One-Pot Trifluoromethylative Functionalization of Amides: Synthesis of Trifluoromethylated Bis(indolyl)arylmethanes and Triarylmethanes

Article abstract of DOI:10.1021/acs.joc.7b02161

Efficient and general one-pot trifluoromethylative functionalization of amides has been accomplished for the synthesis of various trifluoromethylated bis(indolyl)arylmethane, utilizing trifluoromethyltrimethylsilane and substituted indoles as nucleophiles. The developed reaction involves the in situ generation and trapping of a trifluoromethylated iminium ion, derived from the trifluoromethylated hemiaminal of amide, with various substituted indoles. This method has been successfully extended to the synthesis of diverse trifluoromethylated triarylmethanes employing phenols as nucleophiles. Furthermore, the potential of the method was demonstrated via the two-step synthesis of a trifluoromethylated analog of a hypolipidemic and anti-obesity agent.

Full text of DOI:10.1021/acs.joc.7b02161

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Article
One-Pot Trifluoromethylative Functionalization of Amides: Synthesis
of Trifluoromethylated Bis(indolyl)arylmethanes and Triarylmethanes
Vinay Kumar Pandey, and Pazhamalai Anbarasan
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02161 • Publication Date (Web): 13 Nov 2017
Downloaded from http://pubs.acs.org on November 15, 2017
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Page 1 of 28
The Journal of Organic Chemistry
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One-Pot Trifluoromethylative Functionalization of
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Amides: Synthesis of Trifluoromethylated
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Bis(indolyl)arylmethanes and Triarylmethanes
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Vinay Kumar Pandey and Pazhamalai Anbarasan*
Department of Chemistry, Indian Institute of Technology Madras, Chennai - 600036, India
E-mail: anbarasansp@iitm.ac.in
FAX: +91-44-22574202
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O
R1
O
CF3
OEt
CF3
N
R3
R2
R2
A
R2
One-pot
N
R3
N
R3
N
N
CF3TMS, CsF
THF, 0 °C-rt, 3 h
then
O
Me
Me
NR2
up to 91% yield
37 examples
Trifluoromethylated analog
of anti-obesity agents
OH
R1
R1
Tf2O, A/B, DCM
–78 °C-rt, 6 h
R4
B
CF3
up to 86% yield
6 examples
HO
OH
R4 R4
Abstract: Efficient and general one-pot trifluoromethylative functionalization of amides has been
accomplished for the synthesis of various trifluoromethylated bis(indolyl)arylmethane, utilizing
trifluoromethyltrimethylsilane and substituted indoles as nucleophiles. The developed reaction involves
the in-situ generation and trapping of trifluoromethylated iminium ion, derived from trifluoromethylated
hemiaminal of amide, with various substituted indoles. This method has been successfully extended to
the synthesis of diverse trifluoromethylated triarylmethanes employing phenols as nucleophiles.
Furthermore, the potential of the method was demonstrated via the two steps synthesis of
trifluoromethylated analog of hypolipidemic and anti-obesity agent.
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Introduction:
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Substituted bisindolylmethanes (BIMs) are ubiquitous subunits present in various natural products and
biologically interesting molecules. Most of the BIMs exhibit diverse therapeutic activities such as
anticancer, antimicrobial, antioxidant, anti-inflammatory, and etc.1 For example, vibrindole 1a and
streptindole 1b are natural products containing BIM moiety and BIM 2 display broad cytotoxic activity
(Figure 1). Similarly, triarylmethanes (TAMs) have also shown to possess various industrial, biological
and material applications.2
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MeO
OMe
OMe
R
H3C
N
H
N
H
NMe2
N
N
R = H: vibrindole A 1a
H
H
MeO
O
R = OCOCH3: Streptindole 1b
anticancer agent 2
anti cancer agent 3
Figure 1. Examples of bioactive bisindolylmethanes
On the other hand, incorporation of trifluoromethyl group (CF3) in therapeutically important
molecules has the profound effect in their bioactivity and physicochemical properties, compared to
parent molecules.3 As a result, trifluoromethylated functionalized organic compounds have gained
significant interest in various fields such as pharmaceutical, agrochemical, functional materials and etc,4
which also triggered substantial interest in their synthesis.5 However, the synthesis of
trifluoromethylated BIMs is rather limited. The known methods for the synthesis of trifluoromethylated
BIMs include the Friedel Crafts reaction of indole and trifluoromethylketones with a suitable acid
promoter.6 Due to the high potential of BIMs and ‘CF3’ group, the development of general and efficient
synthesis of trifluoromethylated BIMs should be highly warranted.
In general, BIMs are synthesized from aldehydes, ketones and their derivatives with substituted
indoles.7 In this context, to the best of our knowledge, amides were not utilized for the synthesis of
either BIMs or trifluoromethylated derivatives8, in spite their versatile application in the construction of
various C-C bonds9 through nucleophilic addition of organometallic reagents. Particularly, in the recent
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past, various one-pot reductive functionalizations of amides to multisubstituted amines have been
documented,10 due to the potency of the carbonyl carbon to accept two nucleophiles (Scheme 1a).11
Inspired by the one-pot reductive functionalization of amide and our continued interest in the utilization
of trifluoromethylated hemiaminal in the construction of trifluoromethylated scaffolds12, we envisioned
the synthesis of potential trifluoromethylated BIMs from amides via trifluoromethylative
functionalization. Thus, trifluoromethylation of amide to trifluoromethylated hemiaminal A followed by
treatment with triflic anhydride (Tf2O) would afford the trifluoromethylated iminium ion B, which could
be functionalized with indole derivatives, in one-pot, for the synthesis of trifluoromethylated
bis(indolyl)arylmethanes (BIAMs) via the possible generation of α-trifluoromentylated amine C and
alkylideneindoleninium intermediate D13 (Scheme 1b). We herein disclose the development of one-pot
trifluoromethylative functionalization of amides for the general and efficient synthesis of
trifluoromethylated BIAMs. Furthermore, the developed methodology could be easily applied in the
synthesis of trifluoromethylated analog of therapeutically important molecules.
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Scheme 1. Functionalization of amides
a) Chemoselective functionalization of amides:
Nu1
X
Nu1 Nu2
Nu1
Nu2
R1
R1
R1
R
N
R2
R
N
R
N
R2
then Acid
X = O, S
R2
O
b) Trifluoromethylative functionalization of amide:
CF3
previous
work
Tf2O
O
F3C
O
R1
R
R
R1
CF3
N
R2
N
R2
CF3
R1
4
R
R
N
R2
A
B
R3
this work!
R3
N
R4
R4
5
N
N
R
F3C
R1
CF3
R
CF3
H+
5
N
R2
R4
R
N
R4
R3
D
N
R3
C
6
R3
R4
α-trifluoromethylated
amines
trifluoromethylated analog
of bisindolylmethanes
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Results and Discussion
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Based on the hypothesis, we initiated our studies with model substrates Weinreb amide 4a and indole
5a. Reaction of 4a with trifluoromethyltrimethylsilane (CF3TMS) in the presence of fluoride activator
(CsF) at 0 °C in THF followed by changing the reaction medium to DCM and treatment with Tf2O/5a
afforded the trifluoromethylated BIAM 6aa in 31% yield and no formation of α-trifluoromethylated
amine derivative C was observed (Table 1, entry 1).14 Various attempts to control the addition of only
one indole 5a to form α-trifluoromethylated amine derivative C was not successful and led to either 6aa
or no reaction, suggesting that the formed amine derivatives is not stable and highly reactive under the
reaction conditions (Table 1, entries 1-6).
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Table 1. One-pot trifluoromethylative functionalization of Weinreb amide 4a with N-methylindole
5a: Optimizationa
CF3TMS, F– source
solvent 1, 0 °C-rt, 3 h
then
O
OMe
F3C
N
N
Me
Tf2O, 5a, solvent 2
–78 °C-rt, 6 h
N
+
4a
5a
6aa
N
Entry F– source
Solvent 1 5a (equiv)
Solvent 2 Yield (%)b
1
CsF
KF
THF
1
DCM
DCM
DCM
DCM
DCM
-
31 (23)c
2
THF
1
0
3
TBAF
CsF
CsF
CsF
CsF
CsF
CsF
CsF
THF
1
0
4
DCM
1
0
5
Toluene
Toluene
Toluene
Toluene
Toluene
THF
1
34
32
72
79
81
87
6
1
7
2
-
8
2.5
2.5
2.5
-
9
DCM
10
DCM
a Reaction conditions: 4a (50 mg, 0.3 mmol), CF3TMS (86 mg, 0.6 mmol, 2 equiv), F– source (1
equiv), Solvent 1 (2 mL), 0 °C-rt, 3h, then Tf2O (1.1 equiv), 5a (equiv), Solvent (2 mL), –78 °C-rt, 6 h. b
all are isolated yields. c 1.5 equivalents of CsF.
