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Rhodium(III)-Catalyzed C(sp3)–H Bond Aminocarbonylation with Isocyanates Huaiqing Zhao, Xi Zhou, Bo Li, Xiufen Liu, Ningxin Guo, Zhengliang Lu, and Shoufeng Wang J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00086 • Publication Date (Web): 16 Mar 2018 Downloaded from http://pubs.acs.org on March 16, 2018

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The Journal of Organic Chemistry

Rhodium(III)-Catalyzed C(sp3)–H Bond Aminocarbonylation with Isocyanates Huaiqing Zhao,*’† Xi Zhou,† Bo Li,† Xiufen Liu,† Ningxin Guo,† Zhengliang Lu,† Shoufeng Wang‡ †

Key Laboratory of Interfacial Reaction & Sensing Analysis in Universities of

Shandong, School of Chemistry and Chemical Engineering, University of Jinan, Jinan, Shandong, 250022, P. R. China ‡

Shandong Provincial Key Laboratory of Fluorine Chemistry and Chemical Materials,

School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, P. R. China E-mail: [email protected]

Abstract：

Rh(III)-catalyzed C(sp3)–H bond aminocarbonylation of 8-methylquinolines and isocyanates has been realized under mild conditions. This approach is applicable to different aryl and alkyl isocyanates, leading to the synthesis of various α-quinolinyl amide compounds in moderate to excellent yields. A plausible mechanism for this transformation is proposed according to the experimental results obtained.

In the past decades, transition-metal catalyzed C–H functionalization strategy has been rapidly developed as an elegant, straightforward and powerful approach to the construction of important synthetic targets.1 A large array of C(sp2)–H functionalization has been explored using Rh(III) compounds as catalysts due to their efficient reactivity, excellent selectivity and comprehensive functional group

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compatibility.2 To date, there have been many reports of the construction of carbon-carbon bond and carbon-heteroatom bond using Rh(III)-catalyzed C(sp2)–H activations.3 However, less research effort has been paid to Rh(III)-catalyzed inert C(sp3)–H bond functionalization. To the best of our knowledge, although the prevailing Rh(III)-catalyzed C(sp3)–H activation has been executed with the assistance of a directing-group such as nitrogen-heterocycles,4 this type of transformation is still a challenging issue and unsatisfactorily developed. Among the C(sp3)–H bond substrates, 8-methylquinolines as the good substrates which possess the ability to form the cyclometalated complexes have been widely applied to explore the different C–H bond transformation.5 For instance, C(sp3)–H alkenylation,5a amidation,5b arylation,5c acylation5d and alkylation5e of 8-methylquinolines have been accomplished with different coupling partners under Rh(III) catalysis. The polar C−N π-bonds of isocyanates can be easily integrated with C(sp2)–H bonds using a transition-metal catalyst, such as Re(I),6 Rh(III),7 Ru(II),8 and Co(III),9 leading to the formation of various amides. It was noted that the similar cumulated compounds such as ketenes5d and CO25g were successfully coupled with C(sp3)–H bonds respectively accomplished by Li, Mita and Sato’s groups. In contrast, to our knowledge, C(sp3)–H bond addition to isocyanates have not been achieved yet. The reason is likely due to the rate of reaction of the two substrates was incongruous: transition-metal mediated C(sp3)−H bond cleavage is relatively less reactive, while isocyanates can be reactive toward all kinds of nucleophiles such as amines, also can react with themselves. And thus direct catalytic C(sp3)−H bond addition to isocyanates still represents a significant and formidable challenge. Given the feasibility of Rh(III)-catalyzed C(sp3)−H bond activation and the reaction of the polar C=N bonds,10 we herein describe the reaction of Rh(III)-catalyzed intermolecular C(sp3)–H bond aminocarbonylation of 8-methylquinolines with isocyanates under simple and efficient conditions. Moreover, we notice that the α-quinolinyl amide skeleton is present in potentially pharmaceutical compounds and showed biological properties (Scheme 1).11


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Scheme 1. Inhibitor of Protein Arginine Methyltransferase 5 (I) and Inhibitor of JNK N-terminal Kinase (II). Recently, the progress in Rh(III)-catalyzed C–H activation has provided the valuable leading views for our exploration of the C(sp3)–H amidation with isocyanates. For example, Wang and Li’s groups demonstrated the user-friendly Rh(III) catalyzed C(sp3)–H functionalization.5a, 5d We commenced our investigation of the reaction conditions by examining the direct C(sp3)–H bond addition of Rh(III)catalyzed 8-methylquinoline (1a) to p-tolylisocyanate (2a). The reaction, where [Cp*RhCl 2]2 was selected as a catalyst with no other additive, furnished no desired product (Table 1, entry 1). We surmised that the C(sp3)–H bond could not be activated due to the difficulty of dissociating the cationic Rh(III) in this system. In order to surmount this problem, we modified the catalytic system by adding AgSbF6 as additive. The [Cp*Rh(III)](SbF6)2 generated in situ via the stoichiometric reaction of [Cp*RhCl2]2 with AgSbF6 served as the catalyst for the activation of C(sp3)–H bond. To our delight, the desired product (3a) was formed in 50% yield in 1,2-dichloroethane (DCE) at 90 oC under N2 atmosphere for 20 h (entry 2). We next tested the different ratio of the 8-methylquinoline and p-tolyl isocyanate, but the yields were not satisfactory. Then we turned our attention to silver salts and screened different silver salts containing different anions. The experiments revealed that AgSbF6 gave the best result, other salts could not make the reaction better (entries 6-9). This also showed that the active cationic Rh(III) is dependent on the anion. Generally, the additional base could promote C–H bond activation in the concerted metalation-deprotonation mechanism,12 and then, base KOAc (5 mol %) was added to this reaction system to further optimize the reaction condition. However, the yield of the corresponding product was significantly reduced to 18% with the addition of KOAc (entry 10). Further, we studied the influence of reaction temperature and ACS Paragon Plus Environment


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solvent on the catalytic system respectively, found that 60 oC (entries 11-14) and DCE (entries 16-17) gave the better result. By increasing the loading of [Cp*RhCl2]2 catalyst, we were able to obtain a higher yield for the reaction (entry 15). And hence, the optimized conditions in entry 15 were used for subsequent reactions. Table 1. Optimization of the Reaction Conditionsa

a

entry

1a/2a

Additive (mol %)

time (h)

temp (oC) yield (%)b

1

1:2

-

20

90

0

2

1:2

AgSbF6 (10)

20

90

50

3

1:3

AgSbF6 (10)

20

90

43

4

1:1.5

AgSbF6 (10)

20

90

46

5

2:1

AgSbF6 (10)

20

90

44

6

1:2

AgOTf (10)

20

90

10

7

1:2

AgBF4 (10)

20

90

15

8

1:2

AgPF6 (10)

20

90

22

9

1:2

AgNTf2 (10)

20

90

45

10c

1:2

AgSbF6 (10)

20

90

18

11

1:2

AgSbF6 (10)

20

100

48

12

1:2

AgSbF6 (10)

20

60

60

13

1:2

AgSbF6 (10)

24

60

63

14

1:2

AgSbF6 (10)

24

30

52

15d

1:2

AgSbF6 (20)

24

60

77

16d, e

1:2

AgSbF6 (20)

24

60

72

17d, f

1:2

AgSbF6 (20)

24

60

32

Reaction conditions: 1a (0.2 or 0.4 mmol), 2a (0.3, 0.4 or 0.6 mmol) , [Cp*RhCl2]2

(2.5 mol %), DCE (2 mL) as a solvent, N2 atmosphere.


b

Isolated yields.

c

KOAc(5

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mol %) was added. d [Cp*RhCl2]2 (5 mol %). e DCM as a solvent. f THF as a solvent.

