Copper-Catalyzed and Air-Mediated Mild Cross-Dehydrogenative

Subscriber access provided by Kaohsiung Medical University

Note

Copper-Catalyzed and Air-Mediated Mild CrossDehydrogenative Coupling of Aryl Thioureas and Dialkyl H-phosphonates: the Synthesis of Thiophosphonates Cai-Zhu Chang, Xing Liu, Hui Zhu, Li Wu, and Zhi-Bing Dong J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02011 • Publication Date (Web): 16 Oct 2018 Downloaded from http://pubs.acs.org on October 16, 2018

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

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

The Journal of Organic Chemistry

Copper-Catalyzed and Air-Mediated Mild Cross-Dehydrogenative Coupling of Aryl Thioureas and Dialkyl H-phosphonates: the Synthesis of Thiophosphonates Cai-Zhu Chang,a+ Xing Liu,a+ Hui Zhu,a Li Wu,a and Zhi-Bing Dong*a,b School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan 430205, China Department of Chemistry, Ludwig-Maximilians-Universität, Butenandtstrasse 5-13, 81377 München, Germany + These authors contributed equally to this work a b

H N FG

N S

+

O R O P H OR1 1

Cu2O (7 mol%), DMAP (14 mol%)

N FG

CH3CN, air, r.t., 5 h

R1 = Me, Et, i-Pr, n-Bu

FG = F, Cl, Br, CN, CF3, CH3O room temperature

easy performance

broad substrate scope

OR1 P O R 1O S

Key blocks of herbicidals

good to excellent yield

open to air

N

efficient, practical, and inexpensive

18 examples up to 96% yield

ABSTRACT: A copper-catalyzed and air-mediated mild cross-dehydrogenative coupling of aryl thioureas and dialkyl Hphosphonates to produce thiophosphonates has been reported. Without addition of base or acid, air as an oxidant, the phosphorylation occurred smoothly to give the target products in moderate to excellent yields at room temperature. The protocol allows the direct formation of a sulfur-phosphorus bond, tolerates a series of functional groups and shows potential synthetic value for the synthesis of a diversity of thiophosphonates.

The derivatives of thiophosphonates play an importan role in a variety of fields, including agrochemistry, medicinal chemistry, and organic synthesis.1 The thiophosphonate block is universal in a numbers of effective pharmaceuticals and agrochemicals2 (Scheme 1A). Due to the importance of these compounds, the development of synthetic methods for thiophosphonates has attracted the attention and interest of many chemists. Synthetic protocols to thiophosphonates generally involve the reactions of H-phosphinate esters with disulfides,3 tosylhydrazide,4 sulfonyl chlorides,5 sulfenyl chloride6 and sodiumbenzosulfonates7 (Scheme 1B, a), and condensation of phosphorochloridates or phosphorobromidates with thiols8 (Scheme 1B, b). Recently, Goossen et al. reported phosphorothiolate salts as the phosphorothiolation reagents9 (Scheme 1B, c). However, the methodology involved special reagents sensitive to air or moisture, and the prefunctionalization of starting materials, thus they are normally carried out under special reaction conditions, which limits their applications in organic synthesis. In recent years, multicomponent reactions for direct Sarylation of phosphonates have been developed. Tang et al reported Cu-catalyzed phosphorothiolations of diazonium, arylboronic acids or iodonium salts using elemental sulfur as sulfur resource (Scheme 1B, d).10 Although

multicomponent reactions can improve the efficiency of chemical reaction, there are certain limitations for some parallel synthesis and drug discovery in small scale. Crossdehydrogenative couplings (CDCs) is one of the most atrractive strategies since the reaction efficiency could be significantly increased and the atomic economy could also be improved.11 The coupling reaction of phosphonates with thiols for the construction of S-P(O) bond is still challenging because P(O)-H and S-H bond are easily oxidized by strong oxidants (Scheme 1B, e). The oxidative CDC reactions of phosphonates with thiols were reported by using copper,12 iron,13 palladium,14 NCS,15 1,3-dichloro5,5-dimethylhydantoin (DCDMH),16 di-tert-butyl peroxide (DTBP)17 and Cs2CO318 as catalysts. Despite the considerable progress has been made, the development of cheaper, milder, more environmentally benign, and more efficient method is still highly desirable. Recently, we reported an efficient protocol for the synthesis of benzothiazoles via intramolecular cross-dehydrogenative coupling.19 For the persistent efforts on the study of aryl thioureas compounds,20 herein we disclose a set of complementary method for the synthesis of thiophosphonates by a cross-dehydrogenative coupling of dialkyl H-phosphonates with aryl thioureas (Scheme 1C).

ACS Paragon Plus Environment

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

Scheme 1. Synthesis and Application of Thiophosphonates A) Bioactive organosulfur compounds bearing S-P(O) bond. O HO

P

NH

S OH

O P O O Ph antibacterial agent

O

S

NH2

cancer chemotherapy

O P O O N azamethiphos S

N O P OEt EtO S

I Me3N

echothiophate

EtS

O S P OEt EtO

Z

demeton

and THF, which were less effective than MeCN (Table 1, entries 19-21). The optimal reaction conditions are given in entry 18.

O N

Cl

Page 2 of 7

Table 1. Optimization of Reaction Conditions for the Synthesis of 3aa

N

H N

O P R1 X O O Y 1 herbicidal R S

N S

1a

O + EtO P H OEt

N

conditions

N S

3a EtO

2a

OEt P O

B) Known strategies towards the formation of S-P bond. a)

b)

c)

d)

e)

O O R'O P SAr + R'O P H or (RO)3P OR' OR' O O R'O P SAr ArSH + R'O P X OR' OR' X=Cl, Br O OR' O O P O Me4N OR' ArN2 or ArB(OH)2 + or N S R'O P SAr S P OR' OR' OR' O O O R'O P SAr ArN2, ArB(OH)2, ArI Ar + S8 + R'O P H OR' OR' O O ArSH + R'O P H R'O P SAr OR' OR' ArSSAr, ArSO2NHNH2, ArSO2Cl, ArSCl, ArSO2Na

C) Dehydrogenative coupling of aryl thioureas and H-phosphonates (this work). H N

