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org/joc Note

Transition-Metal-Free Stereospecific Oxidative Annulative Coupling

of Indolines with Aziridines
Pallab Karjee, Tanumay Sarkar, Subhradeep Kar, and Tharmalingam Punniyamurthy*
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ABSTRACT: Tandem C−N bond formation for the oxidative annulation of indolines
with aziridines is accomplished employing the combination of DDQ and NaOCl at
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ambient conditions. Optically active aziridine can be coupled with high enantiomeric
purity (>99% ee). The substrate scope, stereocontrol with the enantioenriched
substrate, and scale-up are the important practical advantages.

−N bond formation1 has attracted considerable attention

C due to the ubiquity of the aza-heterocycles in a broad
spectrum of pharmaceuticals, functional materials, and natural
Scheme 1. Optimization of the Reaction Conditions

products.2 In this realm, C−H functionalization of indoles3 has

witnessed impeccable growth, owing to the profuse prom-
inence of the indole frameworks in a myriad of bioactive
molecules. Among them, imidazoindolines represent privileged
structures due to their interesting biological properties.4 oxidant and aqueous NaOCl solution as an additive in 1,4-
Stereospecific syntheses of these fused structural frameworks dioxane. Subsequent screening of the oxidants led to an
in an atom- and step-economical approach5 would thus be increase in the yield of 4aa to 75% using DDQ, whereas p-
valuable. While small ring heterocycles, due to their staple benzoquinone produced inferior results. In contrast, O2,
architecture and intrinsic ring strain, have a propensity to TBHP, and DTBP were not effective. In a set of additives
undergo easy ring scissoring, and are thereby useful for the studied, including aqueous NaOCl, t-BuOCl, and iodine, the
construction of diverse heterocycles.6 Contextually, aziridines former produced the best results. 1,4-Dioxane was found to be
are versatile building blocks for the contemporary synthesis of the solvent of choice, whereas THF, DMF, MeOH, 1,2-
N-heterocycles via a tandem C−N bond formation.7,8 dichloroethane, toluene, and CH3CN produced <57% yield.
Consequently, development of synthetic strategies with these Control experiments confirmed that the combination of DDQ
two heterocyclic units can lead to a potential route to access and NaOCl is essential to furnish the annulated 4aa.
fused structural scaffolds. Recently, NaOCl has been explored Recrystallization of 4aa gave a single crystal, whose structure
as an effective reagent for the oxidation for organic was determined using X-ray analysis (see Supporting
substrates,9a amidation of amines,9b and C−N coupling of 3- Information).
alkylindoles with amino esters.9c,d Herein, we report a Having the optimized reaction conditions, we investigated
stereospecific oxidative annulative coupling of indoles with the scope of the procedure for a series of aziridines 2b−t with
N-sulfonyl aziridines using the combination of DDQ and indoline 1a as a standard substrate (Scheme 2). Aziridines
NaOCl to furnish imidazoindoles at ambient conditions via a having substitution at the 2-position of the aryl ring with
tandem C−N bond formation. The substrate scope, selectivity, bromo 2b, chloro 2c, fluoro 2d, and methyl 2e groups gave the
target heterocycles 4ab−ae in 63−73% yields. Similar results
and transition-metal-free C−N bond formation10 are the
were observed with aziridines bearing substitution at the 3-
important features.
We began our optimization studies employing indoline 1a
and 2-phenyl-1-tosylaziridine 2a as the test substrates using a Received: April 13, 2020
series of oxidants, additives, and solvents (see Scheme 1 and Published: May 29, 2020
Table S1 in the Supporting Information). The heterocycle 4aa
was formed in 10% yield along with the ring opening 3aa in
62% yield when the neat substrates were stirred for 4 h at
ambient conditions and then for 8 h with PhI(OAc)2 as an

© 2020 American Chemical Society https://dx.doi.org/10.1021/acs.joc.0c00899

8261 J. Org. Chem. 2020, 85, 8261−8270
The Journal of Organic Chemistry pubs.acs.org/joc Note

Scheme 2. Substrate Scope of Aziridinesa−c

a
Reaction conditions: 1a (0.2 mmol), 2b−t (0.24 mmol), neat, room temperature, 4 h; then DDQ (0.2 mmol), aq. NaOCl (4.2%, 2.1 mL), 1,4-
dioxane (2 mL), room temperature, 8 h. bIsolated yield. cAccompanied a trace amount of 3 (see Scheme 5 for a structure).

Scheme 3. Substrate Scope of Indolinesa−c

a
Reaction conditions: 1b−i (0.2 mmol), 2a (0.24 mmol), neat, room temperature, 4 h; then DDQ (0.2 mmol), aq. NaOCl (4.2%, 2.1 mL), 1,4-
dioxane (2 mL), room temperature, 8 h. bIsolated yield. cAccompanied a trace amount of 3 (see Scheme 5 for a structure).

position of the aryl ring with bromo 2f and methyl 2g varied N-sulfonyl aryl substituent. Aziridine having N-
functionalities, giving 4af and 4ag in 68 and 64% yields, sulfonylphenyl 2o produced 4ao in 71% yield, whereas the
respectively. The reaction of aziridines containing substituents reaction of aziridines having substitution at the 4-position of
at the 4-position of the aryl ring with bromo 2h, chloro 2i, the N-sulfonyl aryl ring with chloro 2p, nitro 2q, and tert-butyl
methyl 2j, and phenyl 2k groups produced 4ah−ak in 64−71% 2r functionalities, afforded 4ap−ar in 62−72% yields. In
yields. Furthermore, di- and trimethyl substituted aziridines addition, the reaction of 2-alkyl aziridines could be pursued,
2l−m in the aryl ring participated to deliver 4al and 4am in 65 and the ring opening occurred at the sterically less hindered C-
and 63% yields, respectively. In addition, 2-naphthyl aziridine 3 position.11 For examples, aziridines with hexyl 2s and octyl
2n was amenable to furnish 4an in 67% yield. The reaction 2t substituents participated to produce 4as and 4at in 66 and
condition was extended to the coupling of aziridines bearing a 68% yields, respectively.
8262 https://dx.doi.org/10.1021/acs.joc.0c00899
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The scope of the procedure was further extended to the Scheme 5. Plausible Reaction Pathway
annulation of a series of substituted indolines 1b−i with
aziridine 2a as a standard substrate (Scheme 3). The substrates
bearing 3-methyl 1b, 4-bromo 1c, 5-benzyloxy 1d, and 5-
bromo 1e substituents delivered the target heterocycles 4ba−
ea in 58−71% yields, whereas the reaction of the substrates
bearing 6-chloro 1f, 6-fluoro 1g, 7-chloro 1h, and 7-methyl 1i
functionalities afforded 4fa−ia in 63−73% yields. These results
suggest that the procedure can be employed for the annulative
coupling of the broad range of indolines and aziridines.
To understand the stereochemical aspects, the reactions of
1a, 1e, and 1g were studied using (R)-2-phenyl-1-tosylaziridine
2a′ as the representative substrates (Scheme 4). The reaction

Scheme 4. Enantiospecific Synthesisa−c B2pin2 gave 6 in 73% yield. In addition, to reveal the scale-up
synthesis (3 mmol), the coupling of 1a and 2a as the
representative substrates was examined. The reaction was
effective to furnish the annulated target product in 66% yield
(see Scheme S2b).
In conclusion, the stereospecific oxidative annulative
coupling of indolines with aziridines is described, employing
DDQ as the oxidant and NaOCl as the electrophilic
chlorinating reagent at ambient conditions. Enantiomeric
purity, transition-metal-free tandem C−N bond formation,
and substrate scope are the important practical features.
a
Reaction conditions: 1a,e,g (0.2 mmol), (R)-2a′ (0.24 mmol), neat,
room temperature, 4 h; then DDQ (0.2 mmol), aq. NaOCl (4.2%, 2.1
■ EXPERIMENTAL SECTION
General Information. Alkenes, (R)-(−)-2-phenylglycinol (99%),
mL), 1,4-dioxane (2 mL), room temperature, 6 h. bIsolated yield. DDQ (98%), Pd(dppf)Cl2·CH2Cl2 (>99%), and Pd(PPh3)4 (99%)
c
Accompanied a trace amount of 3 (see Scheme 5 for a structure). from Aldrich and NaOCl (4.2% w/v available chlorine) and
chloramine-T hydrate (95%) from Merck were used as received.
Indolines13 and aziridines14 were prepared according to a reported
occurred with high enantiomeric purity (>99% ee). For procedure. SRL silica gel G/GF 254 plates were used for analytical
example, the reaction of 1a furnished 4aa′ in 73% yield and TLC, and SRL silica gel (60−120 mesh) was used for column
99% ee. Similar enantiomeric purity (>99% ee) was observed chromatography. NMR spectra were recorded with Bruker Avance III
with indolines having 5-bromo 1e and 6-fluoro 1g substituents, 600 MHz and Ascend 400 MHz spectrometers using CDCl3 as
providing 4ea′ and 4ga′ in 70 and 68% yields, respectively. solvent and Me4Si as an internal standard. Chemical shifts (δ) and
The absolute configuration of 4aa′ was determined using a spin−spin coupling constant (J) are reported in ppm and in Hz,
single crystal X-ray analysis (see Supporting Information). respectively, and other data are reported as follows: s = singlet, d =
These results suggest that the ring opening of aziridine is doublet, t = triplet, m = multiplet, q = quartet, dd = doublet of
stereospecific (SN2), and the annulation can be realized in high doublets. Melting points were determined using a Büchi B-540
apparatus and are uncorrected. FT-IR spectra were collected on
enantiomeric purity. PerkinElmer IR spectrometer. A Q-Tof ESI-MS instrument (model
To get insight into the reaction pathway, the coupling of 1a HAB 273) was used for recording mass spectra. Optical rotations
with 2a was performed as the representative substrates in the were determined by using an Rudolph autopol I automatic
presence of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) as polarimeter. HPLC analysis was carried out using Waters-2489 with
well as 2,6-di-tert-butyl-4-methylphenol (BHT) (see Scheme Daicel Chiralcel OD-H column using iso-propanol and hexane as an
S1a). As above, the reaction occurred, which suggests that a eluent. Single crystal X-ray data were collected on a Bruker SMART
radical pathway is not likely. In addition, 1a with 2a under neat APEX equipped with a CCD area detector using Mo/Kα radiation,
conditions for 4 h, followed by treatment with DDQ for 2 h in and the structure was solved by direct method using SHELXL-16
1,4-dioxane, produced 3aa in 81% yield (see Scheme S1b). (Göttingen, Germany).
General Procedure for the Preparation of Indolines.13 To a
The latter with NaOCl underwent annulation to produce 4aa solution of indole (3.0 mmol) in AcOH (15 mL) at 0 °C was added
in 77% yield. These experimental results suggest that the NaBH3CN (756 mg, 12.0 mmol) portionwise. The reaction was
stereospecific ring opening (SN2) of aziridines with indolines allowed to stir at room temperature for 8 h. After completion,
can deliver a (Scheme 5).12 The latter can oxidize using DDQ aqueous NaOH (250 μL) was added slowly to the mixture at 0 °C
to furnish 3, which can undergo an electrophilic chlorination and extracted with ethyl acetate (3 × 20 mL). The combined organic
using NaOCl9 to give the iminium ion b that can lead to an layer was washed successively with brine (10 mL) and water (10 mL).
intramolecular cyclization to furnish c. Base promoted Drying (Na2SO4) and evaporation of the solvent produced a residue
dehydrochlorination of c can furnish the target heterocycle 4, that was purified on silica gel column chromatography using ethyl
which can be reduced using NaBH3CN to yield imidazoindo- acetate and hexane as an eluent.
Indolines 1a and b,13a 1c,13b 1d,13a 1e,13b 1f and g,13c 1h,13d and
lines that are privileged structural scaffolds with a broad 13e
1i are known compounds and were synthesized according to the
bioactive spectrum.4 Scheme S2a presents some postsynthetic reported procedure. To show the purity, 1H NMR spectra are
applications for C−C coupling of 4 with organoboranes. The provided.
Pd-catalyzed Suzuki-coupling of 4ea with 1-pyreneboronic acid 4-Bromoindoline 1c.13b Analytical TLC on silica gel, 1:9 ethyl
produced 5 in 85% yield, while the borylation employing acetate/hexane; Rf = 0.49; purification on silica gel column