Next to increase the yield of potential trifluoromethylated BIAM 6aa, number of equivalents of 5a
was raised to two in toluene, which gave the 6aa in 72% yield (Table 1, entry 7). Further increase in
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amount of 5a as well as changing the solvent to DCM for iminium ion generation showed only slight
improvement (Table 1, entries 8 and 9). Use of THF and DCM as solvents for the trifluoromethylation
of 4a and subsequent functionalization with Tf2O and 5a, respectively, gave the best result with 87%
isolated yield of 6aa (Table 1, entry 10). Having optimized the conditions for the trifluoromethylative
functionalization of Weinreb amide 4, in-situ NMR experiment was performed to understand and
evaluate the involvement of possible intermediate. Although the formation of N,O-acetal intermediate A
was observed after the trifluoromethylation of 4a with CF3TMS (see Supporting Information), the
subsequent formation of neither a proposed iminium ion intermediate B nor 2,2,2-trifluoroacetophenone
could be detected. On the other hand, to understand the possible formation of trifluoromethyl ketone as
potential intermediate, 2,2,2-trifluoroacetophenone was subjected under the best-optimized conditions.
This resulted in the formation 6aa in only 56% yield, which is significantly less compared to the one-pot
trifluoromethylative functionalization. Thus, these results favors the involvement of iminium ion B as
potential intermediate in the trifluoromethylative functionalization of 4, but the involvement of
trifluoromethyl ketone could not completely ruled out.
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Next, the scope and limitation of substituted amides were investigated. As can be seen in Scheme 2,
various substituted aryl containing trifluoromethylated BIAMs 6 were synthesized in good to excellent
yield in one-pot from substituted Weinreb amides 4. For instance, alkyl and electron donating methoxy
and N,N-dimethyl substituted Weinreb amides underwent smooth reaction to afford the corresponding
products 6ba-6da in good yield. Readily functionalizable aryl halides containing BIAMs 6ea-6ga were
synthesized in 86%, 90% and 70% yield, respectively. It is important to note that reactive and electron
withdrawing cyano and nitro substituents were also well tolerated under the optimized conditions and
led to the formation 6ha and 6ia in good yield. Pyridine and thiophene, heteroarene derived Weinreb
amides were also successfully converted to corresponding product (6ja and 6ka) in good to moderate
yield. On the other hand, Weinreb amides derived from aliphatic carboxylic acids did not afford the
expected products, which is possibly due to the low reactivity of aliphatic amide and possible
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isomerization of iminium ion to enamine (see supporting information).
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Scheme 2. One-pot trifluoromethylative functionalization: Scope and limitation of amide 4
4
5
6
7
R
CF3TMS, CsF
THF, 0 °C-rt, 3 h
then
O
OMe
N
Me
CF3
Tf2O, 5a, DCM
–78 °C-rt, 6 h
8
9
R
4
N
N
6
10
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Me
MeO
CF3
CF3
CF3
N
N
N
N
N
N
N
N
6aa: 87%
CF3
6ba: 72%
6ca: 71%
CF3
Me2N
Cl
Br
CF3
N
N
N
N
N
6da: 67%
6ea: 86%
6fa: 90%
I
NC
O2N
CF3
CF3
CF3
N
N
N
6ga: 70%
N
N
6ha: 73%
6ia: 85%
N
S
CF3
CF3
N
N
N
N
6ja: 77%
6ka: 35%
Following the successful screening of various substituted Weinreb amides, related dialkyl substituted
amides was also examined to explore the generality of the amide. Trifluoromethylative functionalization
of N,N-dimethylbenzamide 4l with 5a under the optimized conditions afforded the product 6aa in 52%
yield (Scheme 3). Bulky diphenyl and dibenzyl substitution on the nitrogen (4m and 4n) decreased the
reactivity and led to 6aa in low yield. On the other hand, amide derived from morpholine (4o) and
cyclopentylmethyl amine (4p) underwent smooth reaction to 6aa in 26% and 31% yield. These results
revealed the supremacy of Weinreb amide over other amides, which is possibly due to the relatively
higher stability of hemiaminal derived from Weinreb amide compared to other amides.9a,9b
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The Journal of Organic Chemistry
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3
Scheme 3. One-pot trifluoromethylative functionalization of amides 4
4
5
6
O
R
CF3TMS, CsF
THF, 0 °C-rt, 3 h
then
N
R1
+
6aa
N
7
8
9
5a
Tf2O, 5a, DCM
–78 °C-rt, 6 h
4
10
11
12
13
14
15
16
O
Me
O
Ph
O
Bn
O
O
N
Me
N
N
N
O
N
Me
Ph
Bn
4o: 26%
4l: 52%
4n: 15%
4p: 31%
4m: 16%
Having explored the scope and generality of amides, diverse substituted indole derivatives were
screened under the optimized conditions. (Cyclo)Alkyl, allyl and benzyl substitutions on the nitrogen of
indole were well tolerated to furnish the corresponding products 6ab-6ad and 6ai in excellent yield
(Scheme 4). N-Aryl substituted indoles gave 6ae and 6af in comparable yield. On the other hand,
unsubstituted indole and electron withdrawing tosyl at nitrogen did not afford the expected products
(6ag and 6ah). Indoles having electron rich methoxy and halo substituents at 5th position underwent
smooth reaction to give trifluoromethylated BIAMs 6aj-6al in good yield. The structure of 6aj was
unambiguously confirmed by single crystal X-ray analysis.15 Electron withdrawing p-
toluenesulfonyloxy, cyano and nitro at 5th position and methylester at 6th position were highly
compatible with optimized conditions to give expected products (6am-6ao and 6ar) in moderate to good
yield. Most importantly, reactive functional groups such as amide, imide and acetate containing BIMs
6ap, 6aq and 6as were also achieved in good yield. But, expected product was not observed with N-
methyl-7-azaindole, N,2-dimethylindole and N,3-dimethylindole.
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Scheme 4. One-pot trifluoromethylative functionalization: Scope and limitation of indole 5
5
6
7
R1
8
9
O
OMe
CF63TaMj S, CsF
F3C
N
N
R
THF, 0 °C-rt, 3 h
Me
+
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N
R1
then
R
5
Tf2O, 5, DCM
–78 °C-rt, 6 h
4a
6
N
R
R1
R = C6H13; 6ab: 79%
R = allyl; 6ac: 88%
R = C6H5CH2; 6ad: 80%
R = C6H5; 6ae: 59%
R = p-MeOC6H4; 6af: 65%
R = H; 6ag: 0%
F3C
N
R
Ph
N
R = Ts; 6ah: 0%
R
O
Me
R = c-Pentyl; 6ai: 76%
R1
N
Me
R1 = OMe; 6aj: 72%
R1 = C6H5; 6ak: 91%
R1 = Br; 6al: 59%
R1 = OTs; 6am: 36%
R1 = CN; 6an: 63%
R1 = NO2; 6ao: 64%
CF3
N
CF3
Ph
Me
O
Ph
N
O
N
R1
N
6ap: 70%
Me
N
MeO
O
AcO
N
O
CF3
CF3
CF3
Ph
N
Ph
O
Ph
N
N
N
N
6ar: 87%
MeO
N
N
AcO
O
6as: 68%
O
6aq: 41%
Next, synthesis of unsymmetrical bis(indolyl)arylmethane was investigated with mixture of indole
derivatives 5. Reaction of Weinreb amide 4a with equimolar mixture of neutral and electron rich indoles
5a and 5j under the standard conditions afforded the mixture of trifluoromethylated BIAMs 7, 6aa and
6aj in 48% yield and 2:1:1 ratio, where the formation of unsymmetrical BIAM 7 was found to be major
(Scheme 5). Similarly, equimolar mixture of neutral and electron deficient indoles 5a and 5o were also
resulted in the mixture of 8, 6aa and 6ao in 38% yield and 5:1:1 ratio under the optimized conditions.
Unfortunately, various attempts to further improve the yield of unsymmetrical BIAM, such as sequential
addition and changing the ratio of indoles, were not successful.
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Scheme 5. Synthesis of unsymmetrical trifluoromethylated bis(indolyl)arylmethanes
1
2
3
O
4
5
6
7
8
9
10
11
12
13
14
Ph CF3
standard
conditions
(5a and 5j)
4a
4a
+
+
6aa: 11%
6aj: 12%
+
+
1:1 ratio
N
N
N
N
7: 25%
O2N
Ph CF3
standard
conditions
(5a and 5o)
6aa: 5%
6ao: 7%
1:1 ratio
8: 26%
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After successful demonstration of one-pot synthesis of trifluoromethylated BIAMs, we envisioned the
use of various aryl nucleophiles to widen the scope of the present methodology. Among the various aryl
nucleophiles that were studied, 4 equivalents of phenol under the optimized conditions afforded the
expected trifluoromethylated TAM 10a in 49% yield. Interestingly, the yield of the trifluoromethylated
TAM 10a could be increased by increasing either temperature or equivalents of phenol (Scheme 6). For
studying the scope of the transformation, 8 equivalents of phenol derivatives were used under the
optimized conditions.
