Palladium(II)-Catalyzed Sequential Aminopalladation and Oxidative Coupling with Acetylenes/Enones: Synthesis of Newly Substituted Quinolines from 2-Aminophenyl Propargyl Alcohols

Article abstract of DOI:10.1002/adsc.201500805

Palladium catalyzed conversion of 1-(2-aminophenyl)-propargyl alcohols to 3-alkynyl quinolines is realized via a cascade that involves aminopalladation, oxidative coupling with alkynes and dehydration. The method is shown to have a broad substrate scope w

Full text of DOI:10.1002/adsc.201500805

FULL PAPERS
DOI: 10.1002/adsc.201500805
Palladium(II)-Catalyzed Sequential Aminopalladation and Oxida-
tive Coupling with Acetylenes/Enones: Synthesis of Newly Substi-
tuted Quinolines from 2-Aminophenyl Propargyl Alcohols
Nuligonda Thirupathi,+a Surendra Puri,+a Thota Jagadeshwar Reddy,b
Balasubramanian Sridhar,c and Maddi Sridhar Reddya,d,*
a
Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India
E-mail: msreddy@cdri.res.in
SAIF-Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India
Dr. B. Sridhar, X-Ray Crystallography Division, CSIR-IICT, Tarnaka, Hyderabad, 500007, India
Academy of Scientific and Innovative Research, New Delhi 110001, India
b
c
d
+
Contributed equally.
Received: August 29, 2015; Revised: November 10, 2015; Published online: December 22, 2015
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201500805.
Abstract: Palladium catalyzed conversion of 1-(2- well as alkynes. Vinyl ketones as coupling partners in
aminophenyl)-propargyl alcohols to 3-alkynyl quino- the same reaction afforded 3-alkenyl quinolines with
lines is realized via a cascade that involves aminopal- equal ease.
ladation, oxidative coupling with alkynes and dehy-
dration. The method is shown to have a broad sub- Keywords: aminopalladation; cascade reaction; oxi-
strate scope with respect to propargyl alcohols as dative coupling; propargyl alcohol; quinoline
Introduction
try is restricted to 5-membered heterocycles[1–6] while
the pathway to 6-membered counterparts is yet to be
Intramolecular amino/oxy palladation of alkyne is developed.
a remarkable strategy for the synthesis of poly-func-
On the other hand, the wealth of quinolines and
tionalized heterocycles because this approach pro- their derivatives in nature, and their interesting phar-
vides in tandem an avenue for further structural elab- macological, biological activities[7] has provided
À
orations via an in situ coupling on the incipient C Pd a huge driving force for chemists to develop efficient
bond. Apart from step-economy, this mainly avoids methods for their synthesis. Consequently, an ample
the atom wastage that in general occurs in the step- amount of research has been dedicated to the synthe-
wise preformation and prefunctionalization of the re- sis of quinolines for more than a century.[8–9] Among
spective heterocycles. Although very attractive, this them, the strategies using alkyne precursors showed
strategy is still underutilized, because it needs a care- considerable impact in this field recently.[9] For in-
ful development of the reaction conditions as these stance, Gabriele et al. reported an efficient method
two steps (amino/oxy palladation and coupling) inde- for the synthesis of 2,4-disubstituted quinolines from
pendently have different requirements and combining 1-(2-aminophenyl) propargyl alcohols through
them as such is not possible in most cases. Surmount- a copper or palladium catalyzed 6-endo-dig heterocy-
ing these issues some groups developed a few elegant clization.[9k] Subsequently, an elegant capture of the
À
approaches using this tandem strategy for the synthe- C Pd bond in the above pathway by CO/MeOH led
sis of some highly functionalized heterocycles.[1–6]
A
to the synthesis of quinoline 3-carboxylic esters via
few couplings like arylation/allylation,[1] Heck cou-
a tandem aminopalladation/carbonylation sequen-
pling[2] and carboxymethylation[3] are well studied for ce.[3e] In this context, we also earlier reported the syn-
this tandem approach whereas their congeners like thesis of variety of highly substituted quinoline scaf-
Suzuki-,[4] Sonogashira-,[5] Stille-coupling, for example, folds via such electrophilic cyclizations.[9n–p] In contin-
still lacks the attention. Further, most of this chemis- uation, we herein report the synthesis of 3-alkynyl/al-
Adv. Synth. Catal. 2016, 358, 303 – 313
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
303

FULL PAPERS
Nuligonda Thirupathi et al.
non alkynylated quinoline and (2) the competitive
formation of dimer of 3a (Glaser coupling). In the ab-
sence of AcOH, which we thought responsible for
non-alkynylated product, yield was (as expected) im-
proved to 48% (entry 2). Use of base, with or without
AcOH, was found to be detrimental to the reaction
(entries 3–5). The absence of TBAI led to slight re-
duction of the yield (25%, entry 6). Selection of sol-
vent was crucial for the reaction. Changing the sol-
vent from DMSO to others (entries 7–9) sharply re-
duced the yields. Other catalysts such as PdCl2 and
Pd(TFA)2 in the same conditions were found to be
less productive (entries 10–11). Use of other oxidants
such as Cu(OAc)2 or O2 (instead of air) brought little
change in the result (entries 12–13). Pleasingly, using
anhydrous DMSO as a solvent and oxygen balloon in-
Scheme 1. Tandem aminopalladation and alkyne/alkene cou-
pling.
kenyl-2,4-disubstituted quinoline derivatives via stead of open air cleanly furnished the product in
tandem aminopalladation and oxidative coupling 65% (entries 14). Very surprisingly, under nitrogen at-
showing a rare instance of DMSO acting as oxidant mosphere, that is, in the absence of oxygen, the reac-
for regeneration of PdII from Pd(0) (Scheme 1B).
tion was more cleaner and the yield was increased to
73% (entries 15). The surprise was due to the non-re-
quirement of any oxidant (here oxygen) which is nec-
essary for the regeneration of the PdII from Pd(0) to
continue the catalytic cycle (as shown in Scheme 2).
Results and Discussion
At the outset, we aimed at the conversion of 2a to A parallel observation of the release of dimethyl sul-
4aa by using the conditions (Table 1, entry 1) devel- phide (by the characteristic disagreeable odor from
oped by Zhu et al. (Scheme 1A)[5a] for the synthesis the reaction mixture) in the reaction suggested that
of 3-alkynyl indoles from N,N-dimethyl-2-alkynyl ani- the DMSO was acting as the oxidant.[10] It may be at-
lines. Pleasingly, the expected product 4aa was isolat- tributed to the low oxidation potential of Pd(0). How-
ed, but in 30% yield, through a desired cascade of re- ever, when we used diphenylsulphoxide (DPSO) in-
actions (entry 1). Inspired by this initial result, some stead of DMSO as solvent/reagent with an intention
reaction parameters such as catalyst, solvent and addi- of isolating the reduced product DPSO, surprisingly
tive effects were investigated to improve the yield. A no reaction was observed. We reasoned that the re-
close observation revealed that the reasons for low quirement of higher temperature (more than 758C) to
yield in the initial attempt were (1) the formation of melt the solvent (MP of DPSO is 708C) disqualified
the reaction. Also, oxidizing property of DPSO must
be relatively less due to conjugation and hence did
not assist the regeneration of PdII. Attempts to identi-
fy any possible intermediate by mass spectroscopy re-
vealed only a peak corresponding to diaminopalladi-
um (C12H22ON-Pd-NOH22C12 +H+ =595)
Table 1. Optimization studies
With the optimized conditions in hand, the scope
and generality of the tandem reaction was studied.
[a]
Reaction conditions: 3a (2.0 mmol), 2a (1.0 mmol), addi-
tive (1.0 mmol), PdII (0.05 mmol), solvent (0.3m), 608C
for 12 h.
Isolated overall yields.
[b]
Scheme 2. Proposed catalytic cycle.
304
asc.wiley-vch.de
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2016, 358, 303 – 313

FULL PAPERS
Pd(II)-Catalyzed Sequential Aminopalladation and Oxidative Coupling
Table 2. Product scope with respect to 3.[a]
Table 3. Product scope with respect to 2.[a]
[a]
Reaction conditions: 2b–p (1.0 mmol), 3a (2.0 mmol),
TBAI (1.0 mmol), Pd(OAc)2 (0.05 mmol), DMSO (0.3m),
N2 atm, 608C.
cellent irrespective of the substitution (bromo, chloro,
fluoro, methyl, phenyl and tert-butyl) on C2-aryl or
the quinoline core. Note that the halogen groups sur-
vived the equally possible Sonogashira coupling.
Next, C2-alkyl/cyclopropyl substituted adducts were
obtained with equal ease in the established pathway.
[a]
Reaction conditions: terminal alkyne (2.0 mmol),
(1.0 mmol), TBAI (1.0 mmol), Pd(OAc)2 (0.05 mmol),
DMSO (0.3m), N2 atm, 608C.
3
First, a variety of alkynes (3a–p) were tested with Unfortunately, 4-aryl substituted adducts were not
amino propargyl alcohol 2a. As is evident from possible in this way. Then the substrates derived from
Table 2, the method is applicable over a wide range of 2-amino benzaldehydes (2n–p) were transformed into
alkynes. Various acyclic and cyclic aliphatic alkynes the corresponding 4-unsubstituted quinoline adducts
(3b–f) could be installed at C-3 of quinolines very (4na–pa), but in relatively lesser yields (60-68%).
cleanly (75-85%). Enyne 3g also reacted with equal
Encouraged by these results, we next turned our at-
ease to produce 4ag in 78% yield. Then, we chose tention toward the tandem amino palladation/oxida-
various commercially available aryl acetylenes to tive alkenylation reaction (Heck type coupling). Thus
screen through the reaction. Thus, fluorophenyl acety- we have treated the basic substrate 2 with ethyl vinyl
lenes (3h–j) delivered the corresponding products ketone under optimal conditions (Table 4). To our de-
(4ah–aj) in excellent yields while electron rich and light desired product 5a was isolated in 62% yield.
electron poor substrates (3k–m) showed slightly less Yield was improved to 72% by replacing TBAI with
productivity (4ak–am in 55-68% yields). Heteroaryl LiCl. Then different 2-aminophenyl propargylic alco-
alkyne 3n and protected propargyl alcohol 3o also hols were treated in this way to probe the substrate
smoothly reacted under the standard conditions to scope. Thus 2-alkyl adducts (5a–b) were obtained in
produce 4an and 4ao respectively in 66-72% yields. 70–72% yields whereas bromo substitution (5c) led
Notably, the trimethylsilylacetylene afforded 3-alky- to the decrease of yield to 55%. Similarly, 2-aryl ad-
nylated quinoline 4ap without any hassle, which could ducts (5d–h) with varied substitution (Br, Cl, OMe
be easily converted into a free acetylene product or and Ph) were obtained but again in slightly reduced
used as a precursor for further functionalization.
Next, we turned to investigate the scope of the re-
yields (52–62%).