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chromatography using 1:19 ethyl acetate/hexane as eluent; thick 2-(o-Tolyl)-1-tosylaziridine 2e.14c Analytical TLC on silica gel,
liquid; yield 81% (478 mg); 1H NMR (400 MHz, CDCl3) δ 6.88− 1:9 ethyl acetate/hexane; Rf = 0.42; purification on silica gel column
6.79 (m, 2H), 6.53 (d, J = 7.6 Hz, 1H), 3.88 (s, 1H), 3.59 (t, J = 8.4 chromatography using 1:12 ethyl acetate/hexane as eluent; colorless
Hz, 2H), 3.05 (t, J = 8.4 Hz, 2H). solid; yield 71% (203 mg); 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J
6-Chloroindoline 1f.13c Analytical TLC on silica gel, 1:9 ethyl = 8.4 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.19−7.09 (m, 4H), 3.88−
acetate/hexane; Rf = 0.51; purification on silica gel column 3.85 (m, 1H), 2.99 (d, J = 7.2 Hz, 1H), 2.44 (s, 3H), 2.38 (s, 3H),
chromatography using 1:19 ethyl acetate/hexane as eluent; thick 2.32 (d, J = 4.4 Hz, 1H).
liquid; yield 76% (348 mg); 1H NMR (400 MHz, CDCl3) δ 7.19 (s, 2-(3-Bromophenyl)-1-tosylaziridine 2f.14e Analytical TLC on
1H), 7.10 (dd, J = 8.4 Hz, 2.0 Hz, 1H), 6.50 (d, J = 8.0 Hz, 1H), 3.75 silica gel, 1:9 ethyl acetate/hexane; Rf = 0.35; purification on silica gel
(s, 1H), 3.55 (t, J = 8.0 Hz, 2H), 3.01 (t, J = 8.4 Hz, 2H). column chromatography using 1:12 ethyl acetate/hexane as eluent;
6-Fluoroindoline 1g.13c Analytical TLC on silica gel, 1:9 ethyl colorless solid; yield 61% (213 mg); 1H NMR (400 MHz, CDCl3) δ
acetate/hexane; Rf = 0.48; purification on silica gel column 7.87 (d, J = 8.4 Hz, 2H), 7.41−7.38 (m, 1H), 7.35−7.33 (m, 3H),
chromatography using 1:16 ethyl acetate/hexane as eluent; thick 7.16−7.15 (m, 2H), 3.73−3.70 (m, 1H), 2.97 (d, J = 7.2 Hz, 1H),
liquid; yield 73% (301 mg); 1H NMR (400 MHz, CDCl3) δ 6.98 (t, J 2.44 (s, 3H), 2.34 (d, J = 4.4 Hz, 1H).
= 6.8 Hz, 1H), 6.37−6.30 (m, 2H), 3.82 (s, 1H), 3.59 (t, J = 8.4 Hz, 2-(m-Tolyl)-1-tosylaziridine 2g.14b Analytical TLC on silica gel,
2H), 2.97 (t, J = 8.4 Hz, 2H). 1:9 ethyl acetate/hexane; Rf = 0.40; purification on silica gel column
7-Chloroindoline 1h.13d Analytical TLC on silica gel, 1:9 ethyl chromatography using 1:12 ethyl acetate/hexane as eluent; colorless
acetate/hexane; Rf = 0.49; purification on silica gel column solid; yield 69% (198 mg); 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J
chromatography using 1:16 ethyl acetate/hexane as eluent; thick = 8.4 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 7.17 (t, J = 7.6 Hz, 1H), 7.09
liquid; yield 84% (385 mg); 1H NMR (400 MHz, CDCl3) δ 7.00 (t, J (d, J = 7.6 Hz, 1H), 7.02−7.00 (m, 2H), 3.75−3.72 (m, 1H), 2.96 (d,
= 7.6 Hz, 2H), 6.62 (t, J = 7.6 Hz, 1H), 3.97 (s, 1H), 3.62 (t, J = 8.4 J = 7.2 Hz, 1H), 2.43 (s, 3H), 2.38 (d, J = 4.8 Hz, 1H), 2.30 (s, 3H).
Hz, 2H), 3.11 (t, J = 8.4 Hz, 2H). 2-(4-Bromophenyl)-1-tosylaziridine 2h.14a Analytical TLC on
7-Methylindoline 1i.13e Analytical TLC on silica gel, 1:9 ethyl silica gel, 1:9 ethyl acetate/hexane; Rf = 0.38; purification on silica gel
acetate/hexane; Rf = 0.52; purification on silica gel column column chromatography using 1:12 ethyl acetate/hexane as eluent;
chromatography using 1:19 ethyl acetate/hexane as eluent; thick colorless solid; yield 72% (252 mg); 1H NMR (400 MHz, CDCl3) δ
liquid; yield 79% (315 mg); 1H NMR (400 MHz, CDCl3) δ 7.00 (d, J 7.86 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 8.8 Hz, 2H), 7.34 (d, J = 8.0 Hz,
= 7.2 Hz, 1H), 6.87 (d, J = 7.2 Hz, 1H), 6.66 (t, J = 7.2 Hz, 1H), 3.57 2H), 7.09 (d, J = 8.4 Hz, 2H), 3.73−3.70 (m, 1H), 2.98 (d, J = 7.2
(t, J = 8.4 Hz, 2H), 3.06 (t, J = 8.4 Hz, 2H), 2.14 (s, 3H). Hz, 1H), 2.43 (s, 3H), 2.34 (d, J = 4.4 Hz, 1H).
General Procedure for Preparation of Aziridines.14 To a 2-(4-Chlorophenyl)-1-tosylaziridine 2i.14b Analytical TLC on
stirred solution of alkene (1.0 mmol) and benzyltriethylammonium silica gel, 1:9 ethyl acetate/hexane; Rf = 0.37; purification on silica gel
chloride (0.05 mmol, 11.4 mg) in CH2Cl2/H2O (2:1, 15 mL) were column chromatography using 1:12 ethyl acetate/hexane as eluent;
added chloramine-T (1.1 mmol, 250.8 mg) and iodine (0.1 mmol,
colorless solid; yield 65% (199 mg); 1H NMR (400 MHz, CDCl3) δ
25.4 mg) at room temperature. The stirring was continued for 24 h,
7.86 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 7.27−7.26 (m,
and then the solution was treated with a saturated Na2S2O3 (5 mL)
1H), 7.25−7.24 (m, 1H), 7.15 (d, J = 8.4 Hz, 2H), 3.74−3.71 (m,
and extracted with CH2Cl2 (3 × 10 mL). Drying (Na2SO4) and
1H), 2.98 (d, J = 7.2 Hz, 1H), 2.44 (s, 3H), 2.34 (d, J = 4.4 Hz, 1H).
evaporation of the solvent gave a residue that was purified on a silica
2-(p-Tolyl)-1-tosylaziridine 2j.14b Analytical TLC on silica gel,
gel column chromatography using hexane and ethyl acetate as an
1:9 ethyl acetate/hexane; Rf = 0.41; purification on silica gel column
eluent.
chromatography using 1:12 ethyl acetate/hexane as eluent; colorless
Aziridines 2a and b,14e 2c,14c 2d,14e 2e,14c 2f,14e 2g,14b 2h,14a 2i
and j,14b 2k,14d 2l,14c 2m and n,14e 2o−r,14a and 2s and t14c are solid; yield 74% (212 mg); 1H NMR (400 MHz, CDCl3) δ 7.86 (d, J
known compounds and were synthesized according to the reported = 8.4 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 7.09 (s, 3H), 3.75−3.72 (m,
procedure. To show the purity, 1H NMR spectra are provided. 1H), 2.97 (d, J = 7.2 Hz, 1H), 2.42 (s, 3H), 2.38 (d, J = 4.4 Hz, 1H),
2-Phenyl-1-tosylaziridine 2a.14e Analytical TLC on silica gel, 2.30 (s, 3H).
1:9 ethyl acetate/hexane; Rf = 0.41; purification on silica gel column 2-([1,1′-Biphenyl]-4-yl)-1-tosylaziridine 2k.14d Analytical TLC
chromatography using 1:12 ethyl acetate/hexane as eluent; colorless on silica gel, 1:9 ethyl acetate/hexane; Rf = 0.38; purification on silica
solid; yield 73% (199 mg); 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J gel column chromatography using 1:9 ethyl acetate/hexane as eluent;
= 8.4 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 7.30−7.27 (m, 3H), 7.22− colorless solid; yield 59% (205 mg); 1H NMR (400 MHz, CDCl3) δ
7.20 (m, 2H), 3.79−3.76 (m, 1H), 2.99 (d, J = 7.2 Hz, 1H), 2.43 (s, 7.89 (d, J = 8.0 Hz, 2H), 7.55−7.50 (m, 4H), 7.42 (t, J = 7.2 Hz, 2H),
3H), 2.39 (d, J = 4.4 Hz, 1H). 7.36−7.33 (m, 3H), 7.29 (d, J = 8.4 Hz, 2H), 3.83−3.80 (m, 1H),
2-(2-Bromophenyl)-1-tosylaziridine 2b.14e Analytical TLC on 3.02 (d, J = 7.2 Hz, 1H), 2.44−2.42 (m, 4H).
silica gel, 1:9 ethyl acetate/hexane; Rf = 0.38; purification on silica gel 2-(2,4-Dimethylphenyl)-1-tosylaziridine 2l.14c Analytical TLC
column chromatography using 1:12 ethyl acetate/hexane as eluent; on silica gel, 1:9 ethyl acetate/hexane; Rf = 0.35; purification on silica
colorless solid; yield 65% (227 mg); 1H NMR (400 MHz, CDCl3) δ gel column chromatography using 1:9 ethyl acetate/hexane as eluent;
7.91 (d, J = 8.0 Hz, 2H), 7.52 (dd, J = 7.6, 1.2 Hz, 1H), 7.36 (d, J = colorless solid; yield 64% (192 mg); 1H NMR (400 MHz, CDCl3) δ
8.0 Hz, 2H), 7.23−7.11 (m, 3H), 4.00−3.97 (m, 1H), 3.04 (d, J = 7.2 7.90 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 6.98−6.95 (m,
Hz, 1H), 2.45 (s, 3H), 2.27 (d, J = 4.4 Hz, 1H). 2H), 6.91 (d, J = 8.0 Hz, 1H), 3.84−3.81 (m, 1H), 2.97 (d, J = 7.2
2-(2-Chlorophenyl)-1-tosylaziridine 2c.14c Analytical TLC on Hz, 1H), 2.44 (s, 3H), 2.34 (s, 3H), 2.31 (d, J = 4.4 Hz, 1H), 2.27 (s,
silica gel, 1:9 ethyl acetate/hexane; Rf = 0.39; purification on silica gel 3H).
column chromatography using 1:12 ethyl acetate/hexane as eluent; 2-Mesityl-1-tosylaziridine 2m.14e Analytical TLC on silica gel,
colorless solid; yield 68% (208 mg); 1H NMR (400 MHz, CDCl3) δ 1:9 ethyl acetate/hexane; Rf = 0.32; purification on silica gel column
7.90 (d, J = 8.0 Hz, 2H), 7.36−7.31 (m, 3H), 7.23−7.16 (m, 3H), chromatography using 1:9 ethyl acetate/hexane as eluent; colorless
4.05−4.02 (m, 1H), 3.04 (d, J = 7.6 Hz, 1H), 2.44 (s, 3H), 2.29 (d, J solid; yield 67% (211 mg); 1H NMR (400 MHz, CDCl3) δ 7.89 (d, J
= 4.4 Hz, 1H). = 8.4 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 6.78 (s, 2H), 3.87−3.84 (m,
2-(2-Fluorophenyl)-1-tosylaziridine 2d.14e Analytical TLC on 1H), 2.94 (d, J = 7.2 Hz, 1H), 2.45 (s, 3H), 2.30 (s, 6H), 2.23 (s,
silica gel, 1:9 ethyl acetate/hexane; Rf = 0.36; purification on silica gel 3H), 2.17 (d, J = 4.8 Hz, 1H).
column chromatography using 1:12 ethyl acetate/hexane as eluent; 2-(Naphthalen-2-yl)-1-tosylaziridine 2n.14e Analytical TLC on
colorless solid; yield 63% (183 mg); 1H NMR (400 MHz, CDCl3) δ silica gel, 1:9 ethyl acetate/hexane; Rf = 0.37; purification on silica gel
7.88 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.25−7.21 (m, column chromatography using 1:12 ethyl acetate/hexane as eluent;
1H), 7.15−7.11 (m, 1H), 7.07- 6.98 (m, 2H), 3.98−3.96 (m, 1H), colorless solid; yield 61% (197 mg); 1H NMR (400 MHz, CDCl3) δ
3.01 (d, J = 7.2 Hz, 1H), 2.44 (s, 3H), 2.40 (d, J = 4.4 Hz, 1H). 7.90 (d, J = 8.3 Hz, 2H), 7.80−7.72 (m, 4H), 7.48−7.45 (m, 2H),

