one-pot synthesis of hypervalent diaryl(iodo)bismuthanes from...

Research ArticleOne-Pot Synthesis of Hypervalent Diaryl(iodo)bismuthanesfrom o-Carbonyl Iodoarenes by Zincation

Toshihiro Murafuji 12 A F M Hafizur Rahman2 Daiki Magarifuchi3 Masahiro Narita1

Isamu Miyakawa13 Katsuya Ishiguro13 and Shin Kamijo13

1Graduate School of Sciences and Technology for Innovation Yamaguchi University Yamaguchi 753-8512 Japan2Graduate School of Medicine Yamaguchi University Yamaguchi 753-8512 Japan3Graduate School of Science and Engineering Yamaguchi University Yamaguchi 753-8512 Japan

Correspondence should be addressed to Toshihiro Murafuji murafujiyamaguchi-uacjp

Received 31 October 2018 Accepted 22 January 2019 Published 27 February 2019

Academic Editor Oscar Navarro

Copyright copy 2019 Toshihiro Murafuji et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Diaryl(iodo)bismuthanes possessing a hypervalent C=O∙ ∙ ∙BindashI bond were conveniently synthesized in a one-pot reaction byusing arylzinc reagents generated from o-carbonyl iodobenzenes and zinc powder under ultrasonication This method is superiorto the conventional organolithium and Grignard methods because it has a wide functional group tolerance requires no protectinggroup manipulations and proceeds under mild reaction conditions that do not need low temperature control Furthermore nointermediate triarylbismuthane precursor for the hypervalent iodobismuthane is necessary

1 Introduction

Much effort has been devoted to the study of hypervalent bis-muth(III) compounds [1ndash5] Hypervalent bonds are formedefficiently via intramolecular coordination of a neutral donorto a bismuth(III) center [6ndash12] We have used this methodto synthesize various hypervalent organobismuth(III) com-pounds stabilized by intramolecular coordination and havecharacterized their molecular structures [13] Furthermorewe have revealed that these compounds show antifungalactivities against the yeast Saccharomyces cerevisiae [14 15]In particular compounds 1 and 2 which possess diary sulfoneand acetophenone molecular scaffold respectively exhibitedhigh antifungal activities

These compounds are synthesized by directed ortho-lithiation (Scheme 1) Directed lithiation is a very usefuland reliable synthetic method for introducing a molecularscaffold bearing an ortho-coordinative functional groupalthough the method can suffer from various practical dif-ficulties For example the synthesis of 1 and 2 used triaryl-bismuthane as a precursor because the ortho-functionalizedaryllithiums were too reactive to give 1 and 2 directly through

their reactions with BiI3and ArBiX

2 respectively Further-

more the acetyl substituent of acetophenone is incompatiblewith BuLi meaning that the synthesis of 2 started from theprotected silyl enol ether and the harsh reaction conditionsrequiring excess BuLi caused the loss of Ar

2BiCl or the

decomposition of the product lowering the reproducibility ofthe yield [13 14] To facilitate the search for active antifungalcompounds a general and convenient synthetic methodthat has wide functional group compatibility for introducingvarious molecular scaffolds to the bismuth(III) center isrequired

We have reported the synthesis under Grignard con-ditions of p-substituted triarylbismuthanes 3 and 4 whichhave a formyl and ester substituent respectively (Scheme 2)[16] The imino and ester substituents were tolerated despitetheir polarized double bond although 3 required protectionof the formyl substituent and 4 needed low-temperaturecontrol Based on these results we investigated using atype of organometallic reagent that is less reactive thanGrignard reagents Such an organometallic reagent wouldbe compatible with carbonyl functional group and thus asuitable synthetic tool for use in our desired general method

HindawiHeteroatom ChemistryVolume 2019 Article ID 2385064 7 pageshttpsdoiorg10115520192385064

