Ruthenium-catalyzed synthesis of isoquinolones with 8-aminoquinoline as a bidentate directing group in C-H functionalization

Article abstract of DOI:10.1021/jo500424p

Ruthenium-catalyzed oxidative annulation of N-quinolin-8-yl-benzamides with alkynes in open air has been achieved using 8-aminoquinolinyl moiety as a bidentate directing group in the presence of Cu(OAc)₂·H ₂O as an oxidant. This reaction offers a broad substrate scope, and both symmetrical and unsymmetrical alkynes can be applied. High regioselectivity was achieved in the case of unsymmetrical (aryl)alkynes. Reaction with heteroaryl amides was also successful in this catalytic process. A ruthenium-N-quinolin-8-yl-benzamide complex was isolated in the absence of alkyne; in the absence of both N-quinolin-8-yl-benzamide and alkyne, in contrast to literature, only the monoacetate complex RuCl(OAc)(p-cymene), but not the bis-acetate complex Ru(OAc)₂(p-cymene), was isolated. These data suggest that this reaction may proceed via N,N-bidentate chelate complex. Key products were characterized by X-ray crystallography.

Full text of DOI:10.1021/jo500424p

Article
pubs.acs.org/joc
Ruthenium-Catalyzed Synthesis of Isoquinolones with
8‑Aminoquinoline as a Bidentate Directing Group in C−H
Functionalization
Srinivasarao Allu and K. C. Kumara Swamy*
School of Chemistry, University of Hyderabad, Hyderabad 500 046, Andhra Pradesh, India
S
* Supporting Information
ABSTRACT: Ruthenium-catalyzed oxidative annulation of N-
quinolin-8-yl-benzamides with alkynes in open air has been
achieved using 8-aminoquinolinyl moiety as a bidentate
directing group in the presence of Cu(OAc)2·H2O as an
oxidant. This reaction offers a broad substrate scope, and both
symmetrical and unsymmetrical alkynes can be applied. High
regioselectivity was achieved in the case of unsymmetrical
(aryl)alkynes. Reaction with heteroaryl amides was also
successful in this catalytic process. A ruthenium-N-quinolin-
8-yl-benzamide complex was isolated in the absence of alkyne;
in the absence of both N-quinolin-8-yl-benzamide and alkyne,
in contrast to literature, only the monoacetate complex RuCl(OAc)(p-cymene), but not the bis-acetate complex Ru(OAc)2(p-
cymene), was isolated. These data suggest that this reaction may proceed via N,N-bidentate chelate complex. Key products were
characterized by X-ray crystallography.
alkynes leading to isoquinolones13 using pyridylmethylamine
INTRODUCTION
■
as an auxiliary directing group; they find that 8-aminoquino-
line as an ineffective directing group for this transformation.
In our work here, we have observed that in the presence of
{[RuCl2(p-cymene)]}2 and Cu(OAc)2, 8-aminoquinoline
directed oxidative annulation takes place. Also, this reaction
takes place via the formation of monoacetate complex
[RuCl(OAc)(p-cymene)] and not the bis-acetate complex
[Ru(OAc)2(p-cymene)], in contrast to the literature reports.14
Thus, herein we report an efficient and readily applicable
method for the synthesis of isoquinolones via oxidative
annulation of aromatic amides with alkynes using 8-amino-
quinoline as an auxiliary bidentate directing group.
Because of the importance of nitrogen-containing heterocycles
in biology and materials chemistry, various synthetic routes
have been developed for their synthesis and functionalization.
These structural motifs are widely present in natural products
and medicinally relevant compounds.1 Transition metal
catalyzed C−H functionalization is an important tool in
construction of these synthetic targets.2 After the first report
by Murai et al., directing groups received a significant
attention, since they selectively activate the proximal C−H
bond through metal chelation.3 A wide variety of structurally
simple monodentate directing groups like carbonyl,4a,b acid,4c,d
amide,4e,f amine,4g,h pyridine,4i,j imine,4k,l Si,N-type chelation-
assisted auxiliary,4m,n etc., are well explored in C−H bond
transformations. After the discovery of Pd(II)-catalyzed
arylation of unactivated sp3 C−H bonds by Daugulis et al.,5
the use of bidentate directing groups picolinamide,6 8-
aminoquinoline,7 N-(2-pyridylsulfonyl),8 sulfixamine,9 and 2-
methylthioaniline10 were also explored in C−H bond
functionalization, including those in the total synthesis of
natural products.
Isoquinolone skeleton is widely found in diverse natural
products and medicinally important building blocks; hence,
there are many synthetic routes for this class of compounds.11
Chatani et al. recently reported the [Ru]-catalyzed carbon-
ylation12a,b and arylation12c of aromatic amides using
pyridylmethylamine, and 8-aminoquinoline as bidentate
directing groups in which these moieties coordinate in an
N,N-fashion to the ruthenium center. They have also reported
the Ni-catalyzed oxidative annulation of aromatic amides with
RESULTS AND DISCUSSION
■
We began our study by investigating the Ru-catalyzed
oxidative annulation of N-quinolin-8-yl-benzamide 1a with
alkyne 2a. To this end, we have screened several oxidants and
solvents. The reaction of amide 1a (0.4 mmol) with alkyne 2a
(0.6 mmol) in the presence of [{RuCl2(p-cymene)}2] (5 mol
%)/Cu(OAc)2·H2O (0.8 mmol) in tAmOH solvent at 110 °C
afforded the product 3 in 57% yield (Table 1, entry 1). By
increasing the amount of alkyne to 0.8 mmol, complete
conversion of the amide occurred, and the product was
isolated in excellent yield (74%) (entry 2); the reaction
mixture showed complete consumption of the amide. Use of
Received: February 21, 2014
Published: April 14, 2014
© 2014 American Chemical Society
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benzamide (4) gave the isoquinolone derivative in very poor
yield (11%) (Scheme 1). This result suggests that 8-
aminoquinoline (bidentate chelation) is necessary for
completion of the reaction.
Table 1. Optimization Study for the [Ru]-Catalyzed
Oxidative Annulation
a
With the optimization conditions in hand, we investigated
the substrate scope with N-quinolin-8-yl-benzamides (1a−p)
and a variety of internal alkynes (2a−n). Gratifyingly, in all
the cases good to excellent yields of the isoquinolone
products were obtained (Scheme 2, Table 2, compounds 3
and 6−37). The structure of the isoquinolone 3 was
confirmed by X-ray crystallography. The reaction works well
with both electron-rich (4-Me, 4-OMe, 3,5-Me) and electron-
deficient (4-Cl, 4-CF3) symmetrical arylalkynes, affording the
isoquinolone derivatives (6−10) in 66−79% yields. Heteroaryl
alkynes were tolerated under the catalytic conditions, and the
corresponding isoquinolone 11 was formed in good yield
(63%). It was also found that dialkylacetylenes reacted
smoothly with amide 1a. When the reaction was performed
with 3-hexyne or 4-octyne, the corresponding oxidative
cycloaddition products [12, 13 (X-ray)] were obtained in
good yields (60%, 63%). When unsymmetrical phenyl(alkyl)
alkynes were used, interestingly, only one isomer was obtained
in a highly regioselective manner. Thus, the reaction of amide
1a with alkynes 1-phenyl-1-pentyne (2j), 1-phenyl-1-butyne
(2k), or 1-phenyl-1-propyne (2l) afforded the products 14−
16, which contain the C-aryl carbon adjacent to amide
nitrogen, in good yields (62−72%). The regioselectivity of the
product was further confirmed by X-ray crystallography for
compound 16. These results suggest that there might be pi−
pi stacking directing the observed regioselectivity in the
products. However, the selectivity was less significant when 1-
(4-nitrophenyl)-2-(4-tolyl)acetylene (2m) was used; the major
isomer (17; X-ray), though, was the one with the C-
nitrophenyl group adjacent to amide nitrogen. In the case of
usymmetrical dialkylacetylene (n-hexyl)CCMe (2n), iso-
meric products (37) in the ratio 7:3 were observed, thus
showing less selectivity. We also attempted reactions using the
terminal alkyne, phenylacetylene. However, in this case, only
dialkyne product was obtained by self-coupling. Substituted
benzamides (1b−p) with diphenylacetylene (2a) behaved
similarly to afford the isoquinolones 19−32 in good yields
(61−78%). This oxidative annulation process took place in a
highly regioselective manner when we used meta-substituted
amides. Thus, the reactions of meta-iodo or methyl substituted
amides (1k, 1l) reacted smoothly with diphenylacetylene and
gave the isoquinolones 28−29 as single regioisomers, in which
the less hindered C−H bond was functionalized. The reaction
also worked well with ortho-substituted amide 1m or
naphthylamide 1n affording the products 30 (73%) or 31
(64%) in excellent yield. Substitution at the 5-OMe
substituted N-quinolin-8-yl-benzamide also gave good yield
of the corresponding isoquinolone 32. Extension of this
oxidative annulation process to heteroarylamides was
yield
b
entry
oxidant
solvent
(%)
c
1
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
AgOAc
tAmOH
tAmOH
H2O
57
2
74
3
22
4
DMF
45
5
toluene
p-xylene
DCE
56
6
56
7
trace
trace
trace
57
8
tAmOH
tAmOH
nBuOH
tBuOH
tAmOH
tAmOH
tAmOH
tAmOH
tAmOH
9
Ag2CO3
10
11
12
13
14
15
16
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
−
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
68
d
54
trace
e
74
f
22
16
(catalyst: 5.0 mol % cpRuCl(PPh3)2)
17
18
Cu(OAc)2·H2O
tAmOH
tAmOH
trace
27
(catalyst: 5.0 mol % Ru3(CO)12)
Cu(OAc)2·H2O
(30 mol % KOAc used as additive)
a
Reaction conditions: amide (0.4 mmol), alkyne (0.8 mmol), oxidant
(0.8 mmol), solvent (2 mL), 110 °C (oil bath temperature). Isolated
yields. 1.5 equiv of alkyne used. 2.5 mol % catalyst used. In open air.
b
c
d
e
f
0.5 equiv of Cu(OAc)2·H2O used.
other solvents like H2O, DMF, toluene, xylene, DCE, BuOH
did not improve the yield (entries 3−7, 10, 11). Product
formation was not observed when Ag(I) salts were used
instead of Cu(OAc)2·H2O as the oxidant (entries 8−9).