Scheme 6. One-pot trifluoromethylative functionalization of 4a with phenol 9a:
O
OMe
1) CF3TMS, CsF
THF, 0 °C-rt, 3 h
2) Tf2O, 9a, DCM
–78 °C-rt, 6 h
N
OH
CF3
Me
+
4a
9a
HO
OH
10a
Change in conditions Yield
4 equiv. 9a
At 45 °C
49%
63%
72%
8 equiv. 9a
As can be seen in Scheme 7, diverse substituted electron rich phenol derivatives were examined to
demonstrate the scope and generality of the synthesis of trifluoromethylated TAMs 10. Ortho-
substituted phenols, such as o-cresol and 2-phenylphenol, on reaction with Weinreb amide 4a under the
optimized conditions furnished the expected trifluoromethylated TAMs 10b and 10c in 86% and 42%
yield, respectively. Similarly, catechol also gave the corresponding trifluoromethylated TAMs 10d in
81% yield. Sterically hindered m-methoxy- and m-bromophenols also underwent smooth reaction to
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afford 10e and 10f in 66% and 61% yield, respectively. It is important to note that all the phenols tested
1
2
3
afforded the product as single regioisomer, other isomers are not detected in 1H NMR.
4
5
Scheme 7. One-pot synthesis of trifluoromethylated TAMs 10.
6
7
8
9
O
OMe
1) CF3TMS, CsF
THF, 0 °C-rt, 3 h
2) Tf2O, 9a, DCM
–78 °C-rt, 6 h
N
OH
10
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CF3
R
10
Me
+
R
4a
9
HO
OH
R
CF3
CF3
CF3
Me
OH HO
Me Ph
OH HO
Ph
HO
OH
10a: 72%
10b: 86%
10c: 42%
OMe
CF3
Br
CF3
CF3
HO
HO
OH
OH HO
OMe
OH HO
Br
OH
10d: 81%
10e: 66%
10f: 61%
Having demonstrated the general and efficient method for the synthesis of trifluoromethylated BIAMs 6
and TAMs 10, potential application of the developed method was envisioned via the synthesis of
trifluoromethylated analog of hypolipidemic and anti-obesity agent16 12 (Scheme 8). The synthesis of
12 started with 4q, which on trifluoromethylative functionalization under the optimized conditions
furnished the trifluoromethylated BIAM 11, where the deprotection of benzyl group was also observed
under the reaction conditions. Subsequently, alkylation of phenolic hydroxyl in 11 with ethyl 4-
(tosyloxy)butanoate in the presence of K2CO3 furnished the expected trifluoromethyalted analog of
hypolipidemic and anti-obesity agent 12.
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The Journal of Organic Chemistry
Scheme 8. Synthesis of trifluoromethyl analog of anti-obesity agent 10
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CF3TMS, CsF HO
O
THF, 0 °C-rt, 3 h
then
CF3
OMe
N
Tf2O, 5a, DCM
–78 °C-rt, 6 h, 67%
N
Me
BnO
7
4q
11
N
8
OTs
OEt
K2CO3 (2 equiv)
9
CH3CN, reflux
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O
O
O
OEt
CF3
Trifluoromethylated analog of
hypolipidemic and anti-
obesity agents
N
N
12: 90%
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Conclusion
In conclusion, we have successfully demonstrated the one-pot trifluoromethylative functionalization of
amides utilizing the trifluoromethyltrimethylsilane as nucleophilic ‘CF3’source. The reaction involves
the in-situ generation of trifluoromethylated iminium ion from trifluoromethylated hemiaminal of amide
and trapping with substituted indoles. Importantly, the present reaction tolerates diverse reactive and
vital functional groups and allowed the synthesis of potential trifluoromethylated BIAM derivatives in
good to excellent yield. Additionally, the developed methodology has been successfully extended to the
synthesis of diverse trifluoromethylated triarylmethanes employing phenols as nucleophiles.
Furthermore, the potential of the developed methodology was shown via the synthesis of
trifluoromethylated analog of hypolipidemic and anti-obesity agent in two steps.
Experimental Section:
General Comments: All reactions were carried out under an atmosphere of dry nitrogen using reaction
tubes and round bottom flask. Dry toluene was prepared by distilling over sodium ketyl and stored over
molecular sieves 4Å under N2 atmosphere. Dry THF was prepared by sodium ketyl, benzophenone and
freshly distilled and used. Dry DCM were prepared by distilling over calcium hydride and stored over
molecular sieves 4Å under N2 atmosphere. Trifluoromethyltrimethylsilane, TBAF, triflic anhydride,
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substituted benzoyl chloride, Indole and other benzoic acid were obtained from commercially available
sources and they were used as received. All substituted Weinreb amides8 and substituted indoles17
derivatives were synthesized employing known organic synthesis procedure. Column chromatography
was performed using Rankem Silicagel (100-200 mesh) and ethyl acetate/hexanes were used as solvent
system, unless otherwise specified, with various percentage of polarity depending on the nature of the
substrate.
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Analytical Methods: NMR data were recorded on 400 and 500 MHz spectrometers. C and H NMR
19
spectra were referenced to signals of deutero solvents and residual protiated solvents, respectively. F
NMR spectra were recorded on 500 MHz spectrometers using hexafluorobenzene as standard. HRMS
were recorded by electron spry ionization (ESI) method on a Q-TOF Micro with lock spray source.
Melting points are corrected. The crystal data were collected and integrated using a diffractometer, with
graphite monochromated Mo-Kα radiation.
General procedure for the synthesis of trifluoromethylated bis(indolyl)arylmethane 6: Weinreb
amide 4 (50 mg, ~0.3 mmol, 1 equiv.) and CsF (46.0 mg, 0.30 mmol, 1 equiv.) were taken in an oven
dried 10 mL reaction tube, fitted with septum. Next, 2 mL dry THF (Solvent 1) was added under argon
atmosphere and reaction mixture was cooled to 0 °C, at the same temperature CF3TMS (85 mg, 0.6
mmol, 2 equiv.) was added. The reaction mixture was allowed to stir at room temperature for 3-4 hour.
THF was evaporated under reduced pressure and 2 mL dry DCM (Solvent 2) was added, again the
reaction mixture was cooled to –78 °C. Triflic anhydride (93 mg, 0.33 mmol, 1.1 equiv) was added at –
78 °C, stirred for 20 min and then the reaction mixture was allowed to warm upto 0 °C. Indoles 5 (0.75
mmol, 2.5 equiv.) was added at 0 °C and reaction mixture allowed to stir at room temperature for 5-6
hour. After completion of reaction, the reaction mixture was quenched with saturated aqueous NaHCO3
(5 mL), extracted with DCM (2 x 10 mL) and the combined organic layer was dried over Na2SO4.
Solvent was evaporated under reduced pressure and the crude product was purified by column
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The Journal of Organic Chemistry
chromatography using hexane/ethylacetate as eluent.
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6aa:6a 109 mg, 87% yield; brown solid; Rf = 0.46 in 85:15 hexane/ethyl acetate; Mp: 202-204 ºC; IR
5
6
7
8
1
(KBr): 2812, 2725, 1593, 1157, 749, 714 cm–1; H NMR (400 MHz, CDCl3, 24 °C): δ 7.59-7.53 (m,
2H), 7.34-7.28 (m, 5H), 7.22-7.16 (m, 4H), 6.96-6.91 (m, 2H), 6.75 (s, 2H), 3.72 (s, 6H); 13C{1H} NMR
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(125 MHz, CDCl3, 24 °C): δ 139.7, 137.5, 131.0, 129.7, 128.3 (q, J = 286.5 Hz), 128.0, 127.5, 126.9,
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122.5, (q, J = 3.0 Hz), 121.6, 119.3, 113.9, 109.3, 56.0 (q, J = 26.5 Hz), 32.9; F NMR (470 MHz,
CDCl3/C6F6, 24 °C): δ –62.52 (s, 3F, CF3); HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for C26H21N2F3Na:
441.1555; found: 441.1549.
6ba: 86 mg, 72% yield; white solid; Rf = 0.62 in 85:15 hexane/ethyl acetate; Mp: 228-230 ºC; IR (KBr):
2919, 2818, 2360, 1594, 812, 743 cm–1; 1H NMR (400 MHz, CDCl3, 24 °C): δ 7.43 (d, 2H, J = 8.1 Hz),
7.32 (d, 2H, J = 8.1 Hz), 7.22-7.17 (m, 4H), 7.11 (d, 2H, J = 8.1 Hz), 6.94 (t, 2H, J = 7.6 Hz), 6.77 (s,
2H), 3.72 (s, 6H), 2.36 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3, 24 °C): δ 137.5, 137.1, 136.7, 130.9,
129.5, 128.7, 128.3 (q, J = 286.2 Hz), 127.0, 122.6, (q, J = 3.0 Hz), 121.5, 119.2, 114.1, 109.2, 55.6, (q,
J = 26.4 Hz), 32.9, 21.1; 19F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –62.71 (s, 3F, CF3); HRMS (ESI-
TOF) m/z: [M + Na]+ calcd. for C27H23N2F3Na: 455.1703; found: 455.1706.