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7.34 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 1.7 Hz, 1H), 3.94−3.91 (m, Rf = 0.49; purification on silica gel column chromatography using 1:9
1H), 3.07 (d, J = 7.2 Hz, 1H), 2.50 (d, J = 4.4 Hz, 1H), 2.42 (s, 3H). ethyl acetate/hexane as eluent; colorless solid; mp 127−128 °C; yield
2-Phenyl-1-(phenylsulfonyl)aziridine 2o.14a Analytical TLC 81% (63 mg); 1H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 8.4 Hz,
on silica gel, 1:9 ethyl acetate/hexane; Rf = 0.36; purification on silica 2H), 7.63−7.61 (m, 1H), 7.30−7.26 (m, 5H), 7.13−7.06 (m, 6H),
gel column chromatography using 1:12 ethyl acetate and hexane as 6.57 (d, J = 3.2 Hz, 1H), 5.59−5.56 (m, 1H), 4.49−4.45 (m, 1H),
eluent; colorless solid; yield 63% (163 mg); 1H NMR (400 MHz, 3.89−3.83 (m, 1H), 3.76−3.69 (m, 1H), 2.44 (s, 3H); 13C{1H} NMR
CDCl3) δ 8.01−7.98 (m, 2H), 7.66−7.61 (m, 1H), 7.56−7.52 (m, (100 MHz, CDCl3) δ 143.9, 137.6, 136.7, 136.3, 130.0, 129.1, 128.8,
2H), 7.30−7.27 (m, 3H), 7.22−7.20 (m, 2H), 3.82−3.79 (m, 1H), 128.5, 127.1, 126.6, 124.5, 122.2, 121.2, 120.2, 109.9, 103.2, 59.0,
3.02 (d, J = 7.2 Hz, 1H), 2.42 (d, J = 4.4 Hz, 1H). 46.3, 21.7; FT-IR (KBr) 3283, 2922, 1598, 1493, 1458, 1326, 1308,
1-((4-Nitrophenyl)sulfonyl)-2-phenylaziridine 2q.14a Analyt- 1158, 1092 cm−1; HRMS (ESI) m/z [M + H]+ calcd for
ical TLC on silica gel, 1:9 ethyl acetate/hexane; Rf = 0.29; purification C23H23N2O2S: 391.1475, found: 391.1486.
on silica gel column chromatography using 1:9 ethyl acetate/hexane 3-Phenyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole 4aa′.
as eluent; orange solid; yield 51% (155 mg); 1H NMR (400 MHz, Analytical TLC on silica gel, 1:9 ethyl acetate/hexane; Rf = 0.45;
CDCl3) δ 8.39 (d, J = 9.2 Hz, 2H), 8.20 (d, J = 8.8 Hz, 2H), 7.32− purification on silica gel column chromatography using 1:14 ethyl
7.30 (m, 3H), 7.22−7.20 (m, 2H), 3.90−3.88 (m, 1H), 3.12 (d, J = acetate/hexane as eluent; colorless solid; mp 169−170 °C; yield 73%
7.2 Hz, 1H), 2.51 (d, J = 4.8 Hz, 1H). (56 mg); 1H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 8.0 Hz, 2H),
1-((4-tert-Butyl)phenyl)sulfonyl)-2-phenylaziridine 2r.14a 7.45 (d, J = 8.0 Hz, 1H), 7.22−7.18 (m, 1H), 7.15−7.11 (m, 4H),
Analytical TLC on silica gel, 1:9 ethyl acetate/hexane; Rf = 0.32; 6.98−6.94 (m, 1H), 6.82−6.78 (m, 3H), 6.50 (d, J = 8.0 Hz, 1H),
purification on silica gel column chromatography using 1:9 ethyl 6.23 (s, 1H), 5.25−5.21 (m, 1H), 4.57−4.52 (m, 1H), 3.93−3.88 (m,
acetate/hexane as eluent; colorless solid; yield 56% (176 mg); 1H 1H), 2.31 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 145.0, 141.8,
NMR (600 MHz, CDCl3) δ 7.91 (d, J = 8.6 Hz, 2H), 7.55 (d, J = 8.6 137.8, 133.3, 132.6, 130.5, 130.0, 129.2, 128.8, 127.8, 126.3, 120.56,
Hz, 2H), 7.30−7.27 (m, 3H), 7.23−7.22 (m, 2H), 3.81−3.79 (m, 120.52, 109.5, 83.4, 61.2, 58.2, 21.7; FT-IR (KBr) 3053, 2918, 1616,
1H), 2.99 (d, J = 7.2 Hz, 1H), 2.40 (d, J = 4.8 Hz, 1H), 1.34 (s, 9H). 1597, 1566, 1493, 1454, 1422, 1361, 1306, 1168, 1106 cm−1; HRMS
2-Hexyl-1-tosylaziridine 2s.14c Analytical TLC on silica gel, 1:9 (ESI) m/z [M + H]+ calcd for C23H21N2O2S: 389.1318, found:
ethyl acetate/hexane; Rf = 0.36; purification on silica gel column 389.1318; [α]D27 = +54.00 (c = 0.01, CHCl3); HPLC: >99% ee
chromatography using 1:12 ethyl acetate/hexane as eluent; thick [CHIRALCEL OD-H, hexane/iPrOH = 90:10, flow rate: 1 mL/min,
liquid; yield 62% (174 mg); 1H NMR (400 MHz, CDCl3), δ 7.83 (d, λ = 254 nm, tR = 23.67 min (minor), 31.97 min (major)].
J = 8.4 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 2.74−2.68 (m, 1H), 2.64 3-(2-Bromophenyl)-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]-
(d, J = 7.2 Hz, 1H), 2.44 (s, 3H), 2.06 (d, J = 4.8 Hz, 1H), 1.55−1.50 indole 4ab. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane; Rf
(m, 1H), 1.34−1.30 (m, 1H), 1.24−1.17 (m, 8H), 0.84 (t, J = 6.8 Hz, = 0.42; purification on silica gel column chromatography using 1:14
3H). ethyl acetate/hexane as eluent; colorless solid; mp 175−176 °C; yield
2-Octyl-1-tosylaziridine 2t.14c Analytical TLC on silica gel, 1:9 73% (68 mg); 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.4 Hz,
ethyl acetate/hexane; Rf = 0.36; purification on silica gel column 2H), 7.57−7.53 (m, 2H), 7.15−7.06 (m, 4H), 6.97−6.93 (m, 1H),
chromatography using 1:12 ethyl acetate/hexane as eluent; thick 6.88 (t, J = 7.2 Hz, 1H), 6.70 (d, J = 8.0 Hz, 1H), 6.34 (s, 1H), 6.11−
liquid; yield 59% (182 mg); 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J 6.03 (m, 1H), 5.72−5.69 (m, 1H), 4.73−4.68 (m, 1H), 4.10−4.06
= 8.4 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 2.74−2.68 (m, 1H), 2.64 (d, (m, 1H), 2.34 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3) δ 144.9,
J = 6.8 Hz, 1H), 2.44 (s, 3H), 2.06 (d, J = 4.8 Hz, 1H), 1.57−1.50 (m, 141.8, 137.2, 133.1, 132.6, 130.3, 129.9, 129.7, 128.1, 127.7, 126.8,
2H), 1.34−1.20 (m, 12H), 0.87 (t, J = 6.8 Hz, 3H). 122.6, 121.6, 120.8, 120.72, 120.70, 109.7, 83.8, 60.2, 57.2, 21.7; FT-
Procedure for the Preparation of Chiral Aziridine.14e To a IR (KBr) 3054, 2918, 1617, 1567, 1477, 1455, 1421, 1362, 1306,
stirred solution of (R)-(−)-2-phenylglycinol (1.0 mmol, 137 mg), 1167, 1106 cm−1; HRMS (ESI) m/z [M + H]+ calcd for
TsCl (2.2 mmol, 420 mg), and DMAP (0.05 mmol, 6 mg) in dry C23H20BrN2O2S: 467.0423, found: 467.0426.
CH2Cl2 (25 mL) at 0 °C was added Et3N (3.0 mmol). The resultant 3-(2-Chlorophenyl)-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]-
mixture was allowed to warm to room temperature, and the stirring indole 4ac. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane, Rf
was continued for 24 h. The mixture was then treated with a saturated = 0.43; purification on silica gel column chromatography using 1:14
NH4Cl (20 mL) and extracted with CH2Cl2 (3 × 10 mL). Drying ethyl acetate/hexane as eluent; colorless solid; mp 172−173 °C; yield
(Na2SO4) and evaporation of the solvent gave a residue that was 66% (55 mg); 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.4 Hz,
purified on a silica gel column chromatography using hexane and ethyl 2H), 7.56 (d, J = 8.0 Hz, 1H), 7.39 (d, J = 9.2 Hz, 1H), 7.19−7.12
acetate (9:1) as the eluent. (m, 3H), 7.08(t, J = 7.6 Hz, 1H), 6.95 (t, J = 8.0 Hz, 1H), 6.84 (t, J =
General Procedure for the Coupling of Indolines with 7.6 Hz, 1H), 6.71 (d, J = 8.0 Hz, 1H), 6.34 (s, 1H), 6.13 (d, J = 6.8
Aziridines. A mixture of indoline 1 (0.2 mmol) and aziridine 2 (0.24 Hz, 1H), 5.76−5.73 (m, 1H), 4.72−4.67 (m, 1H), 4.11−4.08 (m,
mmol) was stirred for 4 h at room temperature. The resultant mixture 1H), 2.34 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.9, 141.8,
was treated with 1,4-dioxane (2.0 mL), DDQ (45 mg, 0.2 mmol), and 135.7, 133.1, 132.6, 131.8, 130.3, 129.9, 129.8, 129.4, 127.7, 127.4,
aq. NaOCl (4.2%, 2.1 mL, 1.2 mmol), and the stirring was continued 126.6, 120.8, 120.7, 120.6, 109.6, 83.8, 60.1, 54.9, 21.7; FT-IR (KBr)
for an additional 8 h. The reaction mixture was then diluted with ethyl 3054, 2917, 1617, 1595, 1566, 1476, 1455, 1421, 1361, 1305, 1166,
acetate (10 mL), and the organic layer was separated. The aqueous 1106 cm−1; HRMS (ESI) m/z [M + H]+ calcd for C23H20ClN2O2S:
phase was extracted with ethyl acetate (2 × 10 mL). Drying (Na2SO4) 423.0929, found: 423.0929.
and evaporation of the solvent gave a residue that was purified on 3-(2-Fluorophenyl)-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]-
silica gel column chromatography using ethyl acetate and hexane as an indole 4ad. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane; Rf
eluent. = 0.41; purification on silica gel column chromatography using 1:11
General Procedure for the Enantiospecific Annulative ethyl acetate/hexane as eluent; colorless solid; mp 176−177 °C; yield
Coupling. Indoline 1 (0.2 mmol) and (R)-2-phenyl-1-tosylaziridine 63% (51 mg); 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.4 Hz,
2a′ (0.24 mmol) were subjected to the above-described reaction 2H), 7.54 (d, J = 8.0 Hz, 1H), 7.24−7.20 (m, 1H), 7.18 (d, J = 8.0
conditions. The enantiomeric purity was determined using chiral Hz, 2H), 7.09−7.04 (m, 2H), 6.96−6.91 (m, 1H), 6.79 (t, J = 7.6 Hz,
HPLC analysis. 1H), 6.71 (d, J = 8.0 Hz, 1H), 6.34−6.30 (m, 2H), 5.69−5.65 (m,
Scale-up Synthesis of 4aa. Indoline 1a (357 mg, 3 mmol) and 1H), 4.66−4.61(m, 1H), 4.13−4.09 (m, 1H), 2.36 (s, 3H); 13C{1H}
2-phenyl-1-tosylaziridine 2a (983 mg, 3.6 mmol) were subjected to NMR (100 MHz, CDCl3) δ 161.0 (JC−F = 245.3 Hz), 144.9, 141.7,
the reaction condition described in the general procedure to produce 133.3, 132.7, 130.4, 130.1 (JC−F = 8.2 Hz), 129.9, 127.8, 127.0 (JC−F =
4aa in 66% yield (768 mg). 3.4 Hz), 125.4 (JC−F = 12.8 Hz), 124.8 (JC−F = 3.6 Hz), 120.76,
N-(2-(1H-Indol-1-yl)-2-phenylethyl)-4-methylbenzenesulfo- 120.71, 120.6, 115.8 (JC−F = 20.8 Hz), 109.4, 83.7, 60.2, 51.6 (JC−F =
namide 3aa. Analytical TLC on silica gel, 1:6 ethyl acetate/hexane; 4.8 Hz), 21.7; FT-IR (KBr) 3052, 2924, 1616, 1567, 1490, 1455,

