−919. (f) Diener, M. E.;
Metrano, A. J.; Kusano, S.; Miller, S. J. J. Am. Chem. Soc. 2015, 137,
12369−12377. (g) Li, S.-L.; Yang, C.; Wu, Q.; Zheng, H.-L.; Li, X.;
Cheng, J.-P. J. Am. Chem. Soc. 2018, 140, 12836−12843.
(9) (a) Curran, D. P.; Qi, H.; Geib, S. J.; DeMello, N. C. J. Am.
Chem. Soc. 1994, 116, 3131−3132. (b) Curran, D. P.; Hale, G. R.;
Geib, S. J.; Balog, A.; Cass, Q. B.; Degani, A. L. G.; Hernandes, M. Z.;
Freitas, L. C. G. Tetrahedron: Asymmetry 1997, 8, 3955−3975.
(c) Curran, D. P.; Liu, W.; Chen, C. H.-T. J. Am. Chem. Soc. 1999,
121, 11012−11013. (d) Ates, A.; Curran, D. P. J. Am. Chem. Soc.
2001, 123, 5130−5131. (e) Terauchi, J.; Curran, D. P. Tetrahedron:
Asymmetry 2003, 14, 587−592.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from National Natural Science Foundation
of China (Grant 21672098) and National Key Research and
Development Program of China (Grant 2018YFC0310900) is
acknowledged.
REFERENCES
■
(1) (a) Christie, G. H.; Kenner, J. J. Chem. Soc., Trans. 1922, 121,
614−620. (b) Kuhn, R. Molekulare Asymmetrie. In Stereochemie;
Freudenberg, H., Ed.; Franz Deuticke: Leipzig, Germany, 1933; p
803. (c) Oki, M. Recent Advances in Atropisomerism. In Topics in
Stereochemistry; John Wiley & Sons, Inc., 1983; Vol. 14, pp 1−81, .
(2) (a) Rosini, C.; Franzini, L.; Raffaelli, A.; Salvadori, P. Synthesis
1992, 503−517. (b) Bringmann, G.; Menche, D. Acc. Chem. Res.
2001, 34, 615−624. (c) Bringmann, G.; Gulder, T.; Gulder, T. A. M.;
Breuning, M. Chem. Rev. 2011, 111, 563−639. (d) LaPlante, S. R.;
Edwards, P. J.; Fader, L. D.; Jakalian, A.; Hucke, O. ChemMedChem
2011, 6, 381−381. (e) Wencel-Delord, J.; Panossian, A.; Leroux, F.
R.; Colobert, F. Chem. Soc. Rev. 2015, 44, 3418−3430.
(10) For selected examples, see (a) Sakamoto, M.; Utsumi, N.;
Ando, M.; Saeki, M.; Mino, T.; Fujita, T.; Katoh, A.; Nishio, T.;
Kashima, C. Angew. Chem., Int. Ed. 2003, 42, 4360−4363. (b) Tanaka,
K.; Takeishi, K.; Noguchi, K. J. Am. Chem. Soc. 2006, 128, 4586−
4587. (c) Brandes, S.; Bella, M.; Kjaersgaard, A.; Jørgensen, K. A.
Angew. Chem., Int. Ed. 2006, 45, 1147−1151. (d) Brandes, S.; Niess,
B.; Bella, M.; Prieto, A.; Overgaard, J.; Jørgensen, K. A. Chem. - Eur. J.
2006, 12, 6039−6052. (e) Duan, W.-L.; Imazaki, Y.; Shintani, R.;
Hayashi, T. Tetrahedron 2007, 63, 8529−8536. (f) Tanaka, K.;
Takeishi, K. Synthesis 2007, 2920−2923. (g) Tanaka, K. Chem. - Asian
J. 2009, 4, 508−518. (h) Ototake, N.; Morimoto, Y.; Mokuya, A.;
Fukaya, H.; Shida, Y.; Kitagawa, O. Chem. - Eur. J. 2010, 16, 6752−
6755. (i) Zhang, J.; Zhang, Y.; Lin, L.; Yao, Q.; Liu, X.; Feng, X.
Chem. Commun. 2015, 51, 10554−10557. (j) Hirai, M.; Terada, S.;
Yoshida, H.; Ebine, K.; Hirata, T.; Kitagawa, O. Org. Lett. 2016, 18,
5700−5703. (k) Zhang, J.-W.; Xu, J.-H.; Cheng, D.-J.; Shi, C.; Liu, X.-
Y.; Tan, B. Nat. Commun. 2016, 7, 10677. (l) Wang, Y.-B.; Zheng, S.-
C.; Hu, Y.-M.; Tan, B. Nat. Commun. 2017, 8, 15489. (m) Min, C.;
Lin, Y.; Seidel, D. Angew. Chem., Int. Ed. 2017, 56, 15353−15357.
(n) Rae, J.; Frey, J.; Jerhaoui, S.; Choppin, S.; Wencel-Delord, J.;
Colobert, F. ACS Catal. 2018, 8, 2805−2809. (o) Fan, X.; Zhang, X.;
Li, C.; Gu, Z. ACS Catal. 2019, 9, 2286−2291.
(3) (a) Clayden, J. Angew. Chem., Int. Ed. Engl. 1997, 36, 949−951.
(b) Kumarasamy, E.; Raghunathan, R.; Sibi, M. P.; Sivaguru, J. Chem.
Rev. 2015, 115, 11239−11300.
(4) (a) Clayden, J. Synlett 1998, 810−816. (b) Takahashi, I.; Suzuki,
Y.; Kitagawa, O. Org. Prep. Proced. Int. 2014, 46, 1−23.