N S

Cu2O (7 mol%) O DMAP (14 mol%) + EtO P H CH3CN, air, r.t., 5 h OEt

entry

catalyst

base

ligand

solvent

1 2 3 4 5 6 7 8 9 10 11 12 13

CuSO4 Cu(OTf)2 CuI Cu2O Cu2O Cu2O Cu2O Cu2O Cu2O Cu2O Cu2O Cu2O Cu2O (10%) Cu2O (7%) Cu2O (6%) --

Et3N Et3N Et3N Et3N K2CO3 ---------

Cu2O (7%) Cu2O (7%) Cu2O (7%) Cu2O (7%) Cu2O (7%)

--

------1,10-phen Pyc Bpyd DMEDAe L-proline DMAPf DMAP (20%) DMAP (14%) DMAP (12%) DMAP (14%) DMAP (14%) DMAP (14%) DMAP (14%) DMAP (14%) DMAP (14%)

N

14

OEt P O EtO

15

N S

16

The reaction of 1,1-dimethyl-3-phenylthiourea (1a) with diethyl phosphonate (2a) in the certain conditions was investigated, and the reaction condition screenings are listed in Table 1. The model reaction occured and gave the target product 3a in 21% yield shown in entry 1 (30 mol% CuSO4, 2.0 equiv. of Et3N, 60 oC in MeCN). Encouraged by this result, various catalysts were screened, and it revealed that Cu2O is superior to other catalysts, providing the desired product 3a in 44% yield (Table 1, entry 4). The yield dropped to 24% when K2CO3 was used as base (Table 1, entry 5). In addition, target product was furnished in 47% yield without any base (Table 1, entry 6). Among the base tested, inorganic base and organic base showed almost no help for the reaction (for simplification, not shown in the table). Based on this result, we suspected that Et3N might act as a ligand (Table 1, entry 4). We were pleased to find that the corresponding product 3a was generated in 79% yield when 1,10-phenanthroline was added to the reaction as a ligand (Table 1, entry 7). To further optimize the reaction, various ligands were investigated, and DMAP (DMAP = 4-dimethylaminopyridine) gave the best yield (95%) compared with other ligands (Table 1, entries 7-12). Further optimizations for the loading of the catalyst and ligand (Table 1, entries 13-16) showed that 7 mol% Cu2O and 14 mol% DMAP afforded the product in 93% yield (Table 1, entry 14), and no desired product was generated without adding catalyst (Table 1, entry 16). In addition, the yield did not drop when the temperature was dropped to room temperature (Table 1, entry 18). The effects of various solvents were also tested, such as DMF, DMSO

17 18 19 20 21

----

--

MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN

temp. (oC) 60 60 60 60 60 60 60 60 60 60 60 60 60

yield (%)b 21 18 24 44 24 47 79 76 63 57 39 95 94

MeCN

60

93

MeCN

60

83

MeCN

60

0

MeCN

40

93

MeCN

r.t

93

DMF

r.t

84

DMSO

r.t

80

THF

r.t

87

a Reaction conditions: 1a (0.5 mmol), 2a (0.6 mmol), Cat. (30 mol%), base (2.0 equiv), ligand (60 mol%) solvent (2 mL), stirred for 5 h. b Isolated yield based on 1a. c Py = pyridine. d Bpy = 2,2'-bipyridine. e DMEDA = N,N'dimethyl-1,2-ethanediamine. f DMAP = 4-dimethylaminopyridine.

By using the optimized reaction conditions, we investigated the scope of this CDC reaction by testing different aryl thioureas 1 and P(O)-H compounds 2 which were described in Table 2. Initially, we evaluated the scope of aryl thioureas. Both electron-deficient substituents (F, Cl, Br, CN, CF3) and electron-donating groups (OMe) on the phenyl ring provided the target thiophosphonates 3b3g, 3m-3o in moderate to excellent yields. The results show that the electronic effect has almost no effect on this reaction. A subsequent study of the steric effect on this transformation was performed, thus ortho- and metasubstituted aryl thioureas were employed in this CDC reaction, providing the corresponding thiophosphonates 3h-3k, 3p with 68-82% yield, and it showed slight steric effect. Similarly, due to the possible steric hinderance,


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


P(O)-H compounds 2 such as diisopropyl phosphonate and dibutyl phosphonate gave the target thiophosphonates 3l and 3q in slightly lower yields (75% and 69%, respectively). In addition, the dimethyl phosphonate was also suitable for the S-P bond formation under the optimal reaction conditions, the desired product (3r) was furnished in 78% yield. Table 2. Scope Study of the Reactiona H N R

1

O 2 + R O P H OR2

N S

1

Cu2O (7 mol%), DMAP (14 mol%) CH3CN, air, r.t., 5 h

N

N

OEt S P O EtO 3a 93% N Br

F

N NC

3d 96% N

Cl

N

OEt P O EtO 3g 77% NO2 N N

OEt P O EtO 3h 68% Br

N

O S P O O

F

Cl

O S P O O

H3CO

3p 62%

CH3CN, N2, r.t., 5 h

additive

isolated yield

none

93%

TEMPO

83%

N S EtO

OEt P O

Ar2 N

N

N

yield = 21%

N S

CuⅠ Ln O2

B Ar2 H N

N S Ar2

N

O S P O O

N O S P O O

Br

CuⅠ Ln

C

A

N

N S

OBu S P OBu O

N

Ar2

E

3o 75% N

3q 69%

N

CuⅢ Ln

D N

N OR1 S P OR1 O

N S

MeO 3r 78%

OMe P O

a

Reaction conditions: 1 (0.5 mmol), 2 (0.6 mmol), Cu2O (7 mol%), and DMAP (14 mol%) in MeCN at room temperature, open air. Isolated yield based on 1.