Setting a limitation for this tandem approach, the
other Heck coupling partners like styrene and methyl
action with respect to propargylic alcohols
2
(Table 3). Thus a variety of 2-amino substrates with acrylate did not participate in the reaction and only
broad substitution patterns (2b–p) were treated with the uncoupled quinoline products were obtained. A
phenyl acetylene under optimal conditions. Initially, structure from each category of compounds (4ea and
substrates derived from acetophenone and aromatic 5d) was unambiguously confirmed by X-ray crystal-
alkynes (2b–h) were treated with phenyl acetylene. lography (Figure 1).[11]
Thus various 2-aryl-3- alkynyl derivatives were ob-
Next, we became interested in studying the elec-
tained in 60-72% yields. The yields were good to ex- tronic and steric influences on alkyne group in the
Adv. Synth. Catal. 2016, 358, 303 – 313
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
305

FULL PAPERS
Nuligonda Thirupathi et al.
Table 4. Synthesis of 3-Alkenyl Quinolines 5 from 2.[a]
moved to ortho mono substituted 4na for the same
kind of hydration and oxidation reactions. Thus, 4na
when treated with IPrAuCl in presence of AgSbF6
[12c]
furnished the regioseletive hydrated product 9 in
55% yield.
This selectivity must be due to the steric factors.
The other hydrating reagents like HgII salts, AuCl3,
AuCl or In(OTf)3 again failed. Dioxygenation using
PdI2 in DMSO[12] in this case worked well to afford 10
in 62% yield. We next attempted the reduction of
alkyne group. With 4aa, both Pd/C and Pd-BaSO4
stopped the reaction at olefin stage where as in case
of 4na use of either of the reagents led to the com-
plete reduction to alkyl group. The reasons for these
unusual reaction sequences might be steric factors in
earlier case and polarization of the triple bond in
latter case.
[a]
Reaction conditions: Ethyl vinyl ketone (2.0 mmol), 2
(1.0 mmol), LiCl (1.0 mmol) Pd(OAc)2 (0.05 mmol),
DMSO (0.3m), N2 atm, 708C
Conclusions
In summary, we have demonstrated a novel and effi-
cient synthesis of poly functionalized quinolines from
linear and readily accessible substrates, 1-(2-amino-
phenyl)-propargyl alcohols, via a tandem aminopalla-
dation/oxidative coupling with both alkynes and
enones. This method further features atom economy,
mild reaction conditions and broad functional group
tolerance.
Figure 1. X-ray Crystal Structures of 4ea and 5d.
Experimental Section
newly synthesized 3-alkynyl quinolines 4 during deri-
vatization through oxidative and reductive pathways General Information:
(Scheme 3). We first chose 4aa with ortho-disubstitu-
All reagents and solvents were purchased from commercial
tion for the hydration. The substrate was found to be
very adamant with all sorts of hydration processes
available in the literature.[12] Also, dioxygenation to
produce 7 was also met with total failure.[13] This must
be due to steric crowding around alkyne. We next
sources and used without purification. NMR spectra were
1
recorded with a 400 or 500 MHz spectrometer for H NMR,
50, 100 or 125 MHz for 13C NMR spectroscopy. Chemical
shifts are reported relative to the residual signals of tetrame-
thylsilane in CDCl3 or deuterated solvent CDCl3/
[D6]DMSO for 1H and 13C NMR spectroscopy. Multiplicities
are reported as follows: singlet (s), doublet (d), doublet of
doublets (dd), doublet of triplets (dt), triplet (t), quartet (q),
multiplet (m). HRMS were recorded by using QTof mass
spectrometer. Column chromatography was performed with
silica gel (100–200 mesh) as the stationary phase. All reac-
tions were monitored by using TLC. The purity and charac-
terization of compounds were further established by using
HRMS.
General procedure A for the Synthesis 4aa–4ap and
4ba–4pa from 2a–p, taking synthesis of 4aa as an
example :
1-(2-Aminoaryl)-2-yn-1-ols (2a–p) were synthesized by
using literature precedents[9k] and were used as such for next
step without purification. To a stirred solution of 2a
(245 mg, 1 mmol, 1 equiv) in 3 mL of anhydrous DMSO
Scheme 3. Derivatization of 4.
306
asc.wiley-vch.de
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2016, 358, 303 – 313

FULL PAPERS
Pd(II)-Catalyzed Sequential Aminopalladation and Oxidative Coupling
under N2 atm was added Pd(OAc)2 (11.2 mg, 0.05 mmol,
0.05 equiv), TBAI (369 mg, 1 mmol, 1 equiv), phenyl acety-
lene (3a, 204 mg, 2 mmol, 2 equiv) at room temperature.
The reaction mixture was stirred at 608C until the starting
material had been fully consumed (12 h to 24 h). The reac-
tion mixture was diluted with water (20 mL) and extracted
with EtOAc (3”15 mL). The combined organic layers were
washed with brine (15 mL) and dried over Na2SO4. After re-
moval of the solvent under reduced pressure the crude ma-
terial was purified on silica using 2% EtOAc/hexanes to get
4aa (244 mg, 73% two step overall yield) as a brown oil.
2-Ethyl-4-methyl-3-(phenylethynylquinoline (4aa): 4aa
(0.238 g) was obtained from 2a (0.245 g, 1 mmol) following
general procedure A. Two steps overall yield 73%; brown
oil; Rf =0.55 (SiO2, 10% EtOAc/hexanes); 1H NMR
(400 MHz, CDCl3) d 8.07–7.93 (m, 2H), 7.71–7.63 (m, 1H),
7.62–7.56 (m, 2H), 7.54–7.47 (m, 1H), 7.45–7.30 (m, 3H),
3.22 (t, J=8.1 Hz, 2H), 2.90 (s, 3H), 1.96–1.83 (m, 2H),
1.56–1.43 (m, 2H), 1.42–1.28 (m, 4H), 0.87 (t, J=7.0 Hz,
3H); 13C NMR (100 MHz, CDCl3) d 163.2, 146.7, 146.1,
131.5, 129.6, 129.5, 128.7, 128.6, 126.1, 124.0, 123.4, 116.9,
98.7, 86.3, 38.7, 31.9, 29.7, 29.4, 22.7, 16.9, 14.2; IR (neat) n
3398, 2400, 1636, 1384, 1068, 929, 669 cmÀ1; HRMS (ESI-
TOF) calcd for C24H26N [M + H]+ 328.2065, found 328.2057.
(ESI-TOF) calcd for C21H26N [M + H]+ 292.2065, found
292.2062.
3-(Cyclohexylethynyl)-2-ethyl-4-methylquinoline
(4ae):
4ae (0.283 g) was obtained from 2a (0.245 g, 1 mmol) fol-
lowing general procedure A. Two steps overall yield 85%;
light yellow oil; Rf =0.65 (SiO2, 10% EtOAc/hexanes);
1H NMR (400 MHz, CDCl3) d 7.96 (dd, J=25.3, 8.4 Hz,
2H), 7.64–7.60 (m, 1H), 7.49–7.45 (m, 1H), 3.12 (t, J=
7.9 Hz, 2H), 2.79 (s, 3H), 1.95–1.92 (m, 2H), 1.88–1.28 (m,
17H), 0.89 (t, J=7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 163.5, 146.1, 145.8, 129.4, 129.1, 126.1, 125.8, 123.9, 117.6,
104.1, 38.7, 32.8, 31.9, 30.2, 29.7, 29.4, 26.1, 24.9, 22.7, 16.7,
14.2; IR (neat) n 3847, 3643, 3392, 3019, 1384, 1046,
669 cmÀ1; HRMS (ESI-TOF) calcd for C24H32N [M + H]+
334.2535, found 334.2530.
3-(Cyclopentylethynyl)-2-ethyl-4-methylquinoline (4af):
4af (0.264 g) was obtained from 2a (0.245 g, 1 mmol) follow-
ing general procedure A. Two steps overall yield 83%; light
yellow gum; Rf =0.60 (SiO2, 10% EtOAc/hexanes);
1H NMR (400 MHz, CDCl3) d 7.95 (dd, J=25.6, 8.6 Hz,
2H), 7.62 (t, J=7.8 Hz, 1H), 7.47 (t, J=7.8 Hz, 1H), 3.11 (t,
J=8.0 Hz, 2H), 3.05–2.92 (m, 1H), 2.78 (s, 3H), 2.06–1.95
(m, 2H), 1.95–1.57 (m, 6H), 1.56–1.26 (m, 8H), 0.89 (t, J=
6.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 163.5, 146.0,
145.8, 129.4, 129.1, 126.1, 125.8, 123.9, 117.7, 104.4, 76.8,
38.7, 34.1, 31.9, 31.3, 29.7, 29.4, 25.2, 22.7, 16.7, 14.2; IR
(neat) n 3388, 3019, 1400, 1122, 669 cmÀ1; HRMS (ESI-
TOF) calcd for C23H30N [M + H]+ 320.2378, found 320.2379.
3-(Cyclohexenylethynyl)-2-ethyl-4-methylquinoline (4ag):
4ag (0.257 g) was obtained from 2a (0.245 g, 1 mmol) fol-
lowing general procedure A. Two steps overall yield 78%;
light yellow oil; Rf =0.60 (SiO2, 10% EtOAc/hexanes);
1H NMR (400 MHz, CDCl3) d 7.96 (dd, J=24.8, 7.9 Hz,
2H), 7.73–7.56 (m, 1H), 7.55–7.38 (m, 1H), 6.28 (s, 1H),
3.13 (t, J=7.2 Hz, 2H), 2.80 (s, 3H), 2.45–2.08 (m, 4H),
1.96–1.58 (m, 6H), 1.57–1.13 (m, 6H), 1.00–0.68 (m, 3H);
13C NMR (100 MHz, CDCl3) d 163.2, 146.0, 145.9, 135.5,
129.4, 129.3, 126.1, 125.9, 123.9, 121.0, 117.3, 100.7, 83.7,
38.7, 31.9, 29.7, 29.4, 29.3, 25.9, 22.7, 22.4, 21.6, 16.8, 14.2; IR
(neat) n 3399, 3019, 1733, 1384, 1046, 669 cmÀ1; HRMS
(ESI-TOF) calcd for C24H30N [M + H]+ 332.2378, found
332.2370.
3-Ethyl)-((3-fluorophenyl)ethynyl)-4-methylquinoline
(4ah): 4ah (0.265 g) was obtained from 2a (0.245 g, 1 mmol)
following general procedure A. Two steps overall yield
77%; yellow gum; Rf =0.50 (SiO2, 10% EtOAc/hexanes);
1H NMR (400 MHz, CDCl3) d 8.00 (dd, J=17.7, 8.3 Hz,
2H), 7.70–7.66 (m, 1H), 7.54–7.50 (m, 1H), 7.39–7.33 (m,
2H), 7.28–7.26 (m, 1H), 7.11–7.06 (m, 1H), 3.20 (t, J=
7.6 Hz, 2H), 2.89 (s, 3H), 1.93–1.85 (m, 2H), 1.53–1.46 (m,
2H), 1.40–1.27 (m, 4H), 0.87 (t, J=6.9 Hz, 3H); 13C NMR
(100 MHz, CDCl3) d 163.1, 162.7 (d, J=161 Hz), 146.6 (d,
J=79 Hz), 130.1 (d, J=8 Hz), 129.7 (d, J=21 Hz), 127.4,
127.3, 126.2, 125.9, 125.2, 125.1, 124.0, 118.2 (d, J=22 Hz),
116.4, 116.0 (d, J=22 Hz), 97.3, 87.3, 38.6, 31.9, 29.7, 29.4,
22.7, 16.9, 14.2; IR (neat) n 3843, 3019, 2929, 1607, 1384,
1070, 669 cmÀ1; HRMS (ESI-TOF) calcd for C24H25FN [M +
H]+ 346.1971, found 346.1963.