6ca: 80 mg, 71% yield; yellow solid; Rf = 0.46 in 85:15 hexane/ethyl acetate; Mp: 238-240 ºC; IR
(KBr): 2813, 2724, 1595, 1350, 1150, 745 cm–1; 1H NMR (400 MHz, CDCl3, 24 °C): δ 7.45 (d, 2H, J =
8.7 Hz), 7.32-7.28 (m, 2H), 7.21-7.15 (m, 4H), 6.93 (td, 2H, J = 8.0, 1.0 Hz), 6.74 (s, 2H), 6.81 (dd, 2H,
J = 6.9, 2.2 Hz), 3.80 (s, 3H), 3.72 (s, 6H); C{1H} NMR (125 MHz, CDCl3, 24 °C): δ 158.7, 137.5,
13
131.8, 130.9, 129.1, 128.3 (q, J = 285.3 Hz), 127.0, 122.6, (q, J = 3.1 Hz), 121.5, 119.3, 114.2, 113.2,
109.3, 55.3, (q, J = 26.7 Hz), 55.2, 33.0; 19F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –62.50 (s, 3F, CF3);
HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for C27H23ON2F3Na: 471.1653; found: 471.1655.
6da: 74 mg, 67% yield; white solid; Rf = 0.26 in 80:20 hexane/ethyl acetate; Mp: 270-272 ºC; IR (KBr):
1
2925, 2811, 1594, 1351, 1152, 812, 744 cm–1; H NMR (400 MHz, CDCl3, 24 °C): δ 7.36 (d, 2H, J =
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8.8 Hz), 7.29 (d, 2H, J = 8.8 Hz), 7.24-7.13 (m, 4H), 6.92 (td, 2H, J = 8.0, 1.0 Hz), 6.77 (s, 2H), 6.63
(dd, 2H, J = 7.1, 2.0 Hz), 3.72 (s, 6H), 2.94 (s, 6H); 13C{1H} NMR (125 MHz, CDCl3, 24 °C): δ 149.5,
137.5, 130.9, 130.4, 128.5 (q, J = 286.7 Hz), 127.3, 127.1, 122.8 (q, J = 3.1 Hz), 121.4, 119.1, 114.6,
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8
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111.7, 109.2, 55.1 (q, J = 26.5 Hz), 40.5, 32.9; F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –63.07 (s,
9
3F, CF3); HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C28H27N3F3: 462.2152; found: 462.2155.
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6ea: 98 mg, 86% yield; brown solid; 90:10 hexane/ethyl acetate; Mp: 250-252 ºC; IR (KBr): 2812,
1595, 1350, 1151, 1016, 930, 815, 742 cm–1; 1H NMR (400 MHz, CDCl3, 24 °C): δ 7.48 (d, 2H, J = 8.5
Hz), 7.29 (d, 2H, J = 8.5 Hz), 7.42 (d, 2H, J = 8.5 Hz), 7.20-7.12 (m, 4H), 6.96-6.90 (m, 2H), 6.72 (s,
2H), 3.70 (s, 6H); 13C{1H} NMR (125 MHz, CDCl3, 24 °C): δ 138.3, 137.6, 133.5, 131.2, 131.0, 128.2,
128.1 (q, J = 286.1 Hz), 126.7, 122.4 (q, J = 2.7 Hz), 121.7, 119.5, 113.4, 109.4, 55.6 (q, J = 27.2 Hz),
19
33.0; F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –62.83 (s, 3F, CF3); HRMS (ESI-TOF) m/z: [M +
Na]+ calcd. for C26H20ClN2F3Na: 475.1159; found: 475.1161.
6fa: 89 mg, 90% yield; dark brown solid; Rf = 0.55 in 90:10 hexane/ethyl acetate; Mp: 248-250 ºC; IR
(KBr): 2814, 1592, 1350, 1227, 1150, 1074, 813, 743 cm–1; 1H NMR (400 MHz, CDCl3, 24 °C): δ 7.46-
7.40 (m, 4H), 7.32 (d, 2H, J = 8.2 Hz), 7.23-7.15 (m, 4H), 6.96 (td, 2H, J = 8.1, 1.0 Hz) 6.74 (s, 2H)
3.72 (s, 6H); 13C{1H} NMR (125 MHz, CDCl3, 24 °C): δ 138.8, 137.6, 131.5, 131.1, 131.0, 128.0, (q, J
= 286.0 Hz), 126.7, 122.4 (q, J = 3.0 Hz), 121.8, 121.7, 119.5, 113.3, 109.4, 55.7 (q, J = 27.0 Hz), 33.0;
19F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –62.79 (s, 3F, CF3); HRMS (ESI-TOF) m/z: [M + Na]+
calcd. for C26H20BrN2F3Na: 519.0654; found: 519.0651.
6ga: 65 mg, 70% yield; white solid; Rf = 0.62 in 80:20 hexane/ethyl acetate; Mp: 260-262 ºC; IR (KBr):
2811, 2725, 1594, 1350, 1151, 810, 768, 744 cm–1; 1H NMR (400 MHz, CDCl3, 24 °C): δ 7.65 (dd, 2H,
J = 6.8, 1.9 Hz), 7.33-7.27 (m, 4H), 7.22-7.14 (m, 4H), 6.95 (td, 2H, J = 8.0, 0.9 Hz), 6.73 (s, 2H) 3.72
(s, 6H); C{1H} NMR (125 MHz, CDCl3, 24 °C): δ 139.6, 137.6, 137.1, 131.8, 131.0, 128.0, (q, J =
13
286.6 Hz), 126.7, 122.4 (q, J = 3.0 Hz), 121.7, 119.5, 113.3, 109.4, 93.7, 55.8 (q, J = 27.1 Hz), 33.0; 19F
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NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –62.76 (s, 3F, CF3); HRMS (ESI-TOF) m/z: [M + Na]+ calcd.
for C26H20IN2F3Na: 567.0525; found: 567.0516.
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6ha: 84 mg, 73% yield; brown solid; Rf = 0.40 in 70:30 hexane/ethyl acetate; Mp: 220-222 ºC; IR
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(KBr): 2928, 2815, 2237, 1597, 1350, 1154, 749 cm–1; H NMR (400 MHz, CDCl3, 24 °C): δ 7.71 (d,
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2H, J = 8.2 Hz), 7.58 (d, 2H, J = 8.5 Hz), 7.34 (d, 2H, J = 8.2 Hz), 7.29-7.23 (m, 2H), 7.11 (d, 2H, J =
13
8.0 Hz), 6.98-6.93 (m, 2H), 6.74 (s, 2H), 3.74 (s, 6H); C{1H} NMR (125 MHz, CDCl3, 24 °C): δ
145.0, 137.5, 132.9, 131.8, 131.0, 130.6, 127.8 (q, J = 287.1 Hz), 126.5, 122.1, (q, J = 2.6 Hz), 121.9,
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119.7, 112.6, 111.5, 109.6, 56.2 (q, J = 27.1 Hz), 33.0; F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –
62.70 (s, 3F, CF3); HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for C27H20N3F3Na: 466.1505; found:
466.1502.
6ia: 90 mg, 85% yield; yellow solid; Rf = 0.44 in 70:30 hexane/ethyl acetate; Mp: 140-142 ºC; IR
(KBr): 2928, 2818, 1596, 1351, 1163, 744 cm–1; 1H NMR (400 MHz, CDCl3, 24 °C): δ 8.14 (dd, 2H, J
= 7.2, 1.2 Hz), 7.97 (d, 2H, J = 8.8 Hz), 7.35 (d, 2H, J = 8.2 Hz), 7.23 (td, 2H, J = 7.9, 0.6 Hz), 7.13 (d,
2H, J = 8.2 Hz), 6.97 (td, 2H, J = 7.9, 0.6 Hz), 6.76 (s, 2H), 3.75 (s, 6H); C{1H} NMR (125 MHz,
13
CDCl3, 24 °C): δ 147.2, 147.0, 137.6, 131.0, 130.8, 127.6 (q, J = 286.0 Hz), 126.5, 123.1, 122.1, (q, J =
19
2.8 Hz), 122.0, 119.7, 112.5, 109.6, 56.2 (q, J = 27.1 Hz), 33.0; F NMR (470 MHz, CDCl3/C6F6, 24
°C): δ –62.71 (s, 3F, CF3); HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for C26H20O2N3F3Na: 486.1408;
found: 486.1400.
6ja: 97 mg, 77% yield; brown solid; Rf = 0.42 in 70:30 hexane/ethyl acetate; Mp: 212-214 ºC; IR
–1
1
(KBr): 2933, 2814, 2360, 1593, 1350, 1153, 742 cm ; H NMR (400 MHz, CDCl3, 24 °C): δ 8.58 (d,
1H, J = 5.2 Hz), 7.39 (d, 1H, J = 1.7 Hz), 7.29 (d, 2H, J = 8.2 Hz), 7.23 (ddd, 1H, J = 5.2, 3.4, 1.9 Hz),
7.16 (td, 2H, J = 7.9, 0.9 Hz), 7.06 (d, 2H, J = 8.1 Hz) 6.92-6.86 (m, 5H), 3.72 (s, 6H); C{1H} NMR
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(125 MHz, CDCl3, 24 °C): δ 161.1, 149.4, 144.4, 137.4, 130.8, 127.5 (q, J = 287.1 Hz), 126.8, 125.1,
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122.9, 122.1, 121.7, 119.4, 112.1, 109.4, 57.8 (q, J = 26.4 Hz), 33.0; F NMR (470 MHz, CDCl3/C6F6,
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24 °C): δ –63.25 (s, 3F, CF3); HRMS (ESI-TOF) m/z: [M + K]+ calcd. for C25H20N3F3K: 458.1246;
found: 458.1241.