8265 https://dx.doi.org/10.1021/acs.joc.0c00899
J. Org. Chem. 2020, 85, 8261−8270
The Journal of Organic Chemistry pubs.acs.org/joc Note

1422, 1362, 1306, 1168, 1108 cm−1; HRMS (ESI) m/z [M + H]+ 129.9, 129.4, 128.6, 127.8, 127.5, 126.8, 120.75, 120.73, 109.4, 83.7,
calcd for C23H20FN2O2S: 407.1224, found: 407.1226. 61.1, 57.5, 21.7; FT-IR (KBr) 3063, 2922, 1708, 1567, 1492, 1456,
3-(o-Tolyl)-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole 1362, 1306, 1168, 1090 cm−1; HRMS (ESI) m/z [M + H]+ calcd for
4ae. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane; Rf = 0.45; C23H20ClN2O2S: 423.0929, found: 423.0927.
purification on silica gel column chromatography using 1:14 ethyl 3-(p-Tolyl)-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole 4aj.
acetate/hexane as eluent; colorless solid; mp 176−177 °C; yield 67% Analytical TLC on silica gel, 1:9 ethyl acetate/hexane; Rf = 0.44;
(53 mg); 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.0 Hz, 2H), purification on silica gel column chromatography using 1:14 ethyl
7.54 (d, J = 8.0 Hz, 1H), 7.19−7.15 (m, 4H), 7.07−7.03 (m, 1H), acetate/hexane as eluent; colorless solid; mp 135−136 °C; yield 64%
6.91−6.87 (m, 2H), 6.57 (d, J = 8.0 Hz, 1H), 6.329−6.327 (m, 2H), (51 mg); 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.4 Hz, 2H),
5.54−5.51 (m, 1H), 4.68−4.63 (m, 1H), 3.93−3.89 (m, 1H), 2.37 (s, 7.51 (d, J = 7.6 Hz, 1H), 7.23 (d, J = 8.0 Hz, 2H), 7.04−7.01 (m,
3H), 2.28 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.9, 141.9, 3H), 6.89−6.85 (m, 1H), 6.79 (d, J = 8.0 Hz, 2H), 6.57 (d, J = 8.0
135.5, 134.7, 133.3, 132.6, 131.0, 130.9, 130.6, 129.9, 128.3, 127.8, Hz, 1H), 6.29 (s, 1H), 5.28−5.25 (m, 1H), 4.62−4.57 (m, 1H),
126.8, 125.6, 120.58, 120.54, 120.50, 109.6, 83.5, 60.1, 55.1, 21.7, 3.97−3.93 (m, 1H), 2.39 (s, 3H), 2.31 (s, 3H); 13C{1H} NMR (100
19.2; FT-IR (KBr) 3052, 2921, 1616, 1597, 1566, 1477, 1455, 1425, MHz, CDCl3) δ 144.9, 141.8, 138.7, 134.7, 133.3, 132.7, 130.6, 129.9,
1361, 1306, 1168, 1089 cm−1; HRMS (ESI) m/z [M + H]+ calcd for 129.86, 129.81, 127.8, 126.3, 120.5, 120.4, 109.6, 83.3, 61.2, 58.1,
C24H23N2O2S: 403.1475, found: 403.1479. 21.7, 21.2; FT-IR (KBr) 3051, 2922, 1693, 1597, 1566, 1477, 1455,
3-(3-Bromophenyl)-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]- 1360, 1306, 1185, 1168, 1105 cm−1; HRMS (ESI) m/z [M + H]+
indole 4af. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane; Rf calcd for C24H23N2O2S: 403.1475, found: 403.1480.
= 0.43; purification on silica gel column chromatography using 1:14 3-([1,1′-Biphenyl]-4-yl)-1-tosyl-2,3-dihydro-1H-imidazo[1,2-
ethyl acetate/hexane as eluent; colorless solid; mp 95−96 °C; yield a]indole 4ak. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane;
68% (63 mg); 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.4 Hz, Rf = 0.46; purification on silica gel column chromatography using 1:14
2H), 7.53 (d, J = 7.6 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.24 (d, J = ethyl acetate/hexane as eluent; colorless solid; mp 198−199 °C; yield
8.0 Hz, 2H), 7.09−7.00 (m, 3H), 6.91 (t, J = 8.0 Hz, 1H), 6.78 (d, J = 68% (63 mg); 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.0 Hz,
7.6 Hz, 1H), 6.59 (d, J = 8.0 Hz, 1H), 6.31 (s, 1H), 5.28−5.24 (m, 2H), 7.54−7.51 (m, 3H), 7.45−7.42 (m, 4H), 7.35 (t, J = 7.2 Hz,
1H), 4.65−4.61 (m, 1H), 3.99−3.95 (m, 1H), 2.39 (s, 3H); 13C{1H} 1H), 7.23 (d, J = 7.6 Hz, 2H), 7.05 (t, J = 7.2 Hz, 1H), 6.94−6.88 (m,
NMR (100 MHz, CDCl3) δ 145.2, 141.8, 140.3, 133.4, 132.5, 132.0, 3H), 6.65 (d, J = 8.0 Hz, 1H), 6.33(s, 1H), 5.38−5.34 (m, 1H),
130.8, 130.4, 130.0, 129.3, 127.8, 124.9, 123.3, 120.78, 120.71, 109.4, 4.68−4.63 (m, 1H), 4.05−4.00 (m, 1H), 2.35 (s, 3H); 13C{1H} NMR
83.8, 61.0, 57.5, 21.8; FT-IR (KBr) 3052, 2918, 1616, 1596, 1568, (150 MHz, CDCl3) δ 145.0, 141.8, 141.7, 140.2, 136.7, 133.3, 132.6,
1476, 1455, 1420, 1362, 1306, 1185, 1167, 1107, 1089 cm−1; HRMS 130.5, 129.9, 129.0, 127.9, 127.89, 127.81, 127.1, 126.7, 120.59,
(ESI) m/z [M + H]+ calcd for C23H20BrN2O2S: 467.0423, found: 120.56, 109.6, 83.4, 61.2, 58.0, 21.7; FT-IR (KBr) 3030, 2925, 1616,
467.0423. 1597, 1566, 1487, 1456, 1362, 1306, 1260, 1168, 1089 cm−1; HRMS
3-(m-Tolyl)-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole (ESI) m/z [M + H]+ calcd for C29H25N2O2S: 465.1631, found:
4ag. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane; Rf = 0.44; 465.1631.
purification on silica gel column chromatography using 1:14 ethyl 3-(2,4-Dimethylphenyl)-1-tosyl-2,3-dihydro-1H-imidazo-
acetate/hexane as eluent; colorless solid; mp 143−144 °C; yield 64% [1,2-a]indole 4al. Analytical TLC on silica gel, 1:9 ethyl acetate/
(51 mg); 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.4 Hz, 2H), hexane; Rf = 0.44; purification on silica gel column chromatography
7.52 (d, J = 8.0 Hz, 1H), 7.24 (d, J = 8.0 Hz, 2H), 7.12−7.09 (m, using 1:14 ethyl acetate/hexane as eluent; colorless solid; mp 146−
2H), 7.05−7.01 (m, 1H), 6.89−6.85 (m, 1H), 6.70−6.68 (m, 2H), 147 °C; yield 65% (54 mg); 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J
6.58 (d, J = 8.0 Hz, 1H), 6.30 (s, 1H), 5.27−5.23 (m, 1H), 4.63−4.59 = 8.4 Hz, 2H), 7.53 (d, J = 8.0 Hz, 1H), 7.20 (d, J = 8.4 Hz, 2H),
(m, 1H), 3.99−3.94 (m, 1H), 2.39 (s, 3H), 2.22 (s, 3H); 13C{1H} 7.06−7.02 (m, 1H), 6.98 (s, 1H), 6.91−6.86 (m, 1H), 6.70 (d, J = 8.0
NMR (100 MHz, CDCl3) δ 144.9, 141.9, 139.0, 137.7, 133.3, 132.5, Hz, 1H), 6.57 (d, J = 8.0 Hz, 1H), 6.31(s, 1H), 6.27 (s, 1H), 5.51−
130.6, 129.9, 129.6, 129.0, 127.94, 126.96, 123.5, 120.49, 120.45, 5.47 (m, 1H), 4.65−4.60 (m, 1H), 3.89−3.85 (m, 1H), 2.37 (s, 3H),
109.6, 83.3, 61.2, 58.2, 21.7, 21.4; FT-IR (KBr) 3051, 2921, 1615, 2.26−2.22 (m, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.9,
1596, 1566, 1477, 1456, 1421, 1362, 1306, 1185, 1168, 1107, 1089 141.9, 138.1, 134.5, 133.2, 132.6, 132.4, 131.8, 130.6, 129.9, 127.8,
cm−1; HRMS (ESI) m/z [M + H]+ calcd for C24H23N2O2S: 403.1475, 127.5, 120.5, 120.47, 120.44, 109.7, 83.4, 60.2, 55.3, 21.7, 21.1, 19.0;
found: 403.1478. FT-IR (KBr) 3052, 2922, 1615, 1596, 1565, 1477, 1455, 1361, 1306,
3-(4-Bromophenyl)-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]- 1185, 1168, 1103, 1089 cm−1; HRMS (ESI) m/z [M + H]+ calcd for
indole 4ah. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane; Rf C25H25N2O2S: 417.1631, found: 417.1632.
= 0.42; purification on silica gel column chromatography using 1:14 3-Mesityl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole
ethyl acetate/hexane as eluent; colorless solid; mp 171−172 °C; yield 4am. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane; Rf =
71% (66 mg); 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.4 Hz, 0.43; purification on silica gel column chromatography using 1:14
2H), 7.53 (d, J = 7.6 Hz, 1H), 7.31−7.29 (m, 2H), 7.21 (d, J = 8.0 ethyl acetate/hexane as eluent; colorless solid; mp 196−197 °C; yield
Hz, 2H), 7.08−7.04 (m, 1H), 6.93−6.89 (m, 1H), 6.68−6.66 (m, 63% (54 mg); 1H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 8.4 Hz,
2H), 6.60 (d, J = 8.0 Hz, 1H), 6.31 (s, 1H), 5.30−5.27 (m, 1H), 2H), 7.49 (d, J = 7.6 Hz, 1H), 7.27−7.25 (m, 2H), 7.02−6.98 (m,
4.65−5.61 (m, 1H), 3.98−3.94 (m, 1H), 2.40 (s, 3H); 13C{1H} NMR 1H), 6.90 (s, 1H), 6.84−6.80 (m, 1H), 6.67 (s, 1H), 6.39 (d, J = 8.0
(100 MHz, CDCl3) δ 145.1, 141.6, 137.0, 133.3, 132.6, 132.3, 130.4, Hz, 1H), 6.28 (s, 1H), 5.80 (t, J = 9.2 Hz, 1H), 4.58−4.53 (m, 1H),
129.9, 127.9, 127.8, 127.7, 122.7, 120.74, 120.71, 109.4, 83.7, 61.0, 4.01−3.96 (m, 1H), 2.39 (d, J = 2.4 Hz, 6H), 2.24 (s, 3H), 1.22 (s,
57.5, 21.7; FT-IR (KBr) 3051, 2922, 1617, 1596, 1566, 1477, 1455, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 145.1, 141.4, 138.5, 137.3,
1421, 1361, 1306, 1185, 1166, 1071 cm−1; HRMS (ESI) m/z [M + 136.7, 132.9, 132.7, 131.9, 130.6, 129.9, 127.9, 120.4, 120.3, 108.6,
H]+ calcd for C23H20BrN2O2S: 467.0423, found: 467.0423. 83.1, 57.3, 53.8, 21.7, 20.9, 20.8, 18.2; FT-IR (KBr) 2922, 1615, 1457,
3-(4-Chlorophenyl)-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]- 1425, 1363, 1306, 1170, 1090 cm−1; HRMS (ESI) m/z [M + H]+
indole 4ai. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane; Rf calcd for C26H27N2O2S: 431.1788, found: 431.1790.
= 0.41; purification on silica gel column chromatography using 1:14 3-(Naphthalen-2-yl)-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]-
ethyl acetate/hexane as eluent; colorless solid; mp 142−143 °C; yield indole 4an. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane; Rf
69% (58 mg); 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.4 Hz, = 0.47; purification on silica gel column chromatography using 1:14
2H), 7.53 (d, J = 8.0 Hz, 1H), 7.21 (d, J = 8.0 Hz, 2H), 7.17−7.14 ethyl acetate/hexane as eluent; colorless solid; mp 183−184 °C; yield
(m, 2H), 7.07−7.03 (m, 1H), 6.92−6.88 (m, 1H), 6.75−6.73 (m, 67% (58 mg); 1H NMR (400 MHz, CDCl3) δ 7.80−7.76 (m, 3H),
2H), 6.59 (d, J = 8.0 Hz, 1H), 6.31 (s, 1H), 5.32−5.28 (m, 1H), 7.68−7.64 (m, 2H), 7.54 (d, J = 8.0 Hz, 1H), 7.49−7.47 (m, 2H),
4.65−4.60 (m, 1H), 3.98−3.94 (m, 1H), 2.39 (s, 3H); 13C{1H} NMR 7.39 (s, 1H), 7.19 (d, J = 8.4 Hz, 2H), 7.03 (t, J = 8.0 Hz, 1H), 6.89−
(100 MHz, CDCl3) δ 145.1, 141.7, 136.5, 134.6, 133.3, 132.7, 130.4, 6.81 (m, 2H), 6.57 (d, J = 8.0 Hz, 1H), 6.35 (s, 1H), 5.50−5.46 (m,

