CHEMISTRY & BIOLOGY INTERFACE · 2016-11-28 · Chemistry & Biology Interface, 2016, 6, 5, 270-281...

Chemistry & Biology Interface Vol. 6 (5), September – October 2016270

ISSN: 2249 –4820REVIEW PAPER

CHEMISTRY & BIOLOGY INTERFACEAn official Journal of ISCB, Journal homepage; www.cbijournal.com

1.1 Introduction

Diaryliodonium salts are well renowned for their powerful electrophilic arylating behaviour. They have been used as aryl coupling partners for diverse range of alkenes, alkynes and heterocycles under metal and metal-free reaction conditions.[1-3] In current scenario diaryliodonium salts are frequently used as arylating agents besides their interesting applications in the construction of valuable heterocycles with five- and six-membered ring systems. The salient features of diaryliodonium salts are easy to synthesize, non-toxic, benign

safety profile, air and moisture stability.[4]

1.1.1 Structure and Geometry

Diaryliodonium salts 1 (Ar2IX) are a class of iodine (III) reagents with two aryl moieties and an anionic part (X). with ten electrons. The geometry of Ar2IX is pseudo trigonal bipyramidal with the weakly bonded anionic part at apical position, two aryl groups at apical and equatorial and two lone pairs occupied at equatorial position. X-ray studies showed diaryliodonium salts are T-shaped geometry (figure 1) with the bond angle of Ar-I-Ar is 90°. The I-X bond

Chemistry & Biology Interface, 2016, 6, 5, 270-281

Diaryliodonium salts: Emerging reagents for arylations and heterocycles synthesis

Dalip Kumar*, V. Arun, Meenakshi Pilania, Manish K Mehra and Santosh B Khandagale

Department of Chemistry, Birla Institute of Technology and Science, Pilani-333031, Rajasthan, IndiaE-mail: [email protected] 3 October 2016; Accepted 22 October 2016

Abstract: Since the last one decade, a substantial research has been developed in the synthetic applications of diaryliodonium salts. They provide mild and general protocols for the construction of C-C and C-het-eroatom bonds which are indispensable in many useful medicinal, agrochemicals and industrial molecules. This review is focused on the recent advances in synthetic utilities of diaryliodonium salts leading to the formation of heterocyclic frameworks, arylation using C-H functionalization strategies and their related mechanistic details.

Keywords: Diaryliodonium salts, heterocycles, metal-catalysts, C-H functionalization.


in 2 is longer than the average covalent bond length. The high reactivity of iodonium salts 1 is illustrated by the leaving group ability of iodobenzene (106 times > triflate) released from the corresponding diaryliodonium salt. Given the superior solubility and non-nucleophilic character, diaryliodonium salts 1 with triflate and tetrafluoroborate anions are most frequently employed in synthetic transformations.[5]

IδI

Ar Ar1

OTf

1a 2

IAr Ar1

OTs IBF4

Ar Ar1

1b 1c

X

X = -OTf, -OTs, -BF4

Ar

Ar1

Figure 1 Structures and geometry of commonly used diaryliodonium salts

1.1.2 Preparation of diaryliodonium salts

In general, preparation of diaryliodonium salts involves two steps, first oxidation of an aryl iodide (I) to iodine (III) species and next ligand exchange with arenes or organometallic reagents. Diaryliodonium salts 1 were first prepared by Meyer and Hartmann in 1894.[4a] Nevertheless, the synthetic procedure was time-consuming and low-yielding. In 20th century this reagent was rediscovered with the myriad of synthetic transformations. In 1950, Beringer reported the synthesis of symmetrical and unsymmetrical diaryliodonium salts using hypervalent iodine (III) compounds namely, iodosylarenes (ArI=O), (diacetoxyiodo)benzene (IBD), iodoxyarenes (ArIO2) and electron-rich arenes in the presence of sulphuric acid.[6] Later, in 1980 Koser and co-workers prepared diaryliodonium tosylates by employing hydroxy(tosyloxy)iodobenzene and arylsilanes.[7] Afterwards, Kitamura et al. disclosed an improved procedure to access diaryliodonium salts by involving the reaction of (diacetoxyiodo)arenes and electron-rich arenes in triflic acid. Notably, triflic acid was found to be an effective alternative to sulfuric acid, acetic acid and p-toluenesulfonic acid in the terms of reactivity and isolation of

diaryliodonium triflate salts. Next, Widdowson and co-workers prepared

IAr Ar1

X

+Ar Ar1AcOH, Ac2O

Beringer's work, 1953

H2SO4

IO

Ar1

TMS

+

Koser's work, 1980

MeCNreflux

Ar1

Kitamura's work, 2006

Ar +TfOH

-30 °C to RTWiddowson's work, 2000

+Ar Ar1

m-CPBATfOH

0 °C - rtOlofsson's work, 2007

I

X = HSO4, OTs, OTf BF4

Ar + Ar1

I B(OH)2

I(OH)OTs

m-CPBA

BF3.Et2OOlofsson's work, 2008

Ar +

I(OAc)2

DCM,1h

TfOHAr1

B(OH)2

Ar

I(OH)OTs

Figure 2 Methods to prepare diaryliodonium salts

diaryliodonium salts by employing IBD and arylboronic acids in triflic acid.[8] Recently, Olofsson’s group developed an operationally simple, one-pot general protocol to achieve diaryliodonium triflates in good to excellent yields.[9] This convenient method uses the reaction of aryl iodides and arenes in the presence of m-chloroperbenzoic acid (m-CPBA) and triflic acid. Use of mild oxidant m-CPBA is advantageous due to its less solubility in organic solvents which facilitates its removal from the reaction mixture. The protocol is applicable to a range of iodoarenes and arenes. In an alternative route, the same research group[10] prepared various symmetrical and unsymmetrical diaryliodonium salts from iodoarenes and arylboronic acids as outlined in Figure 2.

1.1.3 Plausible catalytic cycle

The reactivity of diaryliodonium salts could be enhanced in the presence of copper and palladium catalysts. Research groups of Gaunt and Sanford disclosed the metal-catalyzed (Cu and Pd) arylation of indoles using diaryliodonium salts, and investigated the mechanistic pathways. In 2008, Gaunt et al. proposed an elegant hypothesis that Cu(I) reduce the iodonium salt with the release of



highly electrophilic arylcopper(III) species and iodoarenes.[11] This in situ generated reactive species could rapidly undergo functionalization with the nucleophile under fairly mild reaction conditions (Figure 3a).

Cu(I)X Ar-Cu-OTfIII

X

Nu-H

TfOHAr-Cu-Nu(III)

X

Nu-Ar

Ar2IOTf -ArI

Ar-Cu-OTf(III)

X

Ar

highly electrophilic

Pd(II)(OAc)2Nu-Pd-OAc

(II)

Nu-H

Nu-Pd-OAcAr

Nu-Ar

Ar2IOTf

-ArIOTf

(IV)

-AcOH

Figure 3a Figure 3b

Figure 3 Plausible catalytic pathways involving Cu and PdIn 2006, Sanford and co-workers described a Pd(II)-catalyzed C-H arylation of indoles and proposed a persuasive PdII/IV catalytic pathway for the formation of 2-arylindoles (Figure 3b).[12]

1.2 Heterocycles synthesis

Heterocyclic compounds are extensively distributed in many natural products, life saving drugs and organic materials. Owing to the high significance and applications in drug discovery research construction of heterocycles is a long-standing interest. Assembly of heterocyclic compounds particularly, five- and six-membered ring systems and arylated heterocycles with interesting biological properties and for being important building blocks which are frequently encountered in natural products and various therapeutic agents. Though there are plethora of protocols to construct useful five and six-membered heterocycles but still straightforward and eco-friendly methods to access these heterocycles are highly desirable. In view of significant advantages, diaryliodonium salts have been widely utilized in the direct arylation and preparation of bio-active heterocycles. In this review article, we have summarized the recent applications of diaryliodonium salts in the arylation of heterocycles and construction

of quinolines, phenanthridines, oxindoles, arylcoumarins, acridines, and acridones.

1.2.1 Quinolines

Chen’s group[13] developed a general and elegant pathway for the synthesis of quinolines 6 using multicomponent approach by employing diaryliodonium salts 3, nitriles 4 and alkynes 5. The reaction proceeded via [2+2+2] regioselective cascade annulation strategy to generate quinoline derivatives in good to excellent yields. Iodonium salts 3 bearing non-coordinating anion PF6 gave better yields than the salts with -OTf, Br- and -OTs counter ions. Use of electron deficient nitriles like ethyl cyanoformate and diethyl cyanophosphate failed to deliver the annulated products. Identified reaction conditions covers variety of internal alkynes, asymmetric alkynes, 1,3-hexadiyenes and diaryliodonium salts to prepare various quinolines (Scheme 1.1).

I+-PF6

+R R1CN Cu(OTf)2 (10 mol %)

DCE, 120 °C

35 examples41-95%

R

N+

R2R

R2

R3

R1

N Ph

CH3

CH3

N

C2H5Ph

SN

C2H5Ph

N

Ph

Ph

Et

CH3

H3C

3 4

6

6a, 66% 6b, 82% 6c, 43% 6d, 74%

R35

Scheme 1.1 Synthesis of quinolines and representative examples

1.2.2 Phenanthiridines

Li et al.[14] reported a copper-catalyzed cascade coupling strategy for the synthesis of phenanthiridine derivatives 9 using diaryliodonium salts as an aryl source. The reaction was smoothly proceeded in the presence of Cu(OTf)2 and dichloroethane at 150 °C to produce 9 in good yields. Mechanistically, in situ generated copper(I) species from Cu(OTf)2 underwent oxidative insertion with diaryliodonium salt to furnish a highly



electrophilic Ar-Cu(III) species. Consecutive nucleophilic addition of nitriles and annulation led to the corresponding phenanthiridines in moderate to excellent yields (Scheme 1.2).

Scheme 1.2 Synthesis of phenanthiridine derivatives

1.2.3 Oxindoles

Zhou co-workers described the copper-catalyzed arylation/vinylation of electron-deficient alkenes 10 to furnish highly substituted oxindoles 12 using diaryliodonium salts 11 as coupling partners.[15] After exploring various parameters, cuprous chloride in the presence of sodium bicarbonate found to be the best catalytic conditions. Formation of C-C bond proceeded with electrophilic addition of Cu(III)-aryl intermediate, followed by aromatization and reductive elimination to produce oxindoles 12 in good yields. The obtained oxindoles 12 were utilized to prepare complex bio-active natural product (±)-esermethole (Scheme 1.3).

I+-OTf

+R1

CuCl (15 mol %)

NaHCO3, DCE, 80 °C

26 examples34-96%

12a, 88% 12b, 45% 12d, 60%12c, 74%

RN O

RN O

Ar

N O

Ph

OMeMeO

MeO N O

Ph

N O

Ph

N O

10 11 12N

NH

MeO

(±)-Esermethole

Scheme 1.3 Synthesis of oxindoles

Likewise, Tang et al.[16] explored the synthesis of oxindoles 12 using diaryliodonium salts

14 and 2,6-ditertbutylpyidine (DTBP) as a base. Later, two different research groups [17-18] have independently reported the synthesis of oxindoles 12 under base-free conditions in the presence of a copper catalyst and diaryliodonium salts 14 (Scheme .131).

+RN O

RN O

R2ArR2

Ar2IOTf

ConditionsA:CuCl(15 mol %), DCM, DTBP, 60 °C, 24hB: Cu(OTf)2(10 mol %),DCE, 130 °C, 16hC: CuI(2.5 mol %), N2, DCE, 100 °C, 24-48h

A, B ,C

13 1412

R1 R1

Scheme 1.31 Synthesis of oxindoles

1.2.4 Carbocyclization

Interestingly, Gaunt and co-workers[19] described the efficient transformation of easily available alkenes and alkynes into substituted tetralins and cyclopentenes in good yields. Air-stable, copper(I) thiophene-2-carboxylate (CuTC), copper(I) chloride and sterically-hindered 2,6-ditertbutylpyidine (DTBP) are the suitable catalysts and base for the carbocyclization of 15 and 17. Detailed mechanistic investigations revealed that concerted 1,2-hydride and 1,5-hydride shifts led to the desired products 16 and 18 in good yields (Scheme 1.4).

R1

R

Ar2IOTf

R`R1

3R2

CuTC( 5 mol%)DCM, 70 °C CuCl( 5 mol%), DTBP

DCM, 70 °C R218 examples52-76%

10 examples51-78%

H

H

H 4

H 5N

OBr

16a, 76% 16c, 52%16b, 73% 16d, 70% 16e, 52%

MeO

MeO i−Bu MeO

PhPh

18a, 51% 18c, 65%18b, 70% 18d, 78%

15

16

17

1814

Scheme 1.4 Synthesis of substituted tetralins and cyclopentenes

1.2.5 Benzocoumarins

An unprecedented, Pd-catalyzed two consecutive C-C bonds forming strategy was employed between diaryliodonium salts 14 and coumarins



19 to construct π-expanded 4,5-dibenzo-coumarins 20. Formation of dibenzocoumarins 20 was smoothly proceeded without any external oxidant, ligand or directing groups. Interestingly, coumarins with hydroxyl group produced 20 without any O-arylation. However, sterically-hindered bis(2,4,6,-trimethylphenyl)iodonium triflate failed to afford the desired fused product 20. The proposed diarylation proceeded via Pd(II/IV) catalytic cycles with the synergistic activations of C-I and vicinal C-H bonds in diaryliodonium salts (Scheme 1.5).[20]

O O

Ar2I OTf

Pd(OAc)2, DMF100 °C, 24h O O

Ar

30 examples50-90 %

O OHO O OPh O OOCH3

O O

O O O O O O

F3C

O O

Me

20h, 90%20g, 88%20f, 88%20e, 70%

20a, 50% 20b, 57% 20c, 91% F 20d, 68%

19

14

20

RR

Scheme 1.5 Synthesis of 4,5-dibenzocoumarins and their representative examples

1.2.6 4-Arylcoumarins

Yang et al.[21] extended the synthetic utility of diaryliodonium salts in the construction of 4-arylcoumarins 23 via Pd-catalyzed arylations and cyclizations of o-hydroxylcinnamates 21. In the presence of CuI and Cu(OTf)2, O-phenylated cinnamates were obtained rather than expected arylcoumarins 22. By changing the catalyst from copper to palladium the reaction progressed in anticipated manner to afford 4-arylcoumarins 23 in better yields. This ligand and base-free approach is well-suited for diverse diaryliodonium salts and o-hydroxyl cinnamates and provided an alternative convenient route for 5-lipoxygenase inhibitor

23 (Scheme 1.6).

OEt

O

OHAr1

Ar2I OTf 14

Pd(OAc)2, DMF80 °C, 3h

O O

Ar

Ar1

27examples60-95%

O O

PhCl

ClO O

Ph

FO O

Ph

N O O

Ph

O O

CF3

O O

NO2

O O

CO2Et

O O

O O

F

NNNF3C

HO

22a, 77% 22c, 85%22b, 87% 22d, 70%

22e, 70% 22f, 60% 22g, 71% 22h, 86%

5-lipoxygenase inhibitor

F

2122

23

Scheme 1.6 Synthesis and selected examples of 4-arylcoumarins

1.2.7 Acridines and Acridones

Recently, Pang et al.[22] reported a domino arylation and Friedel-Crafts acylation between o-acylanilines 24 and diaryliodonium salts 14 to achieve valuable acridine derivatives 25. Interestingly, this reaction proceeded effectively either under copper-catalyzed or metal-free conditions at an elevated temperature (130-135 °C). The reaction of o-aminobenzoates 26 with diaryliodonium salts 14 generated acridone framework 27 in high yields (Scheme 1.7).

NH2

OMe

O

N

Me

NH

OI OTf

ArNH2

O

R R1

R Ar R1 Arcondition 1 : CuI, 65 °Ccondition 2: 135 °C

N

CH3Ph

N

CH3

O

O N

Ph

27a, 89% 27b, 84% 27c, 76%N

CH3

27d, 84%

NH

O

NH

O

CO2Me NH

OF

NH

OBr Cl

25a, 78% 25b, 83% 25c, 96% 25d, 95%

Cu(OTf)2 (20%)DCE, 130°C, 12h

7 examples78-96%

28 examples72-94%

Ar

14

26

27

24

25

Scheme 1.7 Some selected examples of prepared acridines and acridones

1.2.8 Quinazolinimines

Recently, a new tandem approach was developed by Chen and co-workers[23] for the synthesis of quinazolinimines 29 and acridines 30 from easily accessible o-cyanoanilines 28


l


and diaryliodonium salts 14. With the more favourable cyano group in cyanoanilines for arylation , the protocol is well-suited for 1-amino-2-cynaocyclopentene and cyclohexene to afford pyrimidine 29d analogues. Detailed optimization reaction conditions and mechanistic experiments disclosed that half an equivalent of 14 afforded quinazolinones 29, whereas, its excess quantity (2.0 equiv) led to acridines 30 in good yields (Scheme 1.8).

CN

NH2

IOTf

IOTf

( 2.0 equiv)

Cu(OTf)2 10%DCE, 65 °C

(0.5 equiv)

Cu(OTf)2 20%DCE, 110 °C

N

N

NH

H2N

Ar Ar Ar ArAr

N

HN

Ar

Ar

RRR

N

N

NH

H2N

Cl

N

N

NH

H2N

OMe

N

N

NH

H2N

N

N

NH

HN

N

HN

N

HNF

CH3

CH3

N

HN

H3C N

HN

CO2Me

CO2Me

14 14

28

29 30

29a, 79% 29b, 77% 29c, 59% 29d, 71%

30a, 88% 30b, 69% 30c, 77% 30d, 69%

30 examples51-95%

11 examples62-92%

Scheme 1.8 Synthesis of quinazolinimines and acridines

1.2.9 Diaryl sulfones

Kumar et al.[24] disclosed a microwave-assisted, metal-free protocol for the synthesis of diaryl sulfones 32 using easily available diaryliodonium salts 14 and arenesulfinates 31. This high yielding protocol proceeded in benign and bio-degradable solvent polyethyleneglycol-400 (PEG-400). Iodonium salts bearing different substitutents (Cl, Br, Me, COOH, OMe) were smoothly coupled to afford the corresponding sulfones in good to excellent yields. In the presence of cuprous iodide, unsymmetrical iodonium salts selectively transferred the electron-rich aryl moiety to produce appropriate sulfones in good yields. Under the optimized conditions, alkyl sulfone 32d was also achieved in high yield (Scheme 1.9).

IRSO2Na +

R= Phenyl, tolyl methyl

Ar Ar

OTf

RSO2ArPEG-400, MW50 °C, 10 min

17 examples81-96%

SO

OCH3

SO

OSO

OS

H3C32c, 82%32b, 91%32a, 96%

MeSO

OCH3

32d, 83%

3114

32

Scheme 1.9 Synthesis of diaryl sulfones and their representative examples

1.2.10 Diaryloxazines

A chiral copper(II)bisoxazoline-catalyzed reaction of readily available allylic amides 33 and diaryliodonium salts 3 led to enantioselective synthesis of 1,3-oxazines 34 and β,β’-diaryl enamides 35. Sterically hindered base 2,6-ditertbutylpyidine (DTBP) was used in order to avoid the decomposition of chiral catalyst by the release of HPF6. The electronic nature of diaryliodonium salts was found to be crucial for the enantioselective synthesis of 34 and 35. (Scheme 1.10).[25]

IPF6

Ar

35a, 53% 35b, 52% 35c, 60% 35d, 58%

34a, 61% 34b, 80% 34c, 64% 34d, 84%

IPF6

ArNH

O

R

N

O

R

NH

O

RAr

Ar

NH

O

NH

ONH

O

NH

O

N

O

N

O

N

O

Br

N

O

OMeOMe OMe OMe

ClCF3

Cl

ClCO2Et

OMe

CuTC (10 mol%)DCM, DTBP

CuTC (10 mol%)DCM , DTBP

Ar = electron rich14 examples26-74%

Ar = electron poor15 examples46-83%

3334 35

33

NSO2Ph

O

O

Scheme 1.10 Synthesis of various 1,3-oxazines and β,β’-diaryl enamides

1.2.11 β-arylation of ketones

Huang and co-workers illustrated the application of diaryliodonium salts 14 in the selective β-arylation of ketones 36 using Pd-catalyst.[26] This method enabled to arylate various cyclic and linear ketones in excellent yields under oxidant free conditions. Under the reaction conditions, potassium trifluoroacetate (KTFA)



and trifluoroacetic acid (TFA) behaved as buffer pair to maintain the required acidity of reaction medium. From the detailed mechanistic investigation and control experiments, involvement of Pd nanoparticles was suggested in the present catalytic system (Scheme 1.11).

37d, 50%37c, 61%37b, 66%37a, 70%

I+

+ R

Pd(OAc)2 (10 mol%)L (10 mol%)

KTFA (2.0 equiv) water, dioxane, TFA(1:20:2), 80 °C, 12h

R

O

R

OOTf

O O

Ph N

O

MeEtO2C

F3C Ph

PhO

36 14 37

28 examples38-70%

L =S

SPh`

Ph

TsHN

NHTs

Scheme 1.11 Synthesis of β-arylated ketones and their representative examples

1.2.12 Arylheterocyles

39h, 52%39g, 42%39f , 92%39e , 80%

39d, 99%

I+ OTfDGH

DG [(Cp∗IrCl2)2] 20 mol%

NMeO

NHMe

O

MeMe

O

Me2N OH

O

Me

Me

OH

O

Me

NiPr2

O

Me

O

39b, 87%

39i , 92%

AgNTf2 15 mol%PivOH, cyclohexane100 °C

62 examples45-99%

N-OMe

Me

39a, 86%

NN

NMe

39c, 52%

Ar

Ar

Me

38 14

39

Scheme 1.12 Synthesis of arylheterocycles

First example of Ir(III)-catalyzed β-arylation of aliphatic sp3 C-H bonds present in oximes and nitrogen-containing heterocycles like pyrazines, pyrazoles, quinolines, isoxazole, pyridine derivatives, substituted enamides and carboxylic acids, has been discovered. This protocol displayed high functional groups tolerance and also proved an effective synthetic tool for late-stage regioselective C-H arylation of complex triterpenoid molecules, for example, Lanosterol and Oleanolic acid. Outcome of the detailed mechanistic studies and density functional theory calculations suggested that sp3 C-H bond present in the substrates 38

were activated by the concerted metallation–deprotonation process and oxidation of Ir(III) to Ir(IV) (Scheme 1.12).[27]

1.2.13 2-Arylazoles

Kumar and co-workers[28] developed a general and high-yielding protocol for the C-H arylation of various azaheterocycles such as oxadiazoles, thiadiazoles, benzoxazoles and benzothiazoles using diaryliodonium salts 14 at room temperature. The C-H arylation required simple catalytic system (CuBr/t-BuOLi) with reduced reaction time (15 min) to produce arylated azoles 42-43 in fairly good yields. The reactivity order of different heterocycles 40-41 was rationalized by the variable acidity of C2-H (oxadiazoles = benzoxazoles (pKa = 24.8) > thiadiazoles >benzothiazoles (pKa = 27.3). Under the optimized conditions, C2-H arylation of benzothiazole could not be achieved. Modified reaction conditions involving the use of MW successfully afforded 2-arylbenzothiazoles in good yields. The synthetic utility of developed protocol was extended to prepare a Tafamidis analogue 43b which is a well known drug for neurodegenerative diseases (Scheme 1.13).

N

X

N

R H IOTf

Ar Ar1

CuBr (20-30 mol%)t-BuOLi, rtX = O, S

Y

NR1

N

X

N

R Y

NR1

ArAr

N

O

N N

O

N N

S

N

MeO OMe MeO Cl

O

NMeO

O

N

Me

Cl

ClS

NF

23 examples60-89%

22 examples69-89%

H

42a, 60% 42b, 74% 42c, 84%

43a, 72% 43b, 69% 43c, 85%

Y = O, S

40 4142 4314

CuBr/I (20-30 mol%)t-BuOLi, rt/MW

S

N S

43d, 78%

N

S

N

Me42d, 72%

Scheme 1.13 Synthesis of various 2-arylazoles

1.2.14 Arylation of boron dipyrromethenes

Jiao et al.[29] developed a metal-free, α-selective C-H arylation of boron dipyrromethenes 44 by employing mild coupling partners, diaryliodonium salts 14. The developed protocol furnished an array of mono 45 and di-arylated 46 boron dipyrromethenes in moderate to good



yields. No product was formed upon addition of radical inhibitor (BHT) 2,6-di-tert-butyl-4-methylphenol suggested the involvement of an aryl radical. The arylated compounds 45 and 46 displayed promising photophysical properties (Scheme1.14).

NB

NF F

NB

NF F

NB

NF F

ArAr Ar

Ar2IOTf (1.5 equiv)Ar2IOTf (3.0 equiv)

NaOH, DCE NaOH, DCE

NB

NF F

Cl Cl

NB

N

R1

F F

MeO OMe

NB

N

R1

F F

t-Bu t-Bu

NB

N

R1

F F

N

Cl

NB

NF F

NB

N

R1

F FS

Me

NO2

11 examples17-63%

46a, 27% 46b, 37% 46c, 17%

45a, 45% 45b, 39% 45c, 43%

44466 examples

23-45%

45

R1

R1

R1 = 1,3,5-trimethylphenyl

R1 R1 R1

Scheme 1.14 Synthesis of α-arylated boron dipyrromethenes

1.2.15 Benzoxazines

Very recently, an interesting Cu-catalyzed one-pot [2+2+2] cascade annulation of nitriles 47, aldehydes 48 and diaryliodonium salts 14 has been developed by Jinhu et al. to construct benzoxazines 49 frameworks.[30] Iodonium salts 14 bearing functional groups such as aldehyde, halogens, alkyl and naphthyl were tolerated to afford 49 under the optimized reaction conditions. When two aldehyde groups were present in p-phthalaldehyde, then selectively one of –CHO underwent cyclization to give corresponding product (Scheme 1.15).

IOTf

+ ArCN + Ar1CHOCuBr (10 mol%)

DCE, 120 °C, 24h O

N Ar

Ar1

R R

O

N Ph

O

N

O

N PhO

N Ph

Me

CHO

Me

F

OMe

MeMe

OO

Br

49c, 56% 49d, 76%49b, 64%49a, 71%

35 examples50-94%

R

14 47 48 49

Scheme 1.15 Synthesis of benzoxazines and their representative examples

1.2.16 3-Iodochromenes

Togo and his co-workers [31] developed an efficient metal-free synthesis of 3-iodochromenes 51 from easily accessible diaryliodonium salts and aryl/alkly-propyn-1-ols 50. This elegant transformation proceeded via one-pot O-arylation of aryl/alkly-propyn-1-ols in the presence of base t-BuONa and subsequent iodocyclization using N-iodosuccinimide and Lewis acid BF3Et2O. Iodochromenes 51 could be converted into beneficial molecules using metal-catalyzed C-C bond forming strategies (Scheme 1.16).

IOTf

b) NIS, BF3.E t2ODCM, 0°C, 1 h

O

Ar

R R

35 examples50-94%

R +

OH

Ar

a) t-BuONa, MgSO4DCE, benzene0 to 60 °C, 3 h

I

O

O

Me

O

NSO2Ph

O

51c, 77%

O

Cl

O

I I I I I

51e, 72%51b, 54%51a, 62% 51d, 70%

5014 51

Scheme 1.16 Synthesis of iodochromenes

1.2.17 2/4-Aryloxyquinolines

Kumar et al.[32] disclosed a metal- and ligand-free approach for the synthesis of aryloxyquinolines 53 and 55 by the direct O-arylation of readily accessible quinolones



52/54 using diaryliodonium salts 14 as aryl source. The reaction conditions were compatible with 2-/4-quinolones 52/54 and diaryliodonium salts 14 bearing sterically congested and sensitive functional substituents such as mesityl and halides. Moreover, use of microwave energy, mild reaction conditions, good product yields (55-80%) and short reaction time (5 min) are significant features of the protocol. Prepared 4-aryloxyquinolines 55 were utilized in the construction of biologically important benzofuro[3,2-c]quinolines (Scheme 1.17).

NH

O

Me

I OTf

Ar Ar

NH

O

R

N

O

R

Ar

N O

Me

ArK2CO3, toluene100 °C, 5 min, MW

K2CO3, DMF100 °C, 5 min, MW

N O

MeOMe

N O

MeMe

Me

Me

N O

MeBr

N

O Me

N

O

Cl

Br

N

O

Ph

55c, 76%55b, 70%55a, 58%

53a, 65% 53b, 67% 53c, 73%

7 examples 10 examples60-80%

65-80%

14

52

53

54

55 N

O Ar

Benzofuroquinolines

Scheme 1.17 Synthesis of 2-and 4-aryloxyquinolines

1.2.18 Thiochromeno[2,3-b]indoles

An efficient Cu(OTf)2-promoted synthesis of thiochromeno[2,3-b]indoles 57 was developed from alkynylaryl isothiocyanates 56 and diaryliodonium salts 14. The reaction involves successive S-arylation and cyclization to furnish fused heterocycles 57. Under the optimized conditions both electron-rich and electron-poor iodonium salts were smoothly coupled with isothiocyanates 56 to afford the corresponding fused heterocycles 57.in 35-70% yields. Addition of a radical inhibitor led to 57 in excepted yield which suggested the involvement of carbocation mechanism (Scheme 1.18).[33]

NCS

Cu(OTf)2, K2CO3

DCE, 50 °C+

IOTf

Ar Ar1N S

R1R1

R R Ar

24 examples35-70%

N S N S N S N S

S

57a, 70% 57b, 51%

PhMe

Me57c, 35%

FPh

57d, 60%

56 14 57

Scheme 1.18 Synthesis of thiochromeno[2,3-b]indoles

1.2.19 α-Aryl-β-substituted cyclic ketones

Pan et al.[34] reported an efficient method for the construction of α-aryl-β-substituted cyclic ketones 58 using diaryliodonium salts 14. The current transformation involved Cu-promoted one-pot Michael addition followed by stereoselective arylation of cyclohexene-1-one and cyclohepten-1-one using alkyl, aryl and sterically challenging lithium reagents as Michael donors and different diaryliodonium salts 14 as aryl partner. Proposed mechanistic pathway involves reaction of Cu(I) species and diaryliodonium salts to generate an highly electrophilic Cu(III)-aryl species, which believed to react with enolate to produce the desired substituted cyclic ketones 59 in excellent yields (Scheme 1.19).

33 examples32-72%

O

a) R2CuLi.LiCN, Et2O, -78 °C

b) Ar2IOTf 14, Cu(OAc)2 (20 mol%)DMF, -20 °C

OAr

R

OCF3 O

N

Cl

59a, 41% 59b, 38%

O

59c, 38%

O

59d, 32%

58 59

Scheme 1.19 Synthesis of α-aryl-β-substituted cyclic ketones

1.2.20 Oxazolines

Adam et al. demonstrated a novel copper-catalyzed ring closure-carboarylation strategy for the construction of oxazoline derivatives 61



using easily accessible alkylpropargylamides 60 and diaryliodonium salts 11. Iodonium salts 11 having ortho and para substitutents delivered 61 in relatively better yields. This one-pot method provides access to novel oxazolines heterocyclic core with highly substituted exo double bond (Scheme 1.20).[35]

NH

R

O

Ar

+ Ar1

IOTf

NO

R

Ar Ar1

CuCl (2.5 mol%)EtOAc, 50 °C 6-12h

NO

Me

O

61a, 86%

NO

61b, 56%

S

NO

BrBr

61c, 61%

NO

61d, 43%

23 examples40-86%

60 11 61

Scheme 1.20 Synthesis of oxazolines and their representative examples

1.2.21 Pyridones

Recently, Kim and co-workers reported the copper-catalyzed N-arylation of 2-pyridones 62 using solid aryl coupling partner diaryliodonium salts 14 at room temperature. Various symmetrical and unsymmetrical diaryliodonium salts have been employed with 2-pyridones, to furnish the desired products in excellent yields. Pyridones with bulkier C6-phenyl, for example, 2-hydroxy-6-phenylpyridine,upon treatment with iodonium salt produced O-arylate 63g as the major product.. Further investigation of counter ion effect in diaryliodonium salts revealed that OTf, BF4 and PF6 ions yielded the desired products in 63 good yields in shorter time, while OTs, Cl, and Br showed the negative impact on the reaction and delivered the desired products low yields and longer reaction times. Next, the developed protocol was effectively utilized to prepare an antifibrotic drug, Pirfenidone (63i) which is used in the treatment of idiopathic pulmonary fibrosis (Scheme 1.21).[36]

NH

O

toluene, Et3N, r.t.N

O

N

O

MePirfenidone (antifibrotic drug)

I+ OTf

14

CuCl (10 mol%)+

N t-Bu

O

N t-Bu

O

MeO2C63a, 98 % 63b, 98 %

N

O

t-Bu N t-Bu

O

O

Me

63d, 65 %

N

OBr

Br

N

OBr

Br

63e, 95 % 63f, 54 %

N

O

Ph

t-BuN

O

Pht-Bu

63c, 99 %

63h, 24 %63g, 74 %

62 6363i, 99%

27 examples 23-99%

Ar ArR

RAr

Scheme 1.21 N-arylation of 2-pyridones using diaryliodonium salts

1.2.22 2-(Phenylthio)pyrimidine

In 2013, Karade et al.[37] reported the synthesis of biologically important scaffold 2-(phenylthio)pyrimidine (65) via C-S coupling of 4-aryl-3,4-dihydropyrimidine-2(1H)-thione (64) using diaryliodonium salts 14 in the presence of catalytic amount of CuO nanoparticles. This protocol showed good compatibility towards various functional groups and furnished 65 in good to excellent yields. In the case of unsymmetrical iodonium salts, mixture of S-arylated products were obtained. The CuO nanoparticles was recycled and reused for three times without any loss of catalytic activity (Scheme 1.22).

NH

NH

S

R1

Me

O

R2I

OTf

R R

14

nano CuO (10 mol%)K2CO3( 2.5 equiv.)

DMF, reflux, 12 hN

N

S

R1

Me

O

R2

16 examples 63-88%

N

N

SMe

O

EtO

R

64 65

65a, 84%

N

N

SMe

O

EtO

OMe

65b, 76%

N

N

SMe

O

EtO

65c, 64%

NO2

N

N

SMe

O

EtO

Cl

Cl

65d, 70%

Scheme 1.22 Synthesis of 4-aryl-3,4-dihydropyrimidine-2(1H)-thiones

1.2.23 N-(2-Hydroxyaryl)benzotriazoles

Very recently, Dong-Liang Mo and his research group developed a metal-free approach for the synthesis of N-(2-hydroxyaryl)benzotriazoles 68 using N-hydroxybenzotriazoles 66 and



diaryliodonium salts 14.[38] Initially, reaction of N-hydroxybenzotriazoles 66 with 14 at room temperature delivered the O-arylated product 67, which underwent [3,3] sigmatropic rearrangement at 60 °C to provide N-(2-hydroxyaryl)benzotriazoles 68 in good yields. A variety of diaryliodonium salts and N-hydroxybenzotriazoles were examined to show the generality of developed protocol. Authors also showed practical utility of the protocol by the synthesis of novel P, N-type ligands 69 in two steps (Scheme 1.23).

Ar2I OTf

t-BuOK MeCN, r.t.

NN

N

OHN

NN

O

NN

N

OH

3, 3

NN

N

O

NN

N

ON

NN

O

Me

Me

CO2Me67a, 99 % 67b, 89 % 67c, 90 %

NN

N

OMe

67d, 86 %

MeCN, 60 °C

23 examples40-99%

16 examples 43-89%

66 67 68

NN

N

O

Ph2P

P, N-ligand69, 40%

NN

N

OH NN

N

OHN

NN

OH

N

NN

N

OH

68a, 69% 68b, 79% 68c, 82%MeO

68d, 68%

RR

Ar Ar

R14

Scheme 1.23 Synthesis of N-(2-hydroxyaryl)benzotriazoles and representative examples

Conclusions

In summary, we have described the recent achievements of diaryliodonium salts in the constructions of various C-C, C-N, C-S and C-O bonds enabling to access valuable heterocycles under mild reaction conditions. The impressive features of diaryliodonium salts are enhanced electrophilicity, stable solid compounds, no special precaution to handle, easy to prepare and recyclability of released iodoarenes during the reaction. Hopefully, these unique advantageous properties are highly favourable for synthetic community. In recent years, a range of new substrates have been explored for the arylation and manifold novel transformations for the assembly of heterocyclic frameworks. Undoubtedly, the distinctive properties of diaryliodonium salts will open a new avenue for

the design of novel transformations in the fields of metal-free and transition-metal-catalyzed reactions in the future.

Acknowledgments

We are grateful to CSIR, New Delhi for financial support

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CHEMISTRY & BIOLOGY INTERFACE · 2016-11-28 · Chemistry & Biology Interface, 2016, 6, 5, 270-281...

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