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Copper-Catalyzed Selective Diphenylation of Carboxylic Acids with Cyclic Diaryliodonium Salts Hao Xie, Shuai Yang, Chunxia Zhang, Mingruo Ding, Min Liu, Jie Guo, and Fengzhi Zhang J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 26 Apr 2017 Downloaded from http://pubs.acs.org on April 26, 2017

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The Journal of Organic Chemistry

Copper-Catalyzed Selective Diphenylation of Carboxylic Acids with Cyclic Diaryliodonium Salts Hao Xie, Shuai Yang, Chunxia Zhang, Mingruo Ding, Min Liu, Jie Guo and Fengzhi Zhang* College of Pharmaceutical Science & Green Pharmaceutical Collaborative Innovation Center of Yangtze River Delta Region, Zhejiang University of Technology, Hangzhou, 310014, P. R. China Supporting Information Placeholder

R3

Cu-catalyzed selective diphenylation

O

OH R1

+

I R2

I

R3

-OTf

♦ Simple one-step procedure ♦ High atom economy/eco-friendly ♦ Broad substrate scopes ♦ Gram scale synthesis

simple aliphatic or r eadily av ailable cy clic ( heter o)ar yl acids diar yliodonium salts 42 examples; up to 97% yield

O

O R1

R2 valuable biphenyl ester s with iodo-f unct ional handle

ABSTRACT: Herein, we describe a novel one-step copper-catalyzed diphenylation of readily available aliphatic or (hetero)aromatic carboxylic acids with cyclic hypervalent diaryliodonium reagents. The selective diphenylation of benzoic acids with high atom-economy can be achieved without observation of the arylation at the phenyl hydroxyl/thio/amino position. The valuable biphenyl esters with an additional iodo-substituent were obtained in good to excellent yields, which can be further transformed to diversified building blocks for the synthesis of bioactive natural products, pharmaceuticals and functional materials. A wide range of different functional groups are compatible under the optimized reaction conditions.

1.

INTRODUCTION

Functionalized biphenyl esters are commonly encountered in the core structures of therapeutic reagents,1 functional materials,2 bioactive natural products3 and ligands (Figure 1).4 Constructing a C-O bond of monoaryl ether5 or aryl ester6 by metal catalysis is a long-standing interest to organic chemists, and a lot of excellent research works have been reported from different research groups. However, conventional biphenyl ester syntheses still involve the direct esterfication of carboxylic acids with biphenyl alcohol under strongly acidic or basic conditions,7 which might cause side reactions and limit scopes of substrates.8 Furthermore, the esterfication reactions generally rely on the pre-activation of the carboxylic acids to either acyl chloride or mixed anhydride by using a stoichiometric amount of coupling reagents, making them generally expensive and wasteful procedures. Figure 1.

Representative examples of biphenyl esters

1

ACS Paragon Plus Environment

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The biphenyl esters also can be accessed by a two-step procedure either by reacting preformed mono-arylated ester 2 with an aryl coupling component 4 (substituted benzenes,9 arylboronic acids10 or arylzinc reagents11) or a direct C-H functionalization of the preformed ester 3 with linear diaryliodonium salt 5 (Scheme 1a)12. Inspired by Cheng’s work about copper triflate mediated Chan-Lam reaction of carboxylic acids with arylboronic acids,13 Kumaran and co-workers developed a metal-free synthesis of biphenyl ester by coupling arylcarboxylic acids with arylboronic acids.14 Even though the biphenyl ester can be accessed by this one-step procedure, there is only one example reported with benzoic acid as the substrate. Besides, these methodologies still suffered from the inherent drawback of using organometallic reagents and producing harmful byproducts along with the desired biphenyl esters. Scheme 1. Approaches for the synthesis of biphenyl esters

2


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Increasing attention is now being devoted to develop such C-O bond formation which is not only atom-economical but also low cost and more environmentally friendly. A possible solution lies with one-step metal catalysis procedure with hypervalent diaryliodonium salts. Combining the excellent usability, stability, readily availability and high reactivity, linear hypervalent diaryliodonium salts have been extensively investigated as electrophilic arylation agents for the formation of C-C and C-heteroatom bonds.15-16 In 2011 Olofsson group reported a nice example about the mono-arylation of the carboxylic acids under basic conditions. 17 However, this metal-free condition doesn’t work for the biarylation of carboxylic acids with cyclic iodonium salts (entry 1, Table 1). Compared to linear iodonium salts, the employment of cyclic iodonium salts is advantageous in terms of atom economy because both aryl group will be incorporated in the arylated products.18 Our interest in arylation chemistry19 led us to question whether the C-O bonds of biphenyl esters could be constructed by coupling of carboxylic acids with cyclic diaryliodonium salts (Scheme 1b), which are not only highly atom and step-economical but also environmentally friendly. More importantly, this novel reaction will generate the biphenyl esters which may be difficult to obtain by other methods. Furthermore, these esters with very useful iodo-functional handles can be further transformed to valuable diversified building blocks. 2.

RESULTS AND DISCUSSION We initiated the study by performing the reaction of the commercially available 2-amino-3-methylbenzoic

acid 1a with cyclic diaryliodonium salt 7a (Table 1). By choosing a model substrate 1a with both phenyl acid and amino functional groups, we would like to achieve the selective diphenylation at the benzoic acid position without arylation at the phenyl amino position. Firstly, We tried the metal free acid arylation conditions reported by Olofsson and co-workers,17 and we were surprised to observe no desired product at all in the presence of KOtBu as base and toluene as solvent (entry 1), which might because the cyclic diaryl iodonium salts are generally less reactive than the linear counterpart.20 We then tried a catalyst system of Pd(OAc)2/Ag2CO3 and 1,10-phenanthroline in toluene, there was no product detected either (entry 2). With CuSO4 as catalyst reported by Fuson and Albright for the arylation of acetic acid (entry 3),21 the reaction was still failed even with the addition of 1,10-phenanthroline (phen) as the ligand (entry 4). To our delight, 10 mol % CuCl as catalyst with Na2CO3 as base at 150 oC in toluene was proved effective, the desired biphenyl ester 8a was formed selectively in 41% yield without observation of arylation at the phenyl amino position (entry 5). The yields can be further improved by using either Cu(OAc)2 (49%, entry 6) or CuI (63%, entry 7) as catalyst. All attempts to improve the reaction by changing the ligands (entries 8-10) and bases (entries 11-14) did not give better result. The influence of the solvents was then studied (entries 15-19). We found the yield was improved to 70% by using 1, 4-dioxane as the solvent (entry 19). A further jump in yield could be attained by reducing the temperature to 120 oC (84% yield, entry 20) and 95 oC (92% yield, entry 21). However, the yield was dropped to 70% by decreasing the temperature to 70 oC (entry 22). By increasing the amount of the base, there is no further improvement for the reaction (entry 23). The yields were dropped significantly by reducing the amount of either catalyst/ligand (70%, entry 24) or iodonium salts (61%, entry 25). The blank experiments showed that both the catalyst/ligand and base were required for this reaction (entries 26-28). Pleasingly, this reaction was equally effective on gram scale; 5.7 g of biphenyl ester 8a was easily prepared in 88% yield on 15 mmol scale (entry 29).

Table 1. Reaction optimizationa

3



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entrya

catalyst

ligand

base

solventb

temp (oC)

yield (%)c

1

-

-

KOtBu

toluene

100

0

2d

Pd(OAc)2

phen

Na2CO3

toluene

100

0

3

CuSO4

-

NaOAc

toluene

100

0

4

CuSO4

phen

NaOAc

toluene

100

0

5

CuCl

phen

Na2CO3

toluene

150

41

6

Cu(OAc)2

phen

Na2CO3

toluene

150

49

7

CuI

phen

Na2CO3

toluene

150

63

8

CuI

PPh3

Na2CO3

toluene

150

trace

9

CuI

valine

Na2CO3

toluene

150

trace

10

CuI

2,2’-dipyridyl

Na2CO3

toluene

150

53

11

CuI

phen

KOtBu

toluene

150

0

12

CuI

phen

Cs2CO3

toluene

150

trace

13

CuI

phen

NaHCO3

toluene

150

58

14

CuI

phen

K2CO3

toluene

150

60

15

CuI

phen

Na2CO3

DMF

150

0

16

CuI

phen

Na2CO3

DMSO

150

0

17

CuI

phen

Na2CO3

THF

150

40

18

CuI

phen

Na2CO3

DCE

150

45

19

CuI

phen

Na2CO3

1,4-dioxane

150

70

20

CuI

phen

Na2CO3

1,4-dioxane

120

84

4


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a

21

CuI

phen

Na2CO3

1,4-dioxane

95

92

22

CuI

phen

Na2CO3

1,4-dioxane

70

70

23e

CuI

phen

Na2CO3

1,4-dioxane

95

90

24f

CuI

phen

Na2CO3

1,4-dioxane

95

70

25g

CuI

phen

Na2CO3

1,4-dioxane

95

61

26

-

phen

Na2CO3

1,4-dioxane

95

0

27

CuI

-

Na2CO3

1,4-dioxane

95

27

28

CuI

phen

-

1,4-dioxane

95

11

29h

CuI

phen

Na2CO3

1,4-dioxane

95

88

Reaction condtions: benzoic acid (0.25 mmol), iodonium salt (0.5 mmol), catalyst (10 mol %), ligand (10

mol %), base (1.5 equiv), 3 Å molecular sieves (0.4 g/mmol), solvent (1.5 mL), heat, 17 h. bAnhydrous solvent. cIsolated yields. d With the addition of 1 equiv Ag2CO3. eThe amount of Na2CO3 was increased to 3 equiv. fThe yield was decreased to 70% by reducing the loading of both catalyst and ligand to 5 mol %. g The amount of iodonium salt was decreased to 1.5 equiv. h15 mmol Scale. With this optimized procedure in hand, we next examined the scope of this new process using a range of carboxylic acids (Table 2). Yields were generally good to excellent for a variety of simple benzoic acids (8b-8e). We were pleased to find the ortho-hydroxy benzoic acid was effective in the reaction; the desired biphenyl ester 8f was obtained selectively in 85% yield without arylation at the phenyl hydroxyl position. Interestingly, the 2-mercaptobenzoic acid led to the dimerized product 8g in 57% yield. For the anthranilic acid derivatives, both highly electron withdrawing groups (such as NO2, CF3) and electron donating groups (such as OMe) were tolerated under the reaction conditions (8h, 8i, 8p, and 8k). Gratifyingly, all the substrates with different halogenated functionalities (F, Cl, Br and I) were effective to give the desired products in good to excellent yields (8j, 8n-o, and 8q-r). The benzoic acid with ortho-benzoyl functionality also reacted well providing the product 8s in 84% yield with multi-functional handles which allow for further transformations. Importantly, we found that both aliphatic and heterocyclic carboxylic acids were equally effective as the benzoic acids (8t-y).

5



Table 2. Diphenylation of various carboxylic acids

To fully establish the scopes of the diphenylation reaction, a range of substituted cyclic diaryliodonium salts were prepared according to Olofsson’s method and subjected to the optimized reaction protocol with carboxylic acids (Table 3). 22 Good to excellent yields were obtained with alkyl substituted symmetrical cylic diaryliodonium salts (9a-e). The electron rich cyclic diaryliodonium salts only gave the desired product 9f in poor yield.20 For the electron withdrawing halogenated cyclic diaryliodonium salts, we found that both the fluoro and chloro groups were tolerated (9g-l). The reaction was proved insensitive to the steric hindrance on both coupling partners (9m and 9n). For the unsymmetrical cyclic diaryliodonium salts, it was found that 9o was obtained as a single product. However, 9p/9p' and 9q/9q' were obtained as a mixture of products with a ratio around 1:1 respectively. Overall, various functional groups including free phenyl amino and hydroxyl groups were compatible under the optimized reaction conditions.

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Table 3. Diphenylation of carboxylic acids with various cyclic diaryliodonium salts

We already demonstrated the successful diphenylation of aliphatic, aromatic and heteroaromatic carboxylic acids. Our procedure was equally effective for the arylation of carboxylic acids with linear iodonium salts (Scheme 2). To investigate the regioselective arylation of the acid in the presence of the other nucleophile, we especially chose 1a, 6f and 6g as the substrates which contain phenolic amino, hydroxyl and thiol group respectively. Interestingly, compared to Olofsson’s condition,17 the desired products 10 and 11 were obtained in much better yields under our Cu-catalyzed conditions with the phenolic amino, hydroxyl group untouched. However, for the 2-thiolbenzoic acid substrate 6g both the acid and thiol groups were arylated to give the product 12 in poor yield. Scheme 2. Mono-arylation of anthranilic acid derivatives

7



To further understand this diphenylation reaction we carried out the following experiments (Scheme 3): firstly we treated the aniline 13a and phenol 13b with the optimized reaction conditions respectively, and we found that only the diphenylated aniline 14a was obtained in 53% yield, which means the selective diphenylation of aniline derivatives also can be achieved in the presence of free phenyl hydroxyl group under our reaction conditions (Scheme 3a). We then conducted the competition experiment between benzoic acid 6b and aniline 13a (Scheme 3b), interestingly, biphenyl ester 8b was obtained in 95% yield and only 4% yield of 14a was obtained. These experiments demonstrated why the selective diphenylation of benzoic carboxylic acids can be achieved in the presence of phenyl amino or hydroxyl groups. Finally, we performed the reaction of our model substrate 1a with 2,2’-diiodo-1,1’-biphenyl 15 under the optimized conditions (Scheme 3c), and no reaction was happened, which means the diiodo compound 15 is not the intermediate of this diphenylation reaction. Therefore, the possible reaction mechanism might involve a Cu(III)-aryl intermediate I from the cyclic diaryliodonium salt 7a in the presence of CuI, which was then attacked by the carboxylic acid 6 and generated the intermediate II. Finally, the desired product 8 was produced by reductive elimination. Scheme 3. Experiments about selectivity and mechanistic study

8


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To demonstrate the utility of this new copper-catalyzed diphenylation process, the biphenyl ester 8a was transformed to various valuable building blocks. Firstly, we carried out some experiments to functionalize the iodo-position (Scheme 4). Treated ester 8a with trimethylsilylacetylene under the Sonogashira coupling conditions the desired product 16 was obtained in 73% yield, which could be further modified if necessary. By reacting with styrene under Heck coupling conditions the alkene product 17 was prepared in 53% yield. Alkyne 16 and alkene 17 could be cyclized to afford the phenanthrene products via Ruthenium-catalyzed benzannulation Protocol or photocyclization conditions.23 Under the conditions of metal catalysis the iodo-functionalized biphenyl ester 8a can be converted to the cyano ester 1824 or phosphino ester 1925 respectively which potentially could be worked as bidentate ligands for various transformations.

9



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Scheme 4. Further transformations of iodo-functional group

I

R

conditions

O

O H2N

O

O

H2 N

H3C

H3 C 8a 1) 2.5 equiv

SiMe3 10 mol % Pd(PPh3)2Cl2

SiMe3

16, 73%, R =

Et3N, THF, rt, 12 h 2) 1.2 equiv styrene, 5 mol % Pd(OAc)2 2.0 eq. AcOH, 110 oC

17, 53%, R =

3) 1.5 equiv CuCN, NMP, reflux, 12 h

18, 50%, R =

CN

4) 2.0 equiv Ph2PH, 10 mol % Pd(OAc)2 KOAc, DMA, 100 oC, 12 h

19, 54%, R =

PPh2

Ph

We then carried out the further transformations based on the amino-functionality (Scheme 5). By a 3-step one-pot process the amino functionality in biphenyl ester 8a can be removed to give ester 20 in 62% yield. The amino group also can be transformed to azide group in ester 21 by treating ester 8a with tBuONO and TMSN3.26 Scheme 5. Further transformations of amino-functional group

Finally we demonstrated the biphenyl ester 8a can be cyclized to give different valuable heterocycles (Scheme 6). By reacting with tBuONO the biphenyl ester 8a can be cyclized to give the indazole compund 22.27 By a two-step procedure the biphenyl ester 8a can be cyclized successfully to give the benzocoumarin 23, an important skeleton for both pharmaceutical molecules and natural products. 28

10


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Scheme 6. Intramolecular cyclization to form various hetreocycles

3. CONCLUSIONS In summary, we have developed a general and efficient scalable procedure for Cu-catalyzed mono-arylation or diphenylation of carboxylic acids with readily available diaryliodonium salts. The selective diphenylation of benzoic acids with high atom-economy can be achieved without arylation at the phenyl hydroxyl/thio/amino positions. The corresponding dipheylated esters with an iodo-substitutent are obtained in good to excellent yields with various aliphatic, aromatic or heteroaromatic carboxylic acids. This transformation is tolerant to a wide range of functional groups (such as halogens, nitro and free phenyl amino/hydroxyl groups etc.) on both coupling partners. The valuable biphenyl esters can be easily transformed to diversified products which are prevalent building blocks for bioactive natural products, pharmaceuticals, organic electronic devices and bidentate ligands.

4. EXPERIMENTAL SECTION 4.1. General Information. All reagents were obtained from commercial suppliers and used without further purification. Yields for all compounds were determined by the column chromatography which was generally performed on silica gel (200-300 mesh) using petroleum ether 40-60 PE/EtOAc as eluent, and reactions were monitored by thin layer chromatography (TLC) on a glass pate coated with silica gel with fluorescent indicator (GF254) using UV light. The 1H and 13C nuclear magnetic resonance (NMR) spectra were recorded on a Bruker AVANCE III 500 MHz using CDCl3 as solvent with TMS as internal standard. Chemical shifts are given in ppm (δ) referenced to CDCl3 with 7.26 for 1H and 77.16 for 1

DMSO-d6 with 2.50 for H and 39.52 for

13

13

C, and to

C. Signals are abbreviated as follows: s, singlet; d, doublet; t,

triplet; q, quartet; m, multiplet, and coupling constants are expressed in hertz. Melting points were measured on a SGW® X-4B apparatus and uncorrected. HRMS were recorded on Agilent 6210TOF LC/MS mass spectrometer. 11



4.2.

General

procedure

for

the

diphenylation

Page 12 of 25

reaction.

Synthesis

of

2'-iodo-[1,1'-biphenyl]-2-yl 2-amino-3-methylbenzoate (8a, Table 1). The reaction of cyclic diaryliodonium salt 7a, 2-Amino-3-methylbenzoic acid 1a was exemplified here. 2-Amino-3-methylbenzoic acid 1a (37.25 mg, 0.25 mmol), cyclic diphenyleneiodonium 7a (214 mg, 0.50 mmol), Na2CO3 (39.75 mg, 0.375 mmol), CuI (4.8 mg, 0.025 mmol) and 1,10-Phenanthroline (4.5 mg, 0.025 mmol) were dissolved in anhydrous 1,4-dioxane (1.5 mL) in a pressure νessel. 3 Å molecular sieves (100 mg) were then added. The reaction mixture was stirred at 95 oC for 17 h before it was cooled to rt and filtered. The mixture was then extracted with EtOAc (50 mL) and washed with water (10 mL) and brine (10 mL) before the organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (PE/EtOAc = 20:1) on silica gel to provide the desired product 8a (98.9 mg, 92% yield). Mp = 97.9-98.4 oC; Rf = 0.50 (PE/EtOAc = 10:1); 1H NMR (CDCl3; 500 MHz): δ 7.88 (d, J = 8.3 Hz, 1 H), 7.67 (d, J = 8.2 Hz, 1 H), 7.50 (td, J = 7.6, 0.8 Hz, 1 H), 7.36 (td, J = 7.6, 0.6 Hz, 1 H), 7.28-7.33 (m, 4 H), 7.17 (d, J = 7.3 Hz, 1 H), 6.96 (td, J = 7.1, 1.6 Hz, 1 H), 6.52 (t, J =7.6 Hz, 1 H), 5.69 (s, 2 H), 2.12 (s, 3 H) ppm;

13

C NMR

(CDCl3; 126 MHz): δ 166.8, 149.6, 147.9, 142.8, 139.0, 137.9, 135.4, 131.1, 130.5, 129.7, 129.3, 129.3, 128.0, 125.8, 123.1, 122.9, 115.8, 109.2, 99.7, 17.5 ppm; IR (KBr) ν 3491, 3378, 1709, 1615, 1464, 1244, 1196, 1067, 1002, 468 cm -1; HRMS m/z (ESI): calcd for C20H17INO2 [M + H]+ 430.0298, found 430.0303, error 1.02 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl benzoate (8b): Following the general experiment procedure, 8b was purified by PE/EtOAc (30:1) and obtained as a white solid (97% yield). Mp = 46.4-47.2 oC; Rf = 0.60 (PE/EtOAc = 15:1); 1H NMR (CDCl3; 500 MHz): δ 7.90-7.93 (m, 2 H), 7.88 (d, J = 7.6, 1 H), 7.49-7.55 (m, 2 H), 7.34-7.40 (m, 4 H), 7.28-7.32 (m, 3 H), 6.94-7.00 (m, 1 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 164.7, 148.0, 142.7, 138.9, 137.4, 133.4, 131.0, 130.5, 130.1, 129.4, 129.3, 129.2, 128.5, 128.0, 126.0, 122.7, 99.7 ppm; IR (KBr) ν 1737, 1600, 1496, 1462, 1262, 1194, 1062, 497 cm -1; HRMS m/z (ESI): calcd for C19H13INaO2 [M + Na]+ 422.9852, found: 422.9846, error 1.59 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl 2,5-dimethylbenzoate (8c): Following the general experiment procedure, 8c was purified by PE/EtOAc (15:1) and obtained as a white solid (72% yield). Mp = 73.3-74.2 oC; Rf = 0.55 (PE/EtOAc = 6:1); 1H NMR (CDCl3; 500 MHz): δ 7.93 (d, J = 7.6 Hz, 1 H), 7.52 (td, J = 7.8, 0.9 Hz, 1 H), 7.48 (s, 1 H), 7.35-7.40 (m, 2 H), 7.31-7.34 (m, 3 H), 7.19 (d, J = 7.8 Hz, 1 H), 7.08 (d, J = 7.8 Hz, 1 H), 7.00-7.03 (m, 1 H), 2.41 (s, 3 H), 2.28 (s, 3 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 165.6, 148.1, 142.9, 138.8, 137.7, 137.6, 135.2, 133.2, 131.5, 131.5, 130.9, 130.6, 129.4, 129.3, 128.3, 127.9, 125.9, 122.9, 100.0, 21.0, 20.8 ppm; IR (KBr) ν 1745, 1593, 1469, 1244, 1189, 1102, 489 cm -1; HRMS m/z (ESI): calcd for C21H17INaO2 [M + Na]+ 451.0165, found: 451.0162, error 0.67 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl 4-methoxybenzoate (8d): Following the general experiment procedure, 8d was purified by PE/EtOAc (15:1) and obtained as a yellow liquid (80% yield). Rf = 0.28 (PE/EtOAc = 6:1); 1H NMR (CDCl3; 500 MHz): δ 7.87-7.90 (m, 3 H), 7.50 (dd, J = 7.8, 0.9 Hz, 1 H), 7.34-7.38 (m, 2 H), 7.27-7.31 (m, 3 H), 6.94-6.97 (m, 1 H), 6.86 (d, J = 9.0 Hz, 2 H), 3.83 (s, 3 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 164.4, 163.8, 148.1, 142.8, 138.8, 137.5, 132.2, 130.9, 130.5, 129.4, 129.2, 127.9, 125.8, 122.8, 121.7, 113.8, 99.7, 55.5 ppm; IR (KBr) ν 1733, 1604, 1508, 1263, 1173, 1070, 451 cm -1; HRMS m/z (ESI): calcd for C20H15INaO3 [M + Na]+452.9958, found: 452.9956, error 0.44 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl 2-chlorobenzoate (8e): Following the general experiment procedure, 8e was purified by PE/EtOAc (15:1) and obtained as a white solid (65% yield). Mp = 74.6-75.2 oC; Rf = 0.45 (PE/EtOAc = 6:1); 1H NMR (CDCl3; 500 MHz): δ 7.92 (d, J = 8.0 Hz, 1 H), 7.51 (td, J= 7.8, 0.9 Hz, 1 H), 7.46 (dd, J = 7.6, 0.7 Hz, 1 H), 7.30-7.41 (m, 7 H), 7.21 (td, J = 7.8, 1.0 Hz, 1 H), 7.02 (td, J = 7.5, 1.0 Hz, 1 H) ppm;13C NMR (CDCl3; 126 MHz): δ 163.5, 147.8, 142.6, 138.9, 137.6, 134.3, 133.0, 131.5, 131.2, 131.1, 12


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130.6, 129.5, 129.4, 129.2, 128.1, 126.6, 126.3, 122.8, 99.9 ppm; IR (KBr) ν 1744, 1595, 1453, 1244, 1183, 1105, 735, 495 cm -1; HRMS m/z (ESI): calcd for C19H12ClINaO2 [M + Na]+ 456.9463, found: 456.9460, error 0.66 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl 2-hydroxybenzoate (8f): Following the general experiment procedure, 8f was purified by PE/EtOAc (50:1) and obtained as a white oil-liquid (85% yield). Rf = 0.60 (PE/EtOAc = 25:1); 1

H NMR (CDCl3; 500 MHz): δ 10.36 (s, 1 H), 7.90 (d, J = 8.1, 0.5 Hz, 1 H), 7.81 (dd, J = 8.1, 0.9 Hz,1 H),

7.54 (td, J = 7.8, 0.9 Hz, 1 H), 7.41 -7.47 (m, 2 H), 7.30-7.38 (m, 4 H), 6.95-7.00 (m, 2 H), 6.88 (t, J = 7.6, 1 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 168.3, 161.9, 147.2, 142.2, 139.0, 137.4, 136.3, 131.2, 130.4, 130.4, 129.5, 129.4, 128.0, 126.5, 122.5, 119.4, 117.6, 111.6, 99.5 ppm; IR (KBr) ν 3230, 1691, 1615, 1582, 1463, 1249, 1188, 1156, 529 cm -1; HRMS m/z (ESI): calcd for C19H13INaO3 [M + Na]+ 438.9802, found: 438.9802, error 0 ppm. bis(2'-iodo-[1,1'-biphenyl]-2-yl)-2,2'-disulfanediyldibenzoate (8g): Following the general experiment procedure, 8g was purified by PE/EtOAc (30:1) and obtained as a white solid (57% yield). Mp = 84.8-85.9 o

C; Rf = 0.40 (PE/EtOAc = 6:1); 1H NMR (CDCl3; 500 MHz): δ 7.89 (d, J = 7.9 Hz, 2 H), 7.86 (dd, J = 7.8,

0.7 Hz, 2 H), 7.61 (d, J = 8.1 Hz,2 H), 7.52 (td, J = 7.8, 0.8 Hz, 2 H), 7.40-7.42 (m, 2 H), 7.35-7.39 (m, 4 H), 7.30-7.33 (m, 6 H), 7.15 (t, J = 7.6 Hz, 2 H), 6.96-7.00 (m, 2 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 164.5, 147.8, 142.7, 141.1, 138.9, 137.5, 133.5, 131.9, 131.1, 130.7, 129.5, 129.4, 128.1, 126.6, 126.3, 126.0, 125.7, 122.8, 99.8 ppm; IR (KBr) ν 1719, 1585, 1450, 1244, 1189, 1139, 648, 552, 486 cm -1; HRMS m/z (ESI): calcd for C38H24I2NaO4S2 [M + Na]+ 884.9098, found: 884.9096, error 0.05 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl-2-amino-3-nitrobenzoate (8h): Following the general experiment procedure, 8h was purified by PE/EtOAc (15:1) and obtained as a yellow solid (70% yield). Mp= 159.5-160.5 oC; Rf = 0.40 (PE/EtOAc = 6:1); 1H NMR (CDCl3; 500 MHz)：δ 8.35 (dd, J = 8.5, 0.8 Hz, 1 H), 8.29 (s, 2 H), 8.11 (dd, J =7.7, 0.8 Hz, 1 H), 7.87 (dd, J = 8.0, 0.5 Hz, 1 H), 7.53 (td, J=7.8, 0.8 Hz, 1H), 7.41 (td, J = 7.5, 0.6 Hz, 2 H), 7.30-7.33 (m, 2 H), 7.25-7.27 (m, 1 H), 6.98 (td, J = 7.7, 0.9 Hz, 1 H), 6.59 (t, J = 8.1 Hz, 1 H) ppm; 13C NMR (CDCl3; 126 MHz)：δ 165.3, 147.6, 147.4, 142.4, 139.9, 139.0, 137.6, 133.4, 132.9, 131.2, 130.5, 129.6, 129.4, 128.1, 126.5, 122.7, 114.3, 113.4, 99.5 ppm; IR (KBr) ν3476, 3353, 1713, 1619, 1574, 1512, 1354, 1255, 1191, 469 cm -1; HRMS m/z (ESI) : calcd for C19 H13 IN2NaO4 [M + Na]+ 482.9812, found: 482.9816, error 0.79 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl-2-amino-4-(trifluoromethyl) benzoate (8i): Following the general experiment procedure, 8i was purified by PE/EtOAc (30:1) and obtained as a white solid (87% yield). Mp = 133.7-134.6 o

C; Rf = 0.50 (PE/EtOAc = 15:1); 1H NMR (CDCl3; 500 MHz)：δ 7.89 (dd, J = 8.0, 0.5 Hz, 1 H), 7.82 (d, J =

8.3 Hz, 1 H), 7.52 (td, J = 7.8, 0.9 Hz, 1 H), 7.39 (td, J = 7.5, 0.6 Hz, 1 H), 7.30-7.35 (m, 3 H), 7.26-7.28 (m, 1 H), 6.99 (td, J = 7.6, 0.9 Hz, 1 H), 6.84 (s, 1 H), 6.78 (dd, J = 8.4, 0.7 Hz, 1 H), 5.79 (s, 2 H) ppm; 13C NMR (CDCl3; 126 MHz)：δ 165.5, 150.7, 147.6, 142.6, 139.0, 137.6, 136.1, 135.9, 132.6, 131.1, 130.5, 129.5 (d, J = 6.0 Hz), 128.0, 126.2, 122.8, 113.4(d, J = 4.0 Hz), 112.5 (d, J = 3.7 Hz), 112.0, 99.6 ppm; IR (KBr) ν 3518, 3393, 1720, 1599, 1444, 1356, 1246, 1192, 1120, 1071, 500 cm -1; HRMS m/z (ESI): calcd for C20H14F3INO2 [M + H]+ 484.0016, found: 484.0017, error 0.26 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl-2-amino-4-bromobenzoate (8j): Following the general experiment procedure, 8j was purified by PE/EtOAc (15:1) and obtained as a yellow solid (80% yield). Mp = 128.2-129.0 oC; Rf = 0.42 (PE/EtOAc = 6:1); 1H NMR (CDCl3; 500 MHz)：δ 7.74 (dd, J = 8.0, 0.5 Hz, 1 H), 7.43 (d, J = 8.6 Hz, 1 H), 7.36 (td, J = 7.8, 0.9 Hz, 1 H), 7.23 (td, J = 7.5, 0.6, 1 H), 7.16-7.19 (m, 3 H), 7.11-7.13 (m, 1 H), 6.84 (td, J = 7.6, 0.9 Hz, 1 H), 6.63 (d, J = 1.8 Hz, 1 H), 6.55 (dd, J = 8.6, 0.9 Hz, 1 H), 5.51 (s, 2 H) ppm; 13C NMR (CDCl3; 126 MHz)：δ 165.4, 149.1, 147.9, 142.7, 139.1, 137.6, 134.4, 132.3, 131.4, 130.9, 129.6, 129.5, 127.9, 126.3, 122.8, 119.5, 114.8, 113.7, 100.1 ppm; IR (KBr) ν 3489, 3373, 1711, 1603, 1461, 1233, 13



1190, 1058, 555, 496 cm -1; HRMS m/z (ESI): calcd for C19H13 BrINNaO2 [M + Na]+ 515.9067, found: 515.9073, error 1.46 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl-2-amino-4,5-dimethoxybenzoate (8k): Following the general experiment procedure, 8k was purified by PE/EtOAc (5:1) and obtained as a yellow solid (82% yield). Mp = 188.5-189.4 oC; Rf = 0.35 (PE/EtOAc = 2:1); 1H NMR (CDCl3; 500 MHz)：δ 7.88 (d, J = 7.9 Hz, 1 H), 7.51 (td, J = 8.2, 0.9 Hz, 1 H), 7.39 (d, J = 8.2 Hz, 1 H), 7.36 (t, J = 7.5 Hz, 1 H), 7.32 (t, J = 7.5 Hz, 1 H), 7.27-7.29 (m, 2 H), 7.18 (s, 1 H), 6.98 (td, J = 7.4, 1.0 Hz, 1 H), 6.08 (s, 1 H), 5.50 (s, 2 H), 3.85 (s, 3 H), 3.77 (s, 3 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 165.6, 155.3, 147.9, 147.8, 143.2, 140.8, 138.8, 137.6, 130.7, 130.6, 129.3, 129.2, 128.1, 125.7, 123.1, 112.4, 101.0, 99.9, 99.2, 56.4, 55.9 ppm; IR (KBr) ν3494, 3385, 1688, 1599, 1510, 1462, 1163,1042, 499 cm -1; HRMS m/z (ESI): calcd for C21H19INO4 [M + H]+ 476.0353, found: 476.0350, error 0.6 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl 2-aminobenzoate (8l): Following the general experiment procedure, 8l was purified by PE/EtOAc (20:1) and obtained as a yellow oil-liquid (79% yield). Rf = 0.45 (PE/EtOAc = 10:1); 1

H NMR (CDCl3; 500 MHz): δ 7.88 (d, J = 8.3 Hz,1 H), 7.74 (dd, J = 8.1, 0.8 Hz, 1 H), 7.50 (td, J = 7.7, 0.9

Hz, 1 H), 7.36 (td, J = 7.6, 0.6 Hz, 1 H), 7.33 (d, J = 8.2 Hz, 1 H), 7.27-7.32 (m, 3 H), 7.24 (td, J = 7.7, 0.8 Hz, 1 H), 6.97 (td, J = 7.4, 1.2 Hz, 1 H), 6.56-6.60 (m, 2 H), 5.56 (s, 2 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 166.3, 151.1, 147.8, 142.8, 139.0, 137.7, 134.7, 131.7, 131.1, 130.5, 129.4, 129.3, 128.0, 125.9, 123.0, 116.6, 116.5, 109.7, 99.9 ppm; IR (KBr) ν 3488, 3375, 1702, 1616, 1459, 1289, 1239, 1200, 1048, 496 cm -1; HRMS m/z (ESI): calcd for C19H15INO2 [M + H]+416.0142, found: 416.0145, error 0.72 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl-2-amino-5-methylbenzoate (8m): Following the general experiment procedure, 8m was purified by PE/EtOAc (30:1) and obtained as a white solid (74% yield). Mp = 128.4-129.2 oC; Rf = 0.44 (PE/EtOAc = 15:1);1H NMR (CDCl3; 500 MHz): δ 8.40 (d, J = 8.2 Hz, 1 H), 7.99-8.02 (m, 2 H), 7.84-7.88 (m, 2 H), 7.79-7.82 (m, 3 H), 7.57 (dd, J = 8.4, 1.0 Hz, 1 H), 7.48 (td, J = 7.6, 1.1 Hz, 1 H), 7.03 (d, J = 8.4 Hz, 1 H), 5.90 (s, 2 H), 2.68 (s, 3 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 166.2, 148.9, 148.0, 142.8, 138.9, 137.6, 135.9, 131.4, 130.9, 130.5, 129.3, 129.2, 127.9, 125.8, 125.5, 123.0, 116.7, 109.6, 99.8, 20.2 ppm; IR (KBr) ν 3438, 3371, 1693, 1564, 1494, 1292, 1193, 1160, 1051, 497 cm -1; HRMS m/z (ESI): calcd for C20H17INO2 [M + H]+ 430.0298, found: 430.0301, error 0.57 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl-2-amino-5-chlorobenzoate (8n): Following the general experiment procedure, 8n was purified by PE/EtOAc (15:1) and obtained as a yellow solid (70% yield). Mp = 121.9-122.4 oC; Rf = 0.40 (PE/EtOAc = 6:1); 1H NMR (CDCl3; 500 MHz)：δ 7.91 (dd, J = 8.0, 0.6 Hz, 1 H), 7.67 (d, J = 2.6 Hz, 1H), 7.50 (td, J = 7.8, 0.9 Hz, 1 H), 7.31-7.39 (m, 4 H), 7.26-7.29 (m, 1 H), 7.17 (dd, J = 8.8, 1.3 Hz, 1 H), 7.00 (td, J = 7.6, 0.9 Hz, 1 H), 6.52 (d, J = 8.8 Hz, 1 H), 5.42 (s, 2 H) ppm; 13C NMR (CDCl3; 126 MHz)：δ 165.3, 149.7, 147.8, 142.6, 139.1, 137.6, 134.8, 134.6, 131.2, 130.8, 130.5, 129.3, 127.9, 126.2, 122.8, 120.6, 118.2, 110.5, 99.5 ppm; IR (KBr) ν 3502, 3381, 1705, 1618, 1460, 1225, 1187, 746, 492 cm -1; HRMS m/z (ESI): calcd for C19H14ClINO2 [M + H]+449.9752, found: 449.9750, error 0.06 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl-2-amino-5-iodobenzoate (8o): Following the general experiment procedure, 8o was purified by PE/EtOAc (8:1) and obtained as a brown oil-liquid (64% yield). Rf = 0.40 (PE/EtOAc = 3:1); 1H NMR (CDCl3; 500 MHz): δ 7.91 (d, J = 2.2 Hz, 1 H), 7.88 (dd, J = 7.8, 0.5 Hz, 1 H), 7.45 (td, J = 7.8, 0.8 Hz, 1 H), 7.38 (dd, J = 8.7, 1.1 Hz, 1 H), 7.28-7.34 (m, 4 H), 7.22 (dd, J = 7.9, 0.9 Hz, 1 H), 6.97 (td， J = 7.7, 0.9 Hz, 1 H), 6.32 (d，J = 8.8 Hz, 1 H), 5.59 (s, 2 H) ppm; 13C NMR (CDCl3; 126 MHz)：δ 164.9, 150.3, 147.7, 142.8, 142.5, 139.9, 139.1, 137.5, 131.0, 130.5, 129.5, 129.4, 128.0, 126.0, 122.7, 118.7, 111.7, 99.7, 76.0 ppm;IR (KBr) ν 3507, 3396, 1707, 1611, 1462, 1259, 1185, 1074, 501 cm -1; HRMS m/z (ESI): calcd for C19H13I2NNaO2 [M + Na] + 563.8928, found: 563.8920, error 1.37 ppm.

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2'-iodo-[1,1'-biphenyl]-2-yl-2-amino-5-nitrobenzoate (8p): Following the general experiment procedure, 8p was purified by PE/EtOAc (6:1) and obtained as a yellow solid (77% yield). Mp = 134.6-135.5 oC; Rf = 0.34 (PE/EtOAc = 3:1); 1H NMR (CDCl3; 500 MHz)：δ 8.67 (d, J = 2.6 Hz, 1 H), 8.09 (dd, J = 9.2, 1.3 Hz, 1 H), 7.89 (dd, J = 8.0, 1.0 Hz, 1 H), 7.52 (td, J = 7.8, 0.9 Hz, 1 H), 7.32-7.41 (m, 4 H), 7.28-7.30 (m, 1 H), 6.98 (td, J = 7.7, 0.9 Hz, 1 H), 6.60 (d, J = 9.2 Hz, 1 H), 6.53 (s, 2 H) ppm; 13C NMR (CDCl3; 126 MHz)：δ 165.1, 155.2, 147.7, 142.3, 139.5, 137.4, 131.2, 130.4, 129.9, 129.7, 129.5, 129.5, 129.3, 128.3, 126.5, 122.6, 116.3, 108.5, 99.5 ppm; IR (KBr) ν 3453, 3331, 1714, 1626, 1313, 1248, 1192, 1119, 495 cm -1; HRMS m/z (ESI) : calcd for C19H13IN2NaO4 [M + Na]+482.9812, found: 482.9812, error 0 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl-2-amino-6-fluorobenzoate (8q): Following the general experiment procedure, 8q was purified by PE/EtOAc (15:1) and obtained as a white solid (90% yield). Mp = 90.3-91.0 oC; Rf = 0.44 (PE/EtOAc = 6:1); 1H NMR (CDCl3; 500 MHz)：δ 7.89 (d, J = 7.9 Hz, 1 H), 7.49 (td, J = 7.7, 0.9 Hz, 1 H), 7.37 (td, J = 7.5, 0.5 Hz, 1 H), 7.29-7.33 (m, 4 H), 7.09-7.14 (m, 1 H), 6.97-7.00 (m, 1 H), 6.35 (d, J = 8.3 Hz, 1 H), 6.28 (t, J = 9.6 Hz, 1 H), 5.48 (s, 2 H) ppm; 13C NMR (CDCl3; 126 MHz)：δ 165.0 (d, J = 3.7 Hz), 164.5, 162.5, 152.0 (d, J = 4.4 Hz), 147.8, 142.4, 139.0, 137.7, 134.4 (d, J = 12.0 Hz), 131.4, 130.5, 129.3 (d, J = 10.0 Hz), 127.7, 126.0, 122.9, 112.0 (d, J = 3.0 Hz), 104.0, 103.7, 100.6 (d, J = 14.4 Hz), 99.7 ppm; IR (KBr) ν 3491, 3377, 1700, 1625, 1465, 1275, 1191, 1077, 482 cm -1; HRMS m/z (ESI): calcd for C19H14FINO2 [M + H]+ 434.0048, found: 434.0048, error 0 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl-2-amino-6-chlorobenzoate (8r): Following the general experiment procedure, 8r was purified by PE/EtOAc (15:1) and obtained as a white solid (84% yield). Mp = 117.3-117.9 oC; Rf = 0.45 (PE/EtOAc = 6:1); 1H NMR (CDCl3; 500 MHz)：δ 7.91 (d, J = 7.7 Hz, 1 H), 7.51 (td, J = 7.8, 0.8 Hz, 1 H), 7.39 (td, J = 7.5, 0.6 Hz, 1 H), 7.30-7.35 (m, 4 H), 7.01-7.05 (m, 2 H), 6.68 (dd, J = 7.8, 0.5 Hz, 1H), 6.47 (dd, J = 8.4, 0.5 Hz, 1H), 4.46 (s, 2 H) ppm; 13C NMR (CDCl3; 126 MHz)：δ 165.4, 149.0, 147.7, 142.7, 139.1, 137.7, 134.2, 132.4, 131.4, 130.7, 129.6, 129.5, 128.0, 126.3, 122.8, 119.4, 114.9, 113.7, 100.1 ppm; IR (KBr) ν 3484, 3372, 1705, 1608, 1477, 1229, 1191, 753, 520 cm -1; HRMS m/z (ESI) : calcd for C19H14ClINO2 [M + H]+ 449.9752, found: 449.9753, error 0.14 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl-2-(2-aminobenzoyl) benzoate (8s): Following the general experiment procedure, 8s was purified by PE/EtOAc (6:1) and obtained as a yellow solid (84% yield). Mp = 134.6-135.5 o

C; Rf = 0.40 (PE/EtOAc = 3:1); 1H NMR (CDCl3; 500 MHz)：δ 7.87 (dd, J = 8.0, 0.5 Hz, 1 H), 7.79 (dd, J =

7.9, 0.4 Hz, 1H), 7.58 (td, J = 7.5, 0.6 Hz, 1 H), 7.43 (td, J = 7.7, 0.6 Hz, 1 H), 7.37 (td, J = 7.8, 0.8 Hz, 1 H), 7.33 (d, J = 7.6, 0.4, 1 H), 7.21-7.30 (m, 4 H), 7.12 (dd, J = 7.6, 0.8 Hz, 1 H), 7.03 (d, J = 8.1, 0.5 Hz, 1 H), 6.98 (td, J = 7.7, 0.9 Hz, 1 H), 6.93 (d, J = 8.0 , 0.7 Hz, 1 H), 6.67 (dd, J = 8.3, 0.3 Hz, 1 H), 6.47 (td, J = 7.5, 0.5 Hz, 1 H), 5.35 (s, 2 H) ppm; 13C NMR (CDCl3; 126 MHz)：δ 198.9, 164.0, 150.9, 147.8, 143.3, 142.3, 138.9, 137.4, 134.5, 133.9, 132.8, 131.0, 130.5, 130.4, 129.4, 129.2, 129.1, 128.0, 127.8, 127.7, 126.0, 122.5, 118.4, 117.0, 115.6, 99.6 ppm; IR (KBr) ν3469, 3354, 1736, 1633, 1547, 1459, 1246, 1189, 527 cm -1; HRMS m/z (ESI) : calcld for C26 H19INO3 [M + H]+ 520.0404, found: 520.0413, error -1.71 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl-pivalate (8t): Following the general experiment procedure, 8t was purified by PE/EtOAc (60:1) and obtained as a white oil-liquid (97% yield). Rf = 0.38 (PE/EtOAc = 25:1); 1H NMR (CDCl3; 500 MHz): δ 7.92 (dd, J = 8.0, 0.5 Hz, 1 H), 7.46 (td, J = 7.8, 0.8 Hz,1 H), 7.31-7.38 (m, 2 H), 7.22-7.25 (m, 2 H), 7.16 (dd, J = 8.1, 0.5 Hz, 1 H), 7.04 (td, J = 7.7, 0.9 Hz,1 H), 1.02 (s, 9 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 176.5, 148.1, 142.8, 138.7, 137.7, 130.6, 129.3, 129.2, 127.8, 125.8, 122.5, 100.1, 38.9, 26.8 ppm; IR (KBr) ν 1749, 1582, 1461, 1193, 1122, 501 cm -1; HRMS m/z (ESI): calcd for C17H17INaO2 [M + Na]+ 403.0165, found: 403.0168, error 0.74 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl 2-phenylacetate (8u): Following the general experiment procedure, 8u was purified by PE/EtOAc (100:1) and obtained as a white solid (71% yield). Mp = 93.5-94.2 oC; Rf = 0.40 15



(PE/EtOAc = 50:1); 1H NMR (CDCl3; 500 MHz): δ 7.85 (dd, J = 8.0, 0.5 Hz, 1 H), 7.44 (td, J = 7.8, 0.8 Hz, 1 H), 7.32 (td, J = 7.5, 0.6 Hz, 1 H), 7.27 (td, J = 7.5, 0.6 Hz, 1 H),7.22-7.24 (m, 4 H), 7.19 (dd, J = 8.1, 0.5 Hz, 1 H), 7.16 (dd, J = 7.6, 0.8 Hz, 1 H), 6.99-7.04 (m, 3 H), 3.57 (s, 2 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 169.6, 147.8, 142.4, 138.9, 137.4, 133.1, 131.0, 130.4, 129.4, 129.3, 129.2, 128.7, 127.8, 127.1, 126.1, 122.5, 99.6, 41.3 ppm; IR (KBr) ν1756, 1495, 1459, 1189, 1128, 489 cm-1; HRMS m/z (ESI): calcd for C20H15INaO2 [M + Na]+ 437.0009, found: 437.0008, error 0.23 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl-isonicotinate (8v): Following the general experiment procedure, 8ν was purified by PE/EtOAc (4:1) and obtained as a white solid (73% yield). Mp = 106.9-107.8 oC; Rf = 0.25 (PE/EtOAc = 2:1); 1H NMR (CDCl3; 500 MHz): δ 8.72 (d, J = 5.9 Hz, 2 H), 7.87 (dd, J = 8.0, 0.5 Hz,1 H), 7.70 (dd, J = 4.5, 0.8 Hz, 2 H), 7.51 (td, J = 7.8, 0.6 Hz, 1 H), 7.40 (td, J = 7.5, 0.6 Hz, 1 H), 7.36 (dd, J = 8.1, 0.5 Hz, 1 H), 7.31 (td, J = 8.1, 0.8 Hz, 2 H), 7.25 (dd, J = 7.4, 0.8 Hz, 1 H), 6.97 (td, J = 7.8, 0.9 Hz, 1 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 163.3, 150.7, 147.6, 142.4, 139.0, 137.3, 136.6, 131.1, 130.5, 129.6, 129.5, 128.1, 126.5, 123.1, 122.3, 99.5 ppm; IR (KBr) ν 1740, 1562, 1463, 1405, 1266, 1189, 498 cm -1; HRMS m/z (ESI): calcd for C18H13INO2 [M + H]+ 401.9985, found: 401.9984, error 0.25 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl-nicotinate (8w): Following the general experiment procedure, 8w was purified by PE/EtOAc (4:1) and obtained as a white solid (90% yield). Mp = 75.1-75.9 oC; Rf = 0.25 (PE/EtOAc = 2:1); 1H NMR (CDCl3; 500 MHz): δ 9.08 (s,1 H), 8.74 (d, J = 3.6 Hz, 1 H), 8.17 (d, J = 8.0 Hz, 1 H), 7.87 (d, J = 7.8 Hz, 1 H), 7.51 (td, J = 7.7, 0.8 Hz, 1 H), 7.26-7.40 (m, 6 H), 6.96 (td, J = 7.6, 0.9 Hz, 1 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 163.4, 153.8, 151.2, 147.6, 142.4, 139.0, 137.5, 137.3, 131.0, 130.4, 129.5, 129.4, 128.0, 126.4, 125.4, 123.4, 122.5, 99.5 ppm; IR (KBr) ν 1737, 1591, 1495, 1461, 1270, 1189, 497 cm -1; HRMS m/z (ESI): calcd for C18H13INO2 [M + H]+ 401.9985, found: 401.9986, error 0.25 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl-1H-indole-3-carboxylate (8x): Following the general experiment procedure, 8x was purified by PE/EtOAc (6:1) and obtained as a white solid (75% yield). Mp = 218.5-219.1 oC; Rf = 0.25 (PE/EtOAc = 3:1); 1H NMR (DMSO-d6; 500 MHz): δ 12.02 (s, 1 H), 7.97 (d, J = 2.9 Hz, 1 H), 7.88 (dd, J = 7.9, 0.5 Hz,1 H), 7.76 (d, J = 7.9 Hz, 1 H), 7.52 (td, J = 7.8, 0.8 Hz, 1 H), 7.46 (d, J = 8.1 Hz, 1H), 7.34- 7.42 (m, 3 H), 7.27-7.30 (m, 2 H), 7.18 (t, J = 7.6 Hz, 1 H), 7.10 (t, J = 7.5 Hz, 1 H), 7.00 (td, J = 7.6, 0.9 Hz, 1 H) ppm; 13C NMR (DMSO-d6; 126 MHz): δ 162.0, 147.6, 142.5, 138.5, 137.2, 136.3, 133.4, 130.6, 130.3, 129.4, 129.1, 127.9, 125.4, 125.4, 123.2, 122.6, 121.4, 120.4, 112.4, 105.4, 100.1 ppm; IR (KBr) ν 3289, 1688, 1582, 1496, 1460, 1199, 1163, 1123, 485 cm -1; HRMS m/z (ESI): calcd for C21H14INNaO2 [M + Na]+461.9961, found: 461.9962, error 0.22 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl-1H-indole-2-carboxylate (8y): Following the general experiment procedure, 8y was purified by PE/EtOAc (20:1) and obtained as a white solid (78% yield). Mp = 99.1-99.8 oC; Rf = 0.25 (PE/EtOAc = 10:1); 1H NMR (CDCl3; 500 MHz): δ 9.03 (s, 1 H), 7.89 (d, J = 7.9 Hz, 1 H), 7.68 (d, J = 8.0 Hz, 1 H), 7.54 (td, J = 7.8, 0.9 Hz,1H), 7.40-7.43(m, 2 H), 7.31-7.36 (m, 5 H), 7.21 (d, J = 2.0 Hz, 1 H), 7.14-7.17 (m, 1 H), 6.95-6.98 (m, 1 H) ppm;

13

C NMR (CDCl3; 126 MHz): δ 159.9, 147.5, 142.5, 139.0,

137.4, 137.3, 131.2, 130.6, 129.5, 129.4, 128.0, 127.4, 126.2, 126.2, 125.9, 122.9, 122.7, 121.0, 112.1, 110.4, 99.6 ppm; IR (KBr) ν 3340, 1709, 1620, 1526, 1462, 1241, 1192, 1146, 496 cm -1; HRMS m/z (ESI): calcd for C21H14INNaO2 [M + Na]+461.9961, found: 461.9966, error 1.08 ppm. 2'-iodo-4,4'-dimethyl-[1,1'-biphenyl]-2-yl-2-phenylacetate (9a): Following the general experiment procedure, 9a was purified by PE/EtOAc (50:1) and obtained as a white oil-liquid (85% yield). Rf = 0.38 (PE/EtOAc = 25:1); 1H NMR (CDCl3; 500 MHz): δ 7.67 (s, 1 H), 7.22-7.26 (m, 3 H), 7.10-7.15 (m, 2 H), 7.02-7.08 (m, 4 H), 7.01 (s, 1 H), 3.59 (s, 2 H), 2.43 (s, 3 H), 2.35 (s, 3 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 169.6, 147.7, 139.4, 139.4, 139.3, 138.9, 134.4, 133.2, 130.9, 130.1, 129.3, 128.6, 128.5, 126.9,

16


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126.8, 122.9, 99.8, 41.3, 21.3, 20.7 ppm; IR (KBr) ν 1757, 1600, 1476, 1221, 1127, 519 cm-1; HRMS m/z (ESI): calcd for C22H19INaO2 [M + Na]+ 465.0322, found: 465.0323, error 0.28 ppm. 2'-iodo-4,4'-dimethyl-[1,1'-biphenyl]-2-yl-benzoate (9b): Following the general experiment procedure, 9b was purified by PE/EtOAc (100:1) and obtained as a yellow oil-liquid (95% yield). Rf = 0.44 (PE/EtOAc = 50:1); 1H NMR (CDCl3; 500 MHz): δ 7.97 (dd, J = 8.4, 0.5 Hz, 2 H), 7.71 (s, 1 H), 7.54 (t, J = 7.5 Hz, 1 H), 7.40 (t, J = 7.9 Hz, 2 H), 7.15-7.18 (m, 4 H), 7.08 (d, J = 7.7 Hz, 1 H), 2.46 (s, 3 H), 2.26 (s, 3 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 164.9, 147.9, 139.8, 139.6, 139.3, 139.1, 134.5, 133.4, 131.0, 130.3, 130.2, 129.6, 128.8, 128.5, 126.8, 123.2, 99.8, 21.4, 20.6 ppm; IR (KBr) ν 1736, 1621, 1600, 1476, 1451, 1127, 1063, 1025, 511 cm -1; HRMS m/z (ESI): calcld for C21H17INaO2 [M + Na ]+ 451.0165, found: 451.0168, error 0.67 ppm. 2'-iodo-4,4'-dimethyl-[1,1'-biphenyl]-2-yl-2-chlorobenzoate (9c): Following the general experiment procedure, 9c was purified by PE/EtOAc (100:1) and obtained as a white solid (68% yield). Mp = 103.1-103.9 oC; Rf= 0.25 (PE/EtOAc = 50:1); 1H NMR (CDCl3; 500 MHz): δ 7.76 (s, 1 H), 7.51 (dd, J = 7.8, 0.7 Hz, 1 H), 7.36-7.41 (m, 2 H), 7.22 (td, J = 7.4, 0.9 Hz, 1 H), 7.17-7.19 (m, 3 H), 7.16 (s, 1 H), 7.12-7.14 (m, 1 H), 2.46 (s, 3 H), 2.31 (s, 3 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 163.7, 147.6, 139.7, 139.7, 139.3, 134.5, 134.2, 132.9, 131.6, 131.1, 131.0, 130.4, 129.3, 128.9, 127.1, 126.6, 123.2, 100.0, 21.4, 20.6 ppm; IR (KBr) ν 1756, 1590, 1476, 1235, 1032, 743, 499 cm -1; HRMS m/z (ESI): calcd for C21H16ClINaO2 [M + Na]+ 484.9776, found: 484.9775, error 0.21 ppm. 2'-iodo-4,4'-dimethyl-[1,1'-biphenyl]-2-yl-2-amino-3-methylbenzoate

(9d):

Following

the

general

experiment procedure, 9d was purified by PE/EtOAc (15:1) and obtained as a yellow oil-liquid (90% yield). Rf = 0.45 (PE/EtOAc = 6:1); 1H NMR (CDCl3; 500 MHz)：δ 7.74 (dd, J = 8.2, 0.6 Hz, 1 H), 7.71 (s, 1 H), 7.15-7.19 (m, 4 H), 7.08-7.11 (m, 2 H), 6.55 (t, J = 7.7 Hz, 1 H), 5.74 (s, 2 H), 2.46 (s, 3 H), 2.26 (s, 3 H), 2.13 (s, 3 H) ppm; 13C NMR (CDCl3; 126 MHz)：δ 166.9, 149.6, 147.9, 139.8, 139.5, 139.4, 139.1, 135.4, 134.8, 131.1, 130.2, 129.8, 128.8, 126.7, 123.5, 122.9, 115.8, 109.4, 99.9, 21.5, 20.7, 17.5 ppm; IR (KBr) ν3495, 3372, 1702, 1613, 1570, 1514, 1475, 1237, 1160, 499 cm -1; HRMS m/z (ESI) : calcd for C22H21INO2 [M + H]+ 458.0611, found: 458.0615, error 0.73 ppm. 2'-iodo-4,4'-dimethyl-[1,1'-biphenyl]-2-yl-3a,7a-dihydro-1H-indole-3-carboxylate (9e): Following the general experiment procedure, 9e was purified by PE/EtOAc (6:1) and obtained as a white solid (76% yield). Mp = 230.9-231.6 oC; Rf = 0.30 (PE/EtOAc = 3:1); 1H NMR (DMSO-d6; 500 MHz): δ 12.00 (s,1 H), 7.98 (d, J = 3.1 Hz, 1 H), 7.78 (d, J = 8.0 Hz, 1 H), 7.70 (s, 1 H), 7.46 (d, J = 8.1 Hz, 1 H), 7.16-7.20 (m, 3 H), 7.09-7.13 (m, 4 H), 2.40 (s, 3 H), 2.14 (s, 3 H) ppm; 13C NMR (DMSO-d6; 126 MHz): δ 162.1, 147.5, 139.6, 138.8, 138.7, 138.7, 136.3, 134.2, 133.3, 130.6, 130.0, 128.6, 126.0, 125.5, 123.6, 122.6, 121.4, 120.4, 112.4, 105.5, 100.2, 20.7, 19.9 ppm;IR (KBr) ν 3280, 1686, 1524, 1434, 1163, 1122, 499 cm-1; HRMS m/z (ESI): calcd for C23H18INNaO2 [M + Na] + 490.0274, found: 490.0277, error 0.61 ppm. 2'-iodo-4,4'-dimethoxy-[1,1'-biphenyl]-2-yl-2-amino-3-methylbenzoate

(9f):

Following

the

general

experiment procedure, 9f was purified by PE/EtOAc (6:1) and obtained as a yellow solid (13% yield). Mp = 40.6-41.5 oC; Rf = 0.40 (PE/EtOAc = 3:1); 1H NMR (CDCl3; 500 MHz): δ 7.73 (dd, J = 8.1, 0.5 Hz, 1 H), 7.37 (d, J = 2.6 Hz, 1 H), 7.16-7.19 (m, 3 H), 6.88-6.90 (m, 1 H), 6.82-6.84 (m, 2 H), 6.55 (t, J = 7.7 Hz, 1 H), 5.73 (s, 2 H), 3.86 (s, 3 H), 3.74 (s, 3 H), 2.13 (s, 3 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 166.7, 160.2, 159.0, 149.6, 149.1, 135.4, 134.9, 132.0, 131.0, 130.0, 129.8, 124.0, 122.9, 115.9, 114.1, 111.8, 109.3, 108.4, 100.6, 55.6, 55.6, 17.5 ppm; IR (KBr) ν 3494, 3373, 1702, 1615, 1572, 1281, 1241, 1189, 1057, 487 cm -1; HRMS m/z (ESI): calcd for C22H21INO4 [M + H]+ 490.0510, found: 490.0507, error 0.61 ppm. 4,4'-dichloro-2'-iodo-[1,1'-biphenyl]-2-yl-pivalate (9g): Following the general experiment procedure, 9g was purified by PE/EtOAc (100:1) and obtained as a white oil-liquid (91% yield). Rf = 0.37 (PE/EtOAc = 17



Page 18 of 25

50:1); 1H NMR (CDCl3; 500 MHz): δ 7.91(d, J = 2.1 Hz, 1 H), 7.35 (dd, J = 8.2, 1.1 Hz, 1 H), 7.30 (dd, J = 8.2, 1.1 Hz, 1 H), 7.19 (d, J = 2.0 Hz, 1 H), 7.13 (d, J = 3.7 Hz, 1 H), 7.11 (d, J = 3.7 Hz, 1 H), 1.04(s, 9 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 176.1, 148.5, 140.4, 138.1, 135.1, 134.8, 134.4, 131.4, 131.1, 128.1, 126.3, 123.3, 100.0, 39.0, 26.8 ppm; IR (KBr) ν1753, 1577, 1543, 1458, 1196, 1104, 777, 515 cm-1; HRMS m/z (ESI): calcd for C17H15Cl2INaO2 [M + Na]+ 470.9386, found: 470.9387, error 0.21 ppm. 4,4'-difluoro-2'-iodo-[1,1'-biphenyl]-2-yl-nicotinate (9h): Following the general experiment procedure, 9h was purified by PE/EtOAc (6:1) and obtained as a yellow solid (60% yield). Mp = 106.0-106.7 oC; Rf = 0.28 (PE/EtOAc = 3:1); 1H NMR (CDCl3; 500 MHz): δ 9.09 (d, J = 1.5 Hz, 1 H), 8.78 (dd, J = 4.8, 1.5 Hz, 1 H), 8.17 (dt, J = 8.0, 1.9 Hz, 1 H), 7.58 (dd, J = 8.0, 1.3 Hz, 1 H), 7.37 (dd, J = 7.8, 2.5 Hz, 1 H), 7.19-7.26 (m, 2 H), 7.15 (dd, J = 9.0, 1.3 Hz, 1 H), 7.10 (td, J = 8.3, 1.3 Hz, 1 H), 7.03 (td, J = 8.0, 1.3 Hz, 1 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 163.7, 163.0, 162.5, 161.7, 160.5, 154.2, 151.2, 148.4 (d, J = 11.0 Hz), 137.8 (d, J = 3.6 Hz), 137.5, 132.5 (d, J = 3.8 Hz), 132.1 (d, J = 9.3 Hz), 131.3 (d, J = 8.2 Hz), 126.2, 126.0, 124.9, 123.6, 115.5, 115.3, 113.7, 113.6, 110.8, 110.6, 99.3 (d, J = 7.9 Hz) ppm; IR(KBr) ν 1742, 1590, 1489, 1266, 1195, 1101, 502cm-1; HRMS m/z (ESI): calcd for C18H11F2INO2 [M + H]+ 437.9797, found: 437.9793, error 0.91 ppm. 4,4'-difluoro-2'-iodo-[1,1'-biphenyl]-2-yl-benzoaten (9i): Following the general experiment procedure, 9i was purified by PE and obtained as a white solid (94% yield). Mp = 84.3-85.2 oC; Rf = 0.2 (PE); 1H NMR (CDCl3; 500 MHz): δ 7.93 (d, J = 7.3 Hz, 2 H), 7.56-7.61 (m, 2 H), 7.42 (t, J = 7.8 Hz, 2 H), 7.22-7.27 (m, 2 H), 7.15 (dd, J = 9.1, 1.2 Hz, 1 H), 7.09 (td, J = 8.3, 1.3 Hz, 1 H), 7.03 (td, J = 8.3, 1.4 Hz, 1 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 164.3, 163.7, 162.5, 161.7, 160.5, 149.0 (d, J = 11.2 Hz), 138.1 (d, J = 3.1 Hz), 133.9, 132.6 (d, J = 3.8 Hz), 132.0 (d, J = 9.3 Hz), 131.4 (d, J = 8.2 Hz), 130.1, 128.8, 128.7, 126.0, 125.9, 115.4, 115.2, 113.3, 113.2, 110.9, 110.7, 99.4(d, J = 8.0 Hz) ppm; IR (KBr) ν 1732, 1591, 1470, 1253, 1198, 1105, 510 cm -1; HRMS m/z (ESI): calcld for C19H11F2INaO2 [M + Na]+ 458.9664, found: 458.9666, error 0.44 ppm. 4,4'-dichloro-2'-iodo-[1,1'-biphenyl]-2-yl benzoate (9j): Following the general experiment procedure, 9j was purified by PE/EtOAc (80:1) and obtained as a yellow oil-liquid (67% yield). Rf = 0.25 (PE/EtOAc = 50:1); 1H NMR (CDCl3; 500 MHz): δ 7.94 (dd, J = 8.1, 0.5 Hz, 2H), 7.87 (d, J = 2.1 Hz, 1 H), 7.58 (t, J = 7.5 Hz, 1 H), 7.40-7.44 (m, 3 H), 7.36 (dd, J = 8.2, 1.0 Hz, 1 H), 7.29 (dd, J = 8.3, 1.1 Hz, 1 H), 7.17-7.22 (m, 2 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 164.3, 148.5, 140.3, 138.4, 135.0, 135.0, 134.4, 133.9, 131.8, 131.0, 130.2, 128.7, 128.7, 128.4, 126.5, 123.5, 99.5 ppm; IR (KBr) ν 1743, 1601, 1577, 1456, 1260, 1097, 705, 509 cm -1; HRMS m/z (ESI): calcd for C19H11Cl2INaO2 [M + Na]+ 490.9073, found: 490.9070, error 0.61 ppm. 4,4'-difluoro-2'-iodo-[1,1'-biphenyl]-2-yl-2-amino-3-methylbenzoate

(9k):

Following

the

general

experiment procedure, 9k was purified by PE/EtOAc (15:1) and obtained as a white solid (76% yield). Mp = 77.1-77.9 oC; Rf =0.40 (PE/EtOAc = 6:1); 1H NMR (CDCl3; 500 MHz)：δ 7.62 (dd, J = 8.1,0.5 Hz, 1 H), 7.59 (dd, J =8.2, 1.3 Hz, 1 H), 7.19-7.25 (m, 3 H), 7.06-7.10 (m, 2 H), 7.03 (td, J = 8.3, 1.3 Hz, 1 H), 6.54 (t, J = 7.7 Hz, 1 H), 5.54 (s, 2 H), 2.14 (s, 3 H) ppm;

13

C NMR (CDCl3; 126 MHz)：δ 166.3, 163.7, 162.5,

161.7, 160.5, 149.9, 149.0 (d, J = 11.0 Hz), 138.1(d, J = 3.5 Hz), 135.8, 132.9 (d, J = 3.7 Hz), 132.0 (d, J = 9.6 Hz), 131.3 (d, J = 8.3 Hz ), 129.5, 126.1, 125.9, 123.1, 115.9, 115.3 (d, J = 21.1 Hz), 113.1 (d, J = 21.1 Hz), 111.1 (d, J = 24.5 Hz), 108.5, 99.5 (d, J = 7.8 Hz), 17.3 ppm; IR (KBr) ν 3501, 3378, 1705, 1614, 1591, 1473, 1240，1143, 1102, 517 cm -1; HRMS m/z (ESI) : calcd for C20H15F2INO2 [M + H]+ 466.0110, found: 466.0112, error 0.47 ppm. 4,4'-dichloro-2'-iodo-[1,1'-biphenyl]-2-yl-2-amino-3-methylbenzoate

(9l):

Following

the

general

experiment procedure, 9l was purified by PE/EtOAc (30:1) and obtained as a brown oil-liquid (71% yield). 18


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Rf = 0.42 (PE/EtOAc = 15:1); 1H NMR (CDCl3; 500 MHz)：δ 7.87 (d, J = 2.1 Hz, 1 H), 7.64 (dd, J = 8.2,0.6 Hz, 1 H), 7.33-7.36 (m, 2 H), 7.29 (dd, J = 8.3, 1.1 Hz, 1 H), 7.17-7.21 (m, 3 H), 6.55 (t, J = 7.7 Hz, 1H), 5.64 (s, 2 H), 2.14 (s, 3 H) ppm; 13C NMR (CDCl3; 126 MHz)：δ 166.3, 149.9, 148.5, 140.4, 138.5, 135.9, 135.2, 134.9, 134.3, 131.8, 131.0, 129.5, 128.4, 126.2, 123.8, 123.1, 116.0, 108.4, 99.6, 17.5 ppm; IR (KBr) ν 3502, 3377, 1704, 1614, 1571, 1459, 1240, 1197, 1156, 750, 462 cm -1; HRMS m/z (ESI): calcd for C20H15Cl2INO2 [M + H]+ 497.9519, found: 497.9522, error 0.60 ppm. 2'-iodo-3,3',5,5'-tetramethyl-[1,1'-biphenyl]-2-yl-2-amino-3-methylbenzoate (9m): Following the general experiment procedure, 9m was purified by PE/EtOAc (20:1) and obtained as a yellow solid (71% yield). Mp = 150.3-151.2 oC; Rf = 0.46 (PE/EtOAc = 10:1); 1H NMR (CDCl3; 500 MHz)：δ 7.77 (d, J = 7.8 Hz, 1 H), 7.16 (d, J = 7.3 Hz, 1 H), 7.14 (s, 1 H), 6.88-6.91 (m, 3 H), 6.55 (t, J = 7.7 Hz, 1 H), 5.70 (s, 2 H), 2.43 (s, 3 H), 2.38 (s, 3 H), 2.22 (s, 3 H), 2.18 (s, 3 H), 2.12 (s, 3 H) ppm;

13

C NMR (CDCl3; 126 MHz)：δ 166.6,

149.4, 144.5, 143.8, 141.5, 138.8, 137.2, 135.2, 131.3, 130.9, 129.8, 129.6, 129.1, 128.6, 122.8, 115.6, 109.4, 102.7, 29.6, 21.0, 20.7, 17.4, 16.7 ppm; IR (KBr) ν 3498, 3373, 1700, 1613, 1570, -1

1243, 1191, 466

+

cm ; HRMS m/z (ESI) : calcd for C24H25INO2 [M + H] 486.0924, found: 486.0923, error 0.22 ppm. 2'-iodo-3,3',5,5'-tetramethyl-[1,1'-biphenyl]-2-yl-2-hydroxybenzoate

(9n):

Following

the

general

experiment procedure, 9n was purified by PE/EtOAc (100:1) and obtained as a white oil-liquid (55% yield). Rf = 0.43 (PE/EtOAc = 50:1); 1H NMR (CDCl3; 500 MHz): δ 10.38 (s, 1 H), 7.86 (d, J = 8.0 Hz, 1 H), 7.44 (td, J = 7.8, 0.9 Hz, 1 H), 7.16 (s, 1 H), 6.92- 6.94 (m, 2 H), 6.89 (s, 1 H), 6.84-6.87 (m, 2 H), 2.42 (s, 3 H), 2.40 (s, 3 H), 2.25 (s, 3 H), 2.18 (s, 3 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 168.4, 162.0, 143.9, 143.3, 141.7, 138.5, 137.4, 136.4, 136.2, 136.0, 131.5, 130.6, 129.8, 129.3, 128.6, 119.4, 117.5, 111.7, 102.5, 29.6, 21.1, 20.7, 16.6 ppm; IR (KBr) ν 3193, 1683, 1614, 1484, 1454, 1297, 1189, 1132, 501 cm -1; HRMS m/z (ESI): calcd for C23H21INaO3 [M + Na]+ 495.0428, found: 495.0426, error 0.40 ppm. 4-fluoro-2'-iodo-3',5'-dimethyl-[1,1'-biphenyl]-2-yl-2-amino-3-methylbenzoate

(9o):

Following

the

general experiment procedure, 9o was purified by PE/EtOAc (100:1) and obtained as a white oil-liquid (70% yield). Rf = 0.43 (PE/EtOAc = 50:1); 1H NMR (CDCl3; 500 MHz): δ 7.57 (dd, J = 8.2, 0.5 Hz, 1 H), 7.23-7.26 (m, 1 H), 7.17 (d, J = 6.7 Hz, 1 H), 7.13 (dd, J = 9.3, 1.3 Hz, 1 H), 7.06 (dd, J = 8.3, 1.3 Hz, 1H), 6.97 (s, 1 H), 6.88 (s, 1 H), 7.51 (t, J = 7.7 Hz, 1 H), 5.72 (s, 2H), 2.44 (s, 3 H), 2.21 (s, 3 H), 2.13 (s, 3 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 166.3, 163.3, 161.4, 149.7, 148.8 (d, J = 11.1 Hz), 142.6, 141.9, 137.4, 135.6, 134.9 (d, J = 3.6 Hz), 131.8 (d, J = 9.3 Hz), 130.0, 129.7, 128.8, 122.9, 115.7, 112.8, 112.7, 110.9, 110.7, 108.9, 103.0, 29.6, 20.7, 17.4 ppm; IR (KBr) ν 3500, 3376, 1705, 1614, 1572, 1240, 1188, 1052, 464 cm -1; HRMS m/z (ESI): calcd for C22H20FINO2 [M + H]+ 476.0517, found: 476.0514, error 0.63 ppm. 4'-(tert-butyl)-2'-iodo-[1,1'-biphenyl]-2-yl 2-amino-3-methylbenzoate (9p) and 4-(tert-butyl)-2'-iodo-[1,1'-biphenyl]-2-yl-2-amino-3-methylbenzoate

(9p'):

Following

the

general

experiment procedure, 9p and 9p' were purified by PE/EtOAc (20:1) and obtained as an inseparable mixture of white solid (90% yield ). Rf = 0.44 (PE/EtOAc = 10:1); 1H NMR (CDCl3; 500 MHz): δ 7.95 (d, J = 1.9 Hz, 1 H), 7.91 (dd, J = 7.9, 0.5 Hz, 1 H), 7.82 (dd, J = 8.2, 0.6 Hz, 1 H), 7.66 (dd, J = 8.2, 0.6 Hz, 1 H), 7.53 (td, J = 7.4, 1.2 Hz, 1 H), 7.44 (td, J = 8.1, 1.0 Hz, 1 H), 7.35-7.41 (m, 5 H), 7.28-7.33 (m, 3 H), 7.18-7.20 (m, 2 H), 6.95 (td, J = 7.6, 0.9 Hz, 1 H), 6.59 (t, J = 7.7 Hz, 1 H), 6.55 (t, J = 7.7 Hz, 1 H), 5.67 (s, 4 H), 2.13 (s, 6 H), 1.47 (s, 13 H), 1.33 (s, 5 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 166.7, 152.8, 152.4, 149.4, 148.2, 147.6, 142.7, 139.7, 138.9, 137.5, 135.9, 135.3, 134.6, 131.1, 130.6, 130.5, 129.9, 129.7, 129.6, 129.0, 129.0, 127.8, 125.6, 125.0, 122.9, 122.8, 122.8, 122.7, 119.9, 115.7, 115.6, 109.2, 109.2, 99.9, 99.9, 34.9, 34.4, 31.4, 31.2, 27.0, 17.4 ppm; IR (KBr) ν 3504, 3388, 1700, 1615, 1569, 1463, 1241, 1188, 468 cm -1. 2'-iodo-4'-methoxy-4-methyl-[1,1'-biphenyl]-2-yl-2-amino-3-methylbenzoate

(9q)

and

2'-iodo-4-methoxy-4'-methyl-[1,1'-biphenyl]-2-yl-2-amino-3-methylbenzoate (9q'): Following the general 19



experiment procedure, 9q and 9q' were purified by PE/EtOAc (30:1) and obtained as an inseparable mixture of yellow solid (70% yield). Rf = 0.35 (PE/EtOAc = 15:1); 1HNMR (CDCl3; 500 MHz): δ 7.74 (t, J = 8.6 Hz, 2H), 7.70 (s, 1H), 7.40 (d, J = 2.6 Hz, 1 H), 7.15-7.20 (m, 7 H), 7.07- 7.10 (m, 2 H), 6.90 (dd, J = 8.5, 1.3 Hz, 1H), 6.83-6.85 (m, 2 H), 6.55 (td, J = 7.7, 1.1 Hz, 2 H), 5.72 (s, 4 H), 3.86 (s, 3 H), 3.74 (s, 3 H), 2.45 (s, 3 H), 2.26 (s, 3 H), 2.13 (s, 3 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 166.9, 166.7, 160.2, 159.0, 149.6, 149.6, 148.8, 148.1, 139.6, 139.4, 139.4, 139.0, 135.4, 135.4, 135.1, 134.5, 131.8, 131.3, 130.8, 130.4, 130.2, 129.8,129.8, 128.8, 126.6, 124.0, 123.4, 122.9, 115.8, 114.1, 111.8, 109.3, 109.2, 108.4, 100.4, 100.0, 55.6, 55.5, 21.4, 20.6, 17.4 ppm; IR (KBr) ν 3496, 3373, 1696, 1613, 1515, 1472, 1260, 1190, 1031, 466 cm -1

.

4.3 General procedure for the arylation of aromatic acid derivatives with linear diaryliodonium salts The Olofsson's procedure: The carboxylic acid (0.25 mmol), linear diaryliodonium salt 5a (215 mg, 0.50 mmol) and KOtBu (28 mg, 0.25 mmol) were dissolved in anhydrous toluene (1.5 mL) in a pressure νessel. The reaction mixture was stirred at 130 oC for 17 h before it was cooled to rt. The reaction mixture was then transferred to a separatory funnel and diluted with Et2O (50 mL). The organic phase was washed with water (10 mL) and brine (10 mL) respectively before it was dried over anhydrous Mg2SO4 and concentrated in vacuo. The residue was purified by column chromatography to yield the product. Our procedure: The carboxylic acid (0.25 mmol), linear diaryliodonium salt 5a (215 mg, 0.5 mmol), Na2CO3 (39.75 mg, 0.38 mmol), CuI (4.8 mg, 0.025 mmol) and 1,10-Phenanthroline (4.5 mg, 0.025 mmol) were dissolved in anhydrous 1,4-dioxane (1.5 mL) in a pressure νessel. 3 Å Molecular sieves (100 mg) were then added. The reaction mixture was stirred at 95 oC for 17 h before it was cooled to rt and filtered. The mixture was then extracted with EtOAc (50 mL) and washed with water (10 mL) and brine (10 mL) before the organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography to yield the product. phenyl 2-amino-3-methylbenzoate (10): 10 was purified by PE/EtOAc (20:1) and obtained as a white solid. Yield: 21% (Olofsson’s procedure) and 63% (our procedure); Mp = 106.3-107.4 oC; Rf = 0.60 (PE/EtOAc = 10:1); 1H NMR (CDCl3; 500 MHz): δ 8.03 (dd, J = 8.1, 0.5 Hz, 1 H), 7.44 (t, J = 8.0 Hz, 2 H), 7.28 (t, J = 6.4 Hz, 2 H), 7.20 (dd, J = 8.7, 0.6 Hz, 2 H), 6.68 (t, J = 7.7 Hz, 1 H), 5.89 (s, 2 H), 2.21 (s, 3 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 167.4, 151.1, 150.0, 135.7, 129.7, 129.6, 125.9, 123.2, 122.2, 115.9, 109.3, 17.5 ppm; IR (KBr) ν 3452, 3348, 1696, 1613, 1584, 1242, 1192 cm -1; HRMS m/z (ESI) : calcd for C14H14O2 [M + H] + 228.1019, found: 228.1021, error -0.86 ppm. phenyl 2-hydroxybenzoate (11): 11 was purified by PE/EtOAc (20:1) and obtained as a white oil-liquid. Yield: 62% (Olofsson’s procedure) and 85% (our procedure); Rf = 0.50 (PE/EtOAc = 10:1); 1H NMR (CDCl3; 500 MHz): δ 10.53 (s, 1 H), 8.10 (dd, J = 8.0, 0.8 Hz, 1 H), 7.55 (t, J = 7.9 Hz, 1 H), 7.47 (t, J = 7.9 Hz, 2 H), 7.33 (t, J = 7.4 Hz, 1 H), 7.22-7.24 (m, 2 H), 7.06 (dd, J = 8.4, 0.4 Hz, 1 H), 6.99 (t, J = 7.6 Hz, 1 H) ppm;

13

C NMR (CDCl3; 126 MHz): δ 169.1, 162.3, 150.2, 136.6, 130.5, 129.8, 126.5, 121.8, 119.6,

118.0, 112.0 ppm; IR (KBr) ν 3215, 1701,1630,1514,1260,1185 cm-1; HRMS m/z (EI) : calcd for C13H10O3 [M] + 214.0630,found: 214.0645 error 7.0 ppm. phenyl 2-(phenylthio)benzoate (12): 12 was purified by PE/EtOAc (20:1) and obtained as a yellow solid. Yield: 22% (Olofsson’s procedure) and 14% (our procedure); Mp = 81.0-82.2 oC; Rf = 0.38 (PE/EtOAc = 10:1); 1H NMR (CDCl3; 500 MHz): δ 8.23 (dd, J = 7.9, 0.6 Hz, 1 H), 7.58-7.60 (m, 2 H), 7.43-7.45 (m, 5 H), 7.28-7.33 (m, 2 H), 7.25-7.27 (m, 2 H), 7.20 (td, J = 7.5, 0.6 Hz, 1 H), 6.87 (dd, J = 8.2, 0.5 Hz, 1 H) ppm; 13

C NMR (126 MHz, CDCl3): δ 164.9, 150.9, 144.4, 135.8, 133.0, 132.5, 131.7, 129.9, 129.6, 129.4, 127.7,

20


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126.1, 124.5, 122.0, 116.5 ppm; IR (KBr) ν 1699, 1630, 1615, 1514, 1240, 1185 cm-1; HRMS m/z (EI) : calcd for C19H14O2S [M] + 306.0715, found: 306.0723 error 2.6 ppm.

4.4

Experiments

about

selectivity

2'-iodo-N-phenyl-[1,1'-biphenyl]-2-amine

(14a):

and Aniline

mechanistic 13a

(22.8

studies. uL,

0.25

Synthesis mmol),

of

cyclic

diphenyleneiodonium 7a (210 mg, 0.50 mmol), Na2CO3 (39.75 mg, 0.375 mmol), CuI (4.8 mg, 0.025 mmol) and 1,10-Phenanthroline (4.5 mg, 0.025 mmol) were dissolved in anhydrous 1,4-dioxane (1.5 mL) in a pressure νessel. 3 Å molecular sieves (100 mg) were then added. The reaction mixture was stirred at 95 oC for 17 h before it was cooled to rt and filtered. The mixture was then extracted with EtOAc (50 mL) and washed with water (10 mL) and brine (10 mL) before the organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (PE/EtOAc = 60:1) on silica gel to provideprovide a yellow solid 14a (48.7 mg, 53% yield). Mp = 76.2-77.3 oC; Rf = 0.35 (PE/EtOAc = 30:1); 1H NMR (CDCl3; 500 MHz): δ 8.00 (dd, J = 8.0, 0.5 Hz, 1 H), 7.45 (td, J = 7.5, 0.6 Hz, 1 H), 7.37 (dd, J = 8.2, 0.5 Hz, 1 H), 7.35 (dd, J = 7.6, 0.8 Hz, 1 H), 7.31 (td, J = 7.7, 0.8 Hz, 1 H), 7.26 (t, J = 8.0 Hz, 2 H), 7.07-7.12 (m, 4 H), 7.00 (td, J = 7.5, 0.6 Hz, 1 H), 6.96 (t, J = 7.4 Hz, 1 H), 5.21(s, 1 H) ppm;

13

C NMR (CDCl3; 126 MHz): δ 144.0, 142.8,140.8, 139.7, 133.5, 130.9, 130.7, 129.5, 129.3, 129.0,

128.9, 121.8, 120.3, 119.5, 116.3, 101.1 ppm; IR (KBr) ν 3394,1573,1507,1459,512 cm-1; HRMS m/z (ESI): calcd for C18H15NI [M + H]+ 372.0244, found: 372.0245, error -0.35 ppm. The procedure of scheme 3b: The procedure was similar to 14a, Aniline 13a (22.8 uL, 0.25 mmol), benzoic acid (30.7 mg, 0.25 mmol) was used. 14a (3.7 mg, 4%) and 8b (95.0 mg, 95%) were obtained.

4.5 Procedures for the further transformations of products.

Synthesis of

2'-((trimethylsilyl)ethynyl)-[1,1'-biphenyl]-2-yl-2-amino-3-methylbenzoate (16): Compound 8a (107.25mg, 0.25 mmol), 2-TMS-acetylene (45uL, 0.3mmol), Pd(PPh3)2Cl2 (18 mg, 0.025 mmol) and Et3N (0.2 ml, 1.5 mmol) were dissolved in THF (2 ml). The reaction mixture was degassed and stirred under an N2 atmosphere for 20 min before the addition of CuI (4.8 mg, 0.025 mmol). The reaction was then stirred at r.t.for 12 h before itwas diluted with diethyl ether (10 mL). The content was poured into a separate funnel and washed with 0.1 M HCl (10 mL), H2O (10 mL) and brine (10 mL) respectively. The organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (PE/EtOAc = 20:1) on silica gel to provide a yellow solid 16 (72.8 mg, 73% yield). Mp = 108.6-109.4 oC; Rf = 0.40 (PE/EtOAc = 10:1); 1H NMR (CDCl3; 500 MHz): δ 7.85 (d, J = 8.1 Hz, 1 H), 7.52 (dd, J = 7.6, 0.4 Hz, 1 H), 7.45-7.48 (m, 2 H), 7.27- 7.35 (m, 4 H), 7.22 (td, J = 7.5, 0.7 Hz, 1H), 7.18 (d, J = 7.1 Hz, 1 H), 6.56 (t, J = 7.7 Hz, 1 H), 5.72 (s, 2 H), 2.13 (s, 3 H), 0.13 (s, 9 H) ppm;

13

C NMR (CDCl3; 126 MHz): δ

166.9, 149.5, 148.4, 140.8, 135.3, 134.1, 132.2, 131.5, 129.9, 129.8, 128.8, 128.4, 127.4, 125.5, 123.0, 122.8, 122.7, 115.7, 109.5, 104.5, 97.5, 17.4, -0.2 ppm; IR (KBr) ν 3478, 3363, 2158, 1704, 1615, 1475, 1246, 1198 cm -1; HRMS m/z (ESI) : calcd for C25H26NO2Si [M + H] + 400.1727，found: 400.1733, error 1.46 ppm. (E)-2'-styryl-[1,1'-biphenyl]-2-yl-2-amino-3-methylbenzoate (17): Compound 8a (107.25 mg, 0.25 mmol), styrene (32 mg, 0.3 mmol), Pd(OAc)2 (2.8 mg, 0.0125 mmol) and AgOAc (83.5 mg, 0.5 mmol) were dissolved in HOAc (2 mL). The reaction mixture was stirred at 110 oC for 12 h. After that, the reaction mixture was cooled to rt and neutralized with saturated Na2CO3 solution (10 mL). The reaction mixture was extracted by EtOAc (3 ×10 mL), the combined organic phase was washed with H2 O (2 × 10 mL) and brine (10 mL), dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography (PE/EtOAc = 20:1) on silica gel to providea white oil-liquid 17 (53.7 mg, 53% yield). Rf = 0.40 (PE/EtOAc = 10:1); 1H NMR (CDCl3; 500 MHz): δ 7.69 (d, J = 7.8 Hz, 1 H), 7.59 (dd, J = 8.1, 0.6 Hz, 1 H), 7.49 (td, J = 7.6, 1.0 Hz, 1 H), 7.27-7.40 (m, 10 H), 7.22 (t, J = 7.3 Hz, 1 H), 7.13 (d, J = 7.3 Hz, 1 H), 21



6.92-7.03 (m, 2 H), 6.44 (t, J = 7.7 Hz, 1 H), 5.38 (s, 2 H), 2.08 (s, 3 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 166.8, 149.7, 148.6, 137.7, 136.7, 136.2, 135.3, 134.2, 132.0, 130.8, 129.8, 129.7, 128.8, 128.6, 128.1, 127.6, 127.5, 127.3, 126.8, 125.9, 125.2, 123.2, 122.8, 115.6, 109.4, 17.4 ppm; IR (KBr) ν 3498, 3373, 1695, 1611, 1572, 1240, 1199, 1157 cm -1; HRMS m/z (ESI): calcd for C28H24NO2 [M + H]+ 406.1802, found: 406.1799, error 0.74 ppm. 2'-cyano-[1,1'-biphenyl]-2-yl 2-amino-3-methylbenzoate (18): Compound 8a (107.25 mg, 0.25 mmol) and CuCN (67.5 mg, 0.75 mmol) were dissolνed in anhydrous N-methyl pyrrolidone (2 mL). The reaction mixture was refluxed at 180 oC for 12 h before it was cooled to rt and diluted with water (10 mL). The mixture was extracted with EtOAc (3 ×10 mL), the combined organic phase was washed with H2O (3 × 10 mL) and brine (10 mL), dried over anhydrous Na2SO4, and concentrated in νacuo. The residue was purified by column chromatography (PE/EtOAc = 15:1) on silica gel to provide a white solid 18 (41.0 mg, 50% yield). Mp = 116.8-117.4 oC; Rf = 0.50 (PE/EtOAc = 3:1); 1H NMR (CDCl3; 500 MHz): δ 7.84 (dd, J= 8.1, 0.6 Hz, 1 H), 7.69 (dd, J = 7.8, 0.4 Hz, 1H), 7.51-7.56 (m, 2 H), 7.46-7.48 (m, 2 H), 7.33-7.42 (m, 3 H), 7.19 (d, J = 7.2 Hz, 1 H), 6.58 (t, J = 7.7 Hz, 1 H), 5.61 (s, 2 H), 2.12 (s, 3 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 166.5, 149.7, 148.0, 141.3, 135.5, 133.0, 132.5, 131.9, 131.0, 130.8, 130.2, 129.5, 128.1, 126.3, 123.5, 123.0, 118.3, 115.9, 112.9, 108.6, 17.4 ppm; IR (KBr) ν 3468, 3368, 2224, 1697, 1616, 1573, 1238, 1192, 1061 cm -1; HRMS m/z (ESI): calcd for C21 H17N2O2 [M + H]+ 329.1285, found: 329.1291, error -1.82 ppm. 2'-(diphenylphosphino)-[1,1'-biphenyl]-2-yl-2-amino-3-methylbenzoate (19): Compound 8a (107.25 mg, 0.25 mmol), HPPh2 (87 ul, 0.5 mmol), Pd(OAc)2 (5.6 mg, 0.025 mmol) and KOAc (49 mg, 0.3 mmol) were dissolνed in anhydrous DMA (2 mL). The reaction mixture was stirred at 100 oC for 12 h under N2 atmosphere. The reaction mixture was cooled to rt and diluted with water (10 mL). The mixture was extracted with EtOAc (3 × 10 mL). The combined organic phase was washed with H2O (2 ×10 mL) and brine (10 mL), dried over anhydrous Na2SO4, concentrated in vacuo. The residue was purified by column chromatography (PE/EtOAc =20:1) on silica gel to provide a white solid 19 (65.8 mg, 54% yield). Mp = 112.7-113.8 oC, Rf = 0.22 (PE/EtOAc = 10:1). 1H NMR (CDCl3; 500 MHz): δ 7.54 (dd, J = 8.2, 0.6 Hz, 1 H), 7.38 (td, J = 7.8, 0.9 Hz, 1 H), 7.27-7.30 (m, 5 H), 7.16-7.25 (m, 10 H), 7.12 (td, J = 7.5, 0.6 Hz, 1 H), 7.04-7.07 (m, 2 H), 6.48 (t, J = 7.7 Hz, 1 H), 5.72 (s, 2 H), 2.13 (s, 3 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 166.9, 149.6, 148.2, 143.6, 143.4, 137.4-137.6 (m), 137.3, 137.2, 135.3, 134.9 (d, J = 2.8 Hz), 134.2, 134.0, 133.9, 133.7, 132.1 (d, J = 3.9 Hz), 130.3 (d, J = 5.2 Hz), 129.8, 128.8, 128.6, 128.3-128.5(m), 128.0, 125.2, 122.9, 122.8, 115.6, 109.4, 17.5 ppm; IR (KBr) ν 3499, 3373, 2247, 1702, 1613, 1570, 1242, 1191, 1061 cm -1; HRMS m/z (ESI): calcd for C32H27NO2P [M + H]+ 488.1774, found: 488.1777, error 0.61 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl-3-methylbenzoate (20): To a stirred solution of 8a (107.25 mg, 0.25 mmol) in THF (6 mL) was added 4 M aqueous HCl (6 mL), and the solution was cooled in an ice water bath. A solution of NaNO2 (0.25 g, 3.6 mmol) in H2O (1 mL) was added dropwise. The reaction mixture was stirrer for 1 h. After that, stannous chloride dihydrate (345.2 mg, 1.5 mmol) was added. The reaction mixture was stirred for 0.5 h in an ice-bath. The mixture was neutralized with 40% NaOH solution before it was extracted with EtOAc (3 × 10 mL). The combined organic phase were washed with H2O (2 × 10 mL) and brine (10 mL), dried over anhydrous Na2SO4, and concentrated under in vacuo. The residue was purified by column chromatography (PE/EtOAc = 20:1) on silica gel to provide a white solid 20 (64.2 mg, 62% yield). Mp = 82.7-83.9 oC; Rf = 0.60 (PE/EtOAc = 10:1); 1H NMR (CDCl3; 500 MHz): δ 7.89 (d, J = 7.6 Hz, 1 H), 7.73-7.74 (m, 2 H), 7.51 (td, J = 7.8, 0.9 Hz, 1 H), 7.36-7.39 (m, 2 H), 7.34 (s, 1 H), 7.28-7.33 (m, 4 H), 6.95-6.99 (m, 1 H), 2.36 (s, 3 H) ppm;

13

C NMR (CDCl3; 126 MHz): δ 164.9, 148.1, 142.8, 138.9, 138.3,

137.5, 134.2, 131.0, 130.7, 130.6, 129.4, 129.3, 129.2, 128.4, 128.0, 127.2, 126.0, 122.7, 99.7, 21.3 ppm; IR

22


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(KBr) ν1738, 1590, 1462, 1276, 1197, 1070, 490 cm-1; HRMS m/z (ESI): calcd for C20H15INaO2 [M + Na]+ 437.0009，found: 437.0011, error 0.51 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl-2-azido-3-methylbenzoate (21): Compound 8a (107.25 mg, 0.25 mmol) was dissolνed in acetonitrile (2 mL) and cooled in a ice bath. Tert-Butyl nitrite (80 ul, 0.6 mmol) and Trimethylsilylazide (43 ul, 0.3 mmol) were added in dropwise. The resulting solution was stirred 20 min at r.t. Saturated NaHCO3 solution (5 mL) was then added. The mixture was extracted with EtOAc (3 ×10 mL). The combined organic layers were washed with water (10 mL) and brine (10 mL), dried oνer anhydrous Na2SO4, and concentrated in vacuo. The crude residue was purified by silica gel chromatography (PE/EtOAc = 20:1) to provide a white solid 21 (91.0 mg, 80% yield). Mp = 81.4-82.3 oC; Rf = 0.50 (PE/EtOAc = 10:1); 1

H NMR (CDCl3; 500 MHz): δ 7.92 (d, J = 7.5 Hz, 1 H), 7.53 (td, J = 7.8, 0.9 Hz, 1 H), 7.41 (td, J = 7.0, 0.5

Hz, 2 H), 7.37 (td, J = 6.8, 0.6 Hz, 1 H), 7.31-7.33 (m, 4 H), 6.99-7.05 (m, 2 H), 2.33 (s, 3 H) ppm;

13

C

NMR (CDCl3; 126 MHz): δ 163.7, 147.7, 142.6, 139.3, 138.9, 137.5, 135.3, 133.5, 131.1, 130.6, 129.6, 129.5, 129.4, 128.1, 126.3, 125.1, 123.4, 122.9, 99.8, 18.3 ppm; IR (KBr) ν 2120, 1722, 1583, 1454, 1242, 1185, 1118, 495 cm -1; HRMS m/z (ESI): calcd for C20H14IN3NaO2 [M + Na]+ 478.0023, found: 478.0027, error 0.93 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl-1H-indazole-7-carboxylate (22): Compound 8a (107.25 mg, 0.25 mmol) was dissolνed in acetonitrile (2 mL). The mixture was added tert-Butyl nitrite (67 ul, 0.5 mmol) dropwise. The reaction mixture was stirred at rt for 20 h. The mixture was diluted with water (10 mL) and extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with water (2 × 10 mL) and brine (10 mL), dried over anhydrous Na2SO4, and concentrated under in vacuo. The crude residue was purified by silica gel chromatography (PE/EtOAc = 6:1) to provide a yellow solid 22 (59.4 mg, 54% yield). Mp = 84.3-85.4 oC; Rf = 0.23 (PE/EtOAc = 3:1); 1H NMR (CDCl3; 500 MHz): δ 11.06 (s, 1 H), 8.12 (s, 1 H), 8.02 (dd, J = 7.3, 0.4 Hz, 1 H), 7.97 (dd, J = 8.0, 0.3 Hz, 1 H), 7.86 (d, J = 7.8 Hz, 1 H), 7.54 (td, J = 7.8, 0.8 Hz, 1 H), 7.40-7.45 (m, 2 H), 7.28-7.35 (m, 3 H), 7.19 (t, J = 7.7 Hz, 1 H), 6.94 (td, J = 7.4, 1.2 Hz, 1 H) ppm; 13C NMR (CDCl3; 126 MHz): δ 164.3, 147.6, 142.6, 139.0, 138.8, 137.5, 135.2, 131.1, 130.4, 130.1, 129.6, 129.5, 128.2, 127.4, 126.4, 124.6, 122.7, 120.7, 111.7, 99.6 ppm; IR (KBr) ν 3433, 1717, 1616, 1495, 1462, 1191, 1130, 497 cm-1; HRMS m/z (ESI): calcd for C20H14IN2O2 [M +H]+ 441.0094, found: 441.0093, error 0.23 ppm. 2'-iodo-[1,1'-biphenyl]-2-yl-2-iodo-3-methylbenzoate (not shown in the manuscript): To a stirred solution of 8a (429 mg, 1.0 mmol) in THF (3 mL) was added 4 M aqueous HCl (2.4 mL), and the solution was cooled in an ice water bath. A solution of NaNO2 (0.10 g, 1.45 mmol) in H2O (1 mL) was added dropwise. After 20 min, a solution of KI (0.40 g, 2.4 mmol) in H2O (1 mL) was added. The reaction mixture was stirred for 10 min in the ice water bath, then slowly warmed up to r.t. and stirred overnight before 1 M aqueous Na2S2O3 was added until the color of the mixture didn’t change. The phases were separated, and the aqueous phase extracted with EtOAc (10 mL× 3). The combined organic layers were washed with H2O (10 mL × 2) and brine (10 mL), dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (PE/EtOAc = 20:1) to provide the di-iodo compound as a white solid (485.9 mg, 90%). Mp = 128.8-129.4 oC; Rf = 0.50 (PE/EtOAc = 10:1); 1H NMR (CDCl3; 500 MHz): δ 7.94 (dd, J= 8.0, 0.5 Hz, 1 H), 7.52 (td, J= 7.8, 0.9 Hz, 1 H), 7.37-7.40 (m, 2H), 7.35 (dd, J= 7.1, 0.5 Hz, 1 H), 7.32 (td, J= 7.9, 1.0 Hz, 2 H), 7.29 (dd, J= 7.6, 0.5 Hz, 1 H), 7.14 (t, J= 7.6 Hz, 1 H), 7.04 (td, J= 7.5, 1.0 Hz, 1 H), 6.86 (dd, J= 7.6, 0.6 Hz, 1 H), 2.48(s, 3H) ppm;13CNMR (CDCl3; 126 MHz): δ 166.2, 147.8, 143.6, 142.6, 139.0, 137.6, 137.1, 132.2, 131.2, 130.8, 129.6, 129.5, 128.1, 127.8, 127.3, 126.4, 122.8, 100.4, 99.9, 29.8 ppm; IR (KBr) ν 1743, 1571, 1458, 1216, 1120, 510 cm-1; HRMS m/z (ESI): calcd for C20H14I2NaO2 [M + Na]+ 562.8975, found: 562.8974, error 0.18 ppm.

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4-(2-iodophenyl)-10-methyl-6H-benzo[c]chromen-6-one (23): The di-iodo compound above (134.98 mg, 0.25 mmol), Pd(OAc)2 (5.6 mg, 0.025 mmol) and NaOAc (24.61 mg, 0.3 mmol) were dissolved in anhydrous DMF (1 mL). The reaction mixture was stirrer at 150 oC for 3 h. Then the reaction mixture was diluted with water (10 mL) and extracted with EtOAc (10 mLｘ3), washed with water (10 mLｘ2), brine (10 mL), dried over anhydrous Na2SO4, concentrated in vacuo. The residue was purified by column chromatography on silica gel (PE/EtOAc = 20:1) to provide a white solid 23 (52.5 mg, 51% yield). Mp = 181.3-182.4 oC; Rf = 0.28 (PE/EtOAc = 10:1); 1H NMR(CDCl3; 500 MHz): δ 8.40 (dd, J = 8.3, 0.7 Hz, 1 H), 8.37 (dd, J = 7.8, 0.6 Hz, 1 H), 7.98 (dd, J = 8.0, 0.5 Hz, 1 H), 7.68 (dd, J = 7.5, 0.4 Hz, 1 H), 7.49 (t, J = 7.7 Hz, 1 H), 7.45 (td, J = 7.5, 0.6 Hz, 1 H), 7.41 (t, J = 7.8 Hz, 1 H), 7.33-7.36(m, 2 H), 7.11 (td,

J= 7.7, 0.9

13

Hz, 1 H), 2.97(s, 3 H) ppm; C NMR(CDCl3; 126 MHz): δ 161.1, 148.1, 142.0, 139.2, 139.2, 135.1, 133.7, 131.4, 130.5, 129.5, 129.2, 128.4, 128.1, 127.2, 123.4, 122.9, 120.0, 100.0, 25.5 ppm; IR(KBr) ν 1712, 1463, 1409, 1282, 1079, 505 cm-1; HRMS m/z (ESI): calcd for C20H14IO2 [M +H ]+ 413.0033, found: 413.0038, error -1.22 ppm.

ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website. 1

H and 13C NMR spectra of compounds (PDF)

AUTHOR INFORMATION Corresponding Author * Email: [email protected].

Notes The authors declare no competing financial interest.

ACKNOWLEDGMENT We thank the Natural Science Foundation for Distinguished Young Scholars of Zhejiang Province (LR15H300001), Thousand-Talent Program of Zhejiang Province and Zhejiang University of Technology for financial support.

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