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1H), 4.74−4.69 (m, 1H), 4.09−4.05 (m, 1H), 2.34 (s, 3H); 13C{1H} 7.53−7.50 (m, 1H), 7.18 (d, J = 8.0 Hz, 2H), 7.08−7.05 (m, 2H),
NMR (100 MHz, CDCl3) δ 145.0, 141.9, 135.2, 133.3, 133.1, 132.6, 7.01−6.99 (m, 1H), 6.27 (s, 1H), 4.50−4.44 (m, 1H), 3.81−3.77 (m,
130.6, 129.9, 129.4, 128.1, 127.8, 126.8, 126.7, 125.8, 123.2, 120.6, 1H), 3.70−3.67 (m, 1H), 2.34 (s, 3H), 2.06−1.98 (m, 1H), 1.90−
120.58, 120.56, 109.6, 83.6, 61.1, 58.4, 21.7; FT-IR (KBr) 3053, 2923, 1.81 (m, 1H), 1.44−1.25 (m, 8H), 0.88 (t, J = 6.8 Hz, 3H); 13C{1H}
1616, 1597, 1566, 1477, 1456, 1361, 1306, 1185, 1168, 1106, 1089 NMR (150 MHz, CDCl3) δ 144.7, 141.3, 133.9, 132.8, 130.8, 129.9,
cm−1; HRMS (ESI) m/z [M + H]+ calcd for C27H23N2O2S: 439.1475, 127.5, 120.6, 120.5, 120.1, 108.7, 84.8, 66.2, 46.5, 35.8, 31.80, 29.1,
found: 439.1478. 24.8, 22.7, 21.7, 14.2; FT-IR (KBr) 2922, 2859, 1562, 1457, 1428,
3-Phenyl-1-(phenylsulfonyl)-2,3-dihydro-1H-imidazo[1,2- 1306, 1185, 1167, 1090, 1008 cm−1; HRMS (ESI) m/z [M + H]+
a]indole 4ao. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane; calcd for C23H29N2O2S: 397.1944, found: 397.1951.
Rf = 0.44; purification on silica gel column chromatography using 1:14 2-Octyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole 4at.
ethyl acetate/hexane as eluent; colorless solid; mp 174−175 °C; yield Analytical TLC on silica gel, 1:9 ethyl acetate/hexane; Rf = 0.42;
71% (53 mg); 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 7.2 Hz, purification on silica gel column chromatography using 1:11 ethyl
2H), 7.62−7.58 (m, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.47−7.43 (m, acetate/hexane as eluent; colorless solid; mp 90−91 °C; yield 68%
2H), 7.29−7.19 (m, 3H), 7.06−7.02 (m, 1H), 6.90−6.85 (m, 3H), (57 mg); 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 8.4 Hz, 2H),
6.57 (d, J = 8.0 Hz, 1H), 6.33 (s, 1H), 5.33−5.29 (m, 1H), 4.66−4.61 7.53−7.50 (m, 1H), 7.18 (d, J = 8.0 Hz, 2H), 7.09−7.04 (m, 2H),
(m, 1H), 4.00−3.96 (m, 1H); 13C{1H} NMR (150 MHz, CDCl3) δ 7.02−6.99 (m, 1H), 6.27 (s, 1H), 4.50−4.44 (m, 1H), 3.81−3.77 (m,
141.7, 137.6, 135.5, 134.0, 133.3, 130.5, 129.4, 129.2, 128.9, 127.8, 1H), 3.70−3.67 (m, 1H), 2.34 (s, 3H), 2.06−1.98 (m, 1H), 1.90−
126.3, 120.58, 120.56, 109.6, 83.4, 61.2, 58.2; FT-IR (KBr) 3060, 1.81 (m, 1H), 1.45−1.27 (m, 12H), 0.88 (t, J = 6.4 Hz, 3H); 13C{1H}
2924, 1616, 1566, 1477, 1454, 1362, 1307, 1220, 1171, 1090 cm−1; NMR (100 MHz, CDCl3) δ 144.7, 141.3, 134.0, 132.8, 130.8, 129.9,
HRMS (ESI) m/z [M + H]+ calcd for C22H18N2O2S: 375.1162, 127.5, 120.6, 120.5, 120.1, 108.7, 84.8, 66.2, 46.5, 35.8, 31.9, 29.57,
found: 375.1166. 29.51, 29.3, 24.9, 22.7, 21.7, 14.2; FT-IR (KBr) 3051, 2924, 1618,
1-((4-Chlorophenyl)sulfonyl)-3-phenyl-2,3-dihydro-1H- 1597, 1562, 1478, 1457, 1361, 1306, 1276, 1167, 1089 cm−1; HRMS
imidazo[1,2-a]indole 4ap. Analytical TLC on silica gel, 1:9 ethyl (ESI) m/z [M + H]+ calcd for C25H33N2O2S: 425.2257, found:
acetate/hexane; Rf = 0.42; purification on silica gel column 425.2260.
chromatography using 1:11 ethyl acetate/hexane as eluent; colorless 9-Methyl-3-phenyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]-
solid; mp 192−193 °C; yield 72% (58 mg); 1H NMR (400 MHz, indole 4ba. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane; Rf
CDCl3) δ 7.81 (d, J = 8.8 Hz, 2H), 7.53 (d, J = 7.6 Hz, 1H), 7.38− = 0.51; purification on silica gel column chromatography using 1:16
7.36 (m, 2H), 7.31−7.27 (m, 1H), 7.23−7.19 (m, 2H), 7.08−7.04 ethyl acetate/hexane as eluent; colorless solid; mp 130−131 °C; yield
(m, 1H), 6.93−6.89 (m, 1H), 6.81−6.79 (m, 2H), 6.61 (d, J = 8.0 Hz, 64% (53 mg); 1H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 8.4 Hz,
1H), 6.32 (s, 1H), 5.37−5.33 (m, 1H), 4.69−4.64 (m, 1H), 4.02− 3H), 7.279−7.277 (m, 1H), 7.18 (t, J = 7.6 Hz, 2H), 7.13 (d, J = 8.0
3.97 (m, 1H); 13C{1H} NMR (150 MHz, CDCl3) δ 141.2, 140.7, Hz, 2H), 7.09−7.05 (m, 1H), 6.93−6.89 (m, 1H), 6.80 (d, J = 7.2 Hz,
137.7, 134.0, 133.1, 130.5, 129.6, 129.3, 129.1, 128.8, 126.0, 120.8, 2H), 6.45 (d, J = 8.0 Hz, 1H), 4.87 (t, J = 7.6 Hz, 1H), 4.78−4.73 (m,
120.6, 109.7, 83.6, 61.3, 58.1; FT-IR (KBr) 3060, 2925, 1616, 1573, 1H), 4.15−4.10 (m, 1H), 2.55 (s, 3H), 2.36 (s, 3H); 13C{1H} NMR
1475, 1454, 1366, 1307, 1281, 1171, 1092 cm−1; HRMS (ESI) m/z (100 MHz, CDCl3) δ 144.6, 137.8, 137.2, 133.8, 133.3, 130.4, 130.0,
[M + H]+ calcd for C22H17ClN2O2S: 409.0772, found: 409.0777. 129.0, 128.4, 127.8, 126.3, 121.2, 119.8, 119.1, 109.6, 96.2, 63.3, 57.2,