We first examined the reactivities of a spectrum of isocyanates substrates with 8-methylquinoline using the optimized reaction conditions (Table 1, entry 15). Aromatic isocyanates bearing an electron-donating group such as a methyl or a methoxy substituent at different positions of the aryl rings, are allowed to react with 8-methylquinoline in moderate yields (Table 2, 3a-3e). However, the methyl substituent on the 2-position of the aromatic ring resulted in a slightly lower yield due to the steric factor (3b). Substrates bearing electron-withdrawing groups furnished the desired

products

in

moderate

to

good

yields

(3f-3k).

Notably,

4-(trifluoromethyl)phenyl isocyanate yielded the corresponding product 3l in 91% yield. To our delight, alkyl isocyanates are valid in this transformation under the modified reaction conditions using AgNTf2 as additive. Cyclopentyl isocyanate can provide the desired amidation product in only 39% yield under this catalytic system (3m). We speculated that the low yield may be attributed to the steric factor. Then unbranched alkyl isocyanates were tested in this transformation and the corresponding products were afforded in moderate yields (3n, 3o). A reversibility of the amidation was observed by Sim in Rh(III)-catalyzed C−H amidation of indoles with isocyanates.7e The amidation of alkyl isocyanates occurred with relatively lower yields in this system, we considered that the reason may be due to the similar reversible reaction. Thus, we carried out a reversibility experiment using 3n under the corresponding reaction conditions, which provided the recovered 3n in 95% isolated yield. This result indicated that the reversible reaction did not basically occur in this catalytic system. Tosyl isocyanate was also employed in this transformation, but there was no desired product obtained under this catalytic system (3p). Table 2. Scope of Isocyantes. a



a

Reaction conditions: 1a (0.2 mmol), 2 (0.4 mmol), DCE (2 mL), 60 oC, 24 h, N2

atmosphere, isolated yield. b 2 (0.6 mmol).c AgNTf2 replaced AgSbF6.

Additionally, the generality of 8-methylquinolines was evaluated. As shown in Table 3, this protocol is applicable to a series of 8-methylquinoline derivatives with various substituents. It is clear that 8-methyl-quinolines bearing an electron-donating ACS Paragon Plus Environment

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group such as a methyl substituent can furnish the desired products in good yields (4a-4c). But 8-methyl-quinoline containing a methoxy group at 5-position reacted with a moderate yield (4d). Remarkably, the substrates with electron-withdrawing groups, such as halogen substituents, at different positions led to the expected products in slightly decreased yields (4e-4l). Notably, 8-methyl-quinolines bearing electron-withdrawing groups at 7-position gave the corresponding products in lower yields (4e, 4h, 4l). 4-Methylphenanthridine was also applied to this transformation and furnished the desired product in 43% yield (4m). Unfortunately, there was no desired product observed when 8-ethylquinoline was utilized as a substrate in our catalytic system (4n). These data reveal that the steric factor also effect the transformation in this catalytic system. Other functional groups such as oxime or pyridine group were also explored as a directing group, but they were invalid in C(sp3)–H bond aminocarbonylation with isocyanates under this catalytic system.

Table 3. Scope of 8-Methylquinolines. a



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O N C O

Me N

[Cp*RhCl2]2 (5 mol %)

R 1

R 4

O

O

O N H Me

F

N H

N

O

N

F

O N H F

N

F

Me 4c, 90%

O N H

N H

F

Me 4b, 81%

4a, 85%

N

F

AgSbF6 (20 mol %)

F 2f

N

N H

N

F

N H

N

F

F OMe 4d, 55% O

O

O

N H

N

4f, 68%

4e, 48%

F

N H Cl

N

N H

F N

F

Cl

N

F 4g, 63%

4h, 57%

O

O N H

F N

Cl 4j, 65%

4i, 71% O

N H

F N

Br 4k, 60% O N

NH 4m, 43%

a

F

4l, 40%

O F

N H CF3

N

N H

F

4n, 0%

Reaction conditions: 1 (0.2 mmol), 2f (0.4 mmol), DCE (2 mL), 60 oC, 24 h, N2

atmosphere, isolated yield.

In order to obtain some primary insight into the mechanism of the catalytic addition, ACS Paragon Plus Environment

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we first investigated the kinetic isotope effect (KIE) for 8-methyl-quinoline in both parallel and one-pot measurements. The large KIE values of 6.4 in parallel reaction and 8.1 in one-pot competition reaction indicated that the methyl C–H bond cleavage is the rate-limited step in the catalytic cycle (Scheme 2a, 2b).13 A presynthesized cyclometalated Rh(III) complex (rhodacycle) A employed as a catalyst, 5a catalyzed the C(sp3)–H bond aminocarbonylation reaction and furnished the desired product in 60% yield (Scheme 2c), indicating that the rhodacycle A was a plausible activated intermediate in this transformation. Scheme 2. Mechanistic Studies of C(sp3)–H Bond Aminocarbonylation.

Based on the above experiment data obtained in this study and the related Rh-catalyzed C–H bond functionalization reported by others,5,

7, 14

a plausible

mechanism for this transformation is proposed in Scheme 3. The cationic Rh(III) species I is produced from the catalyst precursor [Cp*RhCl2]2 and AgSbF6, which is



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stabilized by coordinating to the nitrogen of 8-methylquinoline, and activates the C(sp3)−H bond to deliver the cyclorhodated intermediate II and HX. Subsequently, isocyanate reacts with the intermediate II furnishing intermediate III, which subsequently undergoes a migratory insertion into the Rh−C bond, generating complex IV. Finally, complex IV is protonated by the acid in the system, affording the desired product and regenerating the cationic Rh(III) catalyst.

Scheme 3. Proposed Mechanism of C(sp3)–H Bond Aminocarbonylation. 1/2 {[Cp*RhCl2]2} 2 AgSbF6 N

HN

R O

3

Me N

2 AgCl [Cp*Rh][SbF6]2

1a

I

HX HX

Cp* N Rh III

N Cp* Rh III

N R II IV

O R N C O

2 N Cp* III Rh

III

O

C

N

R

In conclusion, we have developed the Rh(III)-catalyzed C(sp3)–H bond aminocarbonylation of 8-methylquinolines with isocyanates under mild conditions, and synthesized a series of α-quinolinyl amides for the first time. This protocol enables various 8-methylquinolines to react with both aromatic and aliphatic isocyanates in moderate to excellent yields, providing a complement to existing amidation methods. Further research efforts will be devoted to expanding the C(sp3)– H bond substrate scope of this protocol and a comprehensive mechanistic study are


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currently ongoing in our laboratory.