A number of control experiments were performed to explore the reaction mechanism (Scheme 2). It was found that the oxidation reaction was not inhibited by radical scavengers such as TEMPO (TEMPO = 2,2,6,6tetramethylpiperidinooxy), indicating that the mechanism was not a radical one. Additionally, a control experiment was performed in the N2 circumstance, and the model reaction gave a lower yield (21%), showing that the oxygen in the air was essential, which might serve as oxidant in the reaction. Scheme 2. Control Experiments

N

OEt P O

3l 75%

N

N

EtO

Cu2O (7 mol%), DMAP (14 mol%)

SH

O S P O O

N

3n 85%

3m 82% OCH3 N

N

N

N

Ar2

N

OEt P O EtO 3i 82%

3k 82% N

S

CH3CN, air, r.t., 5 h

S

OEt S P O EtO

3j 74%

OEt S P O EtO 3f 96% N

S

OEt S P O EtO

N

N

N

O + EtO P H OEt

N

N S

Scheme 3. Proposed Reaction Mechanism

EtO 3c 93%

F3C

H N

N

N

N S

Cl

N

OEt S P O EtO 3e 87%

N S

H3CO

OEt S P O EtO 3b 93%

N OEt S P O EtO

N

N

S

Cu2O (7 mol%), DMAP (14 mol%) additive (1.0 equiv)

OEt P O

OR2 P O R 2O

3

N

N S

2

O + EtO P H OEt

N

On the basis of the experimental results and previous reports,21 a plausible reaction pathway is proposed in Scheme 3. Aryl thiourea could be transformed to aryl isothiourea, which could be coordinated with Cu(I) catalyst A to give complex B. The formed B species is then oxidized by O2 in the air to give active intermediate C, which subsequently reacts with Hphosphonates, giving the transmetallated species D. Reductive elimination of complex D affords the product E and regenerates Cu (I) catalyst.

N R1

H N

Ar2

N

N S

OR1 H P OR1 O

CuⅢ Ln O P OR1 OR1

In summary, we reported a Cu2O catalyzed S-P bond coupling reaction by utilizing simple aryl thioureas and dialkyl phosphonates as substrates. Without addition of base or acid, air as an oxidant, the sulfur-phosphorus bond construction could be easily achieved. Experimental simplicity, good functional compatibility, good to excellent yields and environmental friendliness of this protocol, illustrate its potential synthetic value for the synthesis of a diversity of thiophosphonates.

EXPERIMENTAL SECTION All starting materials were purchased from commercial suppliers and used without further purification unless otherwise stated. Yields refer to isolated compounds estimated to be 95% pure as determined by 1H NMR and capillary GC analysis. NMR spectra were recorded on a Bruker AM 400 instrument in CDCl3 using TMS as an internal standard. 31P NMR spectra were proton decoupled and recorded in CDCl3 on a 162 MHz NMR spectrometer. 31P chemical shifts are reported relative to 85% H3PO4 (0.00 ppm) as an external standard. Chemical shifts are



given in ppm and coupling constants (J) are given in Hz. Melting points were determined on the RY-1G melting point instrument and were not corrected. High-resolution mass spectra (HRMS) were recorded on a Finnigan MAT 95Q or Finnigan 90 mass instrument (ESI). TLC was performed using aluminum plates coated with SiO2 (Merck 60, F-254) and visualized with UV light at 254 nm. Column chromatography was performed on silica gel with PE (petroleum ether)-EtOAc as eluent. Typical Procedure (TP) for the synthesis of thiophosphonate derivatives (3a-q): A mixture of aryl thioureas (0.5 mmol), MeCN (2 mL), and phosphonates (0.6 mmol) was stirred in a 10 mL tube, and then Cu2O (7 mol%) and DMAP (14 mol%) were added. The reaction mixture was stirred at room temperature in air until the starting materials were finished (checked by TLC). Then the mixture was quenched with sat. NH4Cl solution (5 mL). The aqueous phase was extracted with EtOAc (3 × 10 mL). The combined organic phases were dried over Na2SO4, and the solvent was removed under vacuum. The obtained crude product was purified by flash column chromatography. Diethyl phosphoric-N,N-dimethyl-N'-phenylcarbamide (3a): According to TP, the residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate = 1:1) to give the target compound 3a as a white solid (147 mg, yield = 93%). m.p.: (76-80 oC). 1H NMR (400 MHz, CDCl , TMS): δ (ppm) 7.27-7.22 (m, 4H), 3 7.06 (t, 1H, J = 8.0 Hz), 4.18 (t, 4H, J = 8.0 Hz), 3.34 (s, 6H), 1.22 (t, 6H, J = 8.0 Hz). 13C NMR (100 MHz, CDCl3, TMS): δ (ppm) 185.5 (d, J = 7.0 Hz), 140.7 (d, J = 3.0 Hz), 129.0, 124.9, 122.6 (d, J = 4.0 Hz), 64.1 (d, J = 6.0 Hz), 43.3, 16.0 (d, J = 7.0 Hz). 31P NMR (162 MHz, CDCl3), δ (ppm) 68.1. HRMS (ESI) m/z [M+H]+ Calcd for C13H22N2O3PS (317.1083), found: 317.1087. Diethyl phosphoric-N'-(4-fluorophenyl)-N,Ndimethylcarbamide (3b): According to TP, the residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate = 1:1) to give the target compound 3b as a colorless oil (155 mg, yield = 93%). 1H NMR (400 MHz, CDCl3, TMS): δ (ppm) 7.33-7.30 (m, 2H), 6.94 (t, 2H, J = 8.0 Hz), 4.16 (t, 4H, J = 8.0 Hz), 3.35 (s, 6H), 1.22 (t, 6H, J = 8.0 Hz). 13C NMR (100 MHz, CDCl3, TMS): δ (ppm) 184.6 (d, J = 7.0 Hz), 159.3 (d, J = 244.0 Hz), 135.6, 125.1 (dd, J = 8.0 Hz, 3.0Hz), 114.7 (d, J = 23.0 Hz), 63.2 (d, J = 5.0 Hz), 42.3, 15.0 (d, J = 7.0 Hz). 19F NMR (377 MHz, CDCl3, ppm) δ (ppm) -116.6. HRMS (ESI) m/z [M+H]+ Calcd for C13H21FN2O3PS (335.0989), found: 335.0994. Diethyl phosphoric-N'-(4-chlorophenyl)-N,Ndimethylcarbamide (3c): According to TP, the residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate = 1:2) to give the target compound 3c as a colorless oil (163 mg, yield = 93%). 1H NMR (400 MHz, CDCl3, TMS): δ (ppm) 7.20 (s, 4H), 4.20-4.15 (m, 4H), 3.33 (s, 6H), 1.22 (t, 6H, J = 8.0 Hz). 13C NMR (100 MHz, CDCl , TMS): δ (ppm) 184.9 (d, J = 7.0 Hz), 3 139.3 (d, J = 3.0 Hz), 130.2, 129.0, 124.0 (d, J = 3.0 Hz), 64.2 (d, J = 6.0 Hz), 43.3, 16.0 (d, J = 6.0 Hz). HRMS (ESI) m/z [M+H]+ Calcd for C13H21ClN2O3PS (351.0694), found: 351.0689. Diethyl phosphoric-N'-(4-bromophenyl)-N,Ndimethylcarbamide (3d): According to TP, the residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate = 1:1) to give the target compound 3d as a colorless oil (189 mg, yield = 96%). 1H NMR (400 MHz, CDCl3, TMS): δ (ppm) 7.35 (d, 2H, J = 8.0 Hz), 7.15 (d, 2H, J = 8.0 Hz), 4.18 (t, 4H, J = 8.0 Hz), 3.34 (s, 6H), 1.23 (t, 6H, J = 8.0 Hz). 13C NMR (100 MHz, CDCl3, TMS): δ (ppm) 183.9 (d, J = 6.0 Hz), 138.8 (d, J = 3.0 Hz), 131.0, 123.1 (d, J = 4.0 Hz), 117.0, 63.3 (d, J = 6.0 Hz), 42.3, 15.0 (d, J = 7.0 Hz). HRMS (ESI) m/z [M+H]+ Calcd for C13H21BrN2O3PS (395.0189), found: 395.0184. Diethyl phosphoric-N'-(4-cyanophenyl)-N,Ndimethylcarbamide (3e): According to TP, the residue was purified