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6ka: 43 mg, 35% yield; black solid; Rf = 0.33 in 80:20 hexane/ethyl acetate; Mp: 236-238 ºC; IR (KBr):
–1
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9
2932, 2814, 1594, 1350, 1237, 1154, 742 cm ; H NMR (400 MHz, CDCl3, 24 °C): δ 7.31-7.21 (m,
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4H), 7.17-7.06 (m, 4H), 6.99-6.92 (m, 3H), 6.86 (t, 2H, J = 7.6 Hz), 3.74 (s, 6H); C{1H} NMR (125
13
MHz, CDCl3, 24 °C): δ 144.3, 137.4, 130.2, 128.1, 127.6 (q, J = 285.8 Hz), 126.9, 126.2, 125.6, 122.3,
(q, J = 2.4 Hz), 121.6, 119.3, 113.5, 109.3, 53.1 (q, J = 28.1 Hz), 33.0; 19F NMR (470 MHz, CDCl3/C6F6,
24 °C): δ –66.57 (s, 3F, CF3); HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for C24H19SN2F3Na: 447.1113;
found: 447.1110.
6ab: 133 mg, 79% yield; yellow liquid; Rf = 0.40 in 90:10 hexane/ethyl acetate; IR (Neat): 2955, 2929,
1465, 1236, 1151, 740 cm–1; 1H NMR (400 MHz, CDCl3, 24 °C): δ 7.53 (dd, 2H, J = 7.9, 2.1 Hz), 7.34-
7.27 (m, 5H), 7.17-7.12 (m, 4H), 6.88 (td, 2H, J = 8.0, 0.9 Hz), 6.78 (s, 2H), 4.03 (t, 4H, J = 7.1 Hz),
1.76 (t, 4H, J = 7.1 Hz), 1.25 (brs, 12H), 0.85 (t, 6H, J = 6.7 Hz); 13C{1H} NMR (125 MHz, CDCl3, 24
°C): δ 139.8, 137.7, 130.2, 129.7, 128.3 (q, J = 286.6 Hz), 128.0, 127.4, 127.1, 122.6 (q, J = 3.0 Hz),
121.3, 119.1, 113.7, 109.8, 56.0 (q, J = 26.8 Hz), 46.4, 31.4, 30.1, 26.6, 22.6, 14.1; 19F NMR (470 MHz,
CDCl3/C6F6, 24 °C): δ –62.57 (s, 3F, CF3); HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for C36H41N2F3Na:
581.3120; found: 581.3097.
6ac: 124 mg, 88% yield; yellow solid; Rf = 0.33 in 90:10 hexane/ethyl acetate; Mp: 114-116 ºC IR
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(KBr): 2928, 2809, 1595, 1349, 1147, 930, 740 cm–1; H NMR (400 MHz, CDCl3, 24 °C): δ 7.60-7.53
(m, 2H), 7.36-7.27 (m, 5H), 7.21-7.12 (m, 4H), 6.94-6.88 (m, 2H), 6.85 (s, 2H), 6.01-5.91 (m, 2H), 5.18
(d, 2H, J = 10.4 Hz), 5.02 (d, 2H, J = 17.1 Hz), 4.68 (dd, 4H, J = 3.5, 1.2 Hz); 13C{1H} NMR (125 MHz,
CDCl3, 24 °C): δ 139.5, 136.9, 133.4, 130.1, 129.7, 128.2 (q, J = 286.3 Hz), 128.0, 127.5, 127.2, 122.6,
121.6, 119.4, 117.1, 114.2, 109.7, 56.0 (q, J = 26.3 Hz), 48.8; 19F NMR (470 MHz, CDCl3/C6F6, 24 °C):
δ –62.67 (s, 3F, CF3); HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for C30H25N2F3Na: 493.1862; found:
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493.1866.
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6ad: 138 mg, 80% yield; yellow solid; %; Rf = 0.30 in 90:10 hexane/ethyl acetate; Mp: 106-108 ºC; IR
5
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7
1
(KBr): 2811, 2724, 1593, 1350, 1151, 764 cm–1; H NMR (400 MHz, CDCl3, 24 °C): δ 7.60-7.53 (m,
8
9
2H), 7.31-7.27 (m, 4H), 7.25-7.18 (m, 6H), 7.15 (d, 2H, J = 8.3 Hz), 7.03 (t, 3H, J = 7.7 Hz), 7.02 (d,
4H, J = 6.8 Hz), 6.93(s, 2H), 6.86 (t, 2H, J = 7.7 Hz), 5.25 (s, 4H); 13C{1H} NMR (125 MHz, CDCl3, 24
°C): δ 139.3, 137.4, 137.1, 130.6, 129.7, 128.8, 128.2 (q, J = 286.4 Hz), 128.1, 127.6, 127.3, 126.5,
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126.0, 122.6 (q, J = 3.0 Hz), 121.8, 119.5, 114.3, 109.9, 55.9 (q, J = 26.9 Hz), 50.1; F NMR (470
MHz, CDCl3/C6F6, 24 °C): δ –62.82 (s, 3F, CF3); HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for
C38H29N2F3Na: 593.2175; found: 593.2177.
6ae: 97 mg, 59% yield as yellow viscous liquid; Rf = 0.44 in 85:15 hexane/ethyl acetate; IR (neat):
3060, 2925, 1500, 1458, 1150, 743 cm–1; 1H NMR (400 MHz, CDCl3, 24 °C): δ 7.72-7.64 (m, 2H), 7.56
(d, 2H, J = 8.3 Hz), 7.52-7.44 (m, 8H), 7.39-7.31 (m, 7H), 7.19 (td, 2H, J = 8.0, 0.8 Hz), 7.14 (s, 2H),
7.02 (td, 2H, J = 8.0, 0.8 Hz); C{1H} NMR (125 MHz, CDCl3, 24 °C): δ 139.4, 139.0, 136.9, 130.2,
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129.7, 128.7, 128.3 (q, J = 285.9 Hz), 128.2, 127.8, 127.7, 126.8, 124.8, 122.8, (q, J = 3.0 Hz), 122.5,
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120.4, 116.1, 110.6, 56.2 (q, J = 26.9 Hz); F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –62.84 (s, 3F,
CF3); HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for C36H25N2F3Na: 565.1862; found: 565.1858.
6af: 117 mg, 65% yield; white solid; Rf = 0.42 in 85:15 hexane/ethyl acetate; Mp: 180-182 ºC; IR
(KBr): 2932, 2836, 1597, 1248, 1149, 746 cm–1; 1H NMR (400 MHz, CDCl3, 24 °C): δ 7.64 (dd, 2H, J
= 5.9, 3.0 Hz), 7.42 (d, 2H, J = 8.3 Hz), 7.37-7.27 (m, 9H), 7.15 (td, 2H, J = 7.9, 1.0 Hz), 7.03 (s, 2H),
7.01-6.94 (m, 6H), 3.85 (s, 6H); 13C{1H} NMR (125 MHz, CDCl3, 24 °C): δ 158.5, 139.2, 137.3, 132.3,
130.6, 129.7, 128.2 (q, J = 286.3 Hz), 128.1, 127.7, 127.3, 126.4, 122.7, 122.2, 120.1, 115.6, 114.7,
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110.5, 56.1 (q, J = 26.6 Hz), 55.6; F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –62.25 (s, 3F, CF3);
HRMS (ESI-TOF) m/z: [M + K]+ calcd. for C38H29O2N2F3K: 641.1813; found: 641.1824.
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6ai: 121 mg, 76% yield; yellow liquid; Rf = 0.40 in 90:10 hexane/ethyl acetate; IR (neat): 2959, 2873,
1536, 1462, 1150, 740 cm–1; 1H NMR (400 MHz, CDCl3, 24 °C): δ 7.56 (dd, 2H, J = 5.5, 2.4 Hz), 7.41
(d, 2H, J = 8.1 Hz), 7.33-7.28 (m, 3H), 7.18-7.12 (m, 4H), 6.93-6.90 (m, 2H), 6.89 (s, 2H), 4.78 (qt, 2H,
J = 6.9 Hz), 2.20-2.11 (m, 4H), 1.90-1.78 (m, 4H), 1.77-1.66 (m, 8H); 13C{1H} NMR (125 MHz, CDCl3,
24 °C): δ 139.8, 136.9, 129.6, 128.3 (q, J = 286.3 Hz), 127.9, 127.4, 127.2, 127.1, 122.5 (q, J = 3.0 Hz),
121.2, 119.1, 113.7, 109.9, 57.0, 56.0 (q, J = 26.4 Hz), 32.5, 23.9; 19F NMR (470 MHz, CDCl3/C6F6, 24
°C): δ –62.50 (s, 3F, CF3); HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for C34H33N2F3Na: 549.2488;
found: 549.2490.