1-((4-Nitrophenyl)sulfonyl)-3-phenyl-2,3-dihydro-1H- 21.7, 8.9; FT-IR (KBr) 2922, 1596, 1457, 1361, 1275, 1168, 1090,
imidazo[1,2-a]indole 4aq. Analytical TLC on silica gel, 1:9 ethyl 1006 cm−1; HRMS (ESI) m/z [M + H]+ calcd for C24H23N2O2S:
acetate/hexane; Rf = 0.40; purification on silica gel column 403.1475, found: 403.1477.
chromatography using 1:11 ethyl acetate/hexane as eluent; orange 8-Bromo-3-phenyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]-
solid; mp 194−195 °C; yield 62% (51 mg); 1H NMR (400 MHz, indole 4ca. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane; Rf
CDCl3) δ 8.20 (d, J = 8.8 Hz, 2H), 8.03 (d, J = 8.8 Hz, 2H), 7.55 (d, J = 0.46; purification on silica gel column chromatography using 1:14
= 8.0 Hz, 1H), 7.27−7.23 (m, 1H), 7.16 (t, J = 7.6 Hz, 2H), 7.08 (t, J ethyl acetate/hexane as eluent; solid; colorless solid; mp 192−193 °C;
= 8.0 Hz, 1H), 6.96−6.92 (m, 1H), 6.77 (d, J = 7.2 Hz, 2H), 6.64 (d, yield 58% (54 mg); 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.4
J = 8.0 Hz, 1H), 6.36 (s, 1H), 5.40−5.37 (m, 1H), 4.75−4.70 (m, Hz, 2H), 7.24−7.16 (m, 4H), 7.15−7.11 (m, 2H), 6.77 (d, J = 7.2 Hz
1H), 4.09−4.05 (m, 1H); 13C{1H} NMR (150 MHz, CDCl3) δ 150.8, 2H), 6.66 (t, J = 8 Hz, 1H), 6.44 (d, J = 8.4 Hz, 1H), 6.31 (s, 1H),
141.2, 140.4, 137.6, 132.8, 130.7, 129.2, 128.9, 128.8, 125.8, 124.4, 5.28−5.25 (m, 1H), 4.58−4.53 (m, 1H), 3.94−3.90 (m, 1H), 2.33 (s,
121.2, 120.9, 120.8, 109.8, 83.9, 61.5, 58.0; FT-IR (KBr) 3104, 2924, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 145.2, 142.2, 137.4, 133.7,
1606, 1595, 1567, 1477, 1454, 1370, 1309, 1256, 1173, 1089 cm−1; 132.5, 130.6, 130.1, 129.3, 129.0, 127.8, 126.2, 123.5, 121.4, 113.8,
HRMS (ESI) m/z [M + H]+ calcd for C22H18N3O4S: 420.1013, 108.5, 83.6, 61.0, 58.4, 21.7; FT-IR (KBr) 3066, 2923, 1611, 1597,
found: 420.1012. 1566, 1493, 1456, 1428, 1363, 1167 cm−1; HRMS (ESI) m/z [M +
1-((4-(tert-Butyl)phenyl)sulfonyl)-3-phenyl-2,3-dihydro-1H- H]+ calcd for C23H20BrN2O2S: 467.0423, found: 467.0426.
imidazo[1,2-a]indole 4ar. Analytical TLC on silica gel, 1:9 ethyl 7-(Benzyloxy)-3-phenyl-1-tosyl-2,3-dihydro-1H-imidazo-
acetate/hexane; Rf = 0.44; purification on silica gel column [1,2-a]indole 4da. Analytical TLC on silica gel, 1:9 ethyl acetate/
chromatography using 1:14 ethyl acetate/hexane as eluent; colorless hexane; Rf = 0.42; purification on silica gel column chromatography
solid; mp 193−194 °C; yield 67% (57 mg); 1H NMR (400 MHz, using 1:11 ethyl acetate/hexane as eluent; colorless solid; mp 150−
CDCl3) δ 7.83 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 8.0 Hz, 1H), 7.46 (d, J 151 °C; yield 67% (66 mg); 1H NMR (400 MHz, CDCl3) δ 7.71 (d, J
= 8.4 Hz, 2H), 7.21 (t, J = 7.6 Hz, 2H), 7.04 (t, J = 8.0 Hz, 1H), = 8.4 Hz, 2H), 7.38−7.36 (m, 2H), 7.32−7.28 (m, 2H), 7.26−7.20
6.89−6.86 (m, 3H), 6.58 (d, J = 8.0 Hz, 1H), 6.32 (s, 1H), 5.35−5.31 (m, 2H), 7.17−7.12 (m, 4H), 7.02 (d, J = 2.4 Hz, 1H), 6.80−6.78 (m,
(m, 1H), 4.65−4.60 (m, 1H), 3.99−3.95 (m, 1H), 1.30 (s, 9H); 2H), 6.54 (dd, J = 8.8, 2.4 Hz, 1H), 6.39 (d, J = 8.8 Hz, 1H), 6.17 (s,
13
C{1H} NMR (100 MHz, CDCl3) δ 157.9, 141.9, 137.8, 133.4, 1H), 5.20−5.17 (m, 1H), 4.98 (s, 2H), 4.55−4.50 (m, 1H), 3.89−
132.4, 130.5, 129.2, 128.9, 127.8, 126.39, 126.38, 120.52, 120.52, 3.85 (m, 1H), 2.32 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3) δ
120.4, 109.5, 83.2, 61.1, 58.2, 35.4, 31.1; FT-IR (KBr) 3057, 2963, 154.0, 145.0, 142.5, 137.76, 137.72, 134.0, 132.5, 130.0, 129.2, 128.8,
1617, 1593, 1566, 1476, 1455, 1361, 1307, 1266, 1131, 1085 cm−1; 128.6, 127.9, 127.8, 127.6, 126.3, 125.8, 110.4, 110.2, 104.8, 83.5,
HRMS (ESI) m/z [M + H]+ calcd for C26H27N2O2S: 431.1788, 70.8, 61.1, 58.4, 21.7; FT-IR (KBr) 3063, 2921, 1621, 1576, 1494,
found: 431.1791. 1478, 1451, 1363, 1289, 1168 cm−1; HRMS (ESI) m/z [M + H]+
2-Hexyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole 4as. calcd for C30H27N2O3S: 495.1737, found: 495.1737.
Analytical TLC on silica gel, 1:9 ethyl acetate/hexane; Rf = 0.43; 7-Bromo-3-phenyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]-
purification on silica gel column chromatography using 1:14 ethyl indole 4ea′. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane;
acetate/hexane as eluent; colorless solid; mp 113−114 °C; yield 66% Rf = 0.45; purification on silica gel column chromatography using 1:14
(52 mg); 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 8.4 Hz, 2H), ethyl acetate/hexane as eluent; colorless solid; mp 186−187 °C; 70%