3-(But-1-ynyl)-2-ethyl-4-methylquinoline
(4ab):
4ab
(0.281 g) was obtained from 2a (0.245 g, 1 mmol) following
general procedure A. Two steps overall yield 84%; brown
oil; Rf =0.60 (SiO2, 10% EtOAc/hexanes); 1H NMR
(400 MHz, CDCl3) d 8.00–7.91 (m, 2H), 7.64–7.60 (m, 1H),
7.50–7.46 (m, 1H), 3.11 (t, J=8.0 Hz, 2H), 2.79 (s, 3H), 2.55
(t, J=7.0 Hz, 2H), 1.85–1.78 (m, 2H), 1.72–1.65 (m, 2H),
1.56–1.28 (m, 12H), 0.93–0.86 (m, 3H); 13C NMR (100 MHz,
CDCl3) d 163.4, 129.2, 129.0, 126.0, 125.7, 123.7, 117.5, 100.0,
38.4, 31.7, 31.4, 29.6, 29.2, 28.8, 28.7, 22.6, 22.6, 19.8, 16.6,
14.1, 14.0; IR (neat) n 3745, 3019, 1730, 1384, 1068,
669 cmÀ1; HRMS (ESI-TOF) calcd for C24H34N [M + H]+
336.2691, found 336.2685.
3-(But-1-ynyl)-2-ethyl-4-methylquinoline
(4ac):
4ac
(0.219 g) was obtained from 2a (0.245 g, 1 mmol) following
general procedure A. Two steps overall yield 75%; light
1
yellow oil; Rf =0.60 (SiO2, 10% EtOAc/hexanes); H NMR
(400 MHz, CDCl3) d 7.96 (dd, J=24.8, 8.1 Hz, 2H), 7.62 (t,
J=7.1 Hz, 1H), 7.48 (t, J=7.1 Hz, 1H), 3.12 (t, J=7.9 Hz,
2H), 2.80 (s, 3H), 2.54 (t, J=6.9 Hz, 2H), 1.88–1.76 (m,
2H), 1.75–1.62 (m, 3H), 1.56–1.28 (m, 5H), 1.12 (t, J=
7.3 Hz, 3H), 0.89 (t, J=9.3 Hz, 3H); 13C NMR (100 MHz,
CDCl3) d 163.5, 146.2, 145.8, 129.4, 129.1, 126.1, 125.8, 123.9,
117.6, 99.9, 77.5, 38.6, 31.9, 29.7, 29.4, 22.7, 22.4, 21.9, 16.7,
14.2, 13.8; IR (neat) n 3746, 3399, 1733, 1384, 1068,
669 cmÀ1; HRMS (ESI-TOF) calcd for C21H28N [M + H]+
294.2222, found 294.2210.
3-(Cyclopropylethynyl)-2-ethyl-4-methylquinoline (4ad):
4ad (0.235 g) was obtained from 2a (0.245 g, 1 mmol) fol-
lowing general procedure A. Two steps overall yield 81%;
1
brown oil; Rf =0.60 (SiO2, 10% EtOAc/hexanes); H NMR
(400 MHz, CDCl3) d 7.99–7.90 (m, 2H), 7.63–7.59 (m, 1H),
7.51–7.42 (m, 1H), 3.08 (t, J=7.9 Hz, 2H), 2.77 (s, 3H),
1.86–1.71 (m, 2H), 1.63–1.55 (m, 1H), 1.51–1.39 (m, 2H),
1.39–1.27 (m, 4H), 0.99–0.81 (m, 8H); 13C NMR (100 MHz,
CDCl3) d 163.5, 146.2, 145.7, 129.4, 129.1, 126.1, 125.8, 123.8,
117.5, 103.2, 77.4, 38.6, 31.9, 29.7, 29.3, 22.7, 16.7, 14.2, 9.1,
0.7; IR (neat) n 3390, 2929, 1402, 1069, 669 cmÀ1; HRMS
3-((2,4-Difluorophenyl)ethynyl)-2-ethyl-4-methylquinoline
(4ai): 4ai (0.257 g) was obtained from 2a (0.245 g, 1 mmol)
following general procedure A. Two steps overall yield
71%; brown gum; Rf =0.45 (SiO2, 10% EtOAc/hexanes);
Adv. Synth. Catal. 2016, 358, 303 – 313
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
307

FULL PAPERS
Nuligonda Thirupathi et al.
1H NMR (400 MHz, CDCl3) d 8.02 (t, J=8.3 Hz, 1H), 7.98
(d, J=8.3 Hz, 1H), 7.73–7.63 (m, 1H), 7.59–7.44 (m, 2H),
6.98–6.87 (m, 2H), 3.21 (t, J=7.9 Hz, 2H), 2.90 (s, 3H),
1.96–1.80 (m, 2H), 1.54–1.43 (m, 2H), 1.43–1.27 (m, 4H),
0.87 (t, J=7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 163.1
(d, J=256 Hz), 163.0, 147.1, 146.3, 133.9 (dd, J=9, 2 Hz),
129.8, 129.6, 126.1, 125.9, 124.0, 116.4, 111.8 (dd, J=22,
3 Hz), 108.4 (dd, J=16, 4 Hz), 104.5 (t, J=25 Hz), 91.3,
90.9, 38.6, 31.9, 29.6, 29.5, 22.7, 16.8, 14.2; IR (neat) n 3381,
3021, 1619, 1381, 1246, 766 cmÀ1; HRMS (ESI-TOF) calcd
for C24H24F2N [M + H]+ 364.1877, found 364.1860.
2-Ethyl-3-((4-fluorophenyl)ethynyl)-4-methylquinoline
(4aj): 4aj (0.293 g) was obtained from 2a (0.245 g, 1 mmol)
following general procedure A. Two steps overall yield
85%; brown oil; Rf =0.50 (SiO2, 10% EtOAc/hexanes);
1H NMR (400 MHz, CDCl3) d 8.00 (dd, J=18.2, 8.3 Hz,
2H), 7.74–7.60 (m, 1H), 7.59–7.45 (m, 3H), 7.10 (t, J=
8.3 Hz, 2H), 3.20 (t, J=8.0 Hz, 2H), 2.89 (s, 3H), 1.96–1.79
(m, 2H), 1.55–1.43 (m, 2H), 1.40–1.28 (m, 4H), 0.86 (t, J=
6.9 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 163.1, 163.0 (d,
J=250 Hz), 146.4 (d, J=54 Hz), 133.3 (d, J=8 Hz), 129.7,
129.6, 126.1, 126.0, 124.0, 119.5, 116.7, 116.1, 115.9, 97.5,
86.1, 38.7, 31.9, 29.7, 29.4, 22.7, 16.9, 14.2; IR (neat) n 3397,
3019, 1629, 1508, 1123, 669 cmÀ1; HRMS (ESI-TOF) calcd
for C24H25FN [M + H]+ 346.1971, found 346.1973.
4-((2-Ethyl-4-methylquinolin-3-yl)ethynyl)benzaldehyde
(4ak): 4ak (0.241 g) was obtained from 2a (0.245 g, 1 mmol)
following general procedure A. Two steps overall yield
68%; light yellow gum; Rf =0.65 (SiO2, 10% EtOAc/hex-
anes); 1H NMR (400 MHz, CDCl3) d 10.05 (s, 1H), 8.10–
7.96 (m, 2H), 7.92 (d, J=7.9 Hz, 2H), 7.81–7.63 (m, 3H),
7.54 (t, J=7.3 Hz, 1H), 3.22 (t, J=8.1 Hz, 2H), 2.92 (s, 3H),
1.99–1.80 (m, 2H), 1.74–1.27 (m, 6H), 0.99–0.75 (m, 3H);
13C NMR (100 MHz, CDCl3) d 191.4, 163.1, 147.5, 146.5,
135.8, 132.0, 130.1, 129.8, 129.6, 129.6, 126.3, 125.9, 124.1,
116.2, 97.6, 90.5, 38.7, 31.9, 29.8, 29.5, 22.7, 17.0, 14.2; IR
(neat) n 3398, 3019, 1603, 1318, 1067, 668 cmÀ1; HRMS
(ESI-TOF) calcd for C25H26NO [M + H]+ 356.2014, found
356.2011.
3-((4-tert-Butylphenyl)ethynyl)-2-ethyl-4-methylquinoline
(4al): 4al (0.210 g) was obtained from 2a (0.245 g, 1 mmol)
following general procedure A. Two steps overall yield
55%; brown gum; Rf =0.60 (SiO2, 10% EtOAc/hexanes);
1H NMR (400 MHz, CDCl3) d 8.00 (dd, J=19.1, 8.2 Hz,
2H), 7.66 (t, J=7.5 Hz, 1H), 7.57–7.46 (m, 3H), 7.42 (d, J=
8.2 Hz, 2H), 3.22 (t, J=7.8 Hz, 2H), 2.89 (s, 3H), 1.97–1.80
(m, 2H), 1.56–1.44 (m, 2H), 1.44–1.28 (m, 13H), 0.87 (t, J=
6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 163.2, 152.1,
146.5, 146.1, 131.3, 129.5, 129.5, 126.1, 126.0, 125.6, 124.0,
120.4, 117.1, 98.9, 85.7, 38.7, 35.0, 31.9, 29.8, 29.7, 29.4, 22.7,
16.9, 14.2; IR (neat) n 3853, 3400, 3019, 2927, 1602, 1069,
669 cmÀ1; HRMS (ESI-TOF) calcd for C28H34N [M + H]+
384.2691, found 384.2673.
2H), 1.43–1.25 (m, 4H), 0.87 (t, J=6.8 Hz, 3H); 13C NMR
(100 MHz, CDCl3) d 163.2, 159.6, 146.8, 146.2, 129.7, 129.6,
129.5, 126.1, 124.4, 124.1, 124.0, 116.8, 116.5, 115.1, 98.6,
86.2, 55.4, 38.7, 31.9, 29.7, 29.4, 22.7, 16.9, 14.2; IR (neat) n
3399, 3019, 1603, 1215, 1047, 668 cmÀ1; HRMS (ESI-TOF)
calcd for C25H28NO [M + H]+ 358.2171, found 358.2169.