EXPERIMENTAL SECTION General Comments All other reagents were purchased and used without further purification. Dicholomethane and 1,2-dichloroethane were distilled from CaH2 under nitrogen and stored under nitrogen. THF was distilled from sodium under nitrogen and stored under nitrogen. 1H NMR (400 MHz or 600 MHz) and

13

C NMR (101 or 151 MHz)

were obtained on Burker spectrometer with CDCl3 as solvent and tetramethylsilane (TMS) as internal standard. Chemical shifts were reported in units (ppm) by assigning TMS resonance in the 1H NMR spectra as 0.00 ppm (chloroform, 7.26 ppm). Data were reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet and m = multiplet), coupling constant (J values) in Hz and integration. Chemical shifts for

13

C NMR spectra were recorded in ppm from

tetramethylsilane using the central peak of CDCl3 (77.00 ppm) as the internal standard. The yields reported are the isolated yields.

The

Preparation

8-methylquinolines,15

of

the

Substrates:

The

4-methylphenanthridine16

substrates and

8-methylquinoline-d35f were prepared according to the related literatures. General catalytic procedure: In a glove box, a 25 mL Schlenk tube equipped with a stir bar was charged with [Cp*RhCl2]2 (5 mol %), AgSbF6 (20 mol%), isocyanate 1 (0.4 mmol). The tube was fitted with a rubber septum, and then removed out from the glove box. Then 8-methylquinoline 2 (0.2 mmol) was added through the rubber septum using a syringe under the atmosphere of N2. 1,2-Dichloroethane (2 mL) was added to the Schlenk tube though the rubber septum using a syringe. The septum was replaced by a Teflon screwcap under N2 flow. The reaction mixture was stirred at 60 o

C (pre-heated to 60 oC) for 24 h. After cooling down, the solvent was removed in

vacuum and the residue was purified by chromatography on silica gel (eluent: EtOAc/PE, v/v) to provide the corresponding product 3. ACS Paragon Plus Environment


2-(quinolin-8-yl)-N-(p-tolyl)acetamide (3a) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/9; 42.5 mg, 77%), mp 140-142 oC. 1H NMR (400 MHz, CDCl3) δ 9.97 (s, 1H), 9.04 (dd, J = 4.2, 1.7 Hz, 1H), 8.22 (dd, J = 8.3, 1.7 Hz, 1H), 7.81 – 7.75 (m, 2H), 7.54 – 7.48 (m, 2H), 7.32 (d, J = 8.4 Hz, 2H), 7.03 (d, J = 8.2 Hz, 2H), 4.30 (s, 2H), 2.24 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 169.4, 149.5, 146.4, 137.4, 136.1, 133.9, 133.0, 131.2, 129.3, 128.9, 127.5, 127.0, 121.4, 119.3, 42.4, 20.8. HRMS (ESI) m/z: [M+H]+ Calcd for C18H17N2O 277.1335; Found 277.1344. 2-(quinolin-8-yl)-N-(o-tolyl)acetamide (3b) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/10; 30.9 mg, 56%), mp 125-127 oC. 1H NMR (400 MHz, CDCl3) δ 9.32 (s, 1H), 8.99 (dd, J = 4.2, 1.7 Hz, 1H), 8.24 (dd, J = 8.3, 1.7 Hz, 1H), 7.96 (d, J = 8.1 Hz, 1H), 7.85 (d, J = 7.1 Hz, 1H), 7.79 (dd, J = 8.2, 1.2 Hz, 1H), 7.57 – 7.53 (m, 1H)，7.50 – 7.47(m, 1H), 7.13 (t, J = 7.7 Hz, 1H), 7.06 (d, J = 7.3 Hz, 1H), 6.96 – 6.92 (m, 1H), 4.37 (s, 2H), 2.06 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 169.7, 149.9, 146.4, 137.3, 136.7, 134.0, 131.1, 130.2, 128.8, 127.5, 127.4, 127.0, 126.6, 124.1, 121.8, 121.3, 42.0, 17.9. HRMS (ESI) m/z: [M+H]+ Calcd for C18H17N2O

277.1335; Found 277.1339.

2-(quinolin-8-yl)-N-(m-tolyl)acetamide (3c) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/9; 35.9 mg, 65%), mp 124-125 oC. 1H NMR (400 MHz, CDCl3) δ 9.97 (s, 1H), 9.05 (dd, J = 4.2, 1.7 Hz, 1H), 8.23 (dd, J = 8.3, 1.7 Hz, 1H), 7.82 – 7.76 (m, 2H), 7.55 – 7.49 (m, 2H), 7.30 (s, 1H), 7.18 (d, J = 8.2 Hz, 1H), 7.10 (t, J = 7.8 Hz, 1H), 6.81 (d, J = 7.4 Hz, 1H), 4.30 (s, 2H), 2.27 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 169.5, 149.5, 146.4, 138.7, 138.6, 137.4, 133.9, 131.2, 128.9, 128.6, 127.5, 127.0, 124.3, 121.4, 119.9, 116.4, 42.5, 21.50. HRMS (ESI) m/z: [M+H]+ Calcd for C18H17N2O 277.1335; Found 277.1339. N-(3,5-dimethylphenyl)-2-(quinolin-8-yl)acetamide (3d) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/9; 41.8 mg, 72%), mp 139-140 oC. 1

H NMR (400 MHz, CDCl3) δ 9.85 (s, 1H), 9.05 (dd, J = 4.2, 1.7 Hz, 1H), 8.23 (dd, J

= 8.3, 1.7 Hz, 1H), 7.82 – 7.76 (m, 2H), 7.55 – 7.50 (m, 2H), 7.06 (s, 2H), 6.64 (s, 1H), 4.29 (s, 2H), 2.23 (s, 6H).

13

C NMR (101 MHz, CDCl3) δ 169.5, 149.5, 146.3,


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138.5, 137.4, 133.9, 131.2, 128.9, 127.5, 127.0, 125.3, 121.4, 117.0, 42.4, 21.4. HRMS (ESI) m/z: [M+H]+ Calcd for C19H19N2O 291.1492; Found 291.1499. N-(4-methoxyphenyl)-2-(quinolin-8-yl)acetamide (3e) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/8; 35.1 mg, 60%), mp 138-140 oC. 1


= 8.3, 1.7 Hz, 1H), 7.82 – 7.76 (m, 2H), 7.55 – 7.48 (m, 2H), 7.36 – 7.32 (m, 2H), 6.79 – 6.75(m, 2H), 4.29 (s, 2H), 3.73 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 169.3, 155.8, 149.5, 146.4, 137.4, 133.9, 131.9, 131.2, 128.9, 127.5, 127.0, 121.3, 120.9, 114.0, 55.5, 42.3. HRMS (ESI) m/z: [M+H]+ Calcd for C18H17N2O2 293.1285; Found 293.1279. N-(4-fluorophenyl)-2-(quinolin-8-yl)acetamide (3f) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/9; 47.1 mg, 84%), mp 117-119 oC. 1