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(65 mg); 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 8.0 Hz, 2H), 1263, 1165, 1090 cm−1; HRMS (ESI) m/z [M + H]+ calcd for
7.55 (d, J = 1.6 Hz, 1H), 7.23−7.12 (m, 5H), 6.89 (dd, J = 8.4, 2.0 C24H23N2O2S: 403.1475, found: 403.1477.
Hz, 1H), 6.75−6.73 (m, 2H), 6.35 (d, J = 8.4 Hz, 1H), 6.17 (s, 1H), 3-Phenyl-7-(pyren-2-yl)-1-tosyl-2,3-dihydro-1H-imidazo-
5.24−5.21 (m, 1H), 4.58−4.53 (m, 1H), 3.93−3.88 (m, 1H), 2.32 (s, [1,2-a]indole 5. Compound 4ea (46 mg, 0.1 mmol), boronic acid
3H); 13C{1H} NMR (100 MHz, CDCl3) δ 145.2, 142.8, 137.3, 134.9, (25 mg, 0.1 mmol), Pd(PPh3)4 (2.3 mg, 0.002 mmol), Na2CO3 (22
132.5, 130.0, 129.2, 129.1, 128.9, 127.8, 126.2, 123.2, 122.9, 113.8, mg, 0.2 mmol) and H2O (50 mL) were stirred in toluene: EtOH (1:1,
110.8, 82.8, 61.1, 58.3, 21.7; FT-IR (KBr) 3063, 2923, 1612, 1595, 2 mL) at 100 °C in an oil bath for 12 h under nitrogen atmosphere.
1565, 1459, 1364, 1275, 1168 cm−1; HRMS (ESI) m/z [M + H]+ After completion, the reaction mixture was cooled to room
calcd for C23H20BrN2O2S: 467.0423, found: 467.0427; [α]D26 = temperature and passed through a short pad of Celite using CH2Cl2
+24.00 (c = 0.01, CHCl3); HPLC: >99% ee [CHIRALCEL OD-H, (10 mL). Evaporation of the solvent gave a residue that was purified
hexane/iPrOH = 90:10, flow rate: 1 mL/min, λ = 254 nm, tR = 18.56 on silica gel column chromatography using 1:14 ethyl acetate/hexane
min (minor), 25.91 min (major)]. as eluent to give 5. Analytical TLC on silica gel, 1:9 ethyl acetate/
6-Chloro-3-phenyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]- hexane; Rf = 0.46; gray solid; mp 151−152 °C; yield 85% (50 mg);
indole 4fa. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane; Rf
1
H NMR (400 MHz, CDCl3) δ 8.23−8.17 (m, 3H), 8.15 (d, J = 7.6
= 0.44; purification on silica gel column chromatography using 1:14 Hz, 1H), 8.10−8.05 (m, 2H), 8.01−7.97 (m, 3H), 7.85 (d, J = 8.4 Hz,
ethyl acetate/hexane as eluent; colorless solid; mp >200 °C; yield 2H), 7.76−7.75(m 1H), 7.36−7.29 (m, 5H), 7.16 (dd, J = 8.0, 1.6 Hz,
63% (53 mg); 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.4 Hz, 1H), 7.01 (d, J = 6.8 Hz, 2H), 6.74 (d, J = 8.4 Hz, 1H), 6.40 (s, 1H),
2H), 7.41 (d, J = 8.4 Hz, 1H), 7.32−7.28 (m, 1H), 7.25−7.21 (m, 5.43−5.39 (m, 1H), 4.71−4.67 (m, 1H), 4.07−4.03 (m, 1H), 2.43 (s,
4H), 7.01 (dd, J = 8.4, 1.6 Hz, 1H), 6.84−6.82 (m, 2H), 6.54 (d, J = 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 145.1, 142.4, 138.9, 137.7,
2.0 Hz, 1H), 6.27 (s, 1H), 5.29−5.25 (m, 1H), 4.64−4.59 (m, 1H), 133.6, 133.5, 132.6, 131.6, 131.1, 130.3, 130.1, 129.9, 129.3, 128.9,
3.99−3.95 (m, 1H), 2.40 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) 128.8, 128.2, 127.9, 127.5, 127.25, 127.23, 126.4, 126.0, 125.9, 125.1,
δ 145.2, 142.3, 137.3, 132.5, 131.8, 130.8, 130.0, 129.3, 129.0, 127.8, 125.0, 124.7, 124.6, 123.5, 122.5, 109.2, 83.5, 61.2, 58.4, 21.8; FT-IR
126.1, 121.2, 121.1, 109.5, 83.3, 61.1, 58.3, 21.7; FT-IR (KBr) 3063, (KBr) 2977, 2926, 1613, 1567, 1435, 1351, 1168, 1143, 1074 cm−1;
2923, 1611, 1597, 1572, 1493, 1456, 1419, 1363, 1279, 1167 cm−1; HRMS (ESI) m/z [M + H]+ calcd for C39H29N2O2S: 589.1944,
HRMS (ESI) m/z [M + H]+ calcd for C23H20ClN2O2S: 423.0929, found: 589.1946.
found: 423.0928. 3-Phenyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-
6-Fluoro-3-phenyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]- tosyl-2,3-dihydro-1H-imida-zo[1,2-a]indole 6. Compound 4ea
indole 4ga′. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane; (46 mg, 0.1 mmol), diboron (25 mg, 0.1 mmol), KOAc (20 mg, 0.2
Rf = 0.42; purification on silica gel column chromatography using 1:11 mmol), and Pd(dppf)Cl2·CH2Cl2 (4 mg, 0.005 mmol) were stirred in
ethyl acetate/hexane as eluent; colorless solid; mp 188−189 °C; yield THF (2 mL) at 100 °C in an oil bath for 12 h under nitrogen
68% (55 mg); 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.4 Hz, atmosphere. The reaction mixture was cooled to room temperature
2H), 7.41−7.38 (m, 1H), 7.32−7.27 (m, 1H), 7.24−7.21 (m, 4H), and passed through a short pad of Celite using CH2Cl2 (15 mL).
6.85- 6.83 (m, 2H), 6.81−6.76 (m, 1H), 6.27 (s, 1H), 6.26−6.23 (m, Evaporation of the solvent gave a residue that was purified on silica
1H), 5.27−5.23 (m, 1H), 4.64−4.59 (m, 1H), 3.99−3.95 (m, 1H), gel column chromatography using 1:14 ethyl acetate/hexane as eluent
2.40 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ 159.4 (JC−F = to give 6. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane, Rf =
235.65 Hz), 145.1, 142.05 (JC−F = 3.15 Hz), 137.2, 132.5, 130.3 (JC−F 0.48; colorless solid; mp 95−96 °C; yield 73% (37 mg); 1H NMR
= 12.45 Hz), 130.0, 129.5, 129.3, 129.0, 127.8, 126.2, 121.0 (JC−F = (400 MHz, CDCl3) δ 8.03 (s, 1H), 7.75 (d, J = 8.0 Hz, 2H), 7.35 (dd,
9.75 Hz), 108.7 (JC−F = 24 Hz), 96.6 (JC−F = 2.67 Hz), 83.2, 61.1, J = 8.0, 0.8 Hz, 1H), 7.24 (t, J = 1.6 Hz, 1H), 7.19−7.16 (m, 4H),
58.2, 21.7; FT-IR (KBr) 3063, 2923, 1622, 1575, 1484, 1421, 1358, 6.80−6.78 (m, 2H), 6.58 (d, J = 8.0 Hz, 1H), 6.31 (s, 1H), 5.35−5.31
1279 1167 cm−1; HRMS (ESI) m/z [M + H]+ calcd for (m, 1H), 4.65−4.61 (m, 1H), 4.02−3.98 (m, 1H), 2.37 (s, 3H), 1.32
C23H20FN2O2S: 407.1224, found: 407.1228; [α]D27 = +22.00 (c = (s, 12H); 13C{1H} NMR (150 MHz, CDCl3) δ 145.0, 141.7, 137.8,
0.01, CHCl3); HPLC: >99% ee [CHIRALCEL OD-H, hexane/iPrOH 132.9, 132.4, 131.2, 129.9, 129.2, 128.7, 128.0, 127.8, 126.9, 126.1,
= 90:10, flow rate: 1 mL/min, λ = 254 nm, tR = 17.63 min (minor), 109.0, 83.7, 83.6, 61.3, 58.0, 25.0, 24.9, 21.7; FT-IR (KBr) 3039,
28.30 min (major)]. 2924, 1739, 1573, 1470, 1456, 1432, 1364, 1311, 1168, 1090 cm−1;
5-Chloro-3-phenyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]- HRMS (ESI) m/z [M + H]+ calcd for C29H32BN2O4S: 515.2170,
found: 515.2184.