Lower yield of the product was observed when the catalyst
loading was decreased to 2.5 mol % (entry 12). A control
experiment showed that Cu(OAc)2·H2O was necessary for the
reaction (entry 13). It is noteworthy that under the same
catalytic conditions in open air also the reaction afforded the
same amount of the product (74%) (entry 14). Rather
surprisingly, when we used atmospheric oxygen as an oxidant
along with Cu(OAc)2·H2O (0.5 equiv), only 22% of the
product was observed (entry 15). We have screened other
ruthenium complexes like Ru3(CO)12 or CpRuCl(PPh3)2, we
did not get good yield (entries 16−17). When KOAc was
used as additive along with Cu(OAc)2·H2O, lower yield of the
product was observed.
Under the above catalytic conditions, the structurally
similar, but monodentate directing group naphthyl substituted
Scheme 1. Oxidative Annulation Reaction Using Naphthyl-Substituted Benzamide
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Scheme 2. [Ru]-Catalyzed Reactions of N-Quinolin-8-yl-benzamides with Internal Alkynes
successful under the catalytic conditions. 3-Thiopheneamide
reacted smoothly with alkyne and furnished the cyclized
product 33 in a regioselective manner. Here, the C−H
functionalization occurred at the more active 2-position of the
thiophene. The 2-substituted heteroamides (thiophenyl,
furanyl and indolyl) also reacted well with alkyne and gave
the isoquinolone derivatives 34−36 in decent yields (51−
61%).
monoacetate complex 38 with an equimolar quantity of
amide 1a in stoichiometric amounts in tAmOH under reflux
conditions yielded the ruthenium complex 40 in quantitative
yield (Scheme 3b). The same complex 40 was also obtained
by treating the N-quinolin-8-yl-benzamide 1a with {RuCl2(p-
cymene)}2 albeit in 52% yield; the yield was better in the
presence of NaOAc. In this complex 40, ruthenium is
coordinated to the N-quinolin-8-yl-benzamidyl moiety in a
N,N-fashion. There was no indication to suggest the
replacement of second chlorine by acetate under these
conditions or even after 36 h. Treatment of chloro ligated
ruthenium complex 40 with Cu(OAc)2·H2O in tAmOH
resulted in some unidentified products, but in the presence of
stoichiometric amount of alkyne 2a, it directly afforded the
isoquinolone derivative 3 in 85% yield. In the absence of
Cu(OAc)2·H2O this annulation reaction did not proceed.
However, we found that use of 40 (10 mol %) as a catalyst
did not perform that well and only ca. 28% yield of the
product was obtained. It should be noted here that in both
cases the amount of ruthenium metal was the same. We have
also checked the catalytic activity of the mono and bis-acetate
ruthenium complexes. Both of these complexes show very
poor activity and result in low yields of 3 (Scheme 3c). It may
be noted that similar reactions using 2-pyridinylmethylamine
in the presence of Ni(cod)2 as the catalyst has been reported
before.13 The latter catalyst is air-sensitive, while {RuCl2(p-
cymene)}2 is air-stable. In addition, the reaction using
Ni(cod)2 had to be conducted in a glovebox, while our
ruthenium catalyzed reaction is conducted in open air.
What Are the Intermediates? For more information on
the reaction pathway, we have conducted some step by step
reactions (Scheme 3). The reaction of [{RuCl2(p-cymene)}2]
Scheme 3. Preliminary Experiments to Know the Reaction
Pathway
On the basis of the above experiments and previous
mechanistic insight,11h,15 we propose a plausible reaction
pathway shown in Scheme 4. First, [RuCl2(p-cymene)]2
undergoes ligand exchange with Cu(OAc)2 to give the
monoacetate species RuCl(OAc)(p-cymene) (38), which
undergoes coordination of nitrogen atom of the quinoline
moiety and the oxidative addition of the N−H bond giving
the metal complex 40. Then in the presence of Cu(OAc)2
and alkyne, complex 40 undergoes ligand exchange with the
acetate ion to lead to (I). This is followed by C−H activation
through the elimination of AcOH, forming the five membered
matallacycle intermediate II. The oxidative addition of alkyne
to II generates the intermediate III. Then reductive
elimination gives compound 3 and the active catalyst is
regenerated. The only disconcerting point here is that on its
own, 40 is not very active as a catalytic intermediate.
(1.0 equiv) with Cu(OAc)2·H2O (40.0 equiv) under reflux
conditions in tAmOH afforded the monoacetate complex
[RuCl(OAc)(p-cymene)] (38) and not the bis(acetate)
complex [Ru(OAc)2(p-cymene)] (39) (Scheme 3a). Pre-
viously, Pozgana and Dixneuf had prepared the latter complex
̌
by reacting [{RuCl2(p-cymene)}2] with 4 mol equiv of KOAc
in NMP.14a Thus, there appears to be difference in the
reactivity of [{RuCl2(p-cymene)}2] under these two con-
ditions. In a further step, the reaction between the
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a
Table 2. Substituted Isoquinolones Synthesized in This Study by C−H Functionalization
a
Reaction conditions: amide (0.4 mmol), alkyne (0.8 mmol), [{RuCl2(p-cymene)}2] (5 mol %)/Cu(OAc)2·H2O (0.8 mmol), tAmOH (2 mL), 110
b
c
d
°C (oil bath temperature), in open air, 24 h. Isolated yield. Combined yield (17 + 18). Amide used was
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1
750; H NMR (400 MHz, CDCl3) δ 10.77 (br s, 1H), 8.89−8.87
(m, 2H), 8.17 (d, J = 8.4 Hz, 1H), 7.63 (s, 1H), 7.58−7.53 (m, 2H),
7.47 (dd, J ∼ 8.2 and 4.2 Hz, 1H), 7.31 (d, J = 3.2 Hz, 1H), 6.59−
6.58 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 156.5, 148.5, 144.6,
138.7, 136.4, 134.3, 128.1, 127.5, 121.9, 121.8, 116.7, 115.2, 112.5;
LC−MS m/z 239 [M + 1]+. Anal. Calcd for C14H10N2O2: C, 70.58;
H, 4.23; N, 11.76. Found: C, 70.46; H, 4.27; N, 11.65.
Scheme 4. Plausible Reaction Pathway for the Formation of
3 (and 6−37)
(ii). General Procedure for the Ruthenium-Catalyzed
Coupling of N-Quinolin-8-yl-benzamides with Alkynes: Syn-
thesis of Compounds 3 and 5−37. A mixture of N-quinolin-8-yl-
benzamide or naphthyl benzamide (0.4 mmol), diphenylacetylene
(0.8 mmol), [RuCl2(p-cymene)]2 (5 mol %), and Cu(OAc)2·H2O
(0.8 mmol) was taken in a Schlenk tube [under ambient conditions;
no inert atmosphere needed]. To this, tAmOH (2 mL) was added,
and the mixture was stirred at 110 °C (oil bath temperature) for 24
h. After cooling to rt, saturated NH4Cl solution (50 mL) was added,
and the contents were extracted with EtOAc (3 × 30 mL). The
combined organic phase was washed with brine solution (30 mL),
dried over anh. Na2SO4, and concentrated in vacuo. The crude
product was purified by column chromatography on silica gel using
n-hexane-EtOAc (1:1) mixture as the eluent.
Compound 3. Yield 0.127 g (74%, white solid): mp 246−248 °C;
IR (KBr, cm−1) 3052, 2926, 1655, 1595, 1490, 1332, 1178, 1030,
1
816, 784, 707; H NMR (400 MHz, CDCl3) δ 8.94 (d, J = 4.0 Hz,
1H), 8.59 (d, J = 7.6 Hz, 1H), 8.07 (d, J = 8.4 Hz, 1H), 7.67 (d, J =
8.0 Hz, 1H), 7.61(t, J ∼ 7.6 Hz, 1H), 7.55−7.49 (m, 2H), 7.40−7.36
(m, 2H), 7.32 (d, J = 8.0 Hz, 1H), 7.27−7.25 (m, 2H), 7.18−7.16
(m, 3H), 6.98 (d, J = 7.6 Hz, 1H), 6.84 (t, J = 7.6 Hz, 1H), 6.76−
6.71 (m, 2H), 6.50 (t, J = 7.6 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 162.8, 150.8, 144.7, 141.9, 138.2, 137.7, 136.6, 136.1,
134.9, 132.5, 131.9, 131.7, 130.9, 130.8, 129.8, 128.8, 128.6, 128.5,
128.1, 127.8, 127.3, 126.8, 126.7, 126.5, 125.8, 125.7, 121.5, 118.6;
HRMS (ESI) Calcd for C30H21N2O [M+ + H] m/z 425.1655, found
425.1656. X-ray structure was determined for this compound.
Compound 5. Yield 0.018 g (11%, white solid): mp 200−204 °C;
IR (KBr, cm−1) 3057, 2926, 1649, 1610, 1484, 1440, 1397, 1254,
CONCLUSIONS
■
In summary, we have developed an efficient method for the
synthesis of isoquinolones via the oxidative annulation of N-
quinolin-8-yl-benzamides with alkynes with the aid of 8-
aminoquinoline as bidentate directing group in the presence
of Ru-catalyst in open air. The reaction features a high
regioselectivity, good substrate scope, and large functional
group tolerance. We have also successfully extended this
method to heterocyclic amides. A ruthenium N-quinolin-8-yl-
benzamide complex is isolated and characterized, showing the
key role played by the quinoline moiety. Further synthetic
applications of directing group methodology and mechanistic
studies may reveal many more useful transformations.