Page 4 of 7

by flash chromatography on silica gel (petroleum ether/ethyl acetate = 1:1) to give the target compound 3e as a colorless oil (148 mg, yield = 87%). 1H NMR (400 MHz, CDCl3, TMS): δ (ppm) 7.53 (d, 2H, J = 12.0 Hz), 7.23 (d, 2H, J = 8.0 Hz), 4.27-4.20 (m, 4H), 3.38 (s, 6H), 1.27 (t, 6H, J = 8.0 Hz). 13C NMR (100 MHz, CDCl3, TMS): δ (ppm) 182.4 (d, J = 5.0 Hz), 143.4 (d, J = 4.0 Hz), 132.2, 118.8 (d, J = 4.0 Hz), 117.7 (d, J = 4.0 Hz), 105.5, 63.7 (d, J = 5.0 Hz), 42.3, 15.0 (d, J = 7.0 Hz). HRMS (ESI) m/z [M+H]+ Calcd for C14H21N3O3PS (342.1036), found: 342.1041. Diethyl phosphoric-N'-(4-(trifluoromethyl)phenyl)-N,Ndimethylcarbamide (3f): According to TP, the residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate = 1:2) to give the target compound 3f as a colorless oil (184 mg, yield = 96%). 1H NMR (400 MHz, CDCl3, TMS): δ (ppm) 7.49 (d, 2H, J = 8.0 Hz), 7.29 (d, 2H, J = 4.0 Hz), 4.25-4.20 (m, 4H), 3.38 (d, 6H, J = 4.0 Hz), 1.28-1.24 (m, 6H). 13C NMR (100 MHz, CDCl3, TMS): δ (ppm) 184.3 (d, J = 6.0 Hz), 143.7, 126.3 (q, J = 4.0 Hz), 125.7 (dd, J = 32.0 Hz, J = 3.0 Hz), 124.0 (q, J = 270.0 Hz), 120.4 (d, J = 3.0 Hz) 64.5 (d, J = 5.0 Hz), 43.3, 16.0 (d, J = 7.0 Hz). HRMS (ESI) m/z [M+H]+ Calcd for C14H21F3N2O3PS (385.0957), found: 385.0952. Diethyl phosphoric-N'-(4-methoxyphenyl)-N,Ndimethylcarbamide (3g): According to TP, the residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate = 1:2) to give the target compound 3g as a colorless oil (133 mg, yield = 77%). 1H NMR (400 MHz, CDCl3, TMS): δ (ppm) 7.30 (d, 2H, J = 8.0 Hz), 6.79 (d, 2H, J = 8.0 Hz), 4.18-4.12 (m, 4H), 3.72 (s, 3H), 3.35 (s, 6H), 1.22 (t, 6H, J = 8.0 Hz). 13C NMR (100 MHz, CDCl3, TMS): δ (ppm) 185.4, 156.7, 132.5 (d, J = 3.0 Hz), 125.9 (d, J = 3.0 Hz), 113.2, 63.1 (d, J = 6.0 Hz), 54.4, 42.4, 15.1 (d, J = 7.0 Hz). HRMS (ESI) m/z [M+H]+ Calcd for C14H24N2O4PS (347.1189), found: 347.1196. Diethyl phosphoric-N'-(2-chlorophenyl)-N,Ndimethylcarbamide (3h): According to TP, the residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate = 1:1) to give the target compound 3h as a colorless oil (119 mg, yield = 68%). 1H NMR (400 MHz, CDCl3, TMS): δ (ppm) 7.83 (d, 1H, J = 8.0 Hz), 7.31-7.15 (m, 3H), 4.15-4.08 (m, 4H), 3.50 (s, 6H), 1.20 (t, 6H, J = 8.0 Hz). 13C NMR (100 MHz, CDCl3, TMS): δ (ppm) 185.1, 138.7, 133.4, 132.2, 130.1, 128.7, 126.7, 64.4 44.8, 16.0 (d, J = 7.0 Hz). HRMS (ESI) m/z [M+H]+ Calcd for C13H21ClN2O3PS (351.0694), found: 351.0697. Diethyl phosphoric-N'-(o-tolyl)-N,N-dimethylcarbamide (3i): According to TP, the residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate = 1:1) to give the target compound 3i as a yellow oil (135 mg, yield = 82%). 1H NMR (400 MHz, CDCl3, TMS): δ (ppm) 7.66 (d, 1H, J = 8.0 Hz), 7.24-7.16 (m, 3H), 4.18-4.10 (m, 4H), 3.46 (s, 6H), 2.30 (s, 3H), 1.26 (t, 6H, J = 8.0 Hz). 13C NMR (100 MHz, CDCl3, TMS): δ (ppm) 186.6, 139.9, 136.6 (d, J = 4.0 Hz), 132.5, 131.2, 128.0, 126.0, 64.5 (d, J = 6.0 Hz), 44.5, 19.5, 16.1 (d, J = 7.0 Hz). HRMS (ESI) m/z [M+H]+ Calcd for C14H24N2O3PS (331.1240), found: 331.1247. Diethyl phosphoric-N'-(2-nitrophenyl)-N,N-dimethylcarbamide (3j): According to TP, the residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate = 1:1) to give the target compound 3j as a colorless oil (133 mg, yield = 74%). 1H NMR (400 MHz, CDCl3, TMS): δ (ppm) 7.92 (d, 1H, J = 8.0 Hz), 7.61-7.52 (m, 2H), 7.38 (t, 1H, J = 8.0 Hz), 4.13-4.06 (m, 4H) 3.37 (s, 6H), 1.20 (t, 6H, J = 8.0 Hz). 13C NMR (100 MHz, CDCl3, TMS): δ (ppm) 183.3, 147.6, 134.1, 132.5, 130.5, 127.6, 122.7, 63.6 (d, J = 6.0 Hz), 43.6, 14.9 (d, J = 7.0 Hz). HRMS (ESI) m/z [M+H]+ Calcd for C13H21N3O5PS (362.0934), found: 362.0937. Diethyl phosphoric-N'-(3-bromophenyl)-N,Ndimethylcarbamide (3k): According to TP, the residue was purified by flash chromatography on silica gel (petroleum ether/ethyl