H NMR (400 MHz, CDCl3) δ 10.11 (s, 1H), 9.04 (dd, J = 4.2, 1.7 Hz, 1H), 8.25 (dd,

J = 8.3, 1.7 Hz, 1H), 7.82 – 7.77 (m, 2H), 7.56 – 7.50 (m, 2H), 7.41 – 7.36 (m, 2H), 6.95 – 6.88 (m, 2H), 4.29 (s, 2H). 13C NMR (101 MHz, CDCl3) δ 169.5, 158.8 (d, J = 242.3 Hz), 157.6, 149.5, 146.4, 137.5, 134.7, 133.7, 131.3, 128.3, 127.6, 127.1, 121.4, 120.8 (d, J = 7.7 Hz), 115.4 (d, J = 22.3 Hz), 42.4. HRMS (ESI) m/z: [M+H]+ Calcd for C17H14FN2O 281.1085; Found 281.1081. N-(2-chlorophenyl)-2-(quinolin-8-yl)acetamide (3g) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/11; 34.3 mg, 58%), mp 110-112 oC. 1


= 8.3, 1.4 Hz, 1H), 8.22 (dd, J = 8.2, 1.7 Hz, 1H), 7.83 – 7.78 (m, 2H), 7.56 – 7.52 (m, 1H), 7.50 – 7.47 (m, 1H), 7.26 (dd, J = 8.0, 1.4 Hz, 1H), 7.20 – 7.15 (m, 1H), 6.95 – 6.90 (m, 1H), 4.39 (s, 2H). 13C NMR (101 MHz, CDCl3) δ 170.0, 150.2, 146.4, 137.0, 135.7, 133.5, 130.9, 128.9, 128.7, 127.6, 127.4, 126.8, 124.0, 122.3, 121.5, 121.4, 42.3. HRMS (ESI) m/z: [M+H]+ Calcd for C17H14ClN2O 297.0789; Found 297.0778. N-(3-chlorophenyl)-2-(quinolin-8-yl)acetamide (3h) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/9; 40.8 mg, 69%), mp 134-135 oC. 1


J = 8.3, 1.7 Hz, 1H), 7.81 – 7.78 (m, 2H), 7.55 – 7.51 (m, 3H), 7.29 – 7.27 (m, 1H), ACS Paragon Plus Environment


7.13 (t, J = 8.1 Hz, 1H), 6.97 – 6.95 (m, 1H), 4.29 (s, 2H).

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13

C NMR (101 MHz,

CDCl3) δ 169.6, 149.5, 146.3, 139.8, 137.5, 134.4, 133.4, 131.4, 129.8, 128.9, 127.7, 127.1, 123.5, 121.5, 119.3, 117.3, 42.5. HRMS (ESI) m/z: [M+H]+ Calcd for C17H14ClN2O 297.0789; Found 297.0785. N-(4-chlorophenyl)-2-(quinolin-8-yl)acetamide (3i) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/9; 45.0 mg, 76%), mp 146-147 oC. 1


J = 8.3, 1.7 Hz, 1H), 7.80 (t, J = 6.7 Hz, 2H), 7.56 – 7.51 (m, 2H), 7.40 – 7.36 (m, 2H), 7.20 – 7.16 (m, 2H), 4.29 (s, 2H). 13C NMR (101 MHz, CDCl3) δ 169.5, 149.5, 146.3, 137.5, 137.3, 133.5, 131.4, 128.9, 128.8, 128.3, 127.7, 127.1, 121.4, 120.5, 42.5. HRMS (ESI) m/z: [M+H]+ Calcd for C17H14ClN2O 297.0789; Found 297.0794. N-(3,5-dichlorophenyl)-2-(quinolin-8-yl)acetamide (3j) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/9; 44.9 mg, 68%), mp 192-193 oC. 1


J = 8.3, 1.7 Hz, 1H), 7.80 (d, J = 8.0 Hz, 2H), 7.57 – 7.53 (m, 2H), 7.38 (d, J = 1.8 Hz, 2H), 6.97 (t, J = 1.8 Hz, 1H), 4.28 (s, 2H).

13

C NMR (101 MHz, CDCl3) δ 169.7,

149.5, 146.1, 140.4, 137.7, 134.9, 133.0, 131.5, 128.9, 127.9, 127.1, 123.4, 121.6, 117.5, 42.6. HRMS (ESI) m/z: [M+H]+ Calcd for C17H13Cl2N2O 331.0399; Found 331.0394. N-(4-bromophenyl)-2-(quinolin-8-yl)acetamide (3k) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/9; 47.6 mg, 70%), mp 147-149 oC. 1


J = 8.3, 1.7 Hz, 1H), 7.81 – 7.78 (m, 2H), 7.56 – 7.51 (m, 2H), 7.35 – 7.30 (m, 4H), 4.29 (s, 2H). 13C NMR (101 MHz, CDCl3) δ 169.6, 149.5, 146.3, 137.7, 137.5,133.5, 131.7, 131.4, 128.9, 127.7, 127.1, 121.4, 120.8, 115.9, 42.5. HRMS (ESI) m/z: [M+H]+ Calcd for C17H14BrN2O 341.0284; Found 341.0275. 2-(quinolin-8-yl)-N-(4-(trifluoromethyl)phenyl)acetamide (3l) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/9; 60.1 mg, 91%), mp 137-139 o

C.

1

H NMR (400 MHz, CDCl3) δ 10.53 (s, 1H), 9.05 (dd, J = 4.3, 1.7 Hz, 1H), 8.24

(dd, J = 8.3, 1.7 Hz, 1H), 7.78 (t, J = 6.7 Hz, 2H), 7.56 – 7.50 (m, 4H), 7.46 (d, J = ACS Paragon Plus Environment

Page 15 of 24 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


8.6 Hz, 2H), 4.31 (s, 2H). 13C NMR (101 MHz, CDCl3) δ 169.9, 149.5, 146.3, 141.7, 137.6, 133.22, 131.4, 129.0, 128.2 (CF3), 127.8, 127.1, 126.1 (d, J = 3.8 Hz), 125.1 (d, J = 32 Hz), 124.2 (q, J = 268 Hz), 124.7 (CF3), 121.5, 120.1 (CF3), 118.9, 42.6. HRMS (ESI) m/z: [M+H]+ Calcd for C18H14F3N2O 331.1053; Found 331.1046. N-cyclopentyl-2-(quinolin-8-yl)acetamide (3m) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/4; 19.8 mg, 39%), mp 114-115 oC. 1H NMR (400 MHz, CDCl3) δ 8.92 (dd, J = 4.1, 1.6 Hz, 1H), 8.20 (d, J = 8.1 Hz, 1H), 7.77 – 7.74 (m, 2H), 7.53 – 7.50 (m, 1H), 7.47 – 7.44 (m, 2H), 4.12 (s, 2H), 4.10 – 4.04 (m, 1H), 1.83 – 1.75 (m, 2H), 1.52 – 1.46 (m, 4H), 1.26 – 1.20 (m, 2H).