1
1029, 914, 777; H NMR (400 MHz, CDCl3) δ 8.61 (d, J = 8.0 Hz,
1H), 7.77 (d, J = 8.0 Hz, 1H), 7.72 (d, J ∼ 8.2 Hz, 1H), 7.69−7.63
(m, 2H), 7.59−7.56 (m, 1H), 7.52−7.43 (m, 2H), 7.35−7.28 (m,
2H), 7.26−7.24 (m, 3H), 7.19−7.14 (m, 3H), 7.00 (d, J = 7.6 Hz,
1H), 6.86 (t, J ∼ 7.4 Hz, 1H), 6.75 (t, J ∼ 7.4 Hz, 1H), 6.61 (d, J =
7.6 Hz, 1H), 6.54−6.52 (m, 1H); 13C NMR (100 MHz, CDCl3) δ
162.7, 142.0, 138.0, 136.4, 134.5, 134.0, 132.8, 131.8, 131.7, 131.1,
131.0, 129.5, 128.64, 128.56, 128.4, 128.1, 128.0, 127.9, 127.4, 127.1,
127.0, 126.8, 126.7, 126.2, 125.8, 125.6, 125.0, 123.0, 119.2; HRMS
(ESI) Calcd for C31H22NO [M+ + H] m/z 424.1702, found
424.1701.
Compound 6. Yield 0.128 g (70%, white solid): mp 278−282 °C;
IR (KBr, cm−1) 3014, 2909, 1660, 1507, 1337, 1178, 1025, 899, 734;
1H NMR (400 MHz, CDCl3) δ 8.94 (d, J = 2.8 Hz, 1H), 8.57 (d, J
= 8.0 Hz, 1H), 8.07 (d, J = 8.0 Hz, 1H), 7.67 (d, J = 8.4 Hz, 1H),
7.59 (t, J ∼ 7.6 Hz, 1H), 7.53−7.46 (m, 2H), 7.39−7.36 (m, 2H),
7.30 (d, J = 8.0 Hz, 1H), 7.14 (d, J = 8.0 Hz, 1H), 7.05 (t, J = 7.2
Hz, 2H), 6.98 (d, J = 8.0 Hz, 1H), 6.85 (d, J = 7.6 Hz, 1H), 6.63 (t,
J ∼ 7.8 Hz, 2H), 6.29 (d, J = 7.6 Hz, 1H), 2.28 (s, 3H), 1.95 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 162.9, 150.7, 144.8, 142.0,
138.5, 137.9, 136.7, 136.1, 133.7, 132.4, 132.1, 131.7, 131.5, 130.9,
130.7, 129.6, 128.8, 128.53, 128.47, 128.4, 127.4, 127.2, 126.5, 125.8,
125.7, 125.6, 121.5, 118.6, 21.3, 21.1; HRMS (ESI) Calcd for
C32H25N2O [M+ + H] m/z 453.1968, found 453.1968.
EXPERIMENTAL SECTION
■
General Comments. Solvents were dried according to known
methods as appropriate.16 1H, 13C spectra (1H, 400 MHz; 13C, 100
MHz) were recorded using a 400 MHz spectrometer in CDCl3 with
shifts referenced to SiMe4 (δ = 0). IR spectra were recorded on an
FTIR spectrophotometer. Melting points were determined by using a
local hot-stage melting point apparatus and are uncorrected.
Elemental analyses were carried out on a CHN analyzer. Mass
spectra were recorded using LC−MS and HRMS (ESI-TOF
analyzer) equipment.
(i). Synthesis of Precursor Amides 1a−1p and 4. All the
amide precursors bearing 8-aminoquinoline moiety were prepared by
the reaction of corresponding acid chlorides with 8-aminoquinoline
according to the literature procedures.17 Compounds 1a−1n and 4
are known. Compounds 1o and 1p are new.
Compound 1o. Yield 1.126 g (81%, yellow solid): mp 120−124
°C; IR (KBr, cm−1) 3375, 2981, 1677, 1551, 1496, 1397, 1282, 1151,
1
Compound 7. Yield 0.139 g (72%, white solid): mp 268−272 °C;
1085, 827, 784, 679; H NMR (400 MHz, CDCl3) δ 10.51 (br s,
IR (KBr, cm−1) 2920, 1649, 1589, 1556, 1474, 1326, 1222, 1025,
1H), 8.88 (s, 2H), 8.86 (s, 1H), 8.61 (dd, J = 8.4 and 1.6 Hz, 1H),
8.09−8.07 (m, 1H), 7.58−7.55 (m, 3H), 7.47 (dd, J = 8.4 and 1.6
Hz, 1H), 6.90 (d, J = 8.8 Hz, 1H), 4.02 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 165.2, 150.5, 148.8, 139.6, 135.5, 131.7, 131.4,
128.8, 128.1, 127.3, 120.9, 120.6, 116.8, 104.5, 55.9; LC−MS m/z
279 [M + 1]+. Anal. Calcd for C17H14N2O2: C, 73.37; H, 5.07; N,
10.07. Found: C, 73.51; H, 5.16; N, 10.15.
1
833, 795, 701; H NMR (400 MHz, CDCl3) δ 8.96 (d, J = 2.4 Hz,
1H), 8.57 (d, J = 8.0 Hz, 1H), 8.07 (d, J = 8.4 Hz, 1H), 7.66 (d, J =
8.0 Hz, 1H), 7.60 (t, J = 7.2 Hz, 1H), 7.51 (t, J ∼ 7.4 Hz, 1H), 7.45
(d, J = 7.2 Hz, 1H), 7.38−7.31 (m, 3H), 6.91 (br s, 1H), 6.78 (br s,
2H), 6.57 (br s, 1H), 6.33 (d, J = 8.4 Hz, 2H), 2.25 (s, 3H), 2.15 (s,
3H), 1.97 (s, 3H), 1.58 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
162.8, 150.6, 145.0, 142.0, 138.4, 138.0, 137.2, 136.8, 136.4, 135.9,
135.6, 135.5, 134.7, 132.3, 130.8, 129.7, 129.5, 128.7, 128.6, 128.4,
Compound 1p. Yield 0.940 g (79%, yellow solid): mp 138−142
°C; IR (KBr, cm−1) 3326, 1682, 1595, 1545, 1332, 1156, 1008, 871,
3967
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128.32, 128.25, 127.8, 126.4, 125.8, 125.7, 125.5, 121.3, 118.5, 21.3,
21.2, 20.9, 20.5; HRMS (ESI) Calcd for C34H29N2O [M+ + H] m/z
481.2281, found 481.2279.
Hz, 1H), 7.79 (d, J = 8.4 Hz, 1H), 7.74−7.67 (m, 3H), 7.47−7.42
(m, 2H), 2.91−2.85 (m, 2H), 2.61−2.55 (m, 1H), 2.12−2.06 (m,
1H), 1.34 (t, J ∼ 7.4 Hz, 3H), 0.89 (t, J = 7.6 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 163.3, 151.4, 144.9, 141.8, 137.5, 136.4, 132.5,
130.7, 130.4, 129.4, 129.2, 128.8, 126.3, 125.7, 125.6, 122.9, 121.9,
114.8, 23.7, 20.7, 15.0, 14.1; HRMS (ESI) Calcd for C22H21N2O [M+
+ H] m/z 329.1655, found 329.1654. X-ray structure was determined
for this compound.
Compound 8. Yield 0.138 g (71%, white solid): mp 236−240 °C;
IR (KBr, cm−1) 3052, 2986, 1660, 1611, 1507, 1474, 1326, 1244,
1
1184, 1025, 893, 816; H NMR (400 MHz, CDCl3) δ 8.93 (d, J =
2.8 Hz, 1H), 8.57 (d, J = 7.6 Hz, 1H), 8.07 (d, J = 7.6 Hz, 1H), 7.68
(d, J = 8.0 Hz, 1H), 7.60 (t, J = 7.2 Hz, 1H), 7.53−7.47 (m, 2H),
7.41−7.36 (m, 2H), 7.32 (d, J = 8.4 Hz, 1H), 7.15 (dd, J = 8.4 and
1.6 Hz, 1H), 7.08 (d, J = 8.4 Hz, 1H), 6.88−6.86 (m, 1H), 6.80 (dd,
J = 8.4 and 2.4 Hz, 1H), 6.73 (dd, J = 8.4 Hz and J = 2.4 Hz, 1H),
6.67−6.65 (m, 1H), 6.38 (dd, J = 8.8 Hz and J = 2.4 Hz, 1H), 6.03
(dd, J = 8.4 Hz and J ∼ 2.2 Hz, 1H), 3.76 (s, 3H), 3.50 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 162.8, 158.2, 150.7, 144.8, 141.9, 138.6,
137.9, 136.1, 132.9, 132.7, 132.4, 132.0, 131.0, 130.9, 129.0, 128.8,
128.5, 128.4, 127.6, 126.5, 125.9, 125.7, 121.5, 118.4, 113.5, 113.4,
112.1, 112.0, 55.1, 54.8; HRMS (ESI) Calcd for C32H25N2O3 [M+ +
H] m/z 485.1866, found 485.1864.
Compound 14. Yield 0.113 g (72%, white solid): mp 144−148
°C; IR (KBr, cm−1) 3052, 2921, 2866, 1655, 1611, 1562, 1490, 1332,
1
1030, 822, 795, 701; H NMR (400 MHz, CDCl3) δ 8.90−8.89 (m,
1H), 8.58 (d, J = 7.6 Hz, 1H), 8.04 (dd, J ∼ 7.8 Hz and ∼1.4 Hz,
1H), 7.83−7.75 (m, 2H), 7.64 (d, J = 8.0 Hz, 1H), 7.54 (t, J ∼ 7.6
Hz, 1H), 7.46−7.44 (m, 1H), 7.38−7.34 (m, 2H), 7.19 (d, J = 7.6
Hz, 1H), 7.12 (d, J ∼ 7.4 Hz, 1H), 6.97 (t, J ∼ 7.4 Hz, 1H), 6.88 (d,
J = 7.6 Hz, 1H), 6.72 (t, J ∼ 7.4 Hz, 1H), 2.49−2.43 (m, 2H), 1.63−
1.59 (m, 2H), 0.85 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 162.6, 150.7, 144.7, 141.1, 137.9, 137.4, 136.0, 135.2,
132.5, 131.0, 130.3, 129.2, 128.9, 128.7, 128.4, 127.8, 127.2, 127.0,
126.4, 126.3, 125.7, 123.6, 121.4, 115.1, 30.7, 23.7, 14.4; HRMS
(ESI) Calcd for C27H23N2O [M+ + H] m/z 391.1811, found
391.1809.