(5) (a) Bringmann, G.; Tasler, S.; Endress, H.; Kraus, J.; Messer, K.;
Wohlfarth, M.; Lobin, W. J. Am. Chem. Soc. 2001, 123, 2703−2711.
(b) Azanli, E.; Rothchild, R.; Sapse, A.-M. Spectrosc. Lett. 2002, 35,
257−274. (c) Blaser, H.-U. Adv. Synth. Catal. 2002, 344, 17−31.
(d) Tokitoh, T.; Kobayashi, T.; Nakada, E.; Inoue, T.; Yokoshima, S.;
Takahashi, H.; Natsugari, H. Heterocycles 2006, 70, 93−99. (e) Bring-
mann, G.; Gulder, T.; Reichert, M.; Meyer, F. Org. Lett. 2006, 8,
1037−1040. (f) Hughes, C. C.; Prieto-Davo, A.; Jensen, P. R.; Fenical,
W. Org. Lett. 2008, 10, 629−631. (g) Cheng, C.; Pan, L.; Chen, Y.;
Song, H.; Qin, Y.; Li, R. J. Comb. Chem. 2010, 12, 541−547.
(6) (a) Trost, B. M.; Van Vranken, D. L. Chem. Rev. 1996, 96, 395−
422. (b) Dai, X.; Virgil, S. Tetrahedron Lett. 1999, 40, 1245−1248.
(c) Clayden, J.; Johnson, P.; Pink, J. H.; Helliwell, M. J. Org. Chem.
2000, 65, 7033−7040. (d) Dai, W.-M.; Yeung, K. K. Y.; Chow, C. W.;
Williams, I. D. Tetrahedron: Asymmetry 2001, 12, 1603−1613.
(e) Horibe, H.; Kazuta, K.; Kotoku, M.; Kondo, K.; Okuno, H.;
(11) (a) Kamikawa, K.; Kinoshita, S.; Matsuzaka, H.; Uemura, M.
Org. Lett. 2006, 8, 1097−1100. (b) Kamikawa, K.; Kinoshita, S.;
D
DOI: 10.1021/acs.orglett.9b01638
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Furusyo, M.; Takemoto, S.; Matsuzaka, H.; Uemura, M. J. Org. Chem.
2007, 72, 3394−3402.
(12) (a) Bringmann, G.; Tasler, S.; Endress, H.; Peters, K.; Peters,
E.-M. Synthesis 1998, 1501−1505. (b) Kanakis, A. A.; Sarli, V. Org.
Lett. 2010, 12, 4872−4875. (c) Zhang, L.; Zhang, J.; Ma, J.; Cheng,
D.-J.; Tan, B. J. Am. Chem. Soc. 2017, 139, 1714−1717.
(13) (a) Guo, R.; Li, K.-N.; Liu, B.; Zhu, H.-J.; Fan, Y.-M.; Gong, L.-
Z. Chem. Commun. 2014, 50, 5451−5454. (b) Yang, Y.; Liu, H.; Peng,
C.; Wu, J.; Zhang, J.; Qiao, Y.; Wang, X.-N.; Chang, J. Org. Lett. 2016,
18, 5022−5025.
(14) (a) Crich, D.; Banerjee, A. Acc. Chem. Res. 2007, 40, 151−161.
(b) Kochanowska-Karamyan, A. J.; Hamann, M. T. Chem. Rev. 2010,
110, 4489−4497. (c) Vitaku, E.; Smith, D. T.; Njardarson, J. T. J.
Med. Chem. 2014, 57, 10257−10274. (d) Stempel, E.; Gaich, T. Acc.
Chem. Res. 2016, 49, 2390−2402.
(15) (a) Qin, Q.; Yu, S. Org. Lett. 2014, 16, 3504−3507. (b) Tong,
K.; Liu, X.; Zhang, Y.; Yu, S. Chem. - Eur. J. 2016, 22, 15669−15673.
(c) Liu, X.; Tong, K.; Zhang, A. H.; Tan, R. X.; Yu, S. Org. Chem.
Front. 2017, 4, 1354−1357.
(16) CCDC 1909079 (3a) and CCDC 1909080 (3a′) contain the
supplementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
(17) (a) Zhang, H.-H.; Wang, C.-S.; Li, C.; Mei, G.-J.; Li, Y.; Shi, F.
Angew. Chem., Int. Ed. 2017, 56, 116−121. (c) He, C.; Hou, M.; Zhu,
Z.; Gu, Z. ACS Catal. 2017, 7, 5316−5320. (d) Qi, L.-W.; Mao, J.-H.;
Zhang, J.; Tan, B. Nat. Chem. 2018, 10, 58−64. (e) Ma, C.; Jiang, F.;
Sheng, F.-T.; Jiao, Y.; Mei, G.-J.; Shi, F. Angew. Chem., Int. Ed. 2019,
58, 3014−3020.
(18) (a) Calvo, P.; Crugeiras, J.; Ríos, A.; Ríos, M. A. J. Org. Chem.
2007, 72, 3171−3178. (b) Calvo, P.; Crugeiras, J.; Ríos, A. J. Org.
Chem. 2009, 74, 5381−5389.
(19) Trifluoromethanesulfonamide is about 3 pK units more acidic
than acetic acid in DMSO, see Bordwell, F. G.; Algrim, D. J. Org.
Chem. 1976, 41, 2507−2508.
(20) Palmisano, G.; Danieli, B.; Lesma, G.; Fiori, G. Synthesis 1987,
137−139.
E
DOI: 10.1021/acs.orglett.9b01638
Org. Lett. XXXX, XXX, XXX−XXX