13

C NMR (101

MHz, CDCl3) δ 170.8, 149.3, 146.3, 137.0, 134.6, 131.0, 128.7, 127.2, 126.9, 121.1, 51.1, 40.9, 32.9, 23.5. HRMS (ESI) m/z: [M+H]+ Calcd for C16H19N2O 255.1492; Found 255.1490. N-butyl-2-(quinolin-8-yl)acetamide (3n) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/4; 27.1 mg, 56%), mp 77-78 oC. 1H NMR (400 MHz, CDCl3) δ 8.92 (dd, J = 4.2, 1.8 Hz, 1H), 8.20 (dd, J = 8.3, 1.7 Hz, 1H), 7.77 – 7.74 (m, 2H), 7.53 – 7.49 (m, 1H), 7.46 – 7.43 (m, 1H), 7.28 (s, 1H), 4.16 (s, 2H), 3.14 – 3.10 (m, 2H), 1.36 – 1.28 (m, 2H), 1.20 – 1.10 (m, 2H), 0.78 (t, J = 7.3 Hz, 3H). 13

C NMR (101 MHz, CDCl3) δ 171.5, 149.5, 146.5, 136.9, 134.6, 130.9, 128.7, 127.3,

126.8, 121.1, 40.7, 39.1, 31.4, 19.9, 13.6. HRMS (ESI) m/z: [M+H]+ Calcd for C15H19N2O

243.1492; Found 243.1498.

N-hexyl-2-(quinolin-8-yl)acetamide (3o) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/4; 28.6 mg, 53%), mp 70-71 oC. 1H NMR (400 MHz, CDCl3) δ 8.92 (d, J = 2.6 Hz, 1H), 8.20 (d, J = 8.0 Hz, 1H), 7.77 – 7.74 (m, 2H), 7.51 (t, J = 7.6 Hz, 1H), 7.46 – 7.43 (m, 1H), 7.29 (s, 1H), 4.16 (s, 2H), 3.14 – 3.09 (m, 2H), 1.35 – 1.28 (m, 2H), 1.16 – 1.09 (m, 6H), 0.78 (t, J = 6.7 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 171.4, 149.5, 146.5, 136.9, 134.6, 130.9, 128.7, 127.3, 126.8, 121.1, 40.7, 39.4, 31.4, 29.3, 26.4, 22.5, 13.9. HRMS (ESI) m/z: [M+H]+ Calcd for C17H23N2O

271.1805; Found 271.1810.

N-(4-fluorophenyl)-2-(7-methylquinolin-8-yl)acetamide (4a) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/10; 50.0 mg, 85%), mp ACS Paragon Plus Environment


106-107 oC.

1

H NMR (400 MHz, CDCl3) δ 9.89 (s, 1H), 9.02 (dd, J = 4.2, 1.7 Hz,

1H), 8.19 (dd, J = 8.2, 1.7 Hz, 1H), 7.67 (d, J = 8.4 Hz, 1H), 7.47 – 7.44 (m, 2H), 7.38 – 7.33 (m, 2H), 6.93 – 6.87 (m, 2H), 4.37 (s, 2H), 2.74 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 169.4, 158.8 (d, J = 242.2 Hz), 157.6, 149.5, 146.6, 139.6, 137.2, 134.8, 134.8 (d, J = 2.7 Hz), 131.2, 130.4, 127.2, 126.5, 120.7 (d, J = 7.7 Hz), 120.5, 115.4 (d, J = 22.3 Hz), 37.5, 20.8. HRMS (ESI) m/z: [M+H]+ Calcd for C18H16FN2O 295.1241; Found 295.1226. N-(4-fluorophenyl)-2-(6-methylquinolin-8-yl)acetamide (4b) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/9; 47.6 mg, 81%), mp 147-149 o

C.

1


(dd, J = 8.3, 1.6 Hz, 1H), 7.65 (d, J = 1.5 Hz, 1H), 7.53 (s, 1H), 7.47 – 7.45 (m, 1H), 7.40 – 7.36 (m, 2H), 6.93 – 6.89 (m, 2H), 4.25 (s, 2H), 2.51 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 169.6, 158.8 (d, J = 245.9 Hz), 148.5, 144.9, 137.1, 136.8, 134.8, 133.6, 133.2, 129.1, 126.4, 121.4, 120.8, 120.7, 115.4 (d, J = 22.3 Hz), 115.2, 42.3, 21.5. HRMS (ESI) m/z: [M+H]+ Calcd for C18H16FN2O 295.1241; Found 295.1242. N-(4-fluorophenyl)-2-(5-methylquinolin-8-yl)acetamide (4c) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/8; 52.9 mg, 90%), mp 152-153 o

C. 1H NMR (400 MHz, CDCl3) δ 10.13 (s, 1H), 9.02 (dd, J = 4.2, 1.7 Hz, 1H), 8.39

(dd, J = 8.5, 1.7 Hz, 1H), 7.67 (d, J = 7.2 Hz, 1H), 7.53 – 7.50 (m, 1H), 7.41 – 7.35 (m, 2H), 7.33 (d, J = 7.2 Hz, 1H), 6.93 – 6.87 (m, 2H), 4.24 (s, 2H), 2.65 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 169.8, 158.8 (d, J = 242.2 Hz), 148.9, 146.6, 134.8 (d, J = 2.7 Hz), 133.9, 131.6, 130.9, 128.3, 127.4, 120.9, 120.8 (d, J = 7.7 Hz), 115.3 (d, J = 22.3 Hz), 42.3, 18.5. HRMS (ESI) m/z: [M+H]+ Calcd for C18H16FN2O 295.1241; Found 295.1248. N-(4-fluorophenyl)-2-(5-methoxyquinolin-8-yl)acetamide (4d) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/8; 34.1 mg, 55%), mp 130-132 o

C.

1


(dd, J = 8.5, 1.8 Hz, 1H), 7.69 (d, J = 8.0 Hz, 1H), 7.49 – 7.46 (m, 1H), 7.40 – 7.35 (m, 2H), 6.94 – 6.88 (m, 2H), 6.83 (d, J = 8.0 Hz, 1H), 4.18 (s, 2H), 3.99 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 170.0, 158.8 (d, J = 242.1 Hz), 154.8, 149.7, 146.8, ACS Paragon Plus Environment

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134.83 (d, J = 2.7 Hz), 132.2, 131.2, 125.3, 121.5, 120.8 (d, J = 7.7 Hz), 120.43, 115.3 (d, J = 22.3 Hz), 104.5, 55.8, 41.8. HRMS (ESI) m/z: [M+H]+ Calcd for C18H16FN2O2 311.1190; Found 311.1194. N-(4-fluorophenyl)-2-(7-fluoroquinolin-8-yl)acetamide (4e) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/8; 28.6 mg, 48%), mp 161-162 o

C.

1


(dd, J = 8.3, 1.7 Hz, 1H), 7.81– 7.77 (m, 1H), 7.51 – 7.48 (m, 1H), 7.44 – 7.37 (m, 3H), 6.95 – 6.89 (m, 2H), 4.32 (d, J = 1.8 Hz, 2H).