Compound 9. Yield 0.156 g (79%, white solid): mp 282−286 °C;
IR (KBr, cm−1) 2921, 1649, 1595, 1490, 1403, 1326, 1145, 1096,
1
1014, 893, 822, 784, 603; H NMR (400 MHz, CDCl3) δ 8.91 (d, J
= 2.4 Hz, 1H), 8.58 (d, J = 8.0 Hz, 1H), 8.11−8.08 (m, 1H), 7.73−
7.71 (m, 1H), 7.63−7.61 (m, 1H), 7.57−7.50 (m, 2H), 7.44−7.38
(m, 2H), 7.25−7.20 (m, 3H), 7.14 (t, J ∼ 7.0 Hz, 2H), 6.91−6.84
(m, 2H), 6.71 (dd, J = 8.4 and 1.2 Hz, 1H), 6.52−6.50 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ 162.7, 150.9, 144.6, 140.9, 137.7, 137.3,
136.2, 134.9, 133.5, 133.2, 133.14, 133.08, 132.9, 132.7, 132.0, 131.1,
130.9, 129.0, 128.9, 128.6, 128.4, 127.2, 127.1, 127.0, 125.9, 125.7,
Compound 15. Yield 0.094 g (62%, white solid): mp 178−182
°C; IR (KBr, cm−1) 2959, 1649, 1611, 1490, 1332, 1151, 1074, 816,
1
784, 701; H NMR (400 MHz, CDCl3) δ 8.90 (d, J = 2.8 Hz, 1H),
8.58 (d, J = 8.0 Hz, 1H), 8.04 (d, J = 8.0 Hz, 1H), 7.86 (d, J = 8.0
Hz, 1H), 7.78 (t, J ∼ 7.4 Hz, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.55 (t,
J = 7.6 Hz, 1H), 7.45 (d, J = 6.4 Hz, 1H), 7.38−7.34 (m, 2H), 7.20
(d, J = 7.2 Hz, 1H), 7.13 (t, J = 7.6 Hz, 1H), 6.98 (t, J ∼ 7.4 Hz,
1H), 6.89 (d, J = 7.6 Hz, 1H), 6.73 (t, J ∼ 7.4 Hz, 1H), 2.59−2.50
(m, 2H), 1.15 (t, J ∼ 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
162.6, 150.8, 144.7, 140.9, 137.9, 137.1, 136.0, 135.3, 132.5, 131.0,
130.2, 129.1, 129.0, 128.8, 128.5, 127.8, 127.4, 127.1, 126.5, 125.8,
123.6, 121.5, 116.3, 21.7, 14.9; HRMS (ESI) Calcd for C26H21N2O
[M+ + H] m/z 377.1655, found 377.1656.
125.4, 121.7, 117.6; HRMS (ESI) Calcd for C30H19Cl2N2O [M+
+
H] 493.0875, found m/z 493.0873, 495.0841 and 497.0816.
Compound 10. Yield 0.149 g (66%, white solid): mp 262−266
°C; IR (KBr, cm−1) 3057, 1660, 1611, 1485, 1321, 1173, 1107, 1063,
1
827, 679; H NMR (400 MHz, CDCl3) δ 8.93 (d, J = 4.0 Hz, 1H),
8.60 (d, J = 7.6 Hz, 1H), 8.10 (d, J = 8.0 Hz, 1H), 7.72 (d, J = 8.0
Hz, 1H), 7.67−7.57 (m, 2H), 7.54−7.52 (m, 2H), 7.48 (d, J = 8.4
Hz, 1H), 7.43−7.39 (m, 2H), 7.34 (t, J ∼ 8.2 Hz, 2H), 7.21 (d, J =
8.0 Hz, 1H), 7.12 (t, J = 9.2 Hz, 2H), 6.93 (d, J = 8.0 Hz, 1H), 6.80
(d, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 162.6, 151.0,
144.5, 140.7, 140.1, 138.1, 137.3, 137.0, 136.3, 132.9, 132.2, 132.0,
131.1, 131.0, 130.3, 129.8, 129.6, 129.5, 129.2, 129.0, 128.7, 127.4,
125.9, 125.4, 125.1, 124.8, 123.9, 123.6, 122.1, 121.8, 117.5; HRMS
(ESI) Calcd for C32H19F6N2O [M+ + H] m/z 561.1402, found
561.1401.
Compound 16. Yield 0.091 g (62%, white solid): mp 186−190
°C; IR (KBr, cm−1) 2921, 1655, 1616, 1485, 1332, 1145, 899, 789,
1
756, 707; H NMR (400 MHz, CDCl3) δ 8.91 (d, J = 2.8 Hz, 1H),
8.57 (d, J = 8.0 Hz, 1H), 8.05 (dd, J = 8.4 and 1.2 Hz, 1H), 7.83−
7.76 (m, 2H), 7.65 (d, J = 8.0 Hz, 1H), 7.56 (t, J ∼ 7.4 Hz, 1H),
7.44 (d, J = 6.8 Hz, 1H), 7.38−7.34 (m, 2H), 7.19−7.12 (m, 2H),
6.98 (t, J ∼ 7.4 Hz, 1H), 6.86 (d, J = 7.6 Hz, 1H), 6.74 (t, J ∼ 7.4
Hz, 1H), 2.13 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 162.7, 150.9,
144.8, 140.9, 138.2, 138.0, 136.0, 135.5, 132.7, 131.0, 130.4, 129.3,
128.7, 128.5, 127.8, 127.4, 127.2, 126.6, 126.0, 125.8, 123.6, 121.5,
110.3, 14.9; HRMS (ESI) Calcd for C25H19N2O [M+ + H] m/z
363.1498, found 363.1498. X-ray structure was determined for this
compound.
Compound 11. Yield 0.110 g (63%, white solid): mp 248−252
°C; IR (KBr, cm−1) 3063, 1660, 1600, 1479, 1321, 1249, 1145, 833,
1
805, 696; H NMR (400 MHz, CDCl3) δ 8.96 (d, J = 2.8 Hz, 1H),
8.56 (d, J = 8.0 Hz, 1H), 8.13 (d, J = 8.4 Hz, 1H), 7.76 (d, J = 8.0
Hz, 1H), 7.69−7.65 (m, 1H), 7.58−7.52 (m, 3H), 7.47−7.40 (m,
2H), 7.27 (br s, 1H), 6.97−6.94 (m, 2H), 6.85 (d, J = 4.8 Hz, 1H),
6.48 (d, J = 2.8 Hz, 1H), 6.35 (dd, J = 3.6, 4.0 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 162.8, 151.0, 144.8, 138.1, 137.4, 137.2, 137.0,
136.3, 134.9, 132.8, 130.6, 130.0, 128.9, 128.4, 127.5, 127.2, 126.6,
126.0, 125.9, 125.8, 125.3, 121.7, 114.0; HRMS (ESI) Calcd for
C26H17N2OS2 [M+ + H] m/z 437.0783, found 437.0784.
Compound 17. Yield 0.067g (34%, combined yield along with 18
was 62%, yellow solid): mp >300 °C; IR (KBr, cm−1) 3052, 1655,
1
1589, 1523, 1479, 1348, 1107, 822, 789, 707; H NMR (400 MHz,
CDCl3) δ 8.93 (dd, J = 4.0 and 1.6 Hz, 1H), 8.60−8.58 (m, 1H),
8.09 (dd, J ∼ 8.2 and 1.4 Hz, 1H), 7.73−7.70 (m, 2H), 7.66−7.62
(m, 1H), 7.59−7.55 (m, 2H), 7.44−7.37 (m, 3H), 7.33 (d, J = 8.0
Hz, 1H), 7.17 (dd, J = 8.4 and 1.6 Hz, 1H), 7.08−7.06 (m, 3H),
7.03−6.99 (m, 2H), 2.28 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
162.5, 151.0, 146.4, 144.4, 141.8, 139.4, 137.9, 137.1, 136.3, 132.7,
132.5, 131.7, 131.5, 131.3, 131.1, 130.9, 129.2, 129.1, 129.0, 128.9,
128.5, 127.3, 125.9, 125.8, 121.9, 121.8, 121.7, 118.9, 21.2; HRMS
(ESI) Calcd for C31H22N3O3[M+ + H] 484.1662, found 484.1665. X-
ray structure was determined for this compound.
Compound 12. Yield 0.086 g (60%, white solid): mp 122−126
°C; IR (KBr, cm−1) 3063, 2959, 1655, 1551, 1496, 1370, 1326, 882,
1
833, 795, 696; H NMR (400 MHz, CDCl3) δ 8.86 (d, J = 4.0 Hz,
1H), 8.46 (d, J = 8.0 Hz, 1H), 8.24 (d, J = 8.4 Hz, 1H), 7.96 (d, J =
7.6 Hz, 1H), 7.76−7.66 (m, 4H), 7.46−7.41 (m, 2H), 2.80−2.75 (m,
2H), 2.51−2.45 (m, 1H), 1.98−1.90 (m, 1H), 1.77−1.70 (m, 2H),
1.39−1.29 (m, 2H), 1.12 (t, J ∼ 7.4 Hz, 3H), 0.54 (t, J = 7.2 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 163.2, 151.3, 144.9, 141.0,
137.7, 137.6, 136.3, 132.4, 130.4, 129.3, 129.1, 128.7, 126.2, 125.7,
125.6, 123.0, 121.8, 113.6, 32.8, 30.0, 23.7, 23.1, 14.6, 14.2; HRMS
(ESI) Calcd for C24H25N2O [M+ + H] m/z 357.1968, found
357.1967.