2-Ethyl-4-methyl-3-(pyridin-2-ylethynyl)quinoline (4an):
4an (0.236 g) was obtained from 2a (0.245 g, 1 mmol) fol-
lowing general procedure A. Two steps overall yield 72%;
brown gum; Rf =0.45 (SiO2, 10% EtOAc/hexanes);
1H NMR (400 MHz, CDCl3) d 8.68–8.67 (m, 1H), 8.04–7.98
(m, 2H), 7.75–7.66 (m, 2H), 7.58–7.50 (m, 2H), 7.30–7.27
(m, 1H), 3.24 (t, J=7.9 Hz, 2H), 2.94 (s, 3H), 1.94–1.86 (m,
2H), 1.56–1.42 (m, 2H), 1.42–1.27 (m, 4H), 0.85 (t, J=
7.9 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 163.3, 150.4,
148.1, 146.4, 143.6, 136.3, 130.0, 129.6, 127.3, 126.2, 125.9,
124.1, 123.1, 116.0, 97.7, 86.1, 38.5, 31.9, 29.6, 29.4, 22.7, 17.1,
14.2; IR (neat) n 3745, 3416, 3019, 1637, 1215, 669 cmÀ1
;
HRMS (ESI-TOF) calcd for C23H25N2 [M + H]+ 329.2018,
found 329.2017.
3-(3-(Benzyloxy)prop-1-ynyl)-2-ethyl-4-methylquinoline
(4ao): 4ao (0.244 g) was obtained from 2a (0.245 g, 1 mmol)
following general procedure A. Two steps overall yield
66%; light yellow gum; Rf =0.70 (SiO2, 10% EtOAc/hex-
anes); 1H NMR (400 MHz, CDCl3) d 8.06–7.90 (m, 2H),
7.71–7.62 (m, 1H), 7.56–7.47 (m, 1H), 7.45–7.28 (m, 5H),
4.74 (s, 2H), 4.55 (s, 2H), 3.15 (t, J=7.9 Hz, 2H), 2.84 (s,
3H), 1.92–1.76 (m, 2H), 1.52–1.39 (m, 2H), 1.39–1.27 (m,
4H), 0.87 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) d
163.2, 147.3, 146.2, 137.5, 129.7, 129.5, 128.6, 128.2, 128.1,
126.1, 125.9, 124.0, 116.3, 94.6, 83.3, 71.8, 58.1, 38.5, 31.9,
29.6, 29.4, 22.7, 16.9, 14.2; IR (neat) n 3398, 2926, 1384,
1069, 668 cmÀ1; HRMS (ESI-TOF) calcd for C26H30NO
[M + H]+ 372.2327, found 372.2324.
2-Ethyl-4-methyl-3-((trimethylsilyl)ethynyl)quinoline
(4ap): 4ap (0.206 g) was obtained from 2a (0.245 g, 1 mmol)
following general procedure A. Two steps overall yield
64%; brown gum; Rf =0.60 (SiO2, 10% EtOAc/hexanes);
1H NMR (400 MHz, CDCl3) d 8.00–7.93 (m, 2H), 7.67–7.63
(m, 1H), 7.52–7.47 (m, 1H), 3.13 (t, J=7.9 Hz, 2H), 2.82 (s,
3H), 1.86–1.78 (m, 2H), 1.48–1.25 (m, 6H), 0.89 (t, J=
7.6 Hz, 3H), 0.31 (s, 9H); 13C NMR (100 MHz, CDCl3) d
163.5, 147.4, 146.1, 129.7, 129.5, 126.0, 125.9, 124.0, 116.9,
104.4, 101.8, 38.7, 31.9, 29.7, 29.4, 22.7, 16.9, 14.2, 0.11; IR
(neat) n 3399, 2926, 1732, 1618, 1046, 669 cmÀ1; HRMS
(ESI-TOF) calcd for C21H30NSi [M + H]+ 324.2148, found
324.2148.
4-Methyl-2-phenyl-3-(phenylethynyl)quinoline:
(4ba):
4ba (0.197 g) was obtained from 2b (0.237 g, 1 mmol) fol-
lowing general procedure A. Two steps overall yield 62%;
1
brown oil; Rf =0.50 (SiO2, 30% EtOAc/hexanes); H NMR
(400 MHz, CDCl3) d 8.15 (d, J=8.3 Hz, 1H), 8.06 (d, J=
8.3 Hz, 1H), 8.02–7.93 (m, 2H), 7.22 (t, J=7.1 Hz, 1H), 7.59
(t, J=7.1 Hz, 1H), 7.56–7.44 (m, 3H), 7.42–7.27 (m, 5H),
3.00 (s, 3H); 13C NMR (100 MHz, CDCl3) d 159.8, 147.7,
146.4, 140.6, 131.3, 130.4, 129.9, 129.7, 128.8, 128.6, 128.5,
127.9, 126.9, 126.3, 124.1, 123.3, 116.2, 99.2, 87.4, 17.2; IR
(neat) n 3398, 2400, 1636, 1384, 1068, 929, 669 cmÀ1; HRMS
(ESI-TOF) calcd for C24H18N [M + H]+ 320.1439, found
320.1440.
2-Ethyl-3-((3-methoxyphenyl)ethynyl)-4-methylquinoline
(4am): 4am (0.213 g) was obtained from 2a (0.245 g,
1 mmol) following general procedure A. Two steps overall
yield 60%; brown oil; Rf =0.60 (SiO2, 20% EtOAc/hex-
anes); 1H NMR (400 MHz, CDCl3) d 8.00 (dd, J=18.6,
8.2 Hz, 2H), 7.67 (t, J=7.5 Hz, 1H), 7.51 (t, J=7.5 Hz, 1H),
7.31 (t, J=8.2 Hz, 1H), 7.18 (d, J=7.5 Hz, 1H), 7.10 (s,
1H), 6.94 (d, J=7.5 Hz, 1H), 3.85 (s, 3H), 3.22 (t, J=
8.0 Hz, 2H), 2.90 (s, 3H), 2.00–1.81 (m, 2H), 1.57–1.43 (m,
6-Bromo-4-methyl-2-phenyl-3-(phenylethynyl)quinoline
(4ca): 4ca (0.262 g) was obtained from 2c (0.315 g, 1 mmol)
308
asc.wiley-vch.de
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2016, 358, 303 – 313

FULL PAPERS
Pd(II)-Catalyzed Sequential Aminopalladation and Oxidative Coupling
following general procedure A. Two steps overall yield
2-(3-Fluorophenyl)-4-methyl-3-(phenylethynyl)quinoline:
(4ha): 4ha (0.239 g) was obtained from 2h (0.255 g, 1 mmol)
following general procedure A. Two steps overall yield
72%; yellow solid; mp 130–1328C; Rf =0.40 (SiO2, 10%
EtOAc/hexanes); 1H NMR (400 MHz, CDCl3) d 8.20–8.01
(m, 2H), 7.85–7.68 (m, 3H), 7.67–7.56 (m, 1H), 7.54–7.28
(m, 6H), 7.23–7.13 (m, 1H), 3.00 (s, 3H); 13C NMR
(100 MHz, CDCl3) d 162.5 (d, J=245.3 Hz), 158.1, 148.0,
146.2, 142.6 (d, J=7.6 Hz), 131.3, 130.3 (d, J=29.2 Hz),
129.4 (d, J=8.1 Hz), 128.8, 128.6, 127.2, 126.4, 125.5, 124.1,
123.1, 117.0, 116.7, 116.0, 115.7 (d, J=21 Hz), 99.5, 87.0,
17.2; IR (neat) n 3746, 3398, 3019, 1589, 1384, 1215,
769 cmÀ1; HRMS (ESI-TOF) calcd for C17H24FN [M + H]+
338.1345, found 338.1339.
66%; white solid; mp 165–1678C; Rf =0.55 (SiO2, 10%
1
EtOAc/hexanes); H NMR (400 MHz, CDCl3) d 8.19 (d, J=
2.0 Hz, 1H), 8.05–7.93 (m, 3H), 7.77 (dd, J=8.9 Hz 2.1 Hz,
1H), 7.58–7.45 (m, 3H), 7.41–7.28 (m, 5H), 2.95 (s, 3H);
13C NMR (100 MHz, CDCl3) d 160.0, 146.6, 144.9, 140.2,
133.2, 132.1, 131.4, 129.7, 129.0, 128.8, 128.5, 128.0, 127.6,
126.4, 123.0, 121.0, 117.7, 99.9, 87.0, 17.2; IR (neat) n 3850,
3745, 3379, 3019, 1598, 1384, 1215, 669 cmÀ1; HRMS (ESI-
TOF) calcd for C24H17BrN [M + H]+ 398.0544, found
398.0541.
4-Methyl-2,6-diphenyl-3-(phenylethynyl)quinoline (4da):
4da (0.272 g) was obtained from 2d (0.313 g, 1 mmol) fol-
lowing general procedure A. Two steps overall yield 69%;
brown solid; mp 155–1578C; Rf =0.50 (SiO2, 15% EtOAc/
6-Bromo-2-(3-fluorophenyl)-4-methyl-3-(phenylethynyl)-
quinoline (4ia): 4ia (0.298 g) was obtained from 2i (0.333 g,
1 mmol) following general procedure A. Two steps overall
yield 72%; white solid; mp 170–1728C; Rf =0.40 (SiO2, 10%
EtOAc/hexanes); 1H NMR (400 MHz, CDCl3) d 8.25–8.15
(m, 1H), 8.04–7.94 (m, 1H), 7.84–7.69 (m, 3H), 7.54–7.29
(m, 6H), 7.24–7.13 (m, 1H), 2.95 (s, 3H); 13C NMR
(100 MHz, CDCl3) d 162.5 (d, J=245 Hz), 158.4, 147.0,
144.8, 142.2 (d, J=7.9 Hz), 133.4, 132.1, 131.4, 129.5 (d, J=
8.3 Hz), 129.0, 128.6, 127.7, 126.5, 125.5 (d, J=2.9 Hz),
122.8, 121.3, 116.9, (d, J=5.5 Hz), 116.4 (d, J=62.9 Hz),
115.9, 100.3, 86.6, 17.2; IR (neat) n 3390, 3019, 2918, 1619,
1
hexanes); H NMR (400 MHz, CDCl3) d 8.26–8.16 (m, 2H),
8.06–7.93 (m, 3H), 7.80–7.71 (m, 2H), 7.61–7.28 (m, 11H),
3.05 (s, 3H); 13C NMR (100 MHz, CDCl3) d 159.6, 147.7,
145.7, 140.8, 140.5, 139.7, 131.3, 130.8, 129.7, 129.6, 129.1,
128.8, 128.6, 128.5, 127.9, 127.9, 127.6, 126.4, 123.3, 121.9,
116.5, 99.5, 87.5, 17.2; IR (neat) n 3397, 3019, 1637, 1384,
1216, 1068, 770 cmÀ1; HRMS (ESI-TOF) calcd for C30H22N
[M + H]+ 396.1752, found 396.1754.
6-(4-Chlorophenyl)-4-methyl-2-phenyl-3-(phenylethynyl)-
quinoline (4ea): 4ea (0.300 g) was obtained from 2e
(0.347 g, 1 mmol) following general procedure A. Two steps
overall yield 70%; light yellow solid; mp 210–2128C; Rf =
0.40 (SiO2, 10% EtOAc/hexanes); 1H NMR (400 MHz,
CDCl3) d 8.27–8.12 (m, 2H), 8.08–7.85 (m, 3H), 7.74–7.61
(m, 2H), 7.58–7.43 (m, 5H), 7.41–7.28 (m, 5H), 3.04 (s,
3H); 13C NMR (100 MHz, CDCl3) d 159.8, 147.7, 145.7,
140.5, 139.3, 138.4, 134.1, 131.3, 131.0, 129.7,129.2, 128.9,
128.9, 128.7, 128.5, 127.9, 126.4, 123.2, 121.9, 116.7, 99.5,
87.4, 17.2; IR (neat) n 3391, 3019, 2400, 1650, 1384, 1215,
1068, 757 cmÀ1; HRMS (ESI-TOF) calcd for C30H21ClN [M
+ H]+ 430.1363, found 430.1364.
2-(4-(tert-Butyl)phenyl)-4-methyl-3-(phenylethynyl)quino-
line: (4 fa): 4 fa (0.232 g) was obtained from 2 f (0.293 g,
1 mmol) following general procedure A. Two steps overall
yield 62%; brown gum; Rf =0.50 (SiO2, 10% EtOAc/hex-
anes); 1H NMR (400 MHz, CDCl3) d 8.18–8.11 (m, 1H),
8.07–8.01 (m, 1H), 7.97–7.89 (m, 2H), 7.75–7.66 (m, 1H),
7.61–7.49 (m, 3H), 7.40–7.28 (m, 5H), 2.99 (s, 3H), 1.40 (s,
9H); 13C NMR (100 MHz, CDCl3) d 159.8, 151.8, 147.4,
146.3, 137.7, 131.3, 130.3, 129.8, 129.3, 128.5, 128.4, 126.7,
126.2, 124.9, 124.0, 123.4, 116.2, 99.1, 87.7, 34.8, 31.5, 17.2;
IR (neat) n 3386, 2918, 1589, 1384, 1218, 1068, 832,
684 cmÀ1; HRMS (ESI-TOF) calcd for C28H26N [M + H]+
376.2065, found 376.2061.
1384, 1216, 770 cmÀ1
;
HRMS (ESI-TOF) calcd for
C24H16BrFN [M + H]+ 416.0450, found 416.0444.
3-Bromo-7-heptyl-5-methyl-6-(phenylethynyl)quinoline
(4ja): 4ja (0.265 g) was obtained from 2j (0.259 g, 1 mmol)
following general procedure A. Two steps overall yield
78%; brown liquid; Rf =0.55 (SiO2, 10% EtOAc/hexanes);
1H NMR (400 MHz, CDCl3) d 8.06–7.93 (m, 2H), 7.71–7.62
(m, 1H), 7.62–7.56 (m, 2H), 7.55–7.48 (m, 1H), 7.44–7.35
(m, 3H), 3.28–3.17 (m, 2H), 2.90 (s, 3H), 1.98–1.81 (m, 2H),
1.56–1.45 (m, 2H), 1.44–1.34 (m 2H), 1.31–1.19 (m, 3H),
0.91–0.79 (m, 3H); 13C NMR (100 MHz, CDCl3) d 163.2,
146.7, 146.2, 131.5, 129.6, 129.5, 128.7, 128.6, 126.1, 126.0,
124.0, 123.4, 116.9, 98.7, 86.4, 38.7, 31.9, 30.0, 29.5, 29.3, 22.7,
16.9, 14.2; IR (neat) n 3399, 3019, 2926, 2855, 1639, 1384,
1216, 1069, 769, 668 cmÀ1; HRMS (ESI-TOF) calcd for
C25H28N [M + H]+ 342.2222, found 342.2222.
4-Methyl-2-octyl-6-phenyl-3-(phenylethynyl)quinoline
(4ka): 4ka (0.323 g) was obtained from 2k (0.349 g, 1 mmol)
following general procedure A. Two steps overall yield
75%; brown gum; Rf =0.55 (SiO2, 10% EtOAc/hexanes);
1H NMR (400 MHz, CDCl3) d 8.18–8.04 (m, 2H), 7.98–7.88
(m, 1H), 7.78–7.68 (m, 2H), 7.64–7.56 (m, 2H), 7.55–7.46
(m, 2H), 7.45–7.36 (m, 4H), 3.23 (t, J=8.1 Hz, 2H), 2.95 (s,
3H), 1.99–1.81 (m, 2H), 1.56–1.44 (m, 2H), 1.44–1.26 (m,
6H), 0.93–0.76 (m, 5H); 13C NMR (100 MHz, CDCl3) d
163.3, 146.8, 145.5, 140.9, 139.0, 131.5, 130.0, 129.3, 129.0,
128.7, 128.6, 127.7, 127.6, 126.2, 123.4, 122.0, 117.3, 98.8,
86.4, 38.7, 32.0, 30.0, 29.7, 29.5, 29.4, 22.8, 17.0, 14.2; IR
2-(4-(tert-Butyl)phenyl)-4-methyl-6-phenyl-3-(phenylethy-
nyl)quinoline (4ga): 4ga (0.270 g) was obtained from 2g
(0.369 g, 1 mmol) following general procedure A. Two steps
overall yield 60%; brown solid; mp 180–1828C; Rf =0.50
1
(SiO2, 10% EtOAc/hexanes); H NMR (400 MHz, CDCl3) d
8.26–8.13 (m, 2H), 8.03–7.89 (m, 3H), 7.82–7.70 (m, 2H),
7.62–7.48 (m, 4H), 7.47–7.28 (m, 6H), 3.04 (s, 3H), 1.41 (s,
9H); 13C NMR (100 MHz, CDCl3) d 159.7, 151.8, 147.5,
145.7, 140.9, 139.5, 137.7, 131.3, 130.8, 129.5, 129.4, 129.1,
128.5, 128.4, 127.8, 127.6, 126.4, 124.9, 123.4, 121.9, 116.5,
99.3, 87.8, 34.8, 31.5, 17.2; IR (neat) n 3399, 3018, 2963,
1598, 1489, 1384, 1069, 834, 669 cmÀ1; HRMS (ESI-TOF)
calcd for C34H30N [M + H]+ 452.2378, found 452.2374.
(neat) n 3399, 3021, 1733, 1374, 1248, 1216, 1046 cmÀ1
;
HRMS (ESI-TOF) calcd for C32H34N [M + H]+ 432.2691,
found 432.2676.
2-Decyl-4-methyl-3-(phenylethynyl)quinoline: (4la): 4la
(0.306 g) was obtained from 2l (0.301 g, 1 mmol) following
general procedure A. Two steps overall yield 80%; brown
oil; Rf =0.50 (SiO2, 10% EtOAc/hexanes); 1H NMR
(400 MHz, CDCl3) d 8.09–7.93 (m, 2H), 7.72–7.63 (m, 1H),
Adv. Synth. Catal. 2016, 358, 303 – 313
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
309

FULL PAPERS
Nuligonda Thirupathi et al.
7.62–7.55 (m, 2H), 7.55–7.47 (m, 1H), 7.44–7.36 (m, 3H),
General procedure B for the Synthesis 3-alkenyl
3.26–3.17 (m, 2H), 2.90 (s, 2H), 1.89 (q, J=15.4 Hz, 7.8 Hz
2H), 1.37–1.11 (m, 11H), 0.93–0.79 (m, 6H); 13C NMR
(100 MHz, CDCl3) d 163.3, 146.8, 146.1, 131.5, 129.6, 129.5,
128.7, 128.6, 126.1, 124.0, 123.4, 116.9, 98.6, 86.4, 38.7, 32.0,
30.1, 29.8, 29.7, 29.7, 29.5, 29.4, 22.8, 16.9, 14.2; IR (neat) n
3399, 3019, 1650, 1384, 1215, 1068, 758, 669 cmÀ1; HRMS
(ESI-TOF) calcd for C28H34N [M + H]+ 384.2691, found
384.2685.
quinolines (5a–h), taking synthesis of 5a as an
example:
To a stirred solution of 2a (245 mg, 1 mmol, 1 equiv) in
3 mL of anhydrous DMSO under N2 atmosphere was added
Pd(OAc)2 (11.2 mg, 0.05 mmol, 0.05 equiv), LiCl (41 mg,
1 mmol, 1 equiv), ethyl vinyl ketone (168 mg, 2 mmol, 2
equiv)) at room temperature. The reaction mixture was
stirred at 7088C until starting material had been fully con-
sumed (12 h to 36 h). The reaction mixture was diluted with
water (20 mL) and extracted with EtOAc (3”15 mL). The
combined organic layers were washed with brine (15 mL)
and dried over Na2SO4. After removal of the solvent under
reduced pressure the crude material was purified on silica
gel using 8% EtOAc/hexanes to get 5a (222 mg, 72% (two
step overall yield)) as a brown gum.
2-Cyclopropyl-4-methyl-3-(phenylethynyl)quinoline:
(4ma): 4ma (0.232 g) was obtained from 2m (0.201 g,
1 mmol) following general procedure A. Two steps overall
yield 82%; brown gum; Rf =0.45 (SiO2, 10% EtOAc/hex-
anes); 1H NMR (400 MHz, CDCl3) d 8.01–7.84 (m, 2H),
7.67–7.54 (m, 3H), 7.50–7.35 (m, 4H), 2.90 (s, 3H), 1.33–
1.26 (m, 3H), 1.15–1.04 (m, 2H); 13C NMR (100 MHz,
CDCl3) d 162.6, 146.4, 146.0, 131.6, 129.5, 129.4, 128.6, 128.6,
125.8, 125.6, 124.0, 123.4, 117.2, 98.8, 86.5, 16.9, 16.1, 10.4;
(E)-1-(2-Ethyl-4-methylquinolin-3-yl)pent-1-en-3-one
IR (neat) n 3388, 1584, 1384, 1217, 1068, 771, 668 cmÀ1
;
(5a): 5a (0.222 g) was obtained from 2a (0.245 g, 1 mmol)
following general procedure B. Two steps overall yield 72%;
brown gum; Rf =0.50 (SiO2, 20% EtOAc/hexanes);
1H NMR (400 MHz, CDCl3) d 8.00–7.92 (m, 2H), 7.86 (d,
J=16.3 Hz, 1H), 7.68 (t, J=7.1 Hz, 1H), 7.52 (t, J=7.1 Hz,
1H), 6.37 (d, J=16.3 Hz, 1H), 2.94 (t, J=8.0 Hz, 2H), 2.74
(q, J=7.1 Hz, 2H), 2.67 (s, 3H), 1.80–1.62 (m, 2H), 1.47–
1.26 (m, 6H), 1.22 (t, J=7.3 Hz, 3H), 0.87 (t, J=7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3) d 200.2, 160.3, 146.8,
141.6, 139.8, 134.2, 129.5, 129.4, 128.1, 126.6, 126.1, 124.2,
37.8, 34.5, 31.8, 29.5, 29.3, 22.6, 16.1, 14.1, 8.2; IR (neat) n
3391, 1614, 1216, 1068, 667 cmÀ1; HRMS (ESI-TOF) calcd
for C21H28NO [M + H]+ 310.2171, found 310.2170.
HRMS (ESI-TOF) calcd for C21H18N [M + H]+ 284.1439,
found 284.1433.