13

C NMR (101 MHz, CDCl3) δ

168.2, 161.3 (d, J = 249.4 Hz), 158.7 (d, J = 213.0 Hz), 150.5, 147.4, 137.3, 134.6 (d, J = 2.7 Hz), 128.8 (d, J = 10.5 Hz), 125.8, 120.9 (d, J = 7.8 Hz), 120.6 (d, J = 2.6 Hz), 118.1 (d, J = 15.6 Hz), 117.6 (d, J = 27.0 Hz), 115.4 (d, J = 22.4 Hz), 33.5. HRMS (ESI) m/z: [M+H]+ Calcd for C17H13F2N2O 299.0990; Found 299.0991. N-(4-fluorophenyl)-2-(6-fluoroquinolin-8-yl)acetamide (4f) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/8; 40.5mg, 68%), mp 163-164 o

C.

1


(dd, J = 8.3, 1.7 Hz, 1H), 7.63 – 7.60 (m, 1H), 7.55 – 7.51 (m, 1H), 7.41 – 7.35 (m, 3H), 6.96 – 6.90 (m, 2H), 4.28 (s, 2H). 13C NMR (101 MHz, CDCl3) δ 168.5, 160.1 (d, J = 248.4 Hz), 158.9 (d, J = 241.1 Hz), 148.7 (d, J = 2.8 Hz), 143.5, 136.9 (d, J = 5.7 Hz), 136.8 (d, J = 9.1 Hz), 134.5 (d, J = 2.8 Hz), 129.7 (d, J = 10.3 Hz), 122.2, 121.6, 121.3, 120.9 (d, J = 7.8 Hz), 115.4 (d, J = 22.4 Hz), 110.3 (d, J = 21.4 Hz), 42.2. HRMS (ESI) m/z: [M+H]+ Calcd for C17H13F2N2O 299.0990; Found 299.0992. N-(4-fluorophenyl)-2-(5-fluoroquinolin-8-yl)acetamide (4g) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/8; 37.6 mg, 63%), mp 176-177 o


(dd, J = 8.4, 1.6 Hz, 1H), 7.77 – 7.73 (m, 1H), 7.60 – 7.57 (m, 1H), 7.39 – 7.36 (m, 2H), 7.22 (dd, J = 9.2, 8.2 Hz, 1H), 6.92 (t, J = 8.7 Hz, 2H), 4.24 (s, 2H). 13C NMR (101 MHz, CDCl3) δ 169.2, 158.9 (d, J = 241.1 Hz), 157.2 (d, J = 254.1 Hz), 150.3, 146.6 (d, J = 2.9 Hz), 134.5 (d, J = 2.8 Hz), 130.7-130.6 (m), 129.6 (d, J = 4.6 Hz), 121.5 (d, J = 2.7 Hz), 120.9 (d, J = 7.7 Hz), 119.7 (d, J = 16.7 Hz), 115.4 (d, J =22.4 Hz), 110.5 (d, J = 19.2 Hz), 41.7. HRMS (ESI) m/z: [M+H]+ Calcd for C17H13F2N2O ACS Paragon Plus Environment


299.0990; Found 299.0990. 2-(7-chloroquinolin-8-yl)-N-(4-fluorophenyl)acetamide (4h) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/8; 35.8 mg, 57%), mp 172-174 o

C.

1


(dd, J = 8.3, 1.7 Hz, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.60 (d, J = 8.8 Hz, 1H), 7.53 – 7.50 (m, 1H), 7.41 – 7.36 (m, 2H), 6.94 – 6.88 (m, 2H), 4.53 (s, 2H). 13C NMR (101 MHz, CDCl3) δ 167.9, 158.9 (d, J = 242.5 Hz), 150. 5, 147.0, 137.2, 136.5, 134.5 (d, J = 2.7 Hz), 131.4, 128.8, 128.0, 127.3, 121.4, 120.9 (d, J = 7.8 Hz), 115.4 (d, J = 22.4 Hz), 37.9. HRMS (ESI) m/z: [M+H]+ Calcd for C17H13ClFN2O 315.0695; Found 315.0700. 2-(6-chloroquinolin-8-yl)-N-(4-fluorophenyl)acetamide (4i) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/8; 44.6 mg, 71%), mp 190-192 o


(dd, J = 8.3, 1.7 Hz, 1H), 7.77 – 7.74 (m, 2H), 7.54 – 7.51 (m, 1H), 7.41 – 7.35 (m, 2H), 6.95 – 6.89 (m, 2H), 4.25 (s, 2H). 13C NMR (101 MHz, CDCl3) δ 168.6, 1589.0 (d, J = 242.7 Hz), 149.6, 144.8, 136.6, 135.7, 134.5 (d, J = 2.7 Hz), 132.7, 131.9, 129.5, 126.1, 122.3, 120.9 (d, J = 7.8 Hz), 115.4 (d, J = 22.4 Hz), 41.9. HRMS (ESI) m/z: [M+H]+ Calcd for C17H13ClFN2O 315.0695; Found 315.0694. 2-(5-chloroquinolin-8-yl)-N-(4-fluorophenyl)acetamide (4j) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/9; 40.8 mg, 65%), mp 178-180 o


(dd, J = 8.5, 1.6 Hz, 1H), 7.74 (d, J = 7.7 Hz, 1H), 7.65 – 7.62 (m, 2H), 7.38 – 7.35 (m, 2H), 6.92 (t, J = 8.7 Hz, 2H), 4.26 (s, 2H). 13C NMR (101 MHz, CDCl3) δ 168.9, 158.9 (d, J = 242.8 Hz), 150.0, 146.9, 134.5 (d, J = 2.7 Hz), 134.4, 133.0, 130.9, 130.8, 127.0, 126.9, 122.2, 120.9 (d, J = 7.8 Hz), 115.4 (d, J = 22.4 Hz), 41.9. HRMS (ESI) m/z: [M+H]+ Calcd for C17H13ClFN2O 315.0695; Found 315.0698. 2-(5-bromoquinolin-8-yl)-N-(4-fluorophenyl)acetamide (4k) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/9; 43.0 mg, 60%), mp 170-172 o


(dd, J = 8.6, 1.7 Hz, 1H), 7.80 (d, J = 7.7 Hz, 1H), 7.65 (d, J = 7.7 Hz, 1H), 7.62 – ACS Paragon Plus Environment

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7.59 (m, 1H), 7.39 – 7.34 (m, 2H), 6.94 – 6.88 (m, 2H), 4.24 (s, 2H). 13C NMR (101 MHz, CDCl3) δ 168.8, 158.9 (d, J = 242.6 Hz), 150.1, 147.0, 136.9, 134.5 (d, J = 2.7 Hz), 133.8, 131.4, 130.7, 128.2, 122.5, 121.3, 120.9 (d, J = 7.8 Hz), 115.4 (d, J = 22.4 Hz), 41.9. HRMS (ESI) m/z: [M+H]+ Calcd for C17H13BrFN2O 359.0190; Found 359.0196. N-(4-fluorophenyl)-2-(7-(trifluoromethyl)quinolin-8-yl)acetamide (4l) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/10; 27.8 mg, 40%), mp 196-198 oC. 1H NMR (400 MHz, CDCl3) δ 9.18 (s, 1H), 9.13 (dd, J = 4.2, 1.7 Hz, 1H), 8.30 (dd, J = 8.3, 1.7 Hz, 1H), 7.93 – 7.86 (m, 2H), 7.64 – 7.61 (m, 1H), 7.40 – 7.35 (m, 2H), 6.96 – 6.90 (m, 2H), 4.60 (d, J = 0.8 Hz, 2H).