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6aj: 105 mg, 72% yield; brown solid; Rf = 0.23 in 80:20 hexane/ethyl acetate; Mp: 218-220 ºC; IR
(KBr): 2952, 2833, 1594, 1492, 1223, 1150, 792 cm–1; 1H NMR (400 MHz, CDCl3, 24 °C): δ 7.61-7.55
(m, 2H), 7.33-7.28 (m, 3H), 7.20 (s, 1H), 7.18 (s, 1H), 6.84 (dd, 2H, J = 8.9, 2.4 Hz), 6.78 (s, 2H), 6.48
(d, 2H, J = 2.2 Hz), 3.70 (s, 6H), 3.51 (s, 6H); 13C{1H} NMR (125 MHz, CDCl3, 24 °C): δ 153.6, 139.5,
132.8, 131.2, 129.9, 128.4 (q, J = 286.2 Hz), 128.0, 127.6, 127.4, 113.2, 112.0, 109.9, 104.2, (q, J = 2.6
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Hz), 55.8 (q, J = 26.4 Hz), 55.6, 33.1; F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –62.87 (s, 3F, CF3);
HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for C28H25O2N2F3Na: 501.1760; found: 501.1760.
6ak: 157 mg, 91% yield; yellow solid; Rf = 0.40 in 85:15 hexane/ethyl acetate; Mp: 256-258 ºC; IR
(KBr): 2810, 2723, 1595, 1349, 1146, 758 cm–1; 1H NMR (400 MHz, CDCl3, 24 °C): δ 7.64 (dd, 2H, J
= 6.0, 1.9 Hz), 7.46 (dd, 2H, J = 8.5, 1.6 Hz), 7.38 (s, 1H), 7.37-7.30 (m, 14H), 7.25-7.21 (m, 2H), 6.85
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(s, 2H), 3.75 (s, 6H); C{1H} NMR (125 MHz, CDCl3, 24 °C): δ 142.6, 139.7, 137.1, 132.7, 131.4,
129.9, 128.6, 128.3 (q, J = 286.0 Hz), 128.1, 127.7, 127.5, 127.4, 126.2, 121.4, 121.1, (q, J = 3.0 Hz),
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114.3, 109.5, 56.0 (q, J = 27.3 Hz), 33.1; F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –62.84 (s, 3F,
CF3); HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for C38H29N2F3Na: 593.2175; found: 593.2175.
6al: 103 mg, 59% yield; black solid; Rf = 0.55 in 80:20 hexane/ethyl acetate; Mp: 268-270 ºC; IR
(KBr): 2923, 2725, 1597, 1475, 1351, 1145, 796, 722, 742 cm–1; 1H NMR (400 MHz, CDCl3, 24 °C): δ
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7.45 (d, 2H, J = 7.3 Hz), 7.36-7.28 (m, 3H), 7.25 (dd, 2H, J = 8.6, 1.7 Hz), 7.21 (s, 2H), 7.16 (d, 2H, J =
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8.6 Hz), 6.70 (s, 2H), 3.70 (s, 6H); C{1H} NMR (125 MHz, CDCl3, 24 °C): δ 138.8, 136.3, 132.0,
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55.7 (q, J = 27.1 Hz), 33.2; F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –62.61 (s, 3F, CF3); HRMS
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(ESI-TOF) m/z: [M + Na]+ calcd. for C26H19Br2N2F3Na: 596.9759; found: 596.9757.
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6am: 83 mg, 36% yield; yellow solid; Rf = 0.24 in 80:20 hexane/ethyl acetate; Mp: 212-214 ºC; IR
(KBr): 2925, 2814, 1596, 1484, 1358, 1153, 938, 773, 552 cm–1; 1H NMR (400 MHz, CDCl3, 24 °C): δ
7.36 (d, 4H, J = 8.2 Hz), 7.32-7.21 (m, 5H), 7.15 (d, 2H, J = 8.8 Hz), 7.09 (d, 4H, J = 8.2 Hz), 6.79 (dd,
2H, J = 8.9, 2.2 Hz), 6.77 (s, 2H), 6.53 (d, 2H, J = 1.9 Hz), 3.72 (s, 6H), 2.32 (s, 6H); C{1H} NMR
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(125 MHz, CDCl3, 24 °C): δ 144.9, 143.2, 138.5, 135.9, 132.3, 132.2, 129.5, 129.3, 128.4, 128.2, 127.9,
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127.7 (q, J = 285.4 Hz), 126.7, 116.5, 115.2, 113.6, 110.0, 55.3 (q, J = 26.8 Hz), 33.3, 21.6; F NMR
(470 MHz, CDCl3/C6F6, 24 °C): δ –63.56 (s, 3F, CF3); HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for
C40H33O6S2N2F3Na: 781.1624; found: 781.1625.
6an: 88 mg, 63% yield; brown solid; Rf = 0.22 in 80:20 hexane/ethyl acetate; Mp: 248-250 ºC IR (KBr):
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2925, 2812, 2219, 1488, 1349, 1148, 743 cm–1; H NMR (400 MHz, CDCl3, 24 °C): δ 7.41-7.36 (m,
7H), 7.36-7.31 (m, 4H), 6.93 (s, 2H), 3.81 (s, 6H); C{1H} NMR (125 MHz, CDCl3, 24 °C): δ 139.0,
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138.1, 132.8, 129.1, 128.5, 128.4, 127.7 (q, J = 286.7 Hz), 127.6 (q, J = 2.6 Hz), 126.4, 124.8, 120.7,
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114.3, 110.7, 102.9, 55.4 (q, J = 27.0 Hz), 33.4; F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –63.17 (s,
3F, CF3); HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for C28H19N4F3Na: 491.1454; found: 491.1460.
6ao: 100 mg, 64% yield; brown solid; Rf = 0.15 in 70:30 hexane/ethyl acetate; Mp: 220-222 ºC; IR
(KBr): 2925, 2812, 1594, 1332, 1146, 1049, 737 cm–1; 1H NMR (400 MHz, CDCl3, 24 °C): δ 8.05 (dd,
2H, J = 9.1, 2.1 Hz), 7.89 (d, 2H, J = 2.1 Hz), 7.45 (d, 2H, J = 7.2 Hz), 7.39-7.31 (m, 5H), 7.03 (s, 2H),
3.85 (s, 6H); C{1H} NMR (125 MHz, CDCl3, 24 °C): δ 141.8, 140.3, 138.0, 133.6, 129.2, 128.7,
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33.6; 19F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –63.44 (s, 3F, CF3); HRMS (ESI-TOF) m/z: [M + Na]+
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calcd. for C26H19O4N4F3Na: 531.1251; found: 531.1245.
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6ap: 118 mg, 70% yield; Rf = 0.17 in ethyl acetate; brown solid; Mp: 222-224 ºC; IR (KBr): 2929,
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1.9 Hz), 7.35-7.25 (m, 5H), 6.99 (s, 2H), 6.91 (dd, 2H, J = 8.4, 1.9 Hz), 6.61, (s, 2H), 3.80 (s, 6H), 3.02
(s, 6H), 1.42 (s, 6H); C{1H} NMR (125 MHz, CDCl3, 24 °C): δ 171.1, 139.0, 136.7, 136.2, 131.7,
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37.5, 33.3, 22.1; F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –63.83 (s, 3F, CF3); HRMS (ESI-TOF)
m/z: [M + Na]+ calcd. for C33H31O2N4F3Na: 583.2291; found: 583.2291.
6aq: 76 mg, 41% yield; white solid; Rf = 0.22 in 80:20 hexane/ethyl acetate; Mp: 198-200 ºC; IR (KBr):
2927, 2812, 1777, 1493, 1357, 1146, 720 cm–1; 1H NMR (400 MHz, CDCl3, 24 °C): δ 7.50 (dd, 2H, J =
6.2, 2.2 Hz), 7.38 (d, 2H, J = 8.6 Hz), 7.34-7.29 (m, 3H), 7.09 (s, 2H), 7.03 (dd, 2H, J = 8.6, 1.7 Hz),
6.79 (s, 2H), 3.73 (s, 6H), 2.80 (s, 8H); 13C{1H} NMR (125 MHz, CDCl3, 24 °C): δ 176.9, 138.8, 137.3,
132.8, 129.4, 128.3, 128.0, (q, J = 286.3 Hz), 127.7, 126.6, 123.6, 121.6, 120.1, 114.1, 110.1, 55.8 (q, J
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= 26.7 Hz), 33.1, 28.4; F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –62.34 (s, 3F, CF3); HRMS (ESI-
TOF) m/z: [M + Na]+ calcd. for C34H27O4N4F3Na: 635.1877; found: 635.1877.