2-Phenyl-3-(phenylethynyl)quinoline (4na): 4na (0.207 g)
was obtained from 2n (0.223 g, 1 mmol) following general
procedure A. Two steps overall yield 68%; brown gum; Rf =
0.60 (SiO2, 10% EtOAc/hexanes); 1H NMR (400 MHz,
CDCl3) d 8.45 (s, 1H), 8.16 (d, J=8.5 Hz, 1H), 8.11–8.04
(m, 2H), 7.83 (d, J=8.3 Hz, 1H), 7.77–7.69 (m, 1H), 7.60–
7.46 (m, 4H), 7.43–7.37 (m, 2H), 7.35–7.30 (m, 3H);
13C NMR (100 MHz, CDCl3) d 159.5, 147.0, 140.7, 139.8,
135.3, 131.5, 130.4, 129.7, 129.1, 128.7, 128.5, 128.0, 127.2,
127.1, 126.4, 123.0, 116.3, 94.7, 88.1; IR (neat) n 3388, 1584,
1384, 1217, 1068, 771, 668 cmÀ1; HRMS (ESI-TOF) calcd for
C23H16N [M + H]+ 306.1283, found 306.1270.
(E)-1-(2-Decyl-4-methylquinolin-3-yl)pent-1-en-3-one
(5b): 5b (0.255 g) was obtained from 2l (0.301 g, 1 mmol)
following general procedure B. Two steps overall yield 70%;
2-(3-Fluorophenyl)-3-(phenylethynyl)quinoline (4oa): 4oa
(0.213 g) was obtained from 2o (0.241 g, 1 mmol) following
general procedure A. Two steps overall yield 66%; yellow
solid; mp 168–1708C; Rf =0.50 (SiO2, 10% EtOAc/hex-
1
brown oil; Rf =0.65 (SiO2, 10% EtOAc/hexanes); H NMR
(500 MHz, CDCl3) d 8.00 (dd, J=15.4, 8.3 Hz, 2H), 7.86 (d,
J=16.4 Hz, 1H), 7.71–7.64 (m, 1H), 7.56–7.48 (m, 1H), 6.36
(d, J=16.4 Hz, 1H), 2.94 (t, J=8.0 Hz, 2H), 2.74 (q, J=
7.3 Hz, 2H), 2.67 (s, 3H), 1.77–1.67 (m, 2H), 1.42–1.34 (m,
2H), 1.33–1.25 (m, 15H), 0.87 (t, J=7.3 Hz, 3H); 13C NMR
(100 MHz, CDCl3) d 200.2, 160.4, 146.9, 141.6, 139.8, 134.2,
129.5, 129.5, 128.2, 126.6, 126.1, 124.2, 37.8, 34.5, 32.0, 29.8,
29.7, 29.7, 29.6, 29.4, 29.3, 22.8, 16.1, 14.2, 8.2; IR (neat) n
3378, 3020, 1619, 1248, 1046, 668 cmÀ1; HRMS (ESI-TOF)
calcd for C25H36NO [M + H]+ 366.2797, found 366.2784.
(E)-1-(6-Bromo-2-heptyl-4-methylquinolin-3-yl)pent-1-en-
3-one (5c): 5c (0.220 g) was obtained from 2q (0.337 g,
1 mmol) following general procedure B. Two steps overall
yield 55%; brown gum; Rf =0.60 (SiO2, 20% EtOAc/hex-
anes); 1H NMR (400 MHz, CDCl3) d 8.12 (d, J=1.6 Hz,
1H), 7.94–7.65 (m, 3H), 6.36 (d, J=16.5 Hz, 1H), 2.91 (t,
J=8.0 Hz, 2H), 2.74 (q, J=7.2 Hz, 2H), 2.62 (s, 3H), 1.81–
1.64 (m, 2H), 1.37–1.20 (m, 8H), 0.91–0.73 (m, 6H);
13C NMR (100 MHz, CDCl3) d 200.0, 160.9, 145.5, 140.6,
139.2, 134.4, 132.8, 131.3, 129.1, 127.9, 126.7, 120.1, 37.7,
34.6, 31.8, 29.8, 29.2, 29.1, 22.7, 16.1, 14.2, 8.1; IR (neat) n
3399, 3019, 1592, 1216, 1123, 669 cmÀ1; HRMS (ESI-TOF)
calcd for C22H29BrNO [M + H]+ 402.1433, found 402.1429.
(E)-1-(4-Methyl-2-phenylquinolin-3-yl)pent-1-en-3-one
(5d): 5d (0.186 g) was obtained from 2b (0.237 g, 1 mmol)
following general procedure B. Two steps overall yield 62%;
brown solid, mp 116–1188C; Rf =0.55 (SiO2, 20% EtOAc/
1
anes); H NMR (400 MHz, CDCl3) d 8.46 (s, 1H), 8.15 (d,
J=8.4 Hz, 1H), 7.94–7.80 (m, 3H), 7.79–7.70 (m, 1H), 7.66–
7.13 (m, 8H); 13C NMR (100 MHz, CDCl3) d 162.7 (d, J=
246 Hz), 157.8, 146.9, 141.8 (d, J=7 Hz), 140.9, 131.5, 130.6,
129.7, 129.5 (d, J=8 Hz), 128.9, 128.6, 127.4, 127.2, 126.6,
125.5 (d, J=2 Hz), 122.8, 116.8 (d, J=22 Hz), 116.1 (d, J=
4 Hz), 115.9, 95.1, 87.6; IR (neat) n 3848, 3745, 3670, 3398,
3021, 1732, 1374, 1216, 769 cmÀ1; HRMS (ESI-TOF) calcd
for C23H15FN [M + H]+ 324.1189, found 324.1173.
3-(Phenylethynyl)-2-p-tolylquinoline (4pa): 4pa (0.191 g)
was obtained from 2p (0.237 g, 1 mmol) following general
procedure A. Two steps overall yield 60%; yellow gum;
1
Rf =0.50 (SiO2, 10% EtOAc/hexanes); H NMR (400 MHz,
CDCl3) d 8.44 (s, 1H), 8.14 (d, J=8.3 Hz, 1H), 8.01 (d, J=
8.1 Hz, 2H), 7.81 (d, J=8.0 Hz, 1H), 7.76–7.69 (m, 1H),
7.59–7.49 (m, 1H), 7.48–7.39 (m, 2H), 7.38–7.28 (m, 5H),
2.45 (s, 3H); 13C NMR (100 MHz, CDCl3) d 159.3, 147.1,
140.8, 139.1, 137.0, 135.8, 131.5, 130.3, 129.7, 128.7, 128.7,
128.5, 127.1, 127.0, 126.3, 123.2, 116.2, 94.5, 88.3, 21.5; IR
(neat) n 3399, 3019, 2927, 1619, 1491, 1383, 1215, 827 cmÀ1
;
HRMS (ESI-TOF) calcd for C24H18N [M + H]+ 320.1439,
found 320.1429.
310
asc.wiley-vch.de
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2016, 358, 303 – 313

FULL PAPERS
Pd(II)-Catalyzed Sequential Aminopalladation and Oxidative Coupling
1
hexanes); H NMR (400 MHz, CDCl3) d 8.19–8.04 (m, 2H),
7.76–7.71 (m, 1H), 7.65 (d, J=16.5 Hz, 1H), 7.63–7.52 (m,
3H), 7.48–7.38 (m, 3H), 6.19 (d, J=16.5 Hz, 1H), 2.80 (s,
3H), 2.49 (q, J=7.3 Hz, 2H), 1.06 (t, J=7.3 Hz, 3H);
13C NMR (125 MHz, CDCl3) d 200.4, 158.6, 146.9, 143.2,
140.8, 140.3, 134.2, 130.3, 130.0, 129.8, 128.6, 128.4, 127.3,
127.0, 126.9, 124.4, 33.9, 16.2, 8.1; IR (neat) n 3386, 3019,
HRMS (ESI-TOF) calcd for C28H26NO2 [M + H]+ 408.1964,
found 408.1961.
1-Phenyl-2-(2-phenylquinolin-3-yl)ethanone
(9):
To
a stirred solution of 4na (305 mg, 1 mmol, 1 equiv) in 6 mL
(2:1) of Dioxane + water was added IPrAuCl (31 mg,
0.05 mmol, 0.05 equiv), AgSbF6 (171 mg, 0.5 mmol, 0.5
equiv) at room temperature. The reaction mixture was
stirred at 1308C for 24 h.The reaction mixture was diluted
with water (20 mL) and extracted with EtOAc (3”15 mL).
The combined organic layers were washed with brine
(15 mL) and dried over Na2SO4.After removal of the solvent
under reduced pressure the crude material was purified on
silica using 5% EtOAc/hexanes to get 9 (177 mg) as a light
yellow gum. yield 55%; Rf =0.55 (SiO2, 20% EtOAc/hex-
anes); 1H NMR (400 MHz, CDCl3) d 8.17 (d, J=8.3 Hz,
1H), 8.13 (s, 1H), 7.85–7.82 (m, 3H), 7.77–7.70 (m, 1H),
7.58–7.52 (m, 4H), 7.44–7.40 (m, 5H), 4.46 (s, 2H);
13C NMR (100 MHz, CDCl3) d 197.5, 160.4, 147.1, 140.4,
138.4, 136.5, 133.5, 129.7, 129.4, 128.9, 128.7, 128.6, 128.5,
128.4, 127.5, 126.8, 126.5, 114.2, 43.0; IR (neat) n3386, 3019,
1399, 1121, 668 cmÀ1
;
HRMS (ESI-TOF) calcd for
C21H20NO [M + H]+ 302.1545, found 302.1540.
(E)-1-(4-Methyl-2,6-diphenylquinolin-3-yl)pent-1-en-3-one
(5e): 5e (0.196 g) was obtained from 2c (0.313 g, 1 mmol)
following general procedure B. Two steps overall yield 52%;
yellow solid, mp 126–1288C; Rf =0.55 (SiO2, 20% EtOAc/
1
hexanes); H NMR (400 MHz, CDCl3) d 8.34–8.10 (m, 2H),
8.00 (d, J=8.2 Hz, 1H), 7.83–7.32 (m, 11H), 6.20 (d, J=
16.8 Hz, 1H), 2.85 (s, 3H), 2.51 (q, J=7.7 Hz, 2H), 1.07 (t,
J=7.7 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 200.4, 158.5,
146.3, 143.3, 140.8, 140.3, 139.8, 134.3, 131.0, 130.8, 129.9,
129.8, 129.1, 128.7, 128.4, 127.9, 127.7, 127.2, 122.3, 33.9,
16.3, 8.1; IR (neat) n 3399, 3019, 1654, 1384, 1046, 669 cmÀ1
;
1399, 1121, 668 cmÀ1
;
HRMS (ESI-TOF) calcd for
HRMS (ESI-TOF) calcd for C27H24NO [M + H]+ 378.1858,
found 378.1854.
C23H18NO [M + H]+ 324.1388, found 324.1382.