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


acetate = 1:1) to give the target compound 3k as a colorless oil (162 mg, yield = 82%). 1H NMR (400 MHz, CDCl3, TMS): δ (ppm) 7.40 (s, 1H), 7.20 (t, 2H, J = 8.0 Hz), 7.11 (t, 1H, J = 8.0 Hz), 4.20 (t, 4H, J = 8.0 Hz), 3.36 (s, 6H), 1.25 (t, 6H, J = 8.0 Hz). 13C NMR (100 MHz, CDCl3, TMS): δ (ppm) 183.6 (d, J = 6.0 Hz), 140.9 (d, J = 3.0 Hz), 129.2, 126.6, 124.0 (d, J = 4.0 Hz), 121.5, 119.7 (d, J = 4.0 Hz), 63.3 (d, J = 5.0 Hz), 42.3, 15.0 (d, J = 7.0 Hz). HRMS (ESI) m/z [M+H]+ Calcd for C13H21BrN2O3PS (395.0189), found: 395.0183. Di-isopropyl phosphoric-N,N-dimethyl-N'-phenylcarbamide (3l): According to TP, the residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate = 1:1) to give the target compound 3l as a colorless oil (129 mg, yield = 75%). 1H NMR (400 MHz, CDCl3, TMS): δ (ppm) 7.24-7.21 (m, 4H), 7.06-7.02 (m, 1H), 4.85-4.77 (m, 2H), 3.37 (s, 6H), 1.27-1.20 (m, 12H). 13C NMR (100 MHz, CDCl3, TMS): δ (ppm) 184.9 (d, J = 6.0 Hz), 140.2 (d, J = 3.0 Hz), 128.1, 123.5, 121.2 (d, J = 4.0 Hz), 72.2 (d, J = 6.0 Hz), 42.5, 22.8 (d, J = 3.0 Hz). HRMS (ESI) m/z [M+H]+ Calcd for C15H26N2O3PS (345.1396), found: 345.1390. Di-isopropyl phosphoric-N'-(4-fluorophenyl)-N,Ndimethylcarbamide (3m): According to TP, the residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate = 1:1) to give the target compound 3m as a colorless oil (148 mg, yield = 82%). 1H NMR (400 MHz, CDCl3, TMS): δ (ppm) 7.34 (d, 2H, J = 12.0 Hz), 7.12 (d, 2H, J = 8.0 Hz), 4.84-4.76 (m, 2H), 3.36 (s, 6H), 1.27-1.21 (m, 12H). 13C NMR (100 MHz, CDCl3, TMS): δ (ppm) 185.1 (d, J = 6.0 Hz), 159.2 (d, J = 244.0 Hz), 136.3, 124.6 (dd, J = 5.0 Hz, J = 4.0 Hz), 114.8 (d, J = 22.0 Hz), 72.3 (d, J = 6.0 Hz), 42.5, 22.8 (t, J = 5.0 Hz). 19F NMR (377 MHz, CDCl3, ppm) δ (ppm) -117.5. HRMS (ESI) m/z [M+H]+ Calcd for C15H25FN2O3PS (363.1302), found: 363.1307. Di-isopropyl phosphoric-N'-(4-chlorophenyl)-N,Ndimethylcarbamide (3n): According to TP, the residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate = 1:1) to give the target compound 3n as a colorless oil (161 mg, yield = 85%). 1H NMR (400 MHz, CDCl3, TMS): δ (ppm) 7.19 (s, 4H), 4.84-4.76 (m, 2H), 3.36 (s, 6H), 1.27-1.21 (m, 12H). 13C NMR (100 MHz, CDCl3, TMS): δ (ppm) 184.2 (d, J = 6.0 Hz), 138.6 (d, J = 3.0 Hz), 128.7, 127.9, 122.3 (d, J = 4.0 Hz), 72.2 (d, J = 6.0 Hz), 42.3, 22.6 (d, J = 5.0 Hz). HRMS (ESI) m/z [M+H]+ Calcd for C15H25ClN2O3PS (379.1007), found: 379.1011. Di-isopropyl phosphoric-N'-(4-bromophenyl)-N,Ndimethylcarbamide (3o): According to TP, the residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate = 1:1) to give the target compound 3o as a colorless oil (158 mg, yield = 75%). 1H NMR (400 MHz, CDCl3, TMS): δ (ppm) 7.34 (d, 2H, J = 12.0 Hz), 7.12 (d, 2H, J = 8.0 Hz), 4.84-4.76 (m, 2H), 3.36 (s, 6H), 1.27-1.21 (m, 12H). 13C NMR (100 MHz, CDCl3, TMS): δ (ppm) 185.2 (d, J = 6.0 Hz), 140.2 (d, J = 4.0 Hz), 132.0, 123.5 (d, J = 4.0 Hz), 117.4, 73.3 (d, J = 6.0 Hz), 43.4, 23.7 (t, J = 5.0 Hz). HRMS (ESI) m/z [M+H]+ Calcd for C15H25BrN2O3PS (423.0502), found: 423.0506. Di-isopropyl phosphoric-N'-(2-methoxyphenyl)-N,Ndimethylcarbamide (3p): According to TP, the residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate = 1:1) to give the target compound 3p as a colorless oil (116 mg, yield = 62%). 1H NMR (400 MHz, CDCl3, TMS): δ (ppm) 7.72 (d, 1H, J = 8.0 Hz), 7.16 (t, 1H, J = 8.0 Hz), 6.90 (t, 1H, J = 8.0 Hz), 6.78 (d, 1H, J = 8.0 Hz), 4.69-4.61 (m, 2H), 3.71 (s, 3H), 3.49 (s, 6H), 1.22-1.16 (m, 12H). 13C NMR (100 MHz, CDCl3, TMS): δ (ppm) 185.7 (d, J = 5.0 Hz), 153.8 (d, J = 5.0 Hz), 129.8, 129.5, 127.0, 119.3, 110.4 72.0 (d, J = 6.0 Hz), 54.5, 43.1, 22.6 (q, J = 5.0 Hz). HRMS (ESI) m/z [M+H]+ Calcd for C16H28N2O4PS (375.1502), found: 375.1502.