6ar: 139 mg, 87% yield; white solid; Rf = 0.33 in 80:20 hexane/ethyl acetate; Mp: 180-182 ºC; IR
(KBr): 2946, 2808, 1720, 1595, 1240, 1145, 768, 720 cm–1; 1H NMR (400 MHz, CDCl3, 24 °C): δ 8.08
(d, 2H, J = 1.0 Hz), 7.57 (dd, 2H, J = 8.6, 1.4 Hz), 7.49 (d, 2H, J = 6.8 Hz), 7.34-7.26 (m, 3H), 7.09 (d,
2H, J = 8.6 Hz), 6.91 (s, 2H), 3.91 (s, 6H), 3.80 (s, 6H); C{1H} NMR (125 MHz, CDCl3, 24 °C): δ
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168.0, 139.0, 137.0, 133.8, 130.4, 129.4, 128.2, 127.9, 127.7 (q, J = 286.3 Hz), 123.5, 121.9 (q, J = 2.9
Hz), 120.4, 114.1, 111.9, 55.7 (q, J = 26.6 Hz), 52.2, 33.2; 19F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –
62.95 (s, 3F, CF3); HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for C30H25O4N2F3Na: 557.1659; found:
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6as: 115 mg, 68% yield; white solid; Rf = 0.40 in 80:20 hexane/ethyl acetate; Mp: 80-82 ºC; IR (KBr):
2811, 2723, 1738, 1591, 1350, 1147, 765 cm–1; 1H NMR (400 MHz, CDCl3, 24 °C): δ 7.51 (dd, 2H, J =
7.7, 1.0 Hz), 7.35-7.27 (m, 5H), 7.13 (d, 2H, J = 8.3 Hz), 6.93 (dd, 2H, J = 8.4, 1.4 Hz), 6.76 (s, 2H),
5.20 (s, 4H), 3.73 (s, 6H), 2.10 (s, 6H); 13C{1H} NMR (125 MHz, CDCl3, 24 °C): δ 171.2, 139.4, 137.4,
131.7, 129.6, 129.2, 128.1 (q, J = 286.5 Hz), 128.0, 127.6, 126.9, 122.6 (q, J = 3.0 Hz), 120.2, 113.9,
109.8, 67.3, 55.8 (q, J = 26.6 Hz), 33.0, 21.3; 19F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –62.75 (s, 3F,
CF3); HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for C32H29O4N2F3Na: 585.1972; found: 585.1976.
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General procedure for the synthesis of unsymmetrical trifluoromethylated bisindolylmethanes 7
and 8: Unsymmetrical trifluoromethylated bisindolylmethane 7 and 8 was synthesized employing standard
procedure. Weinreb amide 4a (100 mg, 0.60 mmol) and CsF (91.0 mg, 0.60 mmol) were taken in an
oven dried 10 mL reaction tube, fitted with septum. Next, 4 mL dry THF (Solvent 1) was added under
argon atmosphere and reaction mixture was cooled to 0 °C, at the same temperature CF3TMS (170 mg,
1.20 mmol) was added. The reaction mixture was allowed to stir at room temperature for 3-4 hour. THF
was evaporated under reduced pressure and 4 mL dry DCM (Solvent 2) was added, again reaction
mixture was cooled to –78 °C. Triflic anhydride (Tf2O, 186.12 mg, 0.66 mmol) was added at –78 °C,
stirred for 20 min and then the reaction mixture was allowed to warm upto 0 °C. Next, equimolar
mixture of indoles 5a and 5j (or 5a and 5o) (1.50 mmol) were added at 0 °C and reaction mixture
allowed to stirred at room temperature for 5-6 hour. After completion of reaction, the reaction mixture
was quenched with saturated aqueous NaHCO3 (5 mL), extracted with DCM (2 x 10 mL) and the
combined organic layer was dried over Na2SO4. Solvent was evaporated under reduced pressure and the
crude product was purified by column chromatography using hexane/ethyl acetate as eluent.
7: 67 mg, 25% yield; light blue solid; Rf = 0.22 in 90:10 hexane/ethyl acetate; Mp: 172-174 ºC; IR
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(KBr): 2926, 2853, 1592, 1491, 1384, 1344, 1224, 806, 1147, 747, 716 cm–1; H NMR (400 MHz,
CDCl3, 24 °C): δ 7.94-7.87 (m, 2H), 7.69-7.61 (m, 4H), 7.57-7.49 (m, 3H), 7.32-7.25 (m, 1H), 7.17 (dd,
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1H, J = 8.8, 2.2 Hz), 7.13-7.05 (m, 2H), 6.81 (s, 1H), 4.06 (s, 3H), 4.04 (s, 3H), 3.85 (s, 3H); C{1H}
NMR (100 MHz, CDCl3, 24 °C): δ 153.6, 139.6, 137.6, 132.8, 131.2, 131.1, 129.8, 128.3 (q, J = 288.0
Hz), 128.0, 127.5, 127.3, 127.0, 122.7 (q, J = 3.3 Hz), 121.6, 119.3, 113.8, 113.3, 112.0, 109.9, 109.3,
104.1 (q, J = 3.3 Hz), 55.7 (q, J = 26.6 Hz), 55.6, 33.1, 32.8; 19F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ
–62.73 (s, 3F, CF3); HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for C27H23ON2F3Na: 471.1660; found:
471.1642.
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8: 72 mg, 26% yield; yellow solid; Rf = 0.26 in 85:15 hexane/ethyl acetate; Mp: 218-220 ºC; IR (KBr):
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2925, 2853, 1592, 1329, 1384, 1161, 1068, 740, 716 cm–1; H NMR (400 MHz, CDCl3, 24 °C): δ 8.05
(dd, 1H, J = 9.0, 2.0 Hz), 8.01 (s, 1H), 7.50 (d, 2H, J = 7.0 Hz), 7.36-7.28 (m, 5H), 7.18 (t, 1H, J = 7.3
Hz), 7.08 (d, 1H, J = 8.1 Hz), 7.01 (s, 1H), 6.91 (t, 1H, J = 7.3 Hz), 6.74 (s, 1H), 3.79 (s, 3H), 3.75 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3, 24 °C): δ 141.7, 140.2, 138.8, 137.6, 133.8, 130.8, 129.4, 128.3,
128.1, 128.0 (q, J = 287.0 Hz), 126.7, 126.2, 122.1 (q, J = 3.0 Hz), 121.9, 119.6, (q, J = 3.0 Hz), 119.5,
117.4, 116.8, 113.1, 109.6, 109.4, 55.7 (q, J = 26.8 Hz), 33.5, 33.0; 19F NMR (470 MHz, CDCl3/C6F6, 24
°C): δ –62.98 (s, 3F, CF3); HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for C26H20O2N3F3Na: 486.1405;
found: 486.1383.
General procedure for the synthesis of triaryltrifluoromethylmethane 10: Weinreb amide 4a (50
mg, 0.30 mmol) and CsF (45.60 mg, 0.30 mmol) were taken in an oven dried 5 mL reaction tube, fitted
with septum. Next, 2 mL dry THF (Solvent 1) was added under argon atmosphere and reaction mixture
was cooled to 0 °C, at the same temperature CF3TMS (85 mg, 0.60 mmol) was added. The reaction
mixture was allowed to stir at room temperature for 3-4 hour. THF was evaporated under reduced
pressure and 2 mL dry DCM (Solvent 2) was added, again reaction mixture was cooled to –78 °C.
Triflic anhydride (Tf2O, 94.38 mg, 0.33 mmol) was added at –78 °C, stirred for 20 min and then the
reaction mixture was allowed to warm upto 0 °C. Next, phenols 9 (2.40 mmol) were added at 0 °C and
reaction mixture allowed to stirred at room temperature for 5-6 hour. After completion of reaction, the
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reaction mixture was quenched with saturated aqueous NaHCO3 (5 mL), extracted with EtOAc (2 x 10
mL) and the combined organic layer was dried over Na2SO4. Solvent was evaporated under reduced
pressure and the crude product was purified by column chromatography using hexane/ethyl acetate as
eluent.
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10a:18 75 mg, 72% yield; light yellow solid; Rf = 0.30 in 70:30 hexane/ethyl acetate; Mp: 224-226 ºC;
IR (KBr): 3474, 2958, 2930 2809, 1510, 1444, 1244, 828 cm–1; 1H NMR (500 MHz, DMSO-d6, 24 °C):
δ 9.60 (brs, 2H), 7.39-7.30 (m, 3H), 7.05 (d, 2H, J = 7.1 Hz), 6.82 (d, 4H, J = 8.7 Hz), 6.74 (d, 4H, J =
8.8 Hz); 13C{1H} NMR (125 MHz, DMSO-d6, 24 °C): δ 156.7, 140.4, 130.5, 129.9, 129.2, 128.4 (q, J =
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284.4 Hz), 128.1, 127.6, 114.9, 63.2 (q, J = 22.9 Hz); F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –
58.17 (s, 3F, CF3); HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for C20H15O2F3Na: 367.0922; found:
367.0957.
10b: 96 mg, 86% yield; light yellow solid; Rf = 0.40 in 70:30 hexane/ethyl acetate; Mp: 169-171 ºC; IR
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(KBr): 3466, 2927, 2857, 1506, 1228, 1139, 819, 624 cm–1; H NMR (400 MHz, DMSO-d6, 24 °C): δ
9.52 (brs, 2H), 7.39-7.29 (m, 3H), 7.04 (d, 2H, J = 7.4 Hz), 6.78-6.70 (m, 4H), 6.64-6.55 (m, 2H), 2.03
(s, 6H); 13C{1H} NMR (100 MHz, DMSO-d6, 24 °C): δ 154.8, 140.5, 131.4, 129.9, 129.3, 128.2 (q, J =
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286.6 Hz), 128.1, 128.0, 127.5, 123.3, 114.0, 63.3 (q, J = 23.1 Hz), 16.4; F NMR (470 MHz,
CDCl3/C6F6, 24 °C): δ –57.82 (s, 3F, CF3); HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C22H20O2F3:
373.1415; found: 373.1410.
10c: 63 mg, 42% yield; white solid; Rf = 0.28 in 70:30 hexane/ethyl acetate; Mp: 72-74 ºC; IR (KBr):
3474, 3233, 2926, 1494, 1437, 1232, 1142, 706, 621 cm–1; 1H NMR (400 MHz, CDCl3, 24 °C): δ 7.48-
7.43 (m, 4H), 7.42-7.36 (m, 6H), 7.34-7.30 (m, 3H), 7.28-7.22 (m, 2H), 7.17-7.12 (m, 2H), 7.02 (dd,
2H, J = 8.6, 2.2 Hz), 6.92 (d, 2H, J = 8.7 Hz), 5.37 (brs, 2H); 13C{1H} NMR (100 MHz CDCl3, 24 °C):
δ 151.9, 140.5, 136.9, 132.7, 131.9, 130.9, 129.9, 129.4, 129.1, 128.3, 128.2 (q, J = 286.3 Hz), 128.1,
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127.8, 127.6, 115.5, 64.2 (q, J = 23.9 Hz); F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –58.73 (s, 3F,
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CF3); HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for C32H23O2F3Na: 519.1548; found: 519.1526.
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10d:19 92 mg, 81% yield; brown solid; Rf = 0.14 in 60:40 hexane/ethyl acetate; Mp: 116-118 ºC; IR
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(KBr): 3416, 2929, 2858, 1527, 1418, 1262, 1139, 812, 620 cm–1; H NMR (400 MHz, DMSO-d6, 24
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°C): δ 9.06 (brs, 2H), 9.01 (brs, 2H), 7.44-7.26 (m, 3H), 7.13-6.99 (m, 2H), 6.69 (d, 2H, J = 7.6 Hz),
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6.56-6.46 (m, 2H), 6.25 (d, 2H, J = 6.7 Hz); C{1H} NMR (100 MHz, DMSO-d6, 24 °C): δ 144.7,
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144.6, 140.6, 130.6, 129.3, 128.2 (q, J = 285.9 Hz), 128.0, 127.5, 120.6, 117.2, 114.9, 63.4 (q, J = 23.0
Hz); 19F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –57.77 (s, 3F, CF3); HRMS (ESI-TOF) m/z: [M + Na]+
calcd. for C20H15O4F3Na: 399.0820; found: 399.0859.
10e: 81 mg, 66% yield; colourless liquid; Rf = 0.75 in 90:10 hexane/ethyl acetate; IR (neat): 3435, 2946,
2857, 1521, 1230, 1143, 812, 752 cm–1; 1H NMR (400 MHz, CDCl3, 24 °C): δ 7.41 (d, 2H, J = 7.8 Hz),
7.37-7.27 (m, 3H), 6.77 (d, 2H, J = 8.8 Hz), 6.71 (d, 2H, J = 2.6 Hz), 6.56 (dd, 2H, J = 8.8, 2.6 Hz),
3.82 (s, 6H); C{1H} NMR (100 MHz, CDCl3, 24 °C): δ 160.6, 152.5, 142.1, 132.5, 129.7, 128.2,
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127.2, 126.5 (q, J = 284.2 Hz), 113.2, 110.4, 100.7, 55.5, 53.1 (q, J = 26.4 Hz); F NMR (470 MHz,
CDCl3/C6F6, 24 °C): δ –76.93 (s, 3F, CF3); HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C22H20O4F3:
405.1308; found: 405.1325.
10f: 93 mg, 61% yield; white solid; Rf = 0.71 in 95:5 hexane/ethyl acetate; Mp: 202-204 ºC; IR (KBr):
3414, 2926, 2867, 1472, 1237, 1159, 933, 626 cm–1; 1H NMR (400 MHz, CDCl3, 24 °C): δ 7.38 (d, 2H,
J = 1.9 Hz), 7.36-7.33 (m, 5H), 7.13 (dd, 2H, J = 8.4, 1.9 Hz), 6.73 (d, 2H, J = 8.4 Hz); 13C{1H} NMR
(100 MHz, CDCl3, 24 °C): δ 151.6, 140.8, 133.1, 129.7, 128.6, 127.8, 126.9, 125.8 (q, J = 285.0 Hz),
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123.3, 119.9, 119.7, 53.6 (q, J = 25.6 Hz); F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –69.67 (s, 3F,
CF3); HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for C20H13O2Br2F3Na: 522.9132; found: 522.9130.
General procedure for the synthesis of trifluoromethylated analogue of hypolipidemic and
antiobesity agents 12: Compound 11 was synthesized employing general experimental procedure in
67% yield as white solid. On the other hand, compound B was synthesized from lactone in two steps,
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first ring opening followed by tosylation of hydroxy group with tosyl chloride in presence of DMAP
and Et3N in DCM. Compound 11 (1 equiv), compound B (1.1 equiv) and K2CO3 (2 equiv) were
dissolved in Dry CH3CN and refluxed for 6 h. After 6 h, reaction mixture was cooled to room
temperature and solvent was evaporated under reduce pressure. Next, the reaction mixture was
dissolved in ethyl acetate and washed twice with water. The organic layer was separated, dried over
Na2SO4 and concentrated under vacuum. The crude product was purified by column chromatography to
yield the desired final product 12.
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11: 105 mg, 67% yield; white solid; Rf = 0.31 in 80:20 hexane/ethyl acetate; Mp: 210-212 ºC; IR (KBr):
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3477, 2814, 2725, 1352, 1168, 821, 740 cm–1; H NMR (400 MHz, CDCl3, 24 °C): δ 7.40 (d, 2H, J =
8.5 Hz), 7.31 (d, 2H, J = 8.5 Hz), 7.22-7.15 (m, 4H), 6.93 (t, 2H, J = 7.9 Hz), 6.25 (m, 2H), 6.76 (d, 2H,
J = 8.7 Hz), 4.98 (brs, 1H), 3.71 (s, 6H); C{1H} NMR (125 MHz, CDCl3, 24 °C): δ 154.8, 137.5,
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132.0, 131.1, 130.9, 128.3 (q, J = 286.0 Hz), 126.9, 122.6 (q, J = 3.0 Hz), 121.5, 119.3, 114.8, 114.1,
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109.3, 55.3 (q, J = 26.9 Hz), 32.9; F NMR (470 MHz, CDCl3/C6F6, 24 °C): δ –63.04 (s, 3F, CF3);
HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for C26H21ON2F3Na: 457.1498; found: 457.1505.
12: 57 mg, 90% yield as white solid; Rf = 0.48 in 85:15 hexane/ethyl acetate; Mp: 170-172 ºC; IR
(KBr): 2812, 2725, 1734, 1597, 1351, 826, 749 cm–1; 1H NMR (400 MHz, CDCl3, 24 °C): δ 7.44 (d, 2H,
J = 8.7 Hz), 7.30 (d, 2H, J = 8.7 Hz), 7.22-7.15 (m, 4H), 6.95-6.90 (m, 2H), 6.79 (dd, 2H, J = 6.9, 2.2
Hz), 6.75 (s, 2H), 4.15 (q, 2H, J = 7.6 Hz), 4.00 (t, 2H, J = 6.1 Hz), 3.71 (s, 6H), 2.25 (t, 2H, J = 7.2
Hz), 2.11 (qt, 2H, J = 6.3 Hz), 1.26 (t, 3H, J = 7.2 Hz); C{1H} NMR (125 MHz, CDCl3, 24 °C): δ
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173.3, 158.0, 137.5, 131.8, 130.9, 130.0, 128.3 (q, J = 286.9 Hz), 126.9, 122.6 (q, J = 2.5 Hz), 121.5,
119.3, 114.2, 113.7, 109.2, 66.7, 60.5, 55.3 (q, J = 26.8 Hz), 32.9, 30.9, 24.8, 14.3; 19F NMR (470 MHz,
CDCl3/C6F6, 24 °C): δ –62.99 (s, 3F, CF3); HRMS (ESI-TOF) m/z: [M + Na]+ calcd. for
C32H31O3N2F3Na: 571.2179; found: 571.2170.
Acknowledgements: We thank Council of Scientific & Industrial Research (CSIR) (Project No.
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02(0092)/12/EMR-II) for financial support. VKP thanks CSIR for a fellowship. We thank Mr.
Ramkumar for single-crystal analysis support.
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Supporting information: Supporting information containing H and C NMR spectra of all the new
compounds and crystallographic data of compound 6aj is provided. “This material is available free of
charge via the Internet at http://pubs.acs.org.”
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(14) Liu, X.-R.; Zhou, Y.-L. Acta Crystallogr., Sect. E 2014, 70, o1156.
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(15) CCDC 1508846 contains the supplementary crystallographic data for the compound 6aj.
The data can be obtained free of charge from The Cambridge Crystallographic Data
Centre via http://www.ccdc.cam.ac.uk/data_request/cif.
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