Compound 18. Yield 0.055 g (28%, combined yield along with 17
was 62%, yellow solid): mp 292−296 °C; IR (KBr, cm−1) 3063,
1
1655, 1589, 1507, 1342, 1189, 1151, 1019, 805, 712; H NMR (400
MHz, CDCl3) δ 8.92 (d, J = 2.8 Hz, 1H), 8.60 (d, J = 7.6 Hz, 1H),
8.13−8.04 (m, 3H), 7.70 (d, J = 8.0, 1H), 7.63 (t, J = 7.6 Hz, 1H),
7.56 (t, J ∼ 7.4 Hz, 1H), 7.49 (d, J = 6.8 Hz, 1H), 7.44−7.36 (m,
4H), 7.20 (d, J = 8.0 Hz, 1H), 6.82 (d, J = 7.6 Hz, 1H), 6.66 (d, J =
7.6 Hz, 1H), 6.60 (d, J = 8.0 Hz, 1H), 6.32 (d, J = 7.6 Hz, 1H), 1.97
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 162.7, 150.8, 146.6, 144.7,
Compound 13. Yield 0.083 g (63%, white solid): mp 190−194
°C; IR (KBr, cm−1) 3074, 2975, 1654, 1588, 1495, 1331, 1216, 1057,
1
832, 783, 701; H NMR (400 MHz, CDCl3) δ 8.88−8.87 (m, 1H),
8.46 (d, J = 8.0 Hz, 1H), 8.25 (d, J = 8.4 Hz, 1H), 7.97 (d, J = 8.0
3968
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1
144.4, 142.7, 137.6, 137.4, 137.1, 136.1, 132.9, 132.8, 132.7, 131.2,
130.8, 130.4, 129.5, 128.8, 127.8, 127.6, 127.1, 125.8, 125.6, 124.8,
123.4, 123.1, 121.6, 116.5, 21.1; HRMS (ESI) Calcd for
C31H22N3O3[M+ + H] 484.1662, found 484.1657.
948, 866, 822, 789, 729, 696; H NMR (400 MHz, CDCl3) δ 8.94
(dd, J ∼ 4.2 Hz and ∼1.4 Hz, 1H), 8.59 (dd, J = 8.8 and 2.0 Hz,
1H), 8.08−8.06 (m, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.50 (d, J = 7.2
Hz, 1H), 7.40−7.36 (m, 2H), 7.28−7.17 (m, 6H), 6.98−6.93 (m,
2H), 6.84 (t, J ∼ 7.8 Hz, 1H), 6.75−6.72 (m, 2H), 6.50 (t, J ∼ 7.4
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 165.6 (d, J = 250.4 Hz),
162.1, 150.9, 144.7, 143.3, 140.8, 140.7, 137.5, 136.0, 134.7, 131.7,
131.5, 130.8, 130.6, 129.6, 128.7, 128.2, 128.0, 127.4, 127.1, 126.7,
126.5, 125.8, 122.2, 121.6, 118.1, 115.3, 115.1, 111.0, 110.7; HRMS
(ESI) Calcd for C30H20FN2O [M+ + H] m/z 443.1560, found
443.1557.
Compound 19. Yield 0.128 g (71%, white solid): mp 280−284
°C; IR (KBr, cm−1) 2926, 1649, 1611, 1485, 1381, 1332, 1227, 1030,
1
937, 849, 784, 723; H NMR (400 MHz, CDCl3) δ 8.95 (dd, J = 8.4
and 1.6 Hz, 1H), 8.51 (d, J = 8.8 Hz, 1H), 8.06 (dd, J = 8.4 and 1.6
Hz, 1H), 7.67−7.65 (m, 1H), 7.51−7.49 (m, 1H), 7.39−7.35 (m,
2H), 7.24−7.21 (m, 2H), 7.18−7.10 (m, 4H), 6.97 (d, J = 7.6 Hz,
1H), 6.83 (t, J = 7.6 Hz, 1H), 6.76−6.70 (m, 2H), 6.68 (d, J = 2.4
Hz, 1H), 6.49 (t, J = 7.6 Hz, 1H), 3.75 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 163.1, 162.5, 150.8, 144.9, 142.6, 140.3, 137.8,
136.7, 136.1, 135.1, 131.9, 131.7, 131.1, 130.8, 130.7, 129.8, 128.8,
128.6, 128.1, 127.9, 127.2, 126.8, 126.7, 126.5, 125.8, 121.5, 119.6,
118.3, 115.4, 107.7, 55.4; HRMS (ESI) Calcd for C31H23N2O2 [M+ +
H] m/z 455.1760, found 455.1757.
Compound 25. Yield 0.134 g (72%, white solid): mp 264−268
°C; IR (KBr, cm−1) 3052, 1666, 1589, 1529, 1463, 1348, 1173, 1129,
1
1019, 915, 816, 784, 701; H NMR (400 MHz, CDCl3) δ 8.94 (dd, J
= 4.0 and 1.6 Hz, 1H), 8.74 (d, J = 8.8 Hz, 1H), 8.27 (dd, J ∼ 8.6
Hz and ∼2.2 Hz, 1H), 8.18 (d, J = 1.6 Hz, 1H), 8.09 (dd, J ∼ 8.2
Hz, and J ∼ 1.4 Hz, 1H), 7.71 (d, J = 8.0 Hz, 1H), 7.51−7.50 (m,
1H), 7.42−7.38 (m, 2H), 7.29−7.19 (m, 5H), 6.98 (d, J = 7.6 Hz,
1H), 6.87 (t, J ∼ 7.4 Hz, 1H), 6.78−6.72 (m, 2H), 6.52 (t, J ∼ 7.4
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 161.6, 151.0, 150.6, 144.5,
144.4, 139.0, 137.0, 136.2, 135.1, 134.2, 131.7, 131.4, 130.6, 130.5,
129.5, 129.2, 129.1, 128.8, 128.6, 128.4, 127.7, 127.6, 126.9, 126.7,
125.8, 121.8, 121.3, 120.3, 118.4; HRMS (ESI) Calcd for
C30H20N3O3 [M+ + H] m/z 470.1505, found 470.1504.
Compound 20. Yield 0.137 g (68%, white solid): mp 294−298
°C; IR (KBr, cm−1) 3058, 2921, 1655, 1589, 1468, 1315, 1151, 1074,
1
1019, 904, 816, 784, 701; H NMR (400 MHz, CDCl3) δ 8.94 (d, J
= 4.0 Hz, 1H), 8.43 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 8.0 Hz, 1H),
7.68 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.50−7.45 (m,
2H), 7.40−7.36 (m, 2H), 7.24−7.17 (m, 5H), 6.96 (d, J = 7.6 Hz,
1H), 6.84 (t, J ∼ 7.4 Hz, 1H), 6.73 (t, J ∼ 8.0 Hz, 2H), 6.50 (t, J =
7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 162.3, 150.9, 144.6,
143.4, 139.8, 137.4, 136.1, 135.8, 134.6, 131.8, 131.6, 130.8, 130.6,
130.3, 130.0, 129.7, 128.8, 128.3, 128.13, 128.08, 128.0, 127.4, 127.1,
126.8, 126.5, 125.8, 124.3, 121.6, 117.6; HRMS (ESI) Calcd for
C30H20BrN2O [M+ + H] m/z 503.0760 and 503.0740, found
503.0761 and 505.0744.
Compound 26. Yield 0.129 g (72%, white solid): mp 256−260
°C; IR (KBr, cm−1) 3063, 2921, 2225, 1660, 1616, 1551, 1496, 1474,
1
1332, 1173, 1019, 893, 789, 718; H NMR (400 MHz, CDCl3) δ
8.93−8.92 (m, 1H), 8.66 (d, J = 8.0 Hz, 1H), 8.08 (d, J = 8.0 Hz,
1H), 7.72−7.68 (m, 2H), 7.65 (s, 1H), 7.50 (d, J = 7.2 Hz, 1H),
7.41−7.37 (m, 2H), 7.29−7.27 (m, 1H), 7.22−7.16 (m, 4H), 6.98
(d, J = 7.6 Hz, 1H), 6.86 (t, J ∼ 7.4 Hz, 1H), 6.77−6.72 (m, 2H),
6.51 (t, J = 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 161.7,
150.9, 144.4, 144.2, 138.5, 137.1, 136.2, 135.2, 134.2, 131.7, 131.4,
130.7, 130.6, 130.5, 129.6, 129.5, 129.0, 128.8, 128.5, 128.3, 128.0,
127.7, 127.5, 126.9, 126.6, 125.8, 121.7, 118.6, 117.7, 116.0; HRMS
(ESI) Calcd for C31H20N3O [M+ + H] m/z 450.1607, found
450.1606.
Compound 21. Yield 0.137 g (78%, white solid): mp 284−288
°C; IR (KBr, cm−1) 2921, 1649, 1595, 1496, 1463, 1321, 1085, 1030,
1
910, 827, 784, 707; H NMR (400 MHz, CDCl3) δ 8.94 (d, J = 2.8
Hz, 1H), 8.51 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 8.0 Hz, 1H), 7.68 (d,
J = 8.0 Hz, 1H), 7.48 (t, J ∼ 7.2 Hz, 2H), 7.40−7.36 (m, 2H), 7.23−
7.17 (m, 6H), 6.96 (d, J = 8.0 Hz, 1H), 6.84 (t, J ∼ 7.4 Hz, 1H),
6.73 (t, J = 7.6 Hz, 2H), 6.50 (t, J = 7.6 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 162.2, 150.9, 144.6, 143.4, 139.6, 139.2, 137.4,
136.1, 135.9, 134.6, 131.8, 131.6, 130.8, 130.6, 130.3, 129.7, 128.8,
128.3, 128.1, 127.4, 127.2, 127.1, 126.8, 126.5, 125.8, 125.0, 124.0,
121.6, 117.8; HRMS (ESI) Calcd for C30H20ClN2O [M+ + H] m/z
459.1265 and 461.1232, found 459.1262 and 461.1237.