Di-butyl phosphoric-N'-(4-methoxyphenyl)-N,Ndimethylcarbamide (3q): According to TP, the residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate = 1:1) to give the target compound 3q as a colorless oil (139 mg, yield = 69%). 1H NMR (400 MHz, CDCl3, TMS): δ (ppm) 7.30 (d, 2H, J = 8.0 Hz), 6.79 (d, 2H, J = 8.0 Hz), 4.13-4.04 (m, 4H), 3.72 (s, 3H), 3.36 (s, 6H), 1.59-1.52 (m, 4H), 1.32-1.23 (m, 4H), 0.82 (t, 6H, J = 8.0 Hz). 13C NMR (100 MHz, CDCl3, TMS): δ (ppm) 186.4 (d, J = 8.0 Hz), 157.7, 133.6 (d, J = 2.0 Hz), 126.8 (d, J = 3.0 Hz), 114.2, 67.7 (d, J = 6.0 Hz), 55.4 (d, J = 4.0 Hz), 43.4, 32.2 (d, J = 7.0 Hz), 18.7, 13.6. 31P NMR (162 MHz, CDCl3), δ (ppm) 68.7. HRMS (ESI) m/z [M+H]+ Calcd for C18H32N2O4PS (403.1815), found: 403.1819. Dimethyl phosphoric-N,N-dimethyl-N'-phenylcarbamide (3r): According to TP, the residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate = 1:1) to give the target compound 3q as a colorless oil (112 mg, yield = 78%). 1H NMR (400 MHz, CDCl3, TMS): δ (ppm) 7.27-7.25 (m, 4H), 7.10 (s, 1H), 3.82-3.77 (m, 6H), 3.34 (s, 6H) 13C NMR (100 MHz, CDCl3, TMS): δ (ppm) 184.5 (d, J = 7.0 Hz), 139.6, 128.4, 124.5, 122.1, 53.8 (d, J = 5.0 Hz), 42.6. HRMS (ESI) m/z [M+H]+ Calcd for C11H18N2O3PS (289.0770), found: 289.0775.

ASSOCIATED CONTENT The Supporting Information is available free of charge on the ACS Publications website. 1H, 13C, 31P, and 19F NMR spectra for new compound (PDF)

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

Notes The authors declare no competing financial interest.

ACKNOWLEDGMENT We are grateful for the National Natural Science Foundation of China (21302150). Z.-B. D. acknowledges the Humboldt Foundation and China Scholarship Council for a fellowship.

REFERENCES (1) (a)Ding, M.; Zhou, F.; Liu, Y. L.; Wang, C. H.; Zhao, X. L.; Zhou, J. Cinchona Alkaloid-Based Phosphoramide Catalyzed Highly Enantioselective Michael Addition of Unprotected 3Substituted Oxindoles to Nitroolefins. Chem. Sci. 2011, 2, 20352039. (b) Khoo, K. K.; Norton, R. S. in Amino Acids, Peptides and Proteins in Organic Chemistry, ed. A. B. Hughes, WileyVCH Weinheim, Germany, 2011, 395. (c) Yamaguchi, K.; Sakagami, K.; Miyamoto, Y.; Jin, X.; Mizuno, N. Oxidative Nucleophilic Strategy for Synthesis of Thiocyanates and Trifluoromethyl Sulfides from Thiols. Org. Biomol. Chem. 2014, 12, 9200-9206. (d) Murdock, L. L.; Hopkins, T. L. Insecticidal, Anticholinesterase, and Hydrolytic Properties of O, O-Dialkyl SAryl Phosphorothiolates in Relation to Structure. J. Agric. Food Chem. 1968, 16, 954-958. (e) Hadaway, A. B.; Barlow, F.; Turner, C. R.; Flower, L. S. The Search for New Insecticides for Tsetse Fly Control. Pestic. Sci. 1977, 8, 172-176. (f) Konecny V.; Kovac, S. The Structure and Properties of O-Ethyl OIsopropyl O-(5-Methoxy-1-Methyl-6-Oxo-1H-Pyridazin-4-yl) Phosphorothioate and By-Products in the Technical Product. Pestic. Sci. 1978, 9, 571-581. (g) Leader H.; Casida, J. E. Resolution and Biological Activity of the Chiral Isomers of O(4-Bromo-2-Chlorophenyl) O-Ethyl S-Propyl Phosphorothioate (Profenofos Insecticide). J. Agric. Food Chem. 1982, 30, 546551. (2) (a) Quin, L. D. A Guide to Organophosphorus Chemistry, Wiley Interscience, New York, 2000. (b) Li, N. S.; Frederiksen, J. K.;



(3)

(4)

(5)

(6) (7)

(8)

(9)