■
indole 4ha. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane; Rf
= 0.43; purification on silica gel column chromatography using 1:11
ethyl acetate/hexane as eluent; colorless solid; mp 164−165 °C; yield ASSOCIATED CONTENT
69% (58 mg); 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.4 Hz, *
sı Supporting Information
2H), 7.41 (d, J = 7.6 Hz, 1H), 7.18−7.14 (m, 3H), 7.09−7.05 (m,
2H), 6.96 (t, J = 8.0 Hz, 1H), 6.89 (d, J = 7.2 Hz, 1H), 6.55 (d, J = 7.6 The Supporting Information is available free of charge at
Hz, 2H), 6.33 (s, 1H), 5.87−5.85 (m, 1H), 4.50−4.46 (m, 1H), https://pubs.acs.org/doi/10.1021/acs.joc.0c00899.
4.18−4.15 (m, 1H), 2.37 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) Table S1, Schemes S1 and S2, HPLC chromatograms,
δ 145.0, 142.7, 141.0, 135.3, 132.5, 130.0, 128.9, 128.0, 127.7, 127.4, and NMR spectra of the starting materials and products
124.6, 121.5, 121.1, 118.9, 116.1, 83.2, 60.8, 59.4, 21.7; FT-IR (KBr) (PDF)
3063, 2924, 1616, 1597, 1575, 1485, 1455, 1429, 1362, 1276, 1167
cm−1; HRMS (ESI) m/z [M + H]+ calcd for C23H20ClN2O2S: Crystallographic data for 4aa (CIF)
423.0929, found: 423.0931. Crystallographic data for 4aa′ (CIF)

■
5-Methyl-3-phenyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]-
indole 4ia. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane; Rf
= 0.46; purification on silica gel column chromatography using 1:14 AUTHOR INFORMATION
ethyl acetate/hexane as eluent; colorless solid; mp 174−175 °C; yield
Corresponding Author
73% (58 mg); 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.4 Hz,
2H), 7.38 (d, J = 7.6 Hz, 1H), 7.17−7.13 (m, 3H), 7.09−7.05 (m, Tharmalingam Punniyamurthy − Department of Chemistry,
2H), 6.96 (t, J = 7.2 Hz, 1H), 6.70 (d, J = 7.2 Hz, 1H), 6.53−6.50 (m, Indian Institute of Technology Guwahati, Guwahati, India;
2H), 6.32 (s, 1H), 5.67−5.64 (m, 1H), 4.53−4.49 (m, 1H), 4.16− orcid.org/0000-0003-4696-8896; Email: tpunni@iitg.ac.in
4.13 (m, 1H), 2.36 (s, 3H), 2.06 (s, 3H); 13C{1H} NMR (150 MHz,
CDCl3) δ 144.8, 141.8, 141.3, 133.4, 132.6, 129.9, 129.8, 129.1, 128.0, Authors
127.7, 124.6, 122.4, 120.9, 120.3, 118.2, 83.1, 60.9, 59.5, 21.7, 17.7; Pallab Karjee − Department of Chemistry, Indian Institute of
FT-IR (KBr) 3049, 2925, 1607, 1597, 1572, 1492, 1455, 1416, 1358, Technology Guwahati, Guwahati, India
8268 https://dx.doi.org/10.1021/acs.joc.0c00899
J. Org. Chem. 2020, 85, 8261−8270
The Journal of Organic Chemistry pubs.acs.org/joc Note

Tanumay Sarkar − Department of Chemistry, Indian Institute of to the Imidazo[1,2-a]pyridine-3-carboxylates. Bioorg. Med. Chem. Lett.
Technology Guwahati, Guwahati, India 2014, 24, 3493.
Subhradeep Kar − Department of Chemistry, Indian Institute of (3) For reviews, see: (a) Leitch, J. A.; Bhonoah, Y.; Frost, C. G.
Technology Guwahati, Guwahati, India Beyond C2 and C3: Transition-Metal-Catalyzed C−H Functionaliza-
tion of Indole. ACS Catal. 2017, 7, 5618. (b) Kalepu, J.; Gandeepan,
Complete contact information is available at: P.; Ackermann, L.; Pilarski, L. T. C4-H Indole Functionalisation:
https://pubs.acs.org/10.1021/acs.joc.0c00899 Precedent and Prospects. Chem. Sci. 2018, 9, 4203. For some
examples, see: (c) Yang, G.; Lindovska, P.; Zhu, D.; Kim, J.; Wang, P.;
Notes Tang, R.-Y.; Movassaghi, M.; Yu, J.-Q. Pd(II)-Catalyzed meta-C-H
The authors declare no competing financial interest. Olefination, Arylation, and Acetoxylation of Indolines Using a U-

■ ACKNOWLEDGMENTS
We thank the Science and Engineering Research Board (CRG/
Shaped Template. J. Am. Chem. Soc. 2014, 136, 10807. (d) Kim, Y.;
Park, J.; Chang, S. A Direct Access to 7-Aminoindoles via Iridium-
Catalyzed Mild C-H Amidation of N-Pivaloylindoles with Organic
Azides. Org. Lett. 2016, 18, 1892. (e) Vargas, D. A.; Tinoco, A.; Tyagi,
2018/000406) for the financial support. We are grateful to the V.; Fasan, R. Myoglobin-Catalyzed C-H Functionalization of
Department of Chemistry (COE-FAST and FIST) and Central Unprotected Indoles. Angew. Chem., Int. Ed. 2018, 57, 9911. and
Instrumentation Facility, Indian Institute of Technology references cited therein.
Guwahati for NMR and HRMS facilities.

■
(4) Martynaitis, V.; Steponavic̆iu̅tė, R.; Krikštolaitytė, S.; Solovjova,
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