13

C NMR (101 MHz,

CDCl3) δ 167.5, 159.0 (d, J = 243.6 Hz), 150.8, 146.5, 137.2, 134.4 (d, J = 2.7 Hz), 133.8, 130.5, 129.9, 128.0, 125.4, 123.3 (d, J = 5.2 Hz), 123.1, 122.7, 121.1 (d, J = 7.8 Hz), 115.4 (d, J = 22.5 Hz), 36.9. HRMS (ESI) m/z: [M+H]+ Calcd for C18H13F4N2O 349.0959; Found 349.0953. N-(4-fluorophenyl)-2-(phenanthridin-4-yl)acetamide (4m) The title compound was isolated as an off-white solid (eluent: EtOAc/PE:1/10; 28.4 mg, 43%), mp 219-221 oC. 1

H NMR (600 MHz, DMSO-d6) δ 10.36 (s, 1H), 9.42 (s, 1H), 8.87 (d, J = 8.3 Hz, 1H),

8.76 (d, J = 7.5 Hz, 1H), 8.24 (d, J = 7.7 Hz, 1H), 7.99 – 7.96 (m, 1H), 7.82 (t, J = 7.4 Hz, 1H), 7.77 (d, J = 6.7 Hz, 1H), 7.72 (t, J = 7.6 Hz, 1H), 7.66 – 7.64 (m, 2H), 7.20 – 7.15 – 7.12 (m, 2H), 4.37 (s, 2H). 13C NMR (151 MHz, DMSO) δ 170.0, 157.8 (d, J = 239.3 Hz), 153.2, 142.8, 135.9 (d, J = 2.4 Hz), 135.1, 132.1, 131.5, 130.4, 128.9, 127.9, 127.3, 126.9, 125.8, 123.6, 122.4, 121.8, 120.6 (d, J = 7.7 Hz), 115.2 (d, J = 22.1 Hz), 40.1. HRMS (ESI) m/z: [M+H]+ Calcd for C21H16FN2O 331.1241; Found 331.1240.

The Mechanistic Experiment Cyclometalated Rhodium(III) complex A5a was prepared according to the reported procedure. A Schlenk tube with a magnetic stir bar was charged with [Cp*RhCl2]2 (62.4 mg, 0.10 mmol), NaOAc (82 mg, 1.0 mmol, 10



equiv), 1a (272 µL, 2.0 mmol, 20 equiv), and MeOH (1.5 mL) under an N2 atmosphere. The resulting mixture was stirred at 80 °C for 24 h and then diluted with 3 mL of dichloromethane. The solution was filtered through a celite pad and washed with 10-20 mL of dichloromethane. The filtrate was concentrated and the residue was purified by column chromatography (PE/EtOAc: 1/2, v/v) to provide the complex A as a red orange solid (17 mg, 20% yield). 1H NMR (600 MHz, CDCl3) δ 8.94 (dd, J = 4.8, 1.1 Hz, 1H), 8.08 (dd, J = 8.3, 1.3 Hz, 1H), 7.62 (dd, J = 6.7, 1.4 Hz, 1H), 7.45 – 7.43 (m, 2H), 7.36 (dd, J = 8.3, 4.9 Hz, 1H), 3.97 (dd, J = 13.3, 1.4 Hz, 1H), 3.70 (d, J = 13.2 Hz, 1H), 1.62 (s, 15H).

13

C NMR (151 MHz, CDCl3) δ 153.6, 151.7, 151.4,

136.6, 130.0, 128.7, 128. 7, 128.0, 123.0, 122.0, 93.9, 93.8, 33.7, 33.5, 9.2.

Stoichiometric reaction using the cyclometalated complex A (Scheme 2c) In a glove box, a 25 mL Schlenk tube equipped with a stir bar was charged with the cyclometalated complex A (10 mol %), AgSbF6 (10 mol %), p-tolylisocyanate (0.2 mmol). The tube was fitted with a rubber septum, and removed out from the glove box. Then 8-methylquinoline (0.1 mmol) was added through the rubber septum using syringe under the atmosphere of N2. 1,2-Dichloroethane (2 mL) was added to the Schlenk tube though the rubber septum using syringes. The septum was replaced by a Teflon screwcap under N2 flow. The reaction mixture was stirred at 60 oC for 24 h. After cooling down, the solvent was removed in vacuo and the residue was purified by chromatography on silica gel to provide the corresponding product ( 17 mg, 60% yield).


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ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website at DOI: Detailed experimental procedures about the studies of the reaction mechanism, spectral data for new compounds.

AUTHOR INFORMATION Corresponding Author *E-mail: [email protected]

Notes The authors declare no competing financial interest. ACKNOWLEDGMENT Financial support from Shandong Provincial Natural Science Foundation, China (ZR2016JL009), National Natural Science Foundation of China (21302184) and University of Jinan is greatly appreciated.

REFERENCES (1) For selected recent reviews on C−H functionalization, see: (a) Topics in Current Chemistry: C-H Activation, ed. by Yu, J.-Q.; Shi, Z. Springer, Berlin, 2010, 292. (b) Arockiam, P. B.; Bruneau, C.; Dixneuf, P. H. Chem. Rev. 2012, 112, 5879. (c) Chen, Z.; Wang, B.; Zhang, J.; Yu, W.; Liu, Z.; Zhang, Y. Org. Chem. Front. 2015, 2, 1107. (d) Wang, F.; Yu, S.; Li, X. Chem. Soc. Rev. 2016, 45, 6462. (e) Yang, Y.; Lan, J.; You, J. Chem. Rev. 2017, 117, 8787. (2) For selected reviews on Rh(III)-catalyzed C−H activation, see: (a) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624. (b) Song, G.; Wang, F.; Li, X. Chem. Soc. Rev. 2012, 41, 3651. (c) Patureau, F. W.; Wencel-Delord, J.; Glorius, F. Aldrichimica Acta 2012, 45, 31. (d) Kuhl, N.; Schröeder, N.; Glorius, F. Adv. Synth. Catal. 2014, 356, 1443. (e) Song, G.; Li, X. Acc. Chem. Res. 2015, 48, 1007. (f) Yang, ACS Paragon Plus Environment