Piccirilli, J. A. Synthesis, Properties, and Applications of Oligonucleotides Containing an RNA Dinucleotide Phosphorothiolate Linkage. Acc. Chem. Res. 2011, 44, 12571269. (c) Kumar, T. S.; Yang, T.; Mishra, S.; Cronin, C.; Chakraborty, S.; Shen, J.-B.; Liang, B. T.; Jacobson, K. A. 5’Phosphate and 5’-Phosphonate Ester Derivatives of (N)Methanocarba Adenosine with in Vivo Cardioprotective Activity. J. Med. Chem. 2013, 56, 902-914. (d) Xie, R.; Zhao, Q.; Zhang, T.; Fang, J.; Mei, X.; Ning, J.; Tang, Y. Design, Synthesis and Biological Evaluation of Organophosphorous-Homodimers as Dual Binding Site Acetylcholinesterase Inhibitors. Bioorg. Med. Chem. 2013, 21, 278-282. (e) Kaboudin, B.; Emadi, S.; Hadizadeh, A. Synthesis of Novel Phosphorothioates and Phosphorodithioates and Their Differential Inhibition of Cholinesterases. Bioorg. Chem. 2009, 37, 101-105. (f) Fraietta, J. A.; Mueller, Y. M.; Do, D. H.; Holmes, V. M.; Howett, M. K.; Lewis, M. G.; Boesteanu, A. C.; Alkan, S. S.; Katsikis, P. D. Phosphorothioate 2’ Deoxyribose Oligomers as Microbicides that Inhibit Human Immunodeficiency Virus Type 1 (HIV-1) Infection and Block Toll-Like Receptor 7 (TLR7) and TLR9 Triggering by HIV-1. Antimicrob. Agents Chemotherapy. 2010, 54, 4064-4073. (g) Cogoi, S.; Rapozzi, V.; Quadrifoglio F.; Xodo, L. Anti-Gene Effect in Live Cells of AG Motif TriplexForming Oligonucleotides Containing an Increasing Number of Phosphorothioate Linkages. Biochem. 2001, 40, 1135-1143. (h) Piekutowska, M.; Pakulski, Z. Synthesis of S-Glycosyl Thiophosphates, Thiophosphonates and Thiophosphinates by the Michaelis-Arbuzov Rearrangement of Anomeric Thiocyanates. Carbohydr. Res. 2008, 343, 785-792. (i) Kiehs, K.; Wuerzer, B.; Meyer, N. US, US4689068[P]. 1987. (a) Gao, Y. X.; Tang, G.; Cao, Y.; Zhao, Y. F. A Novel and General Method for the Formation of S-Aryl, Se-Aryl, and Te-Aryl Phosphorochalcogenoates. Synthesis 2009, 1081-1086. (b) Ouyang, Y. J.; Li, Y. Y.; Li, N. B.; Xu, X. H. A Simple and Convenient Method for the Synthesis of S-Aryl Phosphorothioates Catalyzed by Cesium Hydroxide. Chin. Chem. Lett. 2013, 24, 1103-1105. (c) Mitra, S.; Mukherjee, S.; Sen, S. K.; Hajra, A. Environmentally Benign Synthesis and Antimicrobial Study of Novel Chalcogenophosphates. Bioorg. Med. Chem. Lett. 2014, 24, 21982201. Kumaraswamy, G.; Raju, R. Copper(I)-Induced Sulfenylation of H-Phosphonates, H-Phosphonites and Phosphine Oxides with Aryl/Alkylsulfonylhydrazides as a Thiol Surrogate. Adv. Synth. Catal. 2014, 356, 2591-2598. Bai, J.; Cui, X.; Wang, H.; Wu, Y. Copper-Catalyzed Reductive Coupling of Aryl Sulfonyl Chlorides with H-Phosphonates Leading to S-Aryl Phosphorothioates. Chem. Commun. 2014, 50, 8860-8863. Morrison, D. C. The Reaction of Sulfenyl Chlorides with Trialkyl Phosphites. J. Am. Chem. Soc. 1955, 77, 181-182. Lin, Y. M.; Lu, G. P.; Wang, G. X.; Yi, W. B. Acid/PhosphideInduced Radical Route to Alkyl and Alkenyl Sulfides and Phosphonothioates from Sodium Arylsulfinates in Water. J. Org. Chem. 2016, 82, 382-389. (a) Masson, S.; Saint-Clair, J. F.; Saquet, M. Two Methods for the Synthesis of (2-Mercaptophenyl) Phosphonic Acid. Synthesis 1993, 485-486. (b) Timperley, C. M.; Saunders, S. A.; Szpalek, J.; Waters, M. J. Fluorinated Phosphorus Compounds: Part 8. the Reactions of Bis (Fluoroalkyl) Phosphorochloridates with Sulfur Nucleophiles. J. Fluor. Chem. 2003, 119, 161-171. (c) Panmand, D. S.; Tiwari, A. D.; Panda, S. S.; Monbaliu, J. C. M.; Beagle, L. K.; Asiri, A. M.; Stevens, C. V.; Steel, P. J.; Hall, C. D.; Katritzky, A. R. New Benzotriazole-Based Reagents for the Phosphonylation of Various N-, O-, and S-Nucleophiles. Tetrahedron Lett. 2014, 55, 5898-5901. (d) Qiu, Y.; Worch, J. C.; Chirdon, D. N.; Kaur, A.; Maurer, A. B.; Amsterdam, S.; Collins, C. R.; Pintauer, T.; Yaron, D.; Bernhard, S.; Noonan, K. J. T. Tuning Thiophene with Phosphorus: Synthesis and Electronic Properties of Benzobisthiaphospholes. Chem. Eur. J. 2014, 20, 7746-7751. Kovacs, S.; Bayarmagnai, B.; Aillerie, A.; Goossen, L. J. Practical Reagents and Methods for Nucleophilic and Electrophilic Phosphorothiolations. Adv. Synth. Cata. 2018. 16, 1913-1918.

Page 6 of 7

(10) (a) Xu, J.; Zhang, L.; Li, X.; Gao, Y.; Tang, G.; Zhao, Y. Phosphorothiolation of Aryl Boronic Acids Using P (O) H Compounds and Elemental Sulfur. Org. Lett. 2016, 18, 1266-1269. (b) Zhang, L. L.; Zhang, P. B; Li, X. Q.; Xu, J.; Tang, G.; Zhao, Y. F. Synthesis of S-Aryl Phosphorothioates by Copper-Catalyzed Phosphorothiolation of Diaryliodonium and Arenediazonium Salts. J. Org. Chem. 2016, 81, 5588-5594. (11) (a) Li, C.-J. Cross-Dehydrogenative Coupling (CDC): Exploring C-C Bond Formations Beyond Functional Group Transformations. Acc. Chem. Res. 2008, 42, 335-344. (b) Girard, S. A.; Knauber, T.; Li, C. J. The Cross‐Dehydrogenative Coupling of C-H Bonds: A Versatile Strategy for C-C Bond Formations. Angew. Chem. Int. Ed. 2014, 53, 74-100. (c) Zhang, C.; Tang, C.; Jiao, N. Recent Advances in Copper-Catalyzed Dehydrogenative Functionalization via a Single Electron Transfer (SET) Process. Chem. Soc. Rev. 2012, 41, 3464-3484. (d) Waterman, R. Mechanisms of Metal-Catalyzed Dehydrocoupling Reactions. Chem. Soc. Rev. 2013, 42, 5629-5641. (e) Itazaki M.; Nakazawa, H. Iron-Catalyzed Cross-Dehydrogenative-Coupling Reactions. Top. Organomet. Chem. 2015, 50, 47-81. (f) Yeung C. S.; Dong, V. M. Catalytic Dehydrogenative Cross-Coupling: Forming Carbon-Carbon Bonds by Oxidizing two Carbon-Hydrogen Bonds. Chem. Rev. 2011, 111, 1215-1292. (12) Kaboudin, B.; Abedi, Y.; Kato, J. Y.; Yokomatsu, T. Copper (I) Iodide Catalyzed Synthesis of Thiophosphates by Coupling of H-Phosphonates with Benzenethiols. Synthesis 2013, 45, 23232327. (13) Huang, H.; Ash, J.; Kang, J. Y. Base-Controlled Fe (Pc)-Catalyzed Aerobic Oxidation of Thiols for the Synthesis of S-S And S-P (O) Bonds. Org. Biomol. Chem. 2018, 16, 4236-4242. (14) Zhu, Y.; Chen, T.; Li, S.; Shimada, S.; Han, L. B. Efficient PdCatalyzed Dehydrogenative Coupling of P (O) H with RSH: A Precise Construction of P (O)-S Bonds. J. Am. Chem. Soc. 2016, 138, 5825-5828. (15) Liu, Y. C.; Lee, C. F. N-Chlorosuccinimide-Promoted Synthesis of Thiophosphates From Thiols and Phosphonates under Mild Conditions. Green Chem. 2014, 16, 357-364. (16) Bi, X.; Li, J.; Meng, F.; Wang, H.; Xiao, J. DCDMH-Promoted Synthesis of Thiophosphates by Coupling of H-Phosphonates with Thiols. Tetrahedron 2016, 72, 706-711. (17) Wang, J.; Huang, X.; Ni, Z.; Wang, S.; Pan, Y.; Wu, J. Peroxide Promoted Metal-Free Thiolation of Phosphites by Thiophenols/Disulfides. Tetrahedron 2015, 71, 7853-7859. (18) Song, S.; Zhang, Y.; Yeerlan, A.; Zhu, B.; Liu, J.; Jiao, N. Cs2CO3‐Catalyzed Aerobic Oxidative Cross‐Dehydrogenative Coupling of Thiols with Phosphonates and Arenes. Angew. Chem. Int. Ed. 2017, 56, 2487-2491. (19) Zeng, M. T.; Xu, W.; Liu, M.; Liu, X.; Chang, C. Z.; Zhu, H.; Dong, Z. B. Iodobenzene-Promoted Pd-Catalysed ortho-Directed C-H Activation: the Synthesis of Benzothiazoles via Intramolecular Coupling. Synopen 2017, 1, 1-7. (20) (a) Dong, Z. B.; Liu, X.; Bolm, C. Copper-Catalyzed C(sp2)–S Coupling Reactions for the Synthesis of Aryl Dithiocarbamates with Thiuram Disulfide Reagents. Org. Lett. 2017, 19, 59165919. (b) Liu, X.; Liu, M.; Xu, W.; Zeng, M. T.; Zhu, H.; Chang, C. Z.; Dong, Z. B. An Environmentally Benign and Efficient Synthesis of Substituted Benzothiazole-2-thiols, Benzoxazole-2thiols, and Benzimidazoline-2-thiones in Water. Green Chem. 2017, 19, 5591-5598. (c) Xu, W.; Zeng, M. T.; Liu, M.; Liu, S. S.; Li, Y. S.; Dong, Z. B. Palladium-Catalyzed Synthesis of 2Aminobenzothiazoles Through Tandem Reaction. Synthesis 2017, 49, 3084-3090. (d) Xu, W.; Zeng, M. T.; Liu, M.; Liu, X.; Chang, C. Z.; Zhu, H.; Li, Y. S.; Dong, Z. B. PalladiumCatalyzed Tandem Synthesis of 2-Aminobenzothiazoles Starting from Unreactive 2-Chloroanilines. Chem. Lett. 2017, 46, 641643. (e) Liu, X.; Zhu, H.; Zhang, S. B.; Cheng, Y.; Peng, H. Y.; Dong, Z. B. Facile Synthesis of S-Arylisothioureas via the S-Arylation of Arylthioureas with Aryl Iodides in Water. Tetrahedron Lett. 2018, 59, 3165-3170. (f) Liu, X.; Zhang, S. B.; Zhu H. Dong, Z. B. Copper(I)-Catalyzed Tandem One-Pot Synthesis of 2Arylthiobenzothiazoles and 2-Arylthiobenzoxazoles in Water. J. Org. Chem. 2018, 83, 11703-11711.


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


(21) Allen, S. E.; Walvoord, R. R.; Padillasalinas, R.; Kozlowski, M. C. Aerobic Copper-Catalyzed Organic Reactions. Chem. Rev. 2013,

113, 6234-6458.


Copper-Catalyzed and Air-Mediated Mild Cross-Dehydrogenative

Recommend Documents