Compound 27. Yield 0.142 g (74%, white solid): mp 262−266
°C; IR (KBr, cm−1) 2948, 1655, 1616, 1479, 1392, 1321, 1184, 1019,
1
932, 827, 795, 701; H NMR (400 MHz, CDCl3) δ 8.92 (dd, J ∼ 4.6
Hz and ∼1.8 Hz, 1H), 8.53 (d, J = 8.4 Hz, 1H), 8.05 (d, J = 8.8 Hz,
1H), 7.66−7.60 (m, 2H), 7.50 (d, J = 7.2 Hz, 1H), 7.39−7.32 (m,
3H), 7.26−7.16 (m, 5H), 6.98 (d, J = 7.2 Hz, 1H), 6.85−6.82 (m,
1H), 6.76−6.70 (m, 2H), 6.51−6.47 (m, 1H), 1.28 (s, 9H); 13C
NMR (100 MHz, CDCl3) δ 162.7, 155.9, 150.8, 144.8, 141.8, 138.0,
137.9, 136.7, 136.0, 135.1, 131.9, 131.7, 131.0, 130.9, 129.9, 128.8,
128.5, 128.2, 128.0, 127.7, 127.2, 126.7, 126.6, 125.8, 124.8, 123.4,
121.8, 121.5, 118.9, 35.3, 31.1; HRMS (ESI) Calcd for C34H29N2O
[M+ + H] m/z 481.2281, found 481.2280.
Compound 22. Yield 0.132 g (74%, white solid): mp 270−274
°C; IR (KBr, cm−1) 2921, 1649, 1616, 1490, 1447, 1331, 1178, 1025,
1
816, 789, 723, 701; H NMR (400 MHz, CDCl3) δ 8.93 (d, J = 4.0
Hz, 1H), 8.48 (d, J = 8.0 Hz, 1H), 8.06 (d, J = 8.0 Hz, 1H), 7.66 (d,
J = 8.4 Hz, 1H), 7.49 (d, J = 7.6 Hz, 1H), 7.39−7.35 (m, 3H), 7.24
(br s, 2H), 7.18 (br s, 3H), 7.08 (br s, 1H), 6.96 (d, J = 7.6 Hz,
1H), 6.83 (t, J ∼ 7.4 Hz, 1H), 6.75−6.70 (m, 2H), 6.48 (t, J ∼ 7.6
Hz, 1H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 162.7, 150.8,
144.8, 143.0, 142.0, 138.3, 137.8, 136.7, 136.0, 135.1, 131.9, 131.7,
130.9, 130.8, 129.8, 128.7, 128.51, 128.47, 128.3, 128.0, 127.8, 127.2,
126.7, 126.6, 126.4, 125.8, 125.3, 123.5, 121.5, 118.4, 22.1; HRMS
(ESI) Calcd for C31H23N2O [M+ + H] m/z 439.1811, found
439.1812.
Compound 28. Yield 0.135 g (61%, white solid): mp 222−226
°C; IR (KBr, cm−1) 3063, 1654, 1594, 1495, 1473, 1320, 1134, 1073,
1
1024, 827, 788, 701; H NMR (400 MHz, CDCl3) δ 8.95 (d, J = 2.8
Hz, 1H), 8.91 (br s, 1H), 8.08 (d, J = 8.4 Hz, 1H), 7.86 (dd, J ∼ 8.6
Hz, and ∼1.8 Hz, 1H), 7.68 (d, J = 8.4 Hz, 1H), 7.48 (d, J = 7.6 Hz,
1H), 7.41−7.36 (m, 2H), 7.24−7.20 (m, 2H), 7.16−7.14 (m, 3H),
7.03 (d, J = 8.8 Hz, 1H), 6.95 (d, J = 7.6 Hz, 1H), 6.84 (t, J ∼ 7.6
Hz, 1H), 6.75−6.71 (m, 2H), 6.50 (t, J = 7.6 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 161.6, 150.7, 144.2, 142.5, 141.4, 141.2, 137.3,
137.1, 136.8, 135.9, 134.5, 131.7, 131.5, 131.2, 130.7, 129.6, 128.9,
128.2, 127.9, 127.6, 127.5, 127.3, 127.0, 126.8, 126.6, 126.0, 121.7,
118.5, 91.8; HRMS (ESI) Calcd for C30H20IN2O [M+ + H] m/z
551.0621, found 551.0621.
Compound 23. Yield 0.127 g (65%, white solid): mp 220−224
°C; IR (KBr, cm−1) 3074, 1660, 1595, 1562, 1496, 1430, 1315, 1173,
1
1074, 915, 784, 707; H NMR (400 MHz, CDCl3) δ 8.93 (dd, J =
8.0 and 1.6 Hz, 1H), 8.70 (d, J = 8.4, 1H), 8.08 (dd, J = 8.4 and 1.6
Hz, 1H), 7.73 (d, J = 8.0 Hz, 1H), 7.69 (d, J = 8.0 Hz, 1H), 7.59 (br
s, 1H), 7.50 (dd, J = 7.2 and 1.2 Hz, 1H), 7.41−7.37 (m, 2H), 7.27−
7.19 (m, 5H), 6.98 (d, J = 8.0 Hz, 1H), 6.86 (t, J = 7.6 Hz, 1H),
6.77−6.72 (m, 2H), 6.51 (t, J ∼ 7.4 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 162.0, 150.9, 144.5, 143.6, 138.3, 137.3, 136.1, 135.6,
134.5, 131.7, 131.5, 130.7, 130.6, 129.61, 129.58, 128.9, 128.8, 128.4,
128.2, 127.7, 127.6, 127.3, 126.8, 126.6, 125.8, 122.9, 122.7, 121.7,
118.3; HRMS (ESI) Calcd for C31H20F3N2O [M+ + H] m/z
493.1528, found 493.1527.
Compound 29. Yield 0.118 g (67%, white solid): mp 274−278
°C; IR (KBr, cm−1) 3052, 2910, 1655, 1595, 1501, 1332, 1200, 1025,
1
805, 789, 707; H NMR (400 MHz, CDCl3) δ 8.94−8.93 (m, 1H),
8.40 (br s, 1H), 8.05 (d, J = 8.0 Hz, 1H), 7.66 (d, J = 8.4 Hz, 1H),
7.50 (d, J = 7.2 Hz, 1H), 7.44 (d, J = 8.0 Hz, 1H), 7.39−7.35 (m,
2H), 7.25−7.15 (m, 6H), 6.98 (d, J = 7.2 Hz, 1H), 6.84 (t, J = 7.6
Hz, 1H), 6.75−6.70 (m, 2H), 6.49 (t, J = 7.6 Hz, 1H), 2.52 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 162.7, 150.8, 144.8, 140.9, 137.9,
Compound 24. Yield 0.126 g (71%, white solid): mp 278−282
°C; IR (KBr, cm−1) 3074, 1660, 1611, 1474, 1370, 1326, 1189, 1112,
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Article
136.8, 136.0, 135.9, 135.0, 133.9, 131.9, 131.7, 130.9, 129.9, 128.8,
128.5, 128.0, 127.8, 127.2, 126.70, 126.65, 126.4, 125.8, 125.7, 125.5,
121.5, 118.5, 21.5; HRMS (ESI) Calcd for C31H23N2O [M+ + H] m/
z 439.1811, found 439.1808.
Hz, 1H), 7.49 (d, J = 7.2 Hz, 1H), 7.40−7.36 (m, 2H), 7.17 (br s,
5H), 6.95 (d, J = 7.6 Hz, 1H), 6.86 (t, J ∼ 7.4 Hz, 1H), 6.81−6.74
(m, 2H), 6.62 (d, J = 1.6 Hz, 1H), 6.54 (t, J ∼ 7.4 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 153.6, 150.9, 148.4, 144.8, 142.6, 142.4,
137.1, 136.3, 136.1, 134.7, 134.5, 131.2, 130.5, 130.3, 128.9, 128.8,
128.0, 127.6, 126.9, 126.8, 126.6, 125.8, 121.6, 114.7, 107.9; HRMS
(ESI) Calcd for C28H19N2O2 [M+ + H] 415.1447, found 415.1445.
Compound 36. Yield 0.116 g (61%, white solid): mp 264−268
°C; IR [KBr (for crystals) cm−1] 3036, 1655, 1468, 1321, 1068,
Compound 30. Yield 0.128 g (73%, white solid): mp 276−280
°C; IR (KBr, cm−1) 3052, 2920, 1654, 1610, 1490, 1440, 1320, 1029,
1
821, 783, 690; H NMR (400 MHz, CDCl3) δ 8.94−8.93 (m, 1H),
8.48 (d, J = 8.0 Hz, 1H), 8.06−8.04 (m, 1H), 7.66 (d, J = 8.0 Hz,
1H), 7.50−7.48 (m, 1H), 7.39−7.35 (m, 3H), 7.24 (br s, 2H), 7.18−
7.16 (m, 3H), 7.08 (s, 1H), 6.96 (d, J = 7.6 Hz, 1H), 6.83 (t, J ∼ 7.4
Hz, 1H), 6.75−6.70 (m, 2H), 6.49 (t, J = 7.6 Hz, 1H), 2.40 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 162.7, 150.8, 144.8, 143.1, 142.0,
138.3, 137.9, 136.8, 136.0, 135.1, 131.9, 131.8, 130.9, 130.8, 129.9,
128.8, 128.5, 128.3, 128.0, 127.8, 127.2, 126.7, 126.6, 126.4, 125.8,
125.4, 123.5, 121.5, 118.4, 22.1; HRMS (ESI) Calcd for C31H23N2O
[M+ + H] 439.1811, found 439.1810.