1-Phenyl-2-(2-phenylquinolin-3-yl)ethane-1,2-dione (10):
10 (0.209 g) was obtained from 4na (0.305 g, 1 mmol) fol-
lowing literature procedure.[14] yield 62%; light yellow gum,;
(E)-1-(6-Bromo-4-methyl-2-phenylquinolin-3-yl)pent-1-
en-3-one (5 f): 5 f (0.208 g) was obtained from 2d (0.315 g,
1 mmol) following general procedure B. Two steps overall
yield 55%; light yellow solid, mp 142–1448C; Rf =0.50
1
Rf =0.35 (SiO2, 20% EtOAc/hexanes); H NMR (400 MHz,
CDCl3) d 8.76 (s, 1H), 8.21 (d, J=8.4 Hz, 1H), 8.00 (d, J=
8.0 Hz, 1H), 7.89–7.86 (m, 3H), 7.65–7.62 (m, 1H), 7.57 (t,
J=7.4 Hz, 1H), 7.51–7.49 (m, 2H), 7.39 (t, J=8.0 Hz, 2H),
7.15–7.11 (m, 3H); 13C NMR (100 MHz, CDCl3) d 194.0,
190.6, 158.6, 149.2, 140.7, 140.0, 134.4, 132.6, 132.5, 130.1,
129.7, 129.7, 129.3, 129.0, 128.4, 128.4, 127.6, 126.2; IR
(neat) n3391, 1614, 1216, 1068, 667 cmÀ1; HRMS (ESI-TOF)
calcd for C23H16NO2 [M + H]+ 338.1181, found 338.1187.
(Z)-2-Hexyl-4-methyl-3-styrylquinoline (11): Yield 60%
(with Pd-C) and 75% (with Pd-BaSO4); colorless oil,; Rf =
0.60 (SiO2, 10% EtOAc/hexanes); 1H NMR (400 MHz,
CDCl3) d 8.06 (d, J=8.3 Hz, 1H), 7.93 (d, J=8.2 Hz, 1H),
7.68–7.64 (m, 1H), 7.56–7.41 (m, 1H), 7.16–7.03 (m, 3H),
7.02–6.92 (m, 2H), 6.83 (d, J=12.4 Hz, 2H), 6.73 (d, J=
12.4 Hz, 1H), 3.00–2.79 (m, 2H), 2.47 (s, 3H), 1.84–1.59 (m,
3H), 1.43–1.32 (m, 2H), 1.30–1.11 (m, 3H), 0.85 (t, J=
6.9 Hz, 3H),; 13C NMR (100 MHz, CDCl3) d 161.2, 146.7,
141.0, 136.9, 133.1, 130.0, 129.4, 128.7, 128.5, 128.4, 127.6,
126.8, 126.7, 125.6, 124.1, 37.8, 31.8, 29.6, 29.0, 22.7, 15.4,
14.2; IR (neat) n3390, 2929, 1402, 1069, 669 cmÀ1; HRMS
(ESI-TOF) calcd for C24H28N [M + H]+ 330.2222, found
330.2219.
1
(SiO2, 20% EtOAc/hexanes); H NMR (400 MHz, CDCl3) d
8.23 (s, 1H), 8.03 (d, J=8.5 Hz, 1H), 7.80 (d, J=7.8 Hz,
1H), 7.72–7.35 (m, 6H), 6.19 (d, J=16.7 Hz, 1H), 2.75 (s,
3H), 2.49 (q, J=7.2 Hz, 2H), 1.06 (t, J=7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3) d 200.2, 158.9, 145.3, 142.4,
140.2, 139.6, 134.6, 133.4, 131.9, 129.8, 128.9, 128.4, 128.3,
128.2, 126.8, 121.1, 34.0, 16.3, 8.1; IR (neat) n 3848, 3398,
3019, 1402, 1119, 669 cmÀ1; HRMS (ESI-TOF) calcd for
C21H19BrNO [M + H]+ 380.0650, found 380.0656.
((E)-1-(6-(4-Chlorophenyl)-4-methyl-2-phenylquinolin-3-
yl)pent-1-en-3-one (5g): 5g (0.213 g) was obtained from 2e
(0.347 g, 1 mmol) following general procedure B. Two steps
overall yield 52%; yellow solid, mp 150–1528C; Rf =0.45
1
(SiO2, 20% EtOAc/hexanes); H NMR (500 MHz, CDCl3) d
8.29 (bs, 1H), 8.20 (d, J=1.5 Hz, 1H), 7.96 (d, J=8.5 Hz,
1H), 7.73–7.62 (m, 3H), 7.59 (d, J=6.5 Hz, 2H), 7.53–7.39
(m, 5H), 6.21 (d, J=16.5 Hz, 1H), 2.85 (s, 3H), 2.50 (q, J=
7.4 Hz, 2H), 1.07 (t, J=7.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3) d 200.3, 158.5, 143.8, 139.9, 139.1, 138.7, 134.5, 134.2,
130.6, 129.9, 129.6, 129.3, 128.9, 128.9, 128.4, 127.9, 127.2,
122.2, 34.0, 16.4, 8.1; IR (neat) n 3852, 3675, 3019, 1637,
1068, 669 cmÀ1; HRMS (ESI-TOF) calcd for C27H23ClNO
[M + H]+ 412.1468, found 412.1468.
(E)-1-(6-(4-Methoxyphenyl)-4-methyl-2-phenylquinolin-3-
yl)pent-1-en-3-one (5h): 5h (0.231 g) was obtained from 2r
(0.343 g, 1 mmol) following general procedure B. Two steps
overall yield 57%; yellow solid, mp 145–1478C; Rf =0.55
3-Phenethyl-2-phenylquinoline (12): Yield 65% (with Pd-
BaSO4) and 76% (with Pd-C); light yellow oil; Rf =0.40
1
(SiO2, 10% EtOAc/hexanes); H NMR (400 MHz, CDCl3) d
8.13 (d, J=8.5 Hz, 1H), 8.01 (s, 1H), 7.78 (d, J=8.1 Hz,
1H), 7.72–7.63 (m, 1H), 7.58–7.40 (m, 6H), 7.25–7.11 (m,
3H), 7.00–6.91(m, 2H), 3.13–3.04 (m, 2H), 2.83–2.74 (m,
2H),; 13C NMR (100 MHz, CDCl3) d 160.8, 146.6, 141.2,
140.9, 136.2, 133.1, 129.4, 129.1, 128.8, 128.5, 128.5, 128.3,
127.7, 127.1, 126.6, 126.2, 37.1, 35.4, 29.8; IR (neat) n3399,
3021, 1733, 1374, 1248, 1216, 1046 cmÀ1; HRMS (ESI-TOF)
calcd for C23H20N [M + H]+ 310.1596, found 310.1588.
1
(SiO2, 20% EtOAc/hexanes); H NMR (400 MHz, CDCl3) d
8.32 (bs, 1H), 8.19 (s, 1H), 7.99 (d, J=7.7 Hz, 1H), 7.76–
7.35 (m, 8H), 7.05 (d, J=7.8 Hz, 2H), 6.21 (d, J=16.2 Hz,
1H), 3.89 (s, 3H), 2.85 (s, 3H), 2.50 (q, J=6.7 Hz, 2H), 1.07
(t, J=6.7 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 200.3,
159.8, 157.8, 145.2, 139.9, 139.6, 134.5, 133.0, 130.0, 129.9,
128.9, 128.7, 128.4, 127.7, 127.3, 121.4, 114.6, 55.5, 34.0, 16.5,
8.1; IR (neat) n 3399, 3019, 1592, 1216, 1123, 669 cmÀ1
;
Adv. Synth. Catal. 2016, 358, 303 – 313
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
311

FULL PAPERS
Nuligonda Thirupathi et al.
Marino, S. V. Giofre, B. Gabriele, J. Org. Chem. 2014,
79, 3506–3518; c) B. Gabriele, P. Plastina, G. Salerno,
R. Mancuso, M. Costa, Org. Lett. 2007, 9, 3319–3322;
d) B. Gabriele, G. Salerno, L. Veltri, R. Mancuso, Z. Li,
A. Crispini, A. Bellusci, J. Org. Chem. 2006, 71, 7895–
7898; e) B. Gabriele, R. Mancuso, G. Salerno, E. Lupi-
nacci, G. Ruffolo, M. Costa, J. Org. Chem. 2008, 73,
4971–4977; f) B. Gabriele, R. Mancuso, G. Salerno, L.
Veltri, Chem. Commun. 2005, 271–273; g) A. Arcadi, S.
Cacchi, S. D. Giuseppe, G. Fabrizi, F. Marinelli, Org.
Lett. 2002, 4, 2409–2412.
Acknowledgements
This work was supported by DST (SB/FT/CS-102/2012),
New Delhi. We are thankful to SAIF, CSIR-CDRI, for pro-
viding the analytical facilities and Dr. Tejender S. Thakur,
Molecular and Structural Biology Division, CSIR-CDRI for
supervising the X-ray data collection and structure determina-
tion of compounds 4ea and 5d. N.T. and S.P. thank CSIR
for the fellowships. CDRI Communication No: 9109.
[4] A. Arcadi, S. Cacchi, G. Fabrizi, A. Goggiamani, A.
Lazetti, F. Marinelli, Org. Biomol. Chem. 2013, 11,
545–548.
[5] a) B. Yao, Q. Wang, J. Zhu, Angew. Chem. 2012, 124,
12477–12481; Angew. Chem. Int. Ed. 2012, 51, 12311–
12315; b) B. Yao, Q. Wang, J. Zhu, Chem. Eur. J. 2015,
21, 7413–7416.
References
[1] a) S. Cacchi, G. Fabrizi, A. Goggiamani, Adv. Synth.
Catal. 2006, 348, 1301–1305; b) S. Cacchi, G. Fabrizi, A.
Goggiamani, A. Sferraza, Org. Biomol. Chem. 2011, 9,
1727–1730; c) S. Cacchi, G. Fabrizi, Chem. Rev. 2005,
105, 2873–2920; d) A. Arcadi, S. Cacchi, L. Casia, G.
Fabrizi, F. Marinelli, Org. Lett. 2001, 3, 2501–2504; e) S.
Cacchi, G. Fabrizi, A. Goggiamani, A. Perboni, A. Sfer-
raza, P. Stabile, Org. Lett. 2010, 12, 3279–3281; f) A.
Arcadi, S. Cacchi, G. Fabrizi, F. Marinelli, L. M. Parisi,
J. Org. Chem. 2005, 70, 6213–6217; g) A. Arcadi, R.
Cianci, G. Ferrara, F. Marinelli, Tetrahedron 2010, 66,
2378–2383; h) S. Cacchi, G. Fabrizi, P. Pace, J. Org.
Chem. 1998, 63, 1001–1011; i) C. Chowdhury, B. Das, S.
Mukherjee, B. Achari, J. Org. Chem. 2012, 77, 5108–
5119; j) C. Chowdhury, S. Mukherjee, B. Chakraborty,
B. Achari, Org. Biomol. Chem. 2011, 9, 5856–5862;
k) D. Fujino, H. Yorimistu, A. Osuka, J. Am. Chem.
Soc. 2014, 136, 6255–6258; l) C. Xu, V. K. Murugan,
S. A. Pullarkat, Org. Biomol. Chem. 2012, 10, 3875–
3881; m) K. Iritani, S. Matsubara, K. Utimoto, Tetrahe-
dron Lett. 1988, 29, 1799–1802.
[2] a) R. Alvarez, C. Martinez, Y. Madich, J. G. Denis,
J. M. Aurrecoechea, A. R. D. Lera, Chem. Eur. J. 2010,
16, 12746–12753; b) R. Alvarez, C. Martinez, Y.
Madich, J. G. Denis, J. M. Aurrecoechea, A. R. D. Lera,
Chem. Eur. J. 2012, 18, 13894–13896; c) C. Martinez,
J. M. Aurrecoechea, Y. Madich, J. G. Denis, A. R. D.
Lera, R. Alvarez, Eur. J. Org. Chem. 2012, 6291–6292;
d) Y. Madich, R. Alvarez, J. M. Aurrecoechea, Eur. J.
Org. Chem. 2014, 6263–6271; e) C. Martinez, R. Alvar-
ez, J. M. Aurrecoechea, Org. Lett. 2009, 11, 1083–1086;
f) H. Wang, X. Han, X. Lu, Tetrahedron 2013, 69, 8626–
8631; g) A. Lei, X. Lu, Org. Lett. 2000, 2, 2699–2702;
h) Q. Haung, R. C. Larock, J. Org. Chem. 2003, 68,
980–988; i) P. Zhao, D. Chen, G. Song, K. Han, X. Li, J.
Org. Chem. 2012, 77, 1579–1584; j) Q. Wang, L. Huang,
X. Wu, H. Jiang, Org. Lett. 2013, 15, 5940–5943; k) J.
Li, Z. Zhu, S. Yang, Z. Zhang, W. Wu, H. Jiang, J. Org.
Chem. 2015, 80, 3870–3879; l) C. Zheng, J. J. Chen, R.
Fan, Org. Lett. 2014, 16, 816–819; m) P.-P. Tian, S.-H.
Cai, Q.-J. Liang, X.-Y. Zhou, Y.-H. Xu, T.-P. Loh, Org.
Lett. 2015, 17, 1636–1639; n) Z. Han, L. Zhang, Z. Li,
R. Fan, Angew. Chem. 2014, 126, 6923–6927; Angew.
Chem. Int. Ed. 2014, 53, 6805–6809; o) A. Yasuhara, Y.
Takeda, N. Suzuki, T. Sakamoto, Chem. Pharm. Bull.
2002, 50, 235–238.
[6] a) G. Xia, X. Han, X. Lu, Org. Lett. 2014, 16, 6184–
6187; b) X. Han, X. Lu, Org. Lett. 2010, 12, 3336–3339;
c) G. Battistuzzi, S. Cacchi, G. Fabrizi, F. Marinelli,
L. M. Parisi, Org. Lett. 2002, 4, 1355–1358; d) B. Yao,
Q. Wang, J. Zhu, Angew. Chem. 2012, 124, 5260–5264;
Angew. Chem. Int. Ed. 2012, 51, 5170–5174; e) B. Yao,
Q. Wang, J. Zhu, Angew. Chem. 2013, 125, 13230–
13234; Angew. Chem. Int. Ed. 2013, 52, 12992–12996;
f) T. M. Ha, B. Yao, Q. Wang, J. Zhu, Org. Lett. 2015,
17, 1750–1753; g) N. Thirupathi, M. H. Babu, V. Dwive-
di, M. S. Reddy, Org. Lett. 2014, 16, 2908–2911.
[7] For few recent examples, see: a) Y. Yagi, H. Kimura,
K. Arimitsu, M. Ono, K. Maeda, H. Kusuhara, T. Kaji-
moto, Y. Sugiyama, H. Saji, Org. Biomol. Chem. 2015,
13, 1113–1121; b) K. Singh, H. Kaur, P. Smith, C.
de Kock, K, Chibale, J. Balzarini, J. Med. Chem. 2014,
57, 435–448; c) P. J. Bindu, K. M. Mahadevan, T. R. R.
Naik, B. G. Harish, Chem. Commun. 2014, 5, 1708–
1717; d) A. Matteelli, A. C. C. Carvalho, K. E. Dooley,
A. Kritski, Future Microbiol. 2010, 5, 849–858; e) J. P.
Michael, Nat. Prod. Rep. 2008, 25, 166–187; f) R.
Musiol, J. Jampilek, K. Kralova, D. R. Richardson, D.
Kalinowski, B. Podeszwa, J. Finster, H. Niedbala, A.
Palka, J. Polanski, Bioorg. Med. Chem. 2007, 15, 1280–
1288; g) K. Kaur, M. Jain, R. P. Reddy, R. Jain, Eur. J.
Med. Chem. 2010, 45, 3245–3264; h) F. Hayat, E. Mose-
ley, A. Salahuddin, R. L. V. Zyl, A. Azam, Eur. J. Med.
Chem. 2011, 46, 1897–1905.
[8] For few recent examples, see: a) S. Madapa, A. Tusi, S.
Batra, Curr. Org. Chem. 2008, 12, 1116–1183; b) J.
Marco-Contelles, E. Perez-Mayoral, A. Samadi, M. C.
Carreiras, E. Soriano, Chem. Rev. 2009, 109, 2652–2671;
c) S. M. Prajapati, K. D. Patel, R. H. Vekariya, S. N.
Panchal, H. D. Patel, RSC Adv. 2014, 4, 24463–24476;
d) Q. Gao, S. Liu, X. Wu, A. Wu, Org. Lett. 2014, 16,
4582–4585; e) P. Selig, W. Raven, Org. Lett. 2014, 16,
5192–5195; f) Y. Matsubara, S. Hirakawa, Y. Yamagu-
chi, Z.-I. Yoshida, Angew. Chem. 2011, 123, 7812–7815;
Angew. Chem. Int. Ed. 2011, 50, 7670–7673; g) H. K.
Batchu, S. Bhattacharyya, S. Batra, Org. Lett. 2012, 14,
6330–6333; h) X. Ji, H. Huang, Y. Li, H. Chen, H.
Jiang, Angew. Chem. 2012, 124, 7404–7408; Angew.
Chem. Int. Ed. 2012, 51, 7292–7296; i) P. Zhao, X. Yan,
H. Yin, C. Xi, Org. Lett. 2014, 16, 1120–1123; j) K. Wu,
[3] a) B. Gabriele, L. Veltri, R. Mancuso, G. Salerno, S.
Maggi, B. M. Aresta, J. Org. Chem. 2012, 77, 4005–
4016; b) R. Mancuso, I. Ziccarelli, D. Armentano, N.
312
asc.wiley-vch.de
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2016, 358, 303 – 313

FULL PAPERS
Pd(II)-Catalyzed Sequential Aminopalladation and Oxidative Coupling
Z. Huang, C. Liu, H. Zhang, A. Lei, Chem. Commun.
2015, 51, 2286–2289; k) J. Zhou, G. Wu, M. Zhang, X.
Jie, W. Su, Chem. Eur. J. 2012, 18, 8032–8036.
[10] a) S. Mori, M. Takubo, T. Yanase, T. Maegawa, Y. Mon-
guchi, H. Sajiki, Adv. Synth. Catal. 2010, 352, 1630–
1634; b) C. A. Witham, P. Mauleon, N. D. Shapiro,
B. D. Sherry, F. D. Toste, J. Am. Chem. Soc. 2007, 129,
5838–5839; c) Z. Wan, C. D. Jones, D. Mitchell, J. Y.
Pu, T. Y. Zhang, J. Org. Chem. 2006, 71, 826–828.
[11] CCDC 1058179 and CCDC 1058180 contain the supple-
mentary crystallographic data for this paper. These
data can be obtained free of charge from the Cam-
bridge Crystallographic Data Centre via www.ccdc.
cam.ac.uk/data_request/cif.
[12] a) M. Nishizawa, T. Takemoto, I. Sasaki, M. Nakano, E.
Ho, K. Namba, H. Yamamoto, H. Imagawa, Synlett
2009, 1175–1179; b) R. Casado, M. Contel, M. Laguna,
P. Romero, S. Sanz, J. Am. Chem. Soc. 2003, 125,
11925–11935; c) N. Marion, R. S. Ramon, S. P. Nolan, J.
Am. Chem. Soc. 2009, 131, 448–449; d) A. Arcadi, S.
Cacchi, G. Fabrizi, F. Marinelli, L. M. Parisi, J. Org.
Chem. 2005, 70, 6213–6217; e) Q. Gao, S. Li, Y. Pan, Y.
Xu, H. Wang, Tetrahedron 2013, 69, 3775–3778.
[13] C. Mousset, O. Provot, A. Hamze, J. Bignon, J.-D.
Brion, M. Alami, Tetrahedron 2008, 64, 4287–4294.
[14] C. Mousset, O. Provot, A. Hamze, J. Bignon, J.-D.
Brion, M. Alami, Tetrahedron 2008, 64, 4287–4294.
[9] a) W. Zhou, J. Lei, Chem. Commun. 2014, 50, 5583–
5585; b) M. Movassaghi, M. D. Hill, J. Am. Chem. Soc.
2006, 128, 4592–4593; c) N. Sakai, K. Annaka, T. Kona-
kahara, J. Org. Chem. 2006, 71, 3653–3655; d) H.
Haung, H. Jiang, K. Chen, H. Liu, J. Org. Chem. 2009,
74, 5476–5480; e) Z. Huo, I. D. Gridnev, Y. Yamamoto,
J. Org. Chem. 2010, 75, 1266–1270; f) T. Mitamura, A.
Ogawa, J. Org. Chem. 2011, 76, 1163–1166; g) S.
Khong, O. Kwon, J. Org. Chem. 2012, 77, 8257–8267;
h) B. Liu, H. Gao, Y. Yu, W. Wu, H. Jiang, J. Org.
Chem. 2013, 78, 10319–10328; i) N. Sakai, K. Tamura,
K. Shimamura, R. Ikeda, T. Konakahara, Org. Lett.
2012, 14, 836–839; j) K. K. Toh, S. Sanjaya, S. Sahnoun,
S. Y. Chong, S. Chiba, Org. Lett. 2012, 14, 2290–2292;
k) B. Gabriele, R. Mancuso, G. Salerno, G. Ruffolo, P.
Plastina, J. Org. Chem. 2007, 72, 6873–6877; l) ref 3e;
m) S. Ali, H.-T. Zhu, X.-F. Xia, K.-G. Ji, Y.-F. Yang, X.-
R. Song, Y.-M. Liang, Org. Lett. 2011, 13, 2598–2601;
n) M. S. Reddy, N. Thirupathi, M. H. Babu, Eur. J. Org.
Chem. 2012, 5803–5809; o) M. S. Reddy, N. Thirupathi,
Y. K. Kumar, RSC Adv. 2012, 2, 3986–3992; p) Y. K.
Kumar, G. R. Kumar, T. J. Reddy, B. Sridhar, M. S.
Reddy, Org. Lett. 2015, 17, 2226–1260.
Adv. Synth. Catal. 2016, 358, 303 – 313
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
313