2 Heteroatom Chemistry

S1) BuLi or LTMP

S

BiTol

S

BiI

Ar Ar ArAr =

O

Me

1

BuLi (excess)TMEDA

HexaneO

Me

Bi

X

Ar

2

O

Me

MeCN

N NN

NMeMe

MeMe

LTMP =

2) NaX

Li

2 2 2

2) ４ＩＦＣＦ2

Tol = 4-－6（4

）2

－3３ＣＦ

Ｎ3 NaI1) Ｌ2ＣＦ

2) （2

1) 3∙Ｎ2

－3３Ｃ

ＣＬ2

Scheme 1 Synthesis of 1 and 2 by directed lithiation

BiH

O 3

3

BiOEt

O 3

4

INPr-i

H

i-PrMgBr

IOEt

O

i-PrMgBr

THF 25 ∘C

THF minus40 ∘C

ＣＦ3 then （2

ＣＦ3 then （2

Scheme 2 Synthesis of 3 and 4

Several mild bismuthndashcarbon bond forming reactionshave been reported which include the treatment of aryliodides with bismuth shot in the presence of Cu and CuI byball milling [17] the arylation of bismuth(III) carboxylatesby sodium tetraarylborate [18] and the reaction of BiCl

3

with organozinc reagents [19] To achieve wide functionalgroup tolerance we chose organozinc reagents because theyare compatible with carbonyl functionalities such as esteracetyl and even formyl substituents and the chemistryof these reagents is well established [20ndash22] Herein wereport the synthesis of hypervalent iodobismuthanes 2a and5andash10a which contain a carbonyl group by zincation ofthe corresponding iodoarenes (Scheme 3) The organozincmethod was superior to our previously reported organo-lithium and Grignard methods owing to the high functionalgroup tolerance short synthesis mild reaction conditionsand acceptable yields

2 Materials and Methods

All of the reactions were carried out under argon unlessotherwise noted NN-Dimethylformamide (DMF) was dis-tilled from calcium hydride under reduced pressure 14-Dioxane was distilled from calcium hydride Diethyl etherwas distilled from benzophenone ketyl before use 1H and13C NMR spectra were recorded in CDCl

3or DMSO-

d6 on a BRUKER AVANCE 400S spectrometer Chemicalshifts were referenced to residual solvent peak chloroform

(726 ppm 770 ppm) and DMSO (250 ppm 4045 ppm)IR spectra were obtained as KBr pellets on a Nico-let FT-IR Impact 410 spectrophotometer Melting pointswere determined on a YANAGIMOTO melting pointapparatus without correction Elemental analysis was per-formed on a MICRO CORDER JM10 apparatus (J-SCIENCELAB Co) HRMS were recorded on a Bruker Dalton-ics micrOTOF II (APCI) instrument 21015840-Iodoacetophenoneand ethyl 2-iodobenzoate were commercially available 2-Iodobenzaldehyde 4-fluoro-2-iodobenzaldehyde 2-iodo-5-methoxybenzaldehyde 41015840-fluoro-21015840-iodoacetophenone and3-iodothiophene-2-carboxaldehyde were prepared in highyields by Finkelstein reaction of the corresponding bro-moarenes in accordance with the literature [23]

21 Typical Procedure for the Finkelstein Reaction of Bro-moarenes To a round-bottomed flask (50mL) equippedwitha magnetic stir bar were added bromoarene (25 mmol)CuI (5 mol) NaI (5 mmol) and 13-diaminopropane (10mol) After dry 14-dioxane (25 mL) was added to theflask the mixture was refluxed for 24 h The reaction wasquenched with water (30 mL) at room temperature and theresulting mixture was extracted with ethyl acetate (3 times 30mL)The organic layer was dried (Na

2SO4) and concentrated

to leave a residue which was chromatographed on silica gelwith hexanendashethyl acetate (51) to give the correspondingiodoarene which was used in the next step without furtherpurification

Heteroatom Chemistry 3

O

H

Bi

I

Tol

O

Me

Bi

I

Tol

O

OEt

Bi

I

Tol

10a

X

O

H

Bi

I

Tol

8a

MeO

X

S

O

H

Bi

I

Tol

9a2a X = H5a X = F

6a X = H7a X = F

Scheme 3 Hypervalent iodobismuthanes functionalized with a carbonyl group

22 2-Iodobenzaldehyde Yield 99 (574 mg 248 mmol)Colorless solid mp 39ndash41∘C 1H NMR (400 MHz CDCl

3)

120575 729 (1H dt J = 76 Hz 16 Hz) 747 (1H t J = 76 Hz) 789(1H dd J = 76 Hz 16 Hz) 796 (1H d J = 80 Hz) 1008 (1Hs)

23 4-Fluoro-2-Iodobenzaldehyde Yield 97 (606 mg 243mmol) Colorless solid mp 49ndash51∘C 1H NMR (400 MHzCDