Rhodium(III)-Catalyzed ortho -C-H Alkylation of 2-Arylbenzothiazoles and 2-Arylthiazoles with Potassium Alkyltrifluoroborates

DOI: 10.1055/s-0036-1588936

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Synthesis p. 2015 - 2024 (2017)

Update date:2022-07-30

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Authors:

Ping, Yuanyuan

Chen, Zhaobin

Ding, Qiuping

Peng, Yiyuan

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Article abstract of DOI:10.1055/s-0036-1588936

A general and efficient Rh(III)-catalyzed ortho-C-H alkylation of 2-arylbenzothizazoles and 2-arylthiazoles with potassium alkyltrifluoroborates has been developed. The present method leads to the construction of a library of alkylated 2-arylbenzothiazole

Full text of DOI:10.1055/s-0036-1588936

SYNTHESIS

2017, 49, A–J

paper

Y. Ping et al.

Paper

Synthesis

Rhodium(III)-Catalyzed ortho-C–H Alkylation of 2-Arylbenzothi-

azoles and 2-Arylthiazoles with Potassium Alkyltrifluoroborates

Yuanyuan Ping

Zhaobin Chen

Qiuping Ding*

Yiyuan Peng

R¹

[RhCp*Cl₂]₂(4 mol%)

AgSbF₆(16 mol%)

R¹

R²

RBF₃K

Ag₂O (1.0 equiv)

CH₂Cl₂, 85 °C

(3.0 equiv)

34 examples

up to 99% yield

R = Me, ⁿBu, Bn, ^cPr

Key Laboratory of Small Functional Organic Molecule, Ministry

of Education and Jiangxi’s Key Laboratory of Green Chemistry,

Jiangxi Normal University, Nanchang, Jiangxi 330022,

P. R. of China

dingqiuping@jxnu.edu.cn

Received: 03.11.2016

Accepted after revision: 16.12.2016

Published online: 14.02.2017

boroxine and alkylboronic acids.^18aRecently, Rodríguez and

co-workers developed the Mn(III)-mediated direct alkyla-

tion of polyaromatic hydrocarbons and benzene with alkyl-

boronic acids.^18bZhang^18cand Gevorgyan,^18drespectively,

reported the amino acid-promoted and Pd(II)-catalyzed

pyridyldiisopropylsilyl-directed C–H alkylation using alkyl-

boronic acids as alkyl reagents. In addition, Molander and

co-workers reported manganese(III) acetate catalyzed di-

rect alkylation of heteroaryls using potassium alkyl- and

alkoxymethyltrifluoroborates.^18eIn 2013, Sanford described

Pd(II) and MnF₃co-promoted direct alkylation of arylpyri-

dines and anilides in the presence of potassium organotri-

fluoroborates. Yu disclosed the monoprotected amino acid-

accelerated and Pd(II)-catalyzed alkylation of phenylacetic

and benzoic acids using potassium alkyltrifluoroborated

and alkylboronic acids as coupling partners.^18fIn 2015, Li

also reported the Rh(III)-catalyzed C–H alkylation of arenes

using alkyltrifluoroborates.^18gRecently, Liu also reported

the Rh(III)-catalyzed site-selective C–H alkylation of pyri-

dones using organoboron reagents.^18h

DOI: 10.1055/s-0036-1588936; Art ID: ss-2016-h0772-op

Abstract A general and efficient Rh(III)-catalyzed ortho-C–H alkylation

of 2-arylbenzothizazoles and 2-arylthiazoles with potassium alkyltri-

fluoroborates has been developed. The present method leads to the

construction of a library of alkylated 2-arylbenzothiazoles and 2-arylthi-

azoles with yields up to 99%.

Key words alkylation, alkyltrifluoroborates, 2-arylbenzothiazoles, 2-

arylthiazoles, transition metal

Alkyl, especially methyl is one of the most common

building blocks in small organic molecules, which is a key

structural feature of many biologically active molecules.¹

The introduction of such a simple unit usually can dramati-

cally improve the biological and physical properties of

pharmaceuticals, pesticides, and organic functional materi-

als. It is well known that many marketed drugs contain at

least one methyl group bound to the core skeleton.²

Over the past decade, complementary to traditional

Friedel–Crafts alkylation synthesis strategies, transition-

metal-catalyzed alkylation reactions have been quickly ad-

vanced due to the atom economical and environmental be-

nign properties.³Transition-metal-catalyzed directing

group assisted alkylation has been extensively reported us-

ing various alkylating reagents, such as alkyl halides,⁴al-

kylzinc halides,⁵alcohols,⁶alkanes,⁷alkenes,⁸allyl ace-

tates,⁹amides,¹⁰amino acids,¹¹ethers,¹²epoxides,¹³nitroal-

kanes,¹⁴organotin reagents,¹⁵peroxides,¹⁶α-diazoesters,¹⁷

and organboron reagents.¹⁸

Among these alkyl coupling partners, organboron re-

agents are particularly attractive due to their commercial

availability and synthetic accessibility, low cost, and low

toxicity. In 2006, Yu developed pyridine-directed Pd(II)-cat-

alyzed alkylation of sp²and sp³C–H bonds with methyl-

2-Arylbenzothiazoles are versatile structural motifs in

organic medicinal and material chemistry due to their re-

markable pharmacological activities¹⁹and fluorescent

properties.²⁰Recently, transition-metal-catalyzed C–H

bond functionalization of 2-arylbenzothiazoles with vari-

ous coupling partners has been reported by us²¹and other

groups.^17b,22A series of arylated,^21aacetoxylated,^21bhaloge-

nated,^21c,daminated,^21eacylated,^21f,g,22b,ctrifluoromethylthi-

olated,^21hcyanated,²¹ⁱalkylenated,^22aalkylated (using α-di-

azo esters as alkylating reagents),^17bhydroxylated,^22d,eand

nitrated^22f2-arylbenzothiazole derivatives have been pre-

pared. Based on these precedents, we present herein anoth-

er Rh(III)-catalyzed ortho-alkylation of 2-arylbenzothi-

azoles and 2-arylthiazoles by using alkyltrifluoroborates as

the alkyl group source.

Y. Ping et al.

Paper

Synthesis

Recent investigations of C–H alkylation of arenes pro-

moted us to use Rh(III)/Ag catalytic system for our designed

reaction.^18g,hInitially, we chose 2-(o-tolyl)benzothiazole

(1a) and potassium methyltrifluoroborate (MeBF₃K, 2a) as

model substrates to optimize the coupling reaction condi-

tions, using AgF and Ag₂O as oxidant, respectively (Table 1,

entries 1 and 2). To our delight, Ag₂O was found to promote

the reaction more efficiently than with AgF in ClCH₂CH₂Cl

(DCE). Screening of other solvents revealed that CH₂Cl₂was

the optimal one in this transformation (entries 2–7). Then,

a range of other silver oxidants were screened for this cou-

pling reaction in dichloromethane. Ag₂CO₃and AgOAc were

effective to accelerate this reaction with relatively less

yields 75% (entries 9 and 10), whereas AgNO₃and AgBF₄

were totally ineffective (entries 11 and 12). Fortunately, we

were pleased to find that the efficiency was almost main-

tained even when 1.0 equivalent of oxidant (Ag₂O) was used

(entry 14, 84%). In addition, the use of Ag₂O was very im-

portant, and no reaction took place in the absence of oxi-

dant. Further investigation indicated that lowering the re-

action temperature (85 °C) did not affect the reactivity (en-

try 17, 84%), while a decrease in the amount of MeBF₃K (2.0

equiv) reduced the yield of the desired product 3a to 71%

(entry 19).

The substrate scope of this benzothiazole-assisted or-

tho-C–H methylation with MeBF₃K (2a) was next investi-

gated under the optimal conditions using [RhCp^*Cl₂]₂(4

mol%), AgSbF₆(16 mol%), and Ag₂O (1.0 equiv). As shown in

Scheme 1, moderate to excellent methylation yields were

obtained. The reaction of ortho-substituted 2-arylbenzothi-

azoles 1b,c (R²= OMe, F) was found to be excellent for this

transformation to provide the desired products 3b,c in al-

most quantitative yields. The reaction was also compatible

with 2-(benzothiazol-2-yl)phenol (1d; R²= OH) to give the

corresponding methylated product 3d in moderate yield

(50%). Substrates bearing electron-donating or -withdraw-

ing group (R¹= Me, F, and Cl) on the phenyl ring of benzo-

thiazole afforded smoothly the desired products 3e–h,j–m

in excellent yields (88–99%), apart from 6-fluoro-2-(2-

methoxyphenyl)benzothiazole (1i), which delivered the de-

sired product 3i only in 60% yield under optimal reaction

conditions. It should be noted that the reaction of meta-

methyl-substituted substrate 1n preferentially occurred at

the less hindered position to give the monomethylated 2-

arylbenzothiazole 3n in good yield (88%). Subsequently, the

methylation reaction of symmetrical substrates 1o–r (R²=

4-N,N-dimethyl, 4-NH₂, 4-Me, H) was examined under the

standard reaction conditions, which delivered mono- and

dialkylated products 3o–q, 1a, and 3a in relatively low

yields and regioselectivity.

Table 1 Optimization of Reaction Conditions^a

[RhCp*Cl₂]₂

(4 mol%)

AgSbF₆

(16 mol%)

oxidant

(x equiv)

solvent

MeBF₃K

100 °C, 24 h

Entry

Oxidant (x equiv)

Solvent

Yield (%)^b

AgF (2.8)

DCE

Ag₂O (2.8)

AgF (2.8)

DCE

1,4-dioxane

toluene

MeCN

DMF

CH₂Cl₂

Ag₂CO₃(2.8)

AgOAc (2.8)

AgNO₃(2.8)

AgBF₄(2.8)

Ag₂O (2.0)

Ag₂O (1.0)

Ag₂O (0.5)

–

17^c

18^d

19^e

trace

Ag₂O (1.0)

^aReaction conditions: 2-(o-tolyl)benzothiazole (1a; 0.2 mmol), MeBF₃K (2a;

0.6 mmol, 3.0 equiv), [RhCp^*Cl₂]₂(4.0 mol%), AgSbF₆(16 mol%), oxidant (x

equiv) in a solvent (2.0 mL) at 100 °C for 24 h.

^bIsolated yield.

^cReaction was performed at 85 °C.

^dReaction was performed at 70 °C.

^eReaction was performed using MeBF₃K (2a; 0.4 mmol, 2.0 equiv).

yield. In addition, 2-(2-methoxyphenyl)thiazole (4b) also

underwent the ortho-C–H methylation reaction efficiently

to afford the desired product 5b in 87% yield. Interestingly,

the meta-methyl-substituted 2-(m-tolyl)thiazole (4d) gave

the product 5d selectively at the less sterically hindered po-

sition in good yield (71%).

However, 2-(3-fluorophenyl)thiazole (4e) with a less

hindered fluorine atom at the meta-position of 2-phenyl

ring gave a mixture of dimethylated product 2-(3-fluoro-

2,6-dimethylphenyl)thiazole 5e(di) in 33% isolated yield

and the monomethylated product 2-(5-fluoro-2-methyl-

phenyl)thiazole 5e(mono) in 33% NMR yield (See Support-

ing Information). In the case of 2-(naphthalen-2-yl)thiazole

(4f), mono- and dimethylated products were formed in

Furthermore, the methylation of 2-arylthiazoles 4 with

MeBF₃K (2a) under the same conditions (Scheme 2) was

studied. Fortunately, 2-(o-tolyl)thiazole (4a) was trans-

formed perfectly to give the desired product 5a in 99%

Y. Ping et al.

Paper

Synthesis

R²

[RhCp*Cl₂]₂(4 mol%)

AgSbF₆(16 mol%)

R¹

MeBF₃K

(3.0 equiv)

Ag₂O (1.0 equiv)

CH₂Cl₂, 85 °C

MeO

3b, 99%

3a, 84%

3c, 99%

3d, 50%

3e, 98%

3f, 98%

MeO

3i, 60%

3g, 99%

3h, 95%

3k, 98%

3j, 95%

3l, 95%

MeO

3m, 88%

3o, 30%

3n, 88%

NH₂

83%

mono(1a)/di(3a) = 4:5

3p, 21%

3q, 35%

Scheme 1 Rh(III)-catalyzed methylation of 2-arylbenzothiazoles 1 with various substituents

moderate yields with monomethylated at the less hindered

position as the major product. Symmetrical substrates like

the para-methyl-substituted or unsubstituted 2-phenylthi-

azoles 4g and 4h also reacted with 2a smoothly under the

present conditions and led to mixtures of mono- and di-

methylated products 5g/5g′ and 5h/5h′ in good yields with

moderate selectivity.

Furthermore, the generality of this selective alkylation

of 2-(2-methoxyphenyl)benzothiazole (1b) and 2-(2-meth-

oxyphenyl)thiazole (4b) was explored with different boron

reagent 2 as the alkylating reagent under optimal reaction

conditions (Scheme 3). The results revealed that the cou-

pling partners in this catalytic system are not limited only

to methyl boron reagent MeBF₃K (2a). Long-chain aliphatic

boron reagent 2b efficiently reacted to provide the corre-

Y. Ping et al.

Paper

Synthesis

R¹

[RhCp*Cl₂]₂(4 mol%)

AgSbF₆(16 mol%)

MeBF₃K

(3.0 equiv)

Ag₂O (1.0 equiv)

CH₂Cl₂, 85 °C

MeO

5a, 99%

5b, 87%

5c, 47%

5d, 71%

(Me)H

H(Me)

5e, 77%

mono/di = 4:3

5f, 64%

mono/di = 3:1

5g, 90%

mono/di = 1:2

5h, 60%

mono/di = 1:3

Scheme 2 Rh(III)-catalyzed methylation of 2-arylthiazoles 4

sponding products 3r and 5i in 99% and 63% isolated yield,

respectively. Boron reagents containing a benzyl 2c or cy-

clopropyl group 2d also gave the corresponding benzylation

product 3s and 5j and the cycloalkylation product 3t in

moderate to good yields.

Based on recent Rh-catalyzed direct ortho-C–H bond

functionalization of arenes,^18g,ha plausible mechanism for

the present Rh(III)-catalyzed direct alkylation is shown in

Scheme 4. Initially, an active cationic RhCp^*(SbF₆)₂species

may generate from the precursor [RhCp^*Cl₂]₂promoted by

the addition of AgSbF₆. Then, the active Rh(III) species facil-

itates the formation of a five-membered rhodacycle species

I via C–H bond activation. Subsequently, the intermediate II

is formed through transmetalation between the rhodacycle

species I and boron reagent 2. Finally, C–C reductive elimi-

nation of intermediate II will afford the desired alkylated

product 3 or 5 along with Rh(I) species, which undergoes

reoxidation by oxidant Ag₂O to regenerate the active cation-

ic Rh(III) species for the following catalytic cycle.

In summary, we have successfully developed the rhodi-

um-catalyzed direct ortho-C–H bond alkylation of 2-aryl-

benzothiazoles and 2-arylthiazoles by using alkyltrifluo-

MeO

[RhCp*Cl₂]₂(4 mol%)

AgSbF₆(16 mol%)

RBF₃K

Ag₂O (1.0 equiv)

CH₂Cl₂, 85 °C

(3.0 equiv)

1b/4b

3/5

MeO

ⁿBu

3b, 99%

3r, 99%

3s, 52%

3t, 42%

MeO

ⁿBu

5j, 76%

5b, 87%

5i, 63%

5k, trace

Scheme 3 Scope of alkyl trifluoroborates 2

Y. Ping et al.

Paper

Synthesis

[RhCp*Cl₂]₂

R²

AgSbF₆

AgCl

RhCp*(SbF₆)₂

1 or 4

Ag + H₂O

Ag₂O

C–H activation

Oxidation

HSbF₆

R²

[RhCp*]

III

SbF₆

Cp*

Reductive

elimination

R²

R¹

RBF₃K

R²

Rh^III

Transmetalation

R¹

3 or 5

Cp*

Scheme 4 Proposed catalytic pathway

roborates as the alkyl group source. The results show that

methyl, long-chain aliphatic group, and benzyl as well as

cycloalkyl boron reagents are all compatible with the pres-

ent alkylation protocol. No β-H elimination was observed in

the present catalytic system. The reaction was found to be

highly efficient providing a library of alkylated 2-arylben-

zothiazoles and 2-arylthiazoles, which are widely present

in many pharmaceuticals and biologically active natural

products.

completion of the reaction (monitored by TLC), the solvent was con-

centrated in vacuo, and the residue was purified by flash column

chromatography on silica gel with PE/EtOAc (30:1–20:1) as the eluent

to give the desired product 3.

2-(2,6-Dimethylphenyl)benzo[d]thiazole (3a)^23a

White solid; yield: 40.0 mg (84%); mp 108.8–110.9 °C; R_f= 0.5

(PE/EtOAc, 20:1).

¹H NMR (400 MHz, CDCl₃): δ = 8.12 (d, J = 8.0 Hz, 1 H), 7.95 (d, J = 7.8

Hz, 1 H), 7.53 (t, J = 7.4 Hz, 1 H), 7.44 (t, J = 7.6 Hz, 1 H), 7.26 (d, J = 8.2

Hz, 1 H), 7.14 (d, J = 7.6 Hz, 2 H), 2.21 (s, 6 H).

¹³C NMR (100 MHz, CDCl₃): δ = 167.5, 153.4, 137.3, 136.3, 133.5,

129.5, 127.6, 126.0, 125.1, 123.4, 121.5, 20.1.

Unless otherwise stated, all commercial reagents were used as re-

ceived. All solvents were dried and distilled according to standard

procedures. Flash column chromatography was performed using sili-

ca gel (60 Å pore size, 32–63 μm, standard grade). Analytical TLC was

performed using glass plates pre-coated with 0.25 mm 230–400

mesh silica gel impregnated with a fluorescent indicator (254 nm).

TLC plates were visualized by exposure to ultraviolet light. Organic

solutions were concentrated on rotary evaporator at 25–35 °C/~20

Torr. NMR spectra are recorded in parts per million from internal TMS

on the δ scale. ¹H and ¹³C NMR spectra were recorded in CDCl₃on a

Bruker DRX-400 spectrometer operating at 400 MHz and 100 MHz,

respectively. All chemical shift values are quoted in ppm and coupling

constants in Hz. High-resolution mass spectrometry (HRMS) was car-

ried out on a micrOTOF II Instrument.

2-(2-Methoxy-6-methylphenyl)benzo[d]thiazole (3b)

Pale yellow liquid; yield: 50.0 mg (99%); R_f= 0.4 (PE/EtOAc, 20:1).

¹H NMR (400 MHz, CDCl₃): δ = 8.04 (d, J = 8.2 Hz, 1 H), 7.86 (d, J = 8.0

Hz, 1 H), 7.43 (t, J = 7.6 Hz, 1 H), 7.34 (t, J = 7.6 Hz, 1 H), 7.26 (t, J = 8.0

Hz, 1 H), 6.85 (d, J = 7.6 Hz, 1 H), 6.77 (d, J = 8.4 Hz, 1 H), 3.69 (s, 3 H),

2.20 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 164.7, 157.8, 153.2, 139.5, 136.5,

130.9, 130.6, 125.7, 124.9, 123.4, 122.7, 121.4, 108.5, 55.8, 20.1.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₅H₁₄NOS⁺: 256.0796; found:

256.0791.

2-(2-Fluoro-6-methylphenyl)benzo[d]thiazole (3c)^21c

Rhodium(III)-Catalyzed ortho-C–H Alkylation of 2-Arylbenzothi-

azoles and 2-Arylthiazoles with Potassium Alkyltrifluoroborates;

General Procedure

White solid; yield: 48.0 mg (99%); mp 37.6–43.8 °C; R_f= 0.5 (PE/EtOAc,

20:1).

¹H NMR (400 MHz, CDCl₃): δ = 8.05 (d, J = 8.2 Hz, 1 H), 7.86 (d, J = 8.0

Hz, 1 H), 7.44 (t, J = 7.6 Hz, 1 H), 7.35 (t, J = 7.6 Hz, 1 H), 7.28–7.23 (m,

1 H), 7.03 (d, J = 7.6 Hz, 1 H), 6.95 (t, J = 9.0 Hz, 1 H), 2.32 (s, 3 H).

A suspension of the respective 2-arylbenzodthiazole 1 (0.2 mmol), al-

kylboron reagent 2 (0.6 mmol, 3.0 equiv), [RhCp^*Cl₂]₂(4.9 mg, 4

mol%), AgSbF₆(10.9 mg, 16 mol%), and Ag₂O (46.3 mg, 1.0 equiv) in

CH₂Cl₂(2.0 mL) was stirred at 100 °C under air for 24 h. After the

Y. Ping et al.

Paper

Synthesis

¹³C NMR (100 MHz, CDCl₃): δ = 161.2, 160.6 (d, ¹J_C,F= 248 Hz), 153.2,

¹³C NMR (100 MHz, CDCl₃): δ = 163.6, 157.9, 151.4, 139.5, 136.7,

135.0, 130.5, 127.2, 123.0, 122.8, 122.7, 121.1, 108.6, 55.8, 21.5, 20.1.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₆H₁₆NOS⁺: 270.0953; found:

270.0947.

140.3 (d, J_C,F= 2 Hz), 136.2, 131.0 (d, J_C,F= 10 Hz), 126.2 (d, J_C,F= 3

Hz), 126.1, 125.4, 123.6, 121.8 (d, ²J_C,F= 14 Hz), 121.4, 113.2 (d, ²J_C,F

22 Hz), 20.3.

2-(Benzo[d]thiazol-2-yl)-3-methylphenol (3d)

6-Fluoro-2-(2-methoxy-6-methylphenyl)benzo[d]thiazole (3i)

Pale yellow liquid; yield: 33.0 mg (60%); R_f= 0.4 (PE/EtOAc, 20:1).

¹H NMR (400 MHz, CDCl₃): δ = 8.04 (dd, J = 8.8, 4.8 Hz, 1 H), 7.60 (dd,

J = 8.2, 2.4 Hz, 1 H), 7.34 (t, J = 8.0 Hz, 1 H), 7.23 (dt, J = 2.4, 8.8 Hz, 1

H), 6.93 (d, J = 7.6 Hz, 1 H), 6.85 (d, J = 8.4 Hz, 1 H), 3.78 (s, 3 H), 2.28

(s, 3 H).

White solid; yield: 24.0 mg (50%); mp 85.3–86.9 °C; R_f= 0.4 (PE/EtOAc,

30:1).

¹H NMR (400 MHz, CDCl₃): δ = 13.91 (s, 1 H), 8.04 (d, J = 8.2 Hz, 1 H),

7.94 (d, J = 8.0 Hz, 1 H), 7.54 (t, J = 7.6 Hz, 1 H), 7.43 (t, J = 7.6 Hz, 1 H),

7.26 (t, J = 7.8 Hz, 1 H), 7.02 (d, J = 8.2 Hz, 1 H), 6.82 (d, J = 7.4 Hz, 1 H),

2.79 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 167.7, 159.8, 149.3, 137.5, 133.0,

131.7, 126.8, 125.4, 122.6, 121.9, 120.9, 116.7, 116.3, 23.8.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₄H₁₂NOS⁺: 242.0640; found:

¹³C NMR (100 MHz, CDCl₃): δ = 164.4 (d, J_C,F= 3 Hz), 160.4 (d, J_C,F

244 Hz), 157.9, 149.9 (d, J_C,F= 1 Hz), 139.6, 137.5 (d, J_C,F= 11 Hz),

130.8, 124.3 (d, ³J_C,F= 9 Hz), 122.9, 122.5, 114.3 (d, ²J_C,F= 25 Hz), 108.6,

107.4 (d, ²J_C,F= 26 Hz), 55.9, 20.3.

242.0634.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₅H₁₃FNOS⁺: 274.0702; found:

274.0696.

2-(2,6-Dimethylphenyl)-6-methylbenzo[d]thiazole (3e)

6-Fluoro-2-(2-fluoro-6-methylphenyl)benzo[d]thiazole (3j)^21c

Faint yellow solid; yield: 49.0 mg (98%); mp 80.9–82.3 °C; R_f= 0.5

(PE/EtOAc, 20:1).

White solid; yield: 50.0 mg (95%); mp 62.0–64.3 °C; R_f= 0.4 (PE/EtOAc,

30:1).

¹H NMR (400 MHz, CDCl₃): δ = 7.98 (dd, J = 9.2, 5.2 Hz, 1 H), 7.54 (dd,

J = 8.0, 2.4 Hz, 1 H), 7.30–7.24 (m, 1 H), 7.18 (dt, J = 2.8, 8.8 Hz, 1 H),

7.04 (d, J = 7.6 Hz, 1 H), 6.96 (t, J = 9.0 Hz, 1 H), 2.33 (s, 3 H).

¹H NMR (400 MHz, CDCl₃): δ = 7.91 (d, J = 8.4 Hz, 1 H), 7.64 (s, 1 H),

7.25 (d, J = 8.4 Hz, 1 H), 7.17 (t, J = 7.6 Hz, 1 H), 7.04 (d, J = 7.6 Hz, 2 H),

2.43 (s, 3 H), 2.11 (s, 6 H).

¹³C NMR (100 MHz, CDCl₃): δ = 166.3, 151.6, 137.4, 136.5, 135.2,

133.7, 129.4, 127.5, 122.9, 121.2, 21.5, 20.1.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₆H₁₆NS⁺: 254.0998; found:

254.0992.

¹³C NMR (100 MHz, CDCl₃): δ = 160.9 (d, ⁴J_C,F= 3.4 Hz), 160.7 (d, ¹J_C,F

245 Hz), 160.6 (d, J_C,F= 248 Hz), 160.9 (d, J_C,F= 3.4 Hz), 149.8 (d,

⁴J_C,F= 1.4 Hz), 140.3 (d, ⁴J_C,F= 1.2 Hz), 137.2 (d, ³J_C,F= 11.2 Hz), 131.2 (d,

³J_C,F= 9.2 Hz), 126.3 (d, ⁴J_C,F= 3.2 Hz), 124.5 (d, ³J_C,F= 9.4 Hz), 121.4 (d,

²J_C,F= 13.9 Hz), 114.8 (d, ²J_C,F= 24.7 Hz), 113.2 (d, ²J_C,F= 22 Hz), 107.5

(d, ²J_C,F= 26.5 Hz), 20.3 (d, ⁴J_C,F= 2.5 Hz).

6-Chloro-2-(2,6-dimethylphenyl)benzo[d]thiazole (3f)

Pale yellow liquid; yield: 53.0 mg (98%); R_f= 0.5 (PE/EtOAc, 20:1).

¹H NMR (400 MHz, CDCl₃): δ = 7.93 (d, J = 8.8 Hz, 1 H), 7.83 (d, J = 2.0

Hz, 1 H), 7.40 (dd, J = 8.8, 2.0 Hz, 1 H), 7.19 (t, J = 7.6 Hz, 1 H), 7.05 (d,

J = 7.6 Hz, 2 H), 2.11 (s, 6 H).

¹³C NMR (100 MHz, CDCl₃): δ = 167.9, 152.0, 137.5, 137.3, 133.1,

131.2, 129.7, 127.7, 126.8, 124.2, 121.1, 20.1.

2-(2-Fluoro-6-methylphenyl)-6-methylbenzo[d]thiazole (3k)

White solid; yield: 50.0 mg (98%); mp 72.3–74.5 °C; R_f= 0.4 (PE/EtOAc,

30:1).

¹H NMR (400 MHz, CDCl₃): δ = 8.00 (d, J = 8.4 Hz, 1 H), 7.73 (s, 1 H),

7.35–7.30 (m, 2 H), 7.10 (d, J = 7.6 Hz, 1 H), 7.02 (t, J = 9.0 Hz, 1 H),

2.51 (s, 3 H), 2.39 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 160.6 (d, ¹J_C,F= 248 Hz), 160.1, 151.4,

140.3 (d, ⁴J_C,F= 1 Hz), 136.4 (d, ⁴J_C,F= 1 Hz), 135.6, 130.9 (d, ³J_C,F= 9 Hz),

127.7, 126.2 (d, ³J_C,F= 3 Hz), 123.0, 121.9 (d, ²J_C,F= 14 Hz), 121.1, 113.1

(d, ²J_C,F= 22 Hz), 21.5, 20.2.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₅H₁₃ClNS⁺: 274.0457; found:

274.0456.

2-(2,6-Dimethylphenyl)-6-fluorobenzo[d]thiazole (3g)

White solid; yield: 51.0 mg (99%); mp 54.3–55.5 °C; R_f= 0.5 (PE/EtOAc,

20:1).

¹H NMR (400 MHz, CDCl₃): δ = 7.96 (dd, J = 8.8, 4.8 Hz, 1 H), 7.53 (dd,

J = 8.0, 2.4 Hz, 1 H), 7.23–7.13 (m, 2 H), 7.05 (d, J = 7.6 Hz, 2 H), 2.12 (s,

6 H).

HRMS (ESI): m/z [M + H]⁺calcd for C₁₅H₁₃FNS⁺: 258.0753; found:

258.0753.

6-Chloro-2-(2-fluoro-6-methylphenyl)benzo[d]thiazole (3l)^21c

¹³C NMR (100 MHz, CDCl₃): δ = 167.1 (d, J_C,F= 3 Hz), 160.5 (d, J_C,F

White solid; yield: 53.0 mg (95%); mp 101.2–102.9 °C; R_f= 0.5

(PE/EtOAc, 30:1).

244 Hz), 150.1 (d, J_C,F= 1 Hz), 137.4 (d, J_C,F= 11 Hz), 137.3, 133.2,

129.7, 127.7, 124.4 (d, J_C,F= 10 Hz), 114.6 (d, J_C,F= 25 Hz), 107.7 (d,

¹H NMR (400 MHz, CDCl₃): δ = 8.03 (d, J = 8.8 Hz, 1 H), 7.92 (d, J = 2.0

Hz, 1 H), 7.48 (dd, J = 8.8, 2.0 Hz, 1 H), 7.38–7.33 (m, 1 H), 7.13 (d, J =

8.0 Hz, 1 H), 7.04 (t, J = 9.0 Hz, 1 H), 2.41 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 161.7, 160.6 (d, ¹J_C,F= 249 Hz), 151.7,

140.3 (d, ⁴J_C,F= 1 Hz), 137.4 (d, ⁴J_C,F= 1 Hz), 131.4, 131.2 (d, ³J_C,F= 9 Hz),

126.9, 126.4 (d, ³J_C,F= 3 Hz), 124.3, 121.3 (d, ²J_C,F= 14 Hz), 121.0, 113.3

(d, ²J_C,F= 22 Hz), 20.4.

²J_C,F= 27 Hz), 20.1.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₅H₁₃FNS⁺: 258.0753; found:

258.0756.

2-(2-Methoxy-6-methylphenyl)-6-methylbenzo[d]thiazole (3h)

White solid; yield: 51.0 mg (95%); mp 74.3–76.5 °C; R_f= 0.3 (PE/EtOAc,

20:1).

¹H NMR (400 MHz, CDCl₃): δ = 7.98 (d, J = 8.4 Hz, 1 H), 7.70 (s, 1 H),

7.31 (t, J = 8.2 Hz, 1 H), 7.30 (d, J = 8.0 Hz, 1 H), 6.91 (d, J = 7.6 Hz, 1 H),

6.83 (d, J = 8.0 Hz, 1 H), 3.75 (s, 3 H), 2.50 (s, 3 H), 2.26 (s, 3 H).

6-Chloro-2-(2-methoxy-6-methylphenyl)benzo[d]thiazole (3m)

White liquid; yield: 51.0 mg (88%); R_f= 0.3 (PE/EtOAc, 30:1).

Y. Ping et al.

Paper

Synthesis

¹H NMR (400 MHz, CDCl₃): δ = 8.00 (d, J = 8.8 Hz, 1 H), 7.89 (d, J = 2.0

Hz, 1 H), 7.44 (dd, J = 8.8, 2.0 Hz, 1 H), 7.33 (t, J = 8.0 Hz, 1 H), 6.92 (d,

J = 7.6 Hz, 1 H), 6.84 (d, J = 8.4 Hz, 1 H), 3.78 (s, 3 H), 2.29 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 164.6, 157.9, 153.3, 144.3, 136.6,

130.6, 125.6, 124.9, 123.4, 122.5, 121.8, 121.3, 108.4, 55.8, 33.3, 33.0,

22.4, 13.8.

¹³C NMR (100 MHz, CDCl₃): δ = 165.2, 157.9, 151.8, 139.5, 137.7,

HRMS (ESI): m/z [M + H]⁺calcd for C₁₈H₂₀NOS⁺: 298.1266; found:

130.9, 130.8, 126.5, 124.1, 122.9, 122.3, 120.9, 108.6, 55.8, 20.3.

298.1260.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₅H₁₃ClNOS⁺: 290.0406; found:

290.0407.

2-(2-Benzyl-6-methoxyphenyl)benzo[d]thiazole (3s)

Faint yellow solid; yield: 31.0 mg (47%); mp 76.3–78.4 °C; R_f= 0.2

(PE/EtOAc, 30:1).

2-(2,5-Dimethylphenyl)benzo[d]thiazole (3n)^23b

White liquid; yield: 42.0 mg (88%); R_f= 0.4 (PE/EtOAc, 30:1).

¹H NMR (400 MHz, CDCl₃): δ = 8.03 (d, J = 8.0 Hz, 1 H), 7.80 (d, J = 8.0

Hz, 1 H), 7.40 (t, J = 7.6 Hz, 1 H), 7.31 (t, J = 7.6 Hz, 1 H), 7.26 (t, J = 8.0

Hz, 1 H), 7.10–7.02 (m, 3 H), 6.93 (d, J = 6.4 Hz, 2 H), 6.78 (t, J = 6.8 Hz,

2 H), 3.92 (s, 2 H), 3.68 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 164.4, 158.0, 153.2, 142.6, 140.4,

136.7, 130.8, 129.0, 128.4, 128.3, 128.2, 125.9, 125.7, 124.9, 123.4,

122.8, 122.6, 121.3, 109.0, 55.9, 39.0.

¹H NMR (400 MHz, CDCl₃): δ = 8.09 (d, J = 8.0 Hz, 1 H), 7.91 (d, J = 7.6

Hz, 1 H), 7.58 (s, 1 H), 7.49 (t, J = 7.8 Hz, 1 H), 7.39 (t, J = 7.6 Hz, 1 H),

7.25–7.17 (m, 2 H), 2.61 (s, 3 H), 2.38 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 168.1, 153.8, 138.8, 135.6, 134.1,

132.9, 131.5, 131.0, 130.8, 126.1, 125.0, 123.3, 121.3, 20.8.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₁H₁₈NOS⁺: 332.1102; found:

332.1104.

4-(Benzo[d]thiazol-2-yl)-N,N,3-trimethylaniline (3o)

Yellow granular solid; yield: 16.0 mg (30%); mp 93.4–96.5 °C; R_f= 0.4

(PE/EtOAc, 30:1).

2-(2-Cyclopropyl-6-methoxyphenyl)benzo[d]thiazole (3t)

¹H NMR (400 MHz, CDCl₃): δ = 8.01 (d, J = 8.0 Hz, 1 H), 7.86 (d, J = 8.0

Hz, 1 H), 7.75 (d, J = 8.2 Hz, 1 H), 7.44 (t, J = 7.6 Hz, 1 H), 7.32 (t, J = 7.6

Hz, 1 H), 6.63 (d, J = 2.8 Hz, 1 H), 6.61 (s, 1 H), 3.03 (s, 6 H), 2.72 (s, 3

H).

¹³C NMR (100 MHz, CDCl₃): δ = 168.8, 154.1, 151.3, 138.5, 135.1,

132.0, 125.8, 124.2, 122.6, 121.1, 121.0, 114.4, 109.6, 40.1, 22.5.

Faint yellow solid; yield: 20.0 mg (36%); mp 63.3–65.8 °C; R_f= 0.2

(PE/EtOAc, 30:1).

¹H NMR (400 MHz, CDCl₃): δ = 8.05 (d, J = 8.4 Hz, 1 H), 7.85 (d, J = 8.0

Hz, 1 H), 7.42 (t, J = 7.8 Hz, 1 H), 7.33 (t, J = 7.6 Hz, 1 H), 7.25 (t, J = 8.2

Hz, 1 H), 7.19–7.17 (m, 1 H), 7.12–7.09 (m, 1 H), 6.73 (d, J = 8.4 Hz, 1

H), 6.52 (d, J = 7.6 Hz, 1 H), 3.67 (s, 3 H), 1.79–1.72 (m, 1 H), 0.73–0.66

(m, 2 H), 0.62–0.58 (m, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 164.9, 157.7, 153.4, 145.0, 136.7,

130.9, 128.36 (d, J = 12.2 Hz), 125.9, 125.6, 124.9, 123.4, 121.4, 116.4,

108.2, 55.9, 37.9, 13.2, 9.3.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₆H₁₇N₂S⁺: 269.1102; found:

269.1107.

4-(Benzo[d]thiazol-2-yl)-3-methylaniline (3p)

Yellow solid; yield: 10.0 mg (21%); mp 92.1–94.3 °C; R_f= 0.2 (PE/EtOAc,

30:1).

¹H NMR (400 MHz, CDCl₃): δ = 8.03 (d, J = 8.4 Hz, 1 H), 7.87 (d, J = 8.0

Hz, 1 H), 7.64 (d, J = 8.0 Hz, 1 H), 7.46 (t, J = 7.6 Hz, 1 H), 7.34 (t, J = 7.6

Hz, 1 H), 6.61 (s, 1 H), 6.58 (d, J = 2.0 Hz, 1 H), 3.91 (s, 2 H), 2.64 (s, 3

H).

¹³C NMR (100 MHz, CDCl₃): δ = 168.5, 154.0, 148.1, 139.0, 132.3,

125.9, 124.5, 123.5, 122.9, 121.1, 117.4, 112.5, 83.2, 21.8.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₄H₁₃N₂S⁺: 241.0795; found:

241.0794.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₇H₁₆NOS⁺: 282.0947; found:

282.0955.

2-(2,6-Dimethylphenyl)thiazole (5a)

Pale yellow liquid; yield: 37.0 mg (99%); R_f= 0.4 (PE/EtOAc, 20:1).

¹H NMR (400 MHz, CDCl₃): δ = 7.93 (d, J = 3.6 Hz, 1 H), 7.46 (d, J = 3.4

Hz, 1 H), 7.23 (t, J = 7.8 Hz, 1 H), 7.10 (d, J = 7.6 Hz, 2 H), 2.13 (s, 6 H).

¹³C NMR (100 MHz, CDCl₃): δ = 166.5, 142.8, 137.7, 133.4, 129.1,

127.4, 120.1, 20.1.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₁H₁₂NS⁺: 190.0690; found:

190.0685.

6-Chloro-2-mesitylbenzo[d]thiazole (3q)

White liquid; yield: 20.0 mg (35%); R_f= 0.5 (PE/EtOAc, 30:1).

2-(2-Methoxy-6-methylphenyl)thiazole (5b)

¹H NMR (400 MHz, CDCl₃): δ = 7.93 (d, J = 8.4 Hz, 1 H), 7.83 (d, J = 2.0

Hz, 1 H), 7.40 (dd, J = 8.8, 2.0 Hz, 1 H), 6.88 (s, 2 H), 2.26 (s, 3 H), 2.09

(s, 6 H).

¹³C NMR (100 MHz, CDCl₃): δ = 168.3, 152.1, 139.7, 137.6, 137.1,

131.1, 130.3, 128.5, 126.7, 124.1, 121.1, 21.2, 20.0.

Pale yellow liquid; yield: 36 mg (87%); R_f= 0.3 (PE/EtOAc, 20:1).

¹H NMR (400 MHz, CDCl₃): δ = 7.92 (d, J = 3.6 Hz, 1 H), 7.46 (d, J = 3.6

Hz, 1 H), 7.28 (t, J = 8.0 Hz, 1 H), 6.90 (d, J = 7.6 Hz, 1 H), 6.82 (d, J = 8.4

Hz, 1 H), 3.76 (s, 3 H), 2.24 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 163.5, 157.8, 142.3, 139.6, 130.1,

122.8, 122.5, 120.2, 108.4, 55.7, 20.4.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₆H₁₅ClNS⁺: 288.0612; found:

288.0608.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₁H₁₂NOS⁺: 206.0640; found:

206.0634.

2-(2-Butyl-6-methoxyphenyl)benzo[d]thiazole (3r)

White liquid; yield: 59.0 mg (99%); R_f= 0.3 (PE/EtOAc, 30:1).

2-(2-Fluoro-6-methylphenyl)thiazole (5c)

¹H NMR (400 MHz, CDCl₃): δ = 8.02 (d, J = 7.6 Hz, 1 H), 7.83 (d, J = 8.0

Hz, 1 H), 7.41 (t, J = 7.8 Hz, 1 H), 7.33–7.25 (m, 2 H), 6.86 (d, J = 7.6 Hz,

1 H), 6.74 (d, J = 8.0 Hz, 1 H), 3.66 (s, 3 H), 2.49 (t, J = 8.0 Hz, 2 H),

1.47–1.39 (m, 2 H), 1.16–1.11 (m, 2 H), 0.69 (t, J = 7.2 Hz, 3 H).

Transparent liquid; yield: 18.0 mg (47%); R_f= 0.3 (PE/EtOAc, 20:1).

Y. Ping et al.

Paper

Synthesis

¹H NMR (400 MHz, CDCl₃): δ = 7.98 (d, J = 3.2 Hz, 1 H), 7.53 (d, J = 3.6

Hz, 1 H), 7.34–7.27 (m, 1 H), 7.10 (d, J = 7.6 Hz, 1 H), 7.02 (t, J = 9.0 Hz,

1 H), 2.37 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 160.5 (d, ¹J_C,F= 247 Hz), 160.4, 142.8,

140.3 (d, ⁴J_C,F= 1 Hz), 130.4 (d, ³J_C,F= 9 Hz), 126.3 (d, ³J_C,F= 3 Hz), 121.5

(d, ²J_C,F= 14 Hz), 120.6 (d, ⁴J_C,F= 2 Hz), 113.1 (d, ²J_C,F= 22 Hz), 20.5.

¹³C NMR (100 MHz, CDCl₃): δ = 167.3, 142.9, 134.6, 134.5, 133.8,

131.7, 131.0, 127.8, 126.5, 126.3, 125.6, 124.5, 120.4, 20.9, 16.4.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₅H₁₄NS⁺: 240.0847; found:

240.0842.

2-(2,4-Dimethylphenyl)thiazole [5g(mono)]

HRMS (ESI): m/z [M + H]⁺calcd for C₁₀H₉FNS⁺: 194.0440; found:

Transparent liquid; yield: 12.0 mg (30%); R_f= 0.5 (PE/EtOAc, 10:1).

194.0434.

¹H NMR (400 MHz, CDCl₃): δ = 7.89 (d, J = 3.6 Hz, 1 H), 7.62 (d, J = 7.6

Hz, 1 H), 7.37 (d, J = 3.2 Hz, 1 H), 7.12 (s, 1 H), 7.09 (d, J = 7.6 Hz, 1 H),

2.56 (s, 3 H), 2.37 (s, 3 H).

2-(2,5-Dimethylphenyl)thiazole (5d)^23c

White liquid; yield: 27.0 mg (71%); R_f= 0.6 (PE/EtOAc, 20:1).

¹H NMR (400 MHz, CDCl₃): δ = 7.90 (d, J = 3.2 Hz, 1 H), 7.55 (s, 1 H),

7.37 (d, J = 3.2 Hz, 1 H), 7.19–7.12 (m, 2 H), 2.54 (s, 3 H), 2.36 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 168.1, 142.9, 139.4, 136.3, 132.2,

130.2, 130.1, 126.8, 119.0, 21.3, 21.2.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₁H₁₂NS⁺: 190.0681; found:

190.0685.

¹³C NMR (100 MHz, CDCl₃): δ = 168.0, 142.8, 135.5, 133.3, 132.7,

131.3, 130.5, 130.1, 119.2, 20.9, 20.8.

2-Mesitylthiazole [5g(di)]^23c

2-(3-Fluorophenyl)thiazole (4e)/2-(5-Fluoro-2-methylphenyl)thi-

azole [5e(mono); 4e/5e(mono): 1:1]

White solid; yield: 24.0 mg (60%); mp 51.2–53.3 °C; R_f= 0.3 (PE/EtOAc,

10:1).

Pale yellow liquid; 43 mg; R_f= 0.5 (PE/EtOAc, 20:1).

¹H NMR (400 MHz, CDCl₃): δ = 7.92 (d, J = 3.4 Hz, 1 H), 7.45 (d, J = 3.4

Hz, 1 H), 6.93 (s, 2 H), 2.32 (s, 3 H), 2.10 (s, 6 H).

¹³C NMR (100 MHz, CDCl₃): δ = 166.8, 142.8, 139.0, 137.6, 130.5,

128.3, 120.1, 21.1, 20.1.

¹H NMR (400 MHz, CDCl₃): δ = 7.93 (d, J = 3.6 Hz, 1 H), 7.88 (d, J = 3.2

Hz, 1 H), 7.74–7.69 (m, 2 H), 7.47–7.36 (m, 4 H), 7.27–7.21 (m, 1 H),

7.15–7.09 (m, 2 H), 2.48 (d, J = 2.4 Hz, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 166.8 (d, ⁴J_C,F= 3 Hz), 166.6 (d, ⁴J_C,F= 3

2-(o-Tolyl)thiazole [5h(mono)]^23d

Hz), 163.0 (d, J_C,F= 245 Hz), 161.6 (d, J_C,F= 243 Hz), 143.9, 143.2,

135.5 (d, ³J_C,F= 8 Hz), 135.0 (d, ³J_C,F= 5 Hz), 130.5 (d, ³J_C,F= 8 Hz), 126.8

(d, ³J_C,F= 9 Hz), 125.7 (d, ⁴J_C,F= 2 Hz), 124.1 (d, ²J_C,F= 18 Hz), 122.3 (d,

⁴J_C,F= 3 Hz), 119.9, 119.5, 116.8 (d, ²J_C,F= 21 Hz), 116.0 (d, ²J_C,F= 24 Hz),

113.4 (d, ²J_C,F= 23 Hz), 12.0 (d, ⁴J_C,F= 6 Hz).

Transparent liquid; yield: 5.0 mg (15%); R_f= 0.5 (PE/EtOAc, 20:1).

¹H NMR (400 MHz, CDCl₃): δ = 7.93 (d, J = 3.2 Hz, 1 H), 7.72 (d, J = 7.6

Hz, 1 H), 7.41 (d, J = 3.6 Hz, 1 H), 7.34–7.28 (m, 3 H), 2.59 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 168.0, 143.0, 136.6, 133.0, 131.5,

130.1, 129.4, 126.1, 119.4, 21.4.

2-(3-Fluoro-2,6-dimethylphenyl)thiazole [5e(di)]

Pale yellow liquid; yield: 14.0 mg (34%); R_f= 0.4 (PE/EtOAc, 20:1).

¹H NMR (400 MHz, CDCl₃): δ = 7.96 (d, J = 3.6 Hz, 1 H), 7.51 (d, J = 3.2

Hz, 1 H), 7.09–7.00 (m, 2 H), 2.09 (s, 3 H), 2.04 (d, J = 2.4 Hz, 3 H).

2-(2,6-Dimethylphenyl)thiazole [5h(di)]

Transparent liquid; yield: 17.0 mg (45%); R_f= 0.3 (PE/EtOAc, 20:1).

¹H NMR (400 MHz, CDCl₃): δ = 7.94 (d, J = 3.6 Hz, 1 H), 7.48 (d, J = 3.6

Hz, 1 H), 7.24 (t, J = 7.2 Hz, 1 H), 7.11 (d, J = 7.6 Hz, 2 H), 2.14 (s, 6 H).

¹³C NMR (100 MHz, CDCl₃): δ = 166.6, 142.9, 137.7, 133.4, 129.2,

127.5, 120.2, 20.2.

¹³C NMR (100 MHz, CDCl₃): δ = 165.3 (d, J_C,F= 3 Hz), 159.4 (d, J_C,F

241 Hz), 143.0, 134.9 (d, J_C,F= 5 Hz), 133.2 (d, J_C,F= 3 Hz), 128.2 (d,

³J_C,F= 9 Hz), 125.0 (d, ²J_C,F= 17 Hz), 120.5, 115.8 (d, ²J_C,F= 23 Hz), 19.7,

12.1.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₁H₁₁FNS⁺: 208.0596; found:

HRMS (ESI): m/z [M + H]⁺calcd for C₁₁H₁₂NS⁺: 190.0690; found:

208.0601.

190.0685.

2-(3-Methylnaphthalen-2-yl)thiazole [5f(mono)]

2-(2-Butyl-6-methoxyphenyl)thiazole (5i)

White solid; yield: 20.0 mg (45%); mp 57.8–61.2 °C; R_f= 0.4 (PE/EtOAc,

Transparent liquid; yield: 31.0 mg (63%); R_f= 0.4 (PE/EtOAc, 20:1).

20:1).

¹H NMR (400 MHz, CDCl₃): δ = 7.92 (d, J = 3.2 Hz, 1 H), 7.47 (d, J = 3.2

Hz, 1 H), 7.32 (t, J = 8.0 Hz, 1 H), 6.92 (d, J = 7.6 Hz, 1 H), 6.81 (d, J = 8.4

Hz, 1 H), 3.75 (s, 3 H), 2.51 (t, J = 8.0 Hz, 2 H), 1.48–1.39 (m, 2 H),

1.28–1.19 (m, 2 H), 0.80 (t, J = 7.2 Hz, 3 H).

¹H NMR (400 MHz, CDCl₃): δ = 8.19 (s, 1 H), 7.96 (d, J = 3.6 Hz, 1 H),

7.85 (d, J = 8.0 Hz, 1 H), 7.78 (d, J = 8.0 Hz, 1 H), 7.74 (s, 1 H), 7.52–7.43

(m, 2 H), 7.42 (d, J = 3.2 Hz, 1 H), 2.72 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 167.8, 143.2, 133.7, 133.6, 131.8,

¹³C NMR (100 MHz, CDCl₃): δ = 163.5, 157.9, 144.6, 142.3, 130.2,

131.6, 129.8, 129.4, 128.0, 127.0, 126.9, 125.8, 119.5, 21.7.

122.3, 121.9, 120.2, 108.4, 55.8, 33.3, 33.0, 22.5, 13.8.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₄H₁₂NS⁺: 226.0690; found:

HRMS (ESI): m/z [M + H]⁺calcd for C₁₄H₁₈NOS⁺: 248.1104; found:

226.0685.

248.1116.

2-(1,3-Dimethylnaphthalen-2-yl)thiazole [5f(di)]

2-(2-Benzyl-6-methoxyphenyl)thiazole (5j)

Faint yellow solid; yield: 9.0 mg (18%); mp 90.3–92.9 °C; R_f= 0.2

Pale yellow liquid; yield: 43.0 mg (76%); R_f= 0.3 (PE/EtOAc, 20:1).

(PE/EtOAc, 20:1).

¹H NMR (400 MHz, CDCl₃): δ = 7.90 (d, J = 3.2 Hz, 1 H), 7.41 (d, J = 3.2

Hz, 1 H), 7.30 (t, J = 8.0 Hz, 1 H), 7.17–7.11 (m, 3 H), 6.98 (d, J = 6.8 Hz,

2 H), 6.84 (d, J = 8.0 Hz, 2 H), 3.96 (s, 2 H), 3.75 (s, 3 H).

¹H NMR (400 MHz, CDCl₃): δ = 8.04–8.01 (m, 1 H), 7.98 (d, J = 3.4 Hz, 1

H), 7.81–7.79 (m, 1 H), 7.60 (s, 1 H), 7.54–7.48 (m, 3 H), 2.47 (s, 3 H),

2.24 (s, 3 H).

Y. Ping et al.

Paper

Synthesis

¹³C NMR (100 MHz, CDCl₃): δ = 163.2, 157.9, 142.7, 142.2, 140.6,

130.4, 128.9, 128.1, 125.8, 122.7, 122.6, 120.5, 109.0, 55.8, 39.0.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₇H₁₆NOS⁺: 282.0947; found:

282.0946.

(6) Some recent reports: (a) Lee, D. H.; Kwon, K. H.; Yi, C. S. J. Am.

Chem. Soc. 2012, 134, 7325. (b) Han, S. H.; Choi, M.; Jeong, T.;

Sharma, S.; Mishra, N. K.; Park, J.; Oh, J. S.; Kim, W. J.; Lee, J. S.;

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X.; Xiao, J.; Zhong, S.; She, X.; Fu, Z.; Yin, D. Fuel 2016, 182, 373.

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4869. (e) Deibl, N.; Kempe, R. J. Am. Chem. Soc. 2016, 138, 10786.

(7) Some recent reports: (a) Yonehara, F.; Kido, Y.; Sugimoto, H.;

Morita, S.; Yamaguchi, M. J. Org. Chem. 2003, 68, 6752.

(b) Bajtos, B.; Yu, M.; Zhao, H.; Pagenkopf, B. J. Am. Chem. Soc.

2007, 129, 9631. (c) Zhang, X.; Wang, Z.; Fan, X.; Wang, J. J. Org.

Chem. 2015, 80, 10660.

Acknowledgment

Financial Support from National Natural Science Foundation of China

(21262016, 21662017) and Natural Science Foundation of Jiangxi

Province of China (20133ACB20008) is gratefully acknowledged.

(8) Some recent reports: (a) Tamura, R.; Yamada, Y.; Nakao, Y.;

Hiyama, T. Angew. Chem. Int. Ed. 2012, 51, 5679. (b) Wang, Z.;

Reinus, B. J.; Dong, G. J. Am. Chem. Soc. 2012, 134, 13954.

(d) Pan, S.; Ryu, N.; Shibata, T. J. Am. Chem. Soc. 2012, 134,

17474. (e) Schinkel, M.; Wang, L.; Bielefeld, K.; Ackermann, L.

Org. Lett. 2014, 16, 1876. (f) Tang, S.; Wu, X.; Liao, W.; Liu, K.;

Liu, C.; Luo, S.; Lei, A. Org. Lett. 2014, 16, 3584. (g) Shibata, K.;

Chatani, N. Org. Lett. 2014, 16, 5148. (h) Hu, G.; Xu, J.; Li, P. Org.

Lett. 2014, 16, 6036. (i) Lee, P. S.; Yoshikai, N. Org. Lett. 2015, 17,

22. (j) Pollice, R.; Dastbaravardeh, N.; Marquise, N.; Mihovilovic,

M. D.; Schnurch, M. ACS Catal. 2015, 5, 587. (k) Shibata, K.;

Yamaguchi, T.; Chatani, N. Org. Lett. 2015, 17, 3584. (l) Dang, Y.;

Qu, S.; Tao, Y.; Deng, X.; Wang, Z. X. J. Am. Chem. Soc. 2015, 137,

6279. (m) Hatano, M.; Ebe, Y.; Nishimura, T.; Yorimitsu, H. J. Am.

Chem. Soc. 2016, 138, 4010. (n) Han, S.; Park, J.; Kim, S.; Lee, S.

H.; Sharma, S.; Mishra, N. K.; Jung, Y. H.; Kim, I. S. Org. Lett.

2016, 18, 4666.

(9) Some recent reports: (a) Young, A. J.; White, M. C. J. Am. Chem.

Soc. 2008, 130, 14090. (b) Howell, J. M.; Liu, W.; Young, A. J.;

White, M. C. J. Am. Chem. Soc. 2014, 136, 5750. (c) Bae, S.; Jang,

H. L.; Jung, H.; Joo, J. M. J. Org. Chem. 2015, 80, 690. (d) Deng, H.;

Li, H.; Wang, L. Org. Lett. 2015, 17, 2450.

(10) Meng, G.; Szostak, M. Org. Lett. 2016, 18, 796.

(11) Mai, D. N.; Baxter, R. D. Org. Lett. 2016, 18, 3738.

(12) Pan, S.; Liu, J.; Li, H.; Wang, Z.; Guo, X.; Li, Z. Org. Lett. 2010, 12,

1932.

Supporting Information

Supporting information for this article is available online at

http://dx.doi.org/10.1055/s-0036-1588936.

ortioInfgrmoaitn

ortiInfogrmoaitn

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