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Y.; Li, K.; Cheng, Y.; Wan, D.; Li, M.; You, J. Chem. Commun. 2016, 52, 2872. (g) Gensch, T.; Hopkinson, M. N.; Glorius, F.; Wencel-Delord, J. Chem. Soc. Rev. 2016, 45, 2900. (h) Park, Y.; Kim, Y.; Chang, S. Chem. Rev. 2017, 117, 9247. (3) For selected examples of Rh(III)-catalyzed C–H activations, see: (a) Guimond, N.; Gouliaras, C.; Fagnou, K. J. Am. Chem. Soc. 2010, 132, 6908. (b) Rakshit, S.; Grohmann, C.; Besset, T.; Glorius, F. J. Am. Chem. Soc. 2011, 133, 2350. (c) Morimoto, K.; Itoh, M.; Hirano, K.; Satoh, T.; Shibata, Y.; Tanaka, K.; Miura, M. Angew. Chem., Int. Ed. 2012, 51, 5359. (d) Zhang, G.; Yang, L.; Wang, Y.; Xie, Y.; Huang, H. J. Am. Chem. Soc. 2013, 135, 8850. (e) Zhao, H.; Shang, Y.; Su, W. Org. Lett. 2013, 15, 5106. (f) Zou, M.; Liu, J.; Tang, C.; Jiao, N., Org. Lett. 2016, 18, 3030. (g) Xu, H.-J.; Lu, Y.; Farmer, M. E.; Wang, H.-W.; Zhao, D.; Kang, Y.-S.; Sun, W.-Y.; Yu, J.-Q. J. Am. Chem. Soc. 2017, 139, 2200. (4) (a) Rakshit, S.; Patureau, F. W.; Glorius, F. J. Am. Chem. Soc. 2010, 132, 9585. (b) Huang, X.; Wang, Y.; Lan, J.; You, J. Angew. Chem., Int. Ed. 2015, 54, 9404. (c) Yuan, C.; Tu, G.; Zhao, Y. Org. Lett. 2017, 19, 356. (d) Tan, G.; You, J. Org. Lett. 2017, 19, 4782. (5)

For

selected

examples

on

Rh(III)-catalyzed

C(sp3)–H

activation

of

8-methylquinolines: (a) Liu, B.; Zhou, T.; Li, B.; Xu, S., Wang, B. Angew. Chem., Int. Ed. 2014, 53, 4191. (b) Wang, N.; Li, R.; Li, L., Xu, S., Song, H., Wang, B. J. Org. Chem. 2014, 79, 5379. (c) Wang, X.; Yu, D.-G., Glorius, F. Angew. Chem., Int. Ed. 2015, 54, 10280. (d) Yu, S.; Li, Y.; Kong, L.; Zhou, X.; Tang, G.; Lan, Y.; Li, X. ACS Catal. 2016, 6, 7744. (e) Liu, B.; Hu, P.; Zhou, X.; Bai, D.; Chang, J.; Li, X. Org. Lett. 2017, 19, 2086. (f) Jeong, T.; Mishra, N. K.; Dey, P.; Oh, H.; Han, S.; Lee, S. H.; Kim, H. S.; Park, J.; Kim, I. S. Chem. Commun. 2017, 53, 11197. (g) Mita,T.; Michigami, K.; Sato, Y. Org. Lett., 2012, 14, 3462. (6) Kuninobu, Y.; Tokunaga, Y.; Kawata, A.; Takai, K. J. Am. Chem. Soc. 2006, 128, 202. (7) (a) Hesp, K. D.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2011, 133, 11430. (b) Zhou, B.; Hou, W.; Yang, Y.; Li, Y. Chem. - Eur. J. 2013, 19, 4701. (c) Hou, W.; Zhou, B.; Yang, Y.; Feng, H.; Li, Y. Org. Lett. 2013, 15, 1814. (d) Shi, X.-Y.; ACS Paragon Plus Environment

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Renzetti, A.; Kundu, S.; Li, C.-J. Adv. Synth. Catal. 2014, 356, 723. (e) Jeong, T.; Han, S.; Mishra, N. K.; Sharma, S.; Lee, S.-Y.; Oh, J. S.; Kwak, J. H.; Jung, Y. H.; Kim, I. S. J. Org. Chem. 2015, 80 , 7243. (f) Han, S.; Mishra, N. K.; Sharma, S.; Park, J.; Choi, M.; Lee, S. Y.; Oh, J. S.; Jung, Y. H.; Kim, I. S. J. Org. Chem. 2015, 80, 8026. (g) Jeong, T.; Lee, S. H.; Mishra, N. K.; De, U.; Park, J.; Dey, P.; Kwak, J. H.; Jung, Y. H.; Kim, H. S.; Kim, I. S. Adv. Synth. Catal. 2017, 359, 2329. (8) (a) Muralirajan, K.; Parthasarathy, K.; Cheng, C.-H. Org. Lett. 2012, 14, 4262. (b) Sarkar, S. D.; Ackermann, L. Chem. - Eur. J. 2014, 20, 13932. (9) (a) Hummel, J. R.; Ellman, J. A. Org. Lett. 2015, 17, 2400. (b) Li, J.; Ackermann, L. Angew. Chem., Int. Ed. 2015, 54, 8551. (10) (a) Tsai, A. S.; Tauchert, M. E.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2011, 133, 1248. (b) Li, Y.; Li, B.-J.; Wang, W.-H.; Huang, W.-P.; Zhang, X.-S.; Chen, K.; Shi, Z.-J. Angew. Chem., Int. Ed. 2011, 50, 2115. (11) (a) Sham, H. L.; Konradi, A. W.; Hom, R. K.; Probst, G. D.; Bowers, S.; Truong, A.; Neitz, R. J.; Sealy, J.; Toth, G. PCT Int. Appl., 2010, WO 2010091310. (b) Duncan, K. W.; Chesworth, R.; Boriack-Sjodin, P. A.; Munchhof, M. J.; Jin, L. PCT Int. Appl. 2014, WO 2014100730. (12) (a) Winstein, S.; Traylor, T. G. J. Am. Chem. Soc. 1955, 77, 3747. (b) Lapointe, D.; Fagnou, K. Chem. Lett. 2010, 39, 1118. (13) Simmons, E. M.; Hartwig, J. F. Angew. Chem., Int. Ed. 2012, 51, 3066. (14) Li, Y.; Zhang, X.-S.; Li, H.; Wang, W.-H.; Chen, K.; Li, B.-J.; Shi, Z.-J. Chem. Sci. 2012, 3, 1634. (15) (a) Murchu, C. O' Synthesis 1989, 880. (b) Suggs, J. W.; Pearson, D. N. G. J. Org. Chem. 1980, 45, 1514. (c) Zhang, Y. C.; Wang, M.; Li, P. H.; Wang, L. Org. Lett. 2012, 14, 2206. (d) Evans, P.; Hogg, P.; Grigg, R.; Nurnabi, M.; Hinsley, J.; Sridharan, V.; Suganthan, S.; Korn, S.; Collard, S.; Muir, J. E. Tetrahedron 2005, 61, 9696. (e) Lu, B.; Li, C.-Q.; Zhang, L.-M. J. Am. Chem. Soc. 2010, 132, 14070. (16) Han, W.; Zhou, X.; Yang, S.; Xiang, G.; Cui, B.; Chen, Y. J. Org. Chem. 2015, 80, 11580.




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