1
1030, 822, 751, 707 ; H NMR (400 MHz, CDCl3) δ 8.97 (dd, J ∼
4.2 Hz and ∼1.4 Hz, 1H), 8.07 (dd, J ∼ 4.2 Hz and ∼1.4 Hz, 1H),
7.69 (d, J = 8.0 Hz, 1H), 7.58−7.56 (m, 1H), 7.49−7.37 (m, 5H),
7.32−7.28 (m, 2H), 7.25−7.22 (m, 2H), 7.02 (d, J = 7.6 Hz, 1H),
6.95 (t, J ∼ 7.4 Hz, 1H), 6.85 (t, J ∼ 7.4 Hz, 1H), 6.82−6.78 (m,
2H), 6.74 (t, J ∼ 7.4 Hz, 1H), 6.51 (t, J = 7.6 Hz, 1H), 4.40 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 156.9, 151.0, 145.0, 141.5, 138.2,
137.9, 137.3, 136.1, 134.8, 131.5, 131.22, 131.17, 131.1, 130.4, 128.8,
128.6, 128.2, 128.0, 127.1, 126.6, 126.5, 126.4, 126.2, 125.8, 124.9,
123.1, 122.1, 121.6, 119.8, 117.2, 109.9, 31.5; HRMS (ESI) Calcd for
C33H24N3O [M+ + H] 478.1920, found 478.1919. The compound
Compound 31. Yield 0.121 g (64%, white solid): mp 234−238
°C; IR (KBr, cm−1) 3052, 2926, 1649, 1578, 1534, 1490, 1321, 1156,
1
1123, 833, 805, 740, 696; H NMR (400 MHz, CDCl3) δ 10.28 (d, J
= 8.0 Hz, 1H), 8.93 (dd, J = 4.4 and 1.6 Hz, 1H), 8.07 (d, J = 8.8
Hz, 1H), 7.97 (d, J = 8.8 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.71−
7.66 (m, 2H), 7.62−7.59 (m, 2H), 7.45−7.36 (m, 3H), 7.28−7.20
(m, 5H), 7.02 (d, J = 7.6 Hz, 1H), 6.86 (t, J ∼ 7.4 Hz, 1H), 6.81 (d,
J = 8.0 Hz, 1H), 6.75 (t, J ∼ 7.6 Hz, 1H), 6.52 (t, J ∼ 7.6 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 163.2, 150.9, 144.8, 143.6, 139.7,
138.4, 137.2, 136.1, 135.0, 133.8, 132.4, 132.3, 132.1, 132.0, 130.9,
130.7, 129.6, 128.9, 128.6, 128.4, 128.14, 128.10, 128.0, 127.3, 126.9,
126.7, 126.5, 126.4, 125.9, 123.8, 121.6, 119.0; HRMS (ESI) Calcd
for C34H23N2O [M+ + H] m/z 475.1811, found 475.1810.
1
crystallized as CH3CN solvate (IR, H NMR).
Compound 37. Isomer ratio 7:3; Yield 0.091 g (61%, gummy
liquid); IR (neat, cm−1) 2921, 1660, 1611, 1496, 1332, 1227, 800,
1
762; H NMR (400 MHz, CDCl3) for major isomer δ 8.90−8.89
(m, 1H), 8.49−8.45 (m, 1H), 8.25 (d, J = 8.4 Hz, 1H), 7.98−7.96
(m, 1H), 7.77−7.68 (m, 5H), 7.48−7.43 (m, 3H), 2.55−2.48 (m,
1H), 2.39 (s, 3H), 2.03−1.97 (m, 1H), 1.67−1.61 (m, 1H), 1.48 (br
s, 1H), 1.36−1.35 (m, 4H), 1.05−1.00 (m, 2H), 0.72 (t, J ∼ 7.0 Hz,
3H); 13C NMR for major isomer (100 MHz, CDCl3) δ 163.3, 151.4,
144.9, 140.9, 138.4, 138.0, 137.6, 136.4, 132.5, 130.3, 130.1, 129.8,
129.5, 129.4, 129.1, 128.8, 128.5, 128.0, 126.5, 126.3, 125.8, 125.6,
125.5, 125.2, 122.8, 121.9, 113.9, 108.7, 31.0, 30.9, 29.0, 28.8, 22.3,
13.9, 13.7; HRMS (ESI) Calcd for C25H27N2O [M+ + H] m/z
371.2124, found 371.2124. Many peaks for the minor isomer in the
1H and 13C NMR spectra were buried in those due to the major
isomer (see Supporting Information, Figures S75−S76).
Compound 32. Yield 0.173 g (64%, white solid): mp 278−282
°C; IR (KBr, cm−1) 3057, 2942, 1649, 1594, 1479, 1408, 1331, 1260,
1
1090, 783, 701; H NMR (400 MHz, CDCl3) δ 8.92 (d, J = 2.8 Hz,
1H), 8.59 (d, J = 7.6 Hz, 1H), 8.47−8.45 (m, 1H), 7.60 (t, J ∼ 7.2
Hz, 1H), 7.52 (t, J ∼ 7.4 Hz, 1H), 7.39 (d, J = 8.4 Hz, 1H), 7.34
(dd, J = 8.4 and 4.4 Hz, 1H), 7.30 (d, J = 8.4 Hz, 1H), 7.24 (br s,
2H), 7.17 (br s, 3H), 6.98 (d, J = 7.2 Hz, 1H), 6.85 (t, J ∼ 7.4 Hz,
1H), 6.80 (d, J = 7.6 Hz, 1H), 6.75 (t, J = 7.6 Hz, 1H), 6.67 (d, J =
8.0 Hz, 1H), 6.53 (t, J = 7.6 Hz, 1H), 3.92 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 163.0, 155.1, 151.0, 145.2, 142.4, 138.2, 136.8,
135.2, 132.4, 131.9, 131.7, 130.84, 130.77, 130.3, 129.9, 128.5, 128.0,
127.8, 127.2, 126.7, 126.63, 126.58, 126.5, 125.6, 121.1, 120.5, 118.4,
103.4, 55.8; HRMS (ESI) Calcd for C31H23N2O2[M+ + H] 455.1760,
found 455.1757.
(iii). Synthesis of RuCl(OAc)(p-cymene) (38). To a solution of
[{RuCl2(p-cymene)}2] (0.200g, 0.33 mmol) in tAmOH (35 mL),
Cu(OAc)2·H2O (2.64g, 13.2 mmol) was added. The mixture was
heated under reflux for 24 h. The resulting suspension was filtered
through Celite to give a clear orange solution from which solvent
was removed to get RuCl(OAc)(p-cymene) as an orange solid in
64% yield (0.137g). The spectroscopic data and melting point
matched with the literature data.18
Compound 33. Yield 0.089 g (51%, white solid): mp 212−216
°C; IR (KBr, cm−1) 3052, 1644, 1556, 1523, 1496, 1326, 1271, 1030,
(iv). Preparation of Complex 40. This compound could be
prepared by two slightly different methods.
1
915, 811, 778, 712; H NMR (400 MHz, CDCl3) δ 8.95−8.94 (m,
1H), 8.08−8.06 (m, 1H), 7.71−7.67 (m, 2H), 7.50 (d, J = 7.2 Hz,
1H), 7.40−7.37 (m, 2H), 7.24−7.16 (m, 5H), 7.05 (d, J = 5.2 Hz,
1H), 6.96 (d, J = 7.6 Hz, 1H), 6.85 (t, J = 7.6 Hz, 1H), 6.79−6.75
(m, 2H), 6.53 (t, J ∼ 7.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
158.7, 150.9, 146.8, 144.8, 143.1, 137.3, 137.0, 136.1, 134.5, 133.3,
131.04, 130.99, 130.1, 129.4, 128.8, 127.9, 127.5, 126.8, 126.6, 125.8,
125.2, 121.6, 117.5; HRMS (ESI) Calcd for C28H19N2OS [M+ + H]
431.1219, found 431.1217.
A mixture of the amide 1a (0.020g, 0.08 mmol) and 38 (0.026g,
0.08 mmol) was heated under reflux in tAmOH (5 mL) for 24 h.
The resulting suspension was passed through a Celite pad, washed
with DCM (10 mL) and concentrated in vacuo to give the complex
40 in quantitative yield.
A mixture of [{RuCl2(p-cymene)}2] (0.122g, 0.2 mmol), N-
quinolin-8-yl-benzamide 1a (0.050g, 0.2 mmol) and NaOAc (0.033g,
0.4 mmol) was taken in MeOH (8 mL) and heated under reflux for
2 h at 70 °C. The reaction mixture was concentrated in vacuo, and
the product was purified by column chromatography on silica gel
using EtOAc as eluent to afford the ruthenium complex 40. It was
crystallized from dichloromethane−hexane (1:1) mixture.
Compound 34. Yield 0.106 g (62%, white solid): mp 258−262
°C; IR (KBr, cm−1) 3063, 1655, 1562, 1490, 1441, 1326, 1238, 1085,
1
1025, 860, 822, 712; H NMR (400 MHz, CDCl3) δ 8.95 (dd, J =
4.0 and 1.6 Hz), 8.07 (dd, J = 4.4 and 1.6 Hz, 1H), 7.80 (d, J = 5.2
Hz, 1H), 7.69−7.67 (m, 1H), 7.50−7.48 (m, 1H), 7.40−7.36 (m,
2H), 7.32−7.28 (m, 3H), 7.23−7.12 (m, 3H), 6.98 (d, J = 8.0 Hz,
1H), 6.86 (t, J ∼ 7.4 Hz, 1H), 6.80−6.77 (m, 2H), 6.54 (t, J ∼ 7.6
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 159.3, 151.4, 150.9, 144.8,
141.9, 137.5, 137.0, 136.1, 134.3, 130.9, 130.4, 130.0, 129.7, 128.8,
128.2, 127.6, 127.4, 126.9, 126.7, 126.2, 125.8, 124.9, 121.6, 116.5;
HRMS (ESI) Calcd for C28H19N2OS [M+ + H] 431.1219, found
431.1218.
Compound 40. Yield 0.084 g (81%, orange crystals): mp 226−
230 °C; IR (KBr, cm−1) 3074, 2964, 1594, 1561, 1506, 1380, 1238,
1
1139, 1073, 925, 832, 723; H NMR (400 MHz, CDCl3) δ 9.08 (d, J
= 4.0 Hz, 1H), 8.37 (d, J = 8.0 Hz, 1H), 8.15−8.13 (m, 3H), 7.42−
7.40 (m, 5H), 7.16 (d, J = 7.6 Hz, 1H), 5.56 (d, J = 5.6 Hz, 1H),
5.23 (d, J = 6.8 Hz, 1H), 5.11 (d, J = 5.6 Hz, 1H), 3.96 (d, J = 4.8
Hz, 1H), 2.32 (t, J = 7.4 Hz, 1H), 2.13 (s, 3H), 0.95 (d, J = 6.8 Hz,
3H), 0.84 (d, J = 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
180.5, 151.0, 150.9, 145.3, 142.5, 137.8, 129.8, 129.5, 129.3, 127.7,
122.9, 121.6, 117.1, 105.2, 97.9, 86.2, 85.9, 82.2, 80.6, 30.8, 22.5,
21.9, 19.1; HRMS (ESI) Calcd for C26H25ClN2ORuNa [M+ + Na]
541.0597, found 541.0602.
Compound 35. Yield 0.092 g (56%, white solid): mp 252−256
°C; IR (KBr, cm−1) 3057, 2986, 1676, 1588, 1539, 1490, 1364, 1282,
1
1073, 788, 755; H NMR (400 MHz, CDCl3) δ 8.94−8.93 (m, 1H),
8.06 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 2.0 Hz, 1H), 7.68 (d, J = 8.4
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(v). Synthesis of Isoquinolone 3 Using Ruthenium Complex
40. A mixture of 40 (40 mg, 0.08 mmol), diphenylacetylene (27 mg,
0.15 mmol) and Cu(OAc)2·H2O (30 mg, 0.15 mmol), and tAmOH
(1 mL) was taken in a Schlenk tube. The resulting solution was
heated on an oil bath at 110 °C for 24 h. The reaction mixture was
filtered through a plug of Celite using EtOAc (30 mL) and
concentrated in vacuo. The crude product was purified by column
chromatography on silica gel using hexane:EtOAc (1:1) to afford the
isoquinolone 3 (28 mg, 85%).
Q. Angew. Chem., Int. Ed. 2009, 48, 5094. (c) Ackermann, L. Chem.
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̈
(vi). X-ray Data. X-ray data for compounds 3, 13, 16, 17, and 40
were collected using Mo Kα (λ = 0.710 73 Å) radiation. The
structures were solved and refined by standard methods.19 The
CCDC numbers are CCDC 984683−984687.
2011, 40, 4740.
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2030. (g) Chen, Q.; Llies, L.; Nakamura, E. J. Am. Chem. Soc. 2011,
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3, 244. (i) Stowers, K. J.; Fortner, K. C.; Sanford, M. S. J. Am. Chem.
Soc. 2011, 133, 6541. (j) Villuendas, P.; Urriolabeitia, E. P. J. Org.
Chem. 2013, 78, 5254. (k) Pan, S.; Endo, K.; Shibata, T. Org. Lett.
2011, 13, 4692. (l) Zhao, P.; Wang, F.; Han, K.; Li, X. Org. Lett.
2012, 14, 5506. (m) Wang, L.; Ackermann, L. Org. Lett. 2013, 15,
176. (n) Ghavtadze, N.; Melkonyan, F. S.; Gulevich, A. V.; Huang,
C.; Gevorgyan, V. Nat. Chem. 2014, 6, 122.
3: C H N O, M = 424.48, Triclinic, space group P1, a =
̅
30 20
2
10.4838(12), b = 14.518(2), c = 15.9147(18) Å, V = 2196.2(5) Å3, α
= 79.164(11), β = 73.907(10), γ = 71.712(11), Z = 4, μ = 0.078
mm−1. Data/restraints/parameters: 7726/2/595. R indices (I >
2σ(I)): R1 = 0.0596, wR2 (all data) = 0.1313. CCDC No. 984683.
13: C22H20N2O, M = 328.40, Monoclinic, space group P2(1)/c, a
= 13.1006(16), b = 14.6841(17), c = 8.7923(8).Å, β = 100.348(9), V
= 1663.9(3) Å3, Z = 4, μ = 0.081 mm−1. Data/restraints/parameters:
2941/0/228. R indices (I > 2σ(I)): R1 = 0.0464, wR2 (all data) =
0.1201. CCDC No. 984684.
16: C H N O, M = 362.41, Triclinic, space group P1, a =
̅
25 18
2
7.4501(15), b = 8.7551(18), c = 14.931(3) Å, α = 95.20(3), β =
98.89(3), γ = 103.19(3), V = 928.8(3) Å3, Z = 2, μ = 0.080 mm−1.
Data/restraints/parameters: 3613/0/254. R indices (I > 2σ(I)): R1 =
0.0494, wR2 (all data) = 0.1434. CCDC No. 984685.
(5) Zaitsev, V. G.; Shabashov, D.; Daugulis, O. J. Am. Chem. Soc.
2005, 127, 13154.
17: C31H21N3O3, M = 483.51, Monoclinic, space group P2(1)/n, a
= 9.5537(15), b = 16.927(3), c = 15.612(3) Å, β = 105.520(3), V =
2432.6(7) Å3, Z = 4, μ = 0.086 mm−1. Data/restraints/parameters:
4266/0/335. R indices (I > 2σ(I)): R1 = 0.0736, wR2 (all data) =
0.2303. CCDC No. 984686.
40: C26H25ClN2ORu, M = 518.00, Orthorhombic, space group
P2(1)2(1)2(1), a = 7.8508(2), b = 15.8682(4), c = 18.2984(4) Å, V
= 2279.57(10) Å3, Z = 4, μ = 6.798 mm−1. Data/restraints/
parameters: 3629/0/283. Flack parameter 0.49(1). R indices (I >
2σ(I)): R1 = 0.0340, wR2 (all data) = 0.0915. CCDC No. 984687.
(6) For selected examples of picolinamide directed C−H
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15, 4394. (e) Nadres, E. T.; Daugulis, O. J. Am. Chem. Soc. 2012,
134, 7. (f) Ju, L.; Yao, J.; Wu, Z.; Liu, Z.; Zhang, Y. J. Org. Chem.
2013, 78, 10821.
(7) For selected examples of 8-aminoquinoline directed C−H
functionalization, see: (a) Reddy, B. V. S.; Reddy, L. R.; Corey, E. J.
Org. Lett. 2006, 8, 3391. (b) Feng, Y.; Chen, G. Angew. Chem., Int.
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Daugulis, O. J. Org. Chem. 2013, 78, 9689. (d) Feng, Y.; Wang, Y.;
Landgraf, B.; Liu, S.; Chen, G. Org. Lett. 2010, 12, 3414. (e) Ano, Y.;
Tobisu, M.; Chatani, N. J. Am. Chem. Soc. 2011, 133, 12984. (f) He,
G.; Zhang, S.-Y.; Nack, W. A.; Li, Q.; Chen, G. Angew. Chem., Int.
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Chem. Soc. 2012, 134, 18237. (h) Nishino, M.; Hirano, K.; Satoh, T.;
Miura, M. Angew. Chem., Int. Ed. 2013, 52, 4457. (i) Roane, J.;
Daugulis, O. Org. Lett. 2013, 15, 5842. (j) Corbet, M.; De Campo, F.
Angew. Chem., Int. Ed. 2013, 52, 9896.
(8) (a) Garcia-Rubia, A.; Arrayas, R. G.; Carretero, J. C. Angew.
Chem., Int. Ed. 2009, 48, 6511. (b) Garcia-Rubia, A.; Urones, B.;
Arrayas, R. G.; Carretero, J. C. Chem.Eur. J. 2010, 16, 9676.
(c) Garcia-Rubia, A.; Urones, B.; Arrayas, R. G.; Carretero, J. C.
Angew. Chem., Int. Ed. 2011, 50, 10927. (d) Rodriguez, N.; Romero-
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2013, 4, 175.
ASSOCIATED CONTENT
■
S
* Supporting Information
Figures and CIF files giving ORTEP drawings as shown by X-
ray crystallography, and copies of H and 13C NMR spectra of
1
all new products. This material is available free of charge via
the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Fax: (+91)-40-23012460. E-mail: kckssc@yahoo.com,
kckssc@uohyd.ac.in.
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank Department of Science & Technology (DST, New
Delhi) for financial support, single crystal X-ray diffractometer,
and HRMS facility. K.C.K. thanks DST for a J. C. Bose
fellowship. A.S.R. thanks CSIR (New Delhi) for a fellowship.
(9) Rit, R. K.; Yadav, M. R.; Sahoo, A. K. Org. Lett. 2012, 14, 3724.
(10) Shabashov, D.; Daugulis, O. J. Am. Chem. Soc. 2010, 132,
3965.
(11) (a) Ruchelman, A. L.; Houghton, P. J.; Zhou, N.; Liu, A.; Liu,
L. F.; La Voie, E. J. J. Med. Chem. 2005, 48, 792. (b) Kajita, Y.;
Matsubara, S.; Kurahashi, T. J. Am. Chem. Soc. 2008, 130, 6058.
(c) Hyster, T. K.; Rovis, T. J. Am. Chem. Soc. 2010, 132, 10565.
(d) Mochida, S.; Umeda, N.; Hirano, K.; Satoh, T.; Miura, M. Chem.
Lett. 2010, 39, 744. (e) Song, G.; Chen, D.; Pan, C.-L.; Crabtree, R.
H.; Li, X. J. Org. Chem. 2010, 75, 7487. (f) Guimond, N.; Gouliaras,
C.; Fagnou, K. J. Am. Chem. Soc. 2010, 132, 6908. (g) Guimond, N.;
Gorelsky, S. I.; Fagnou, K. J. Am. Chem. Soc. 2011, 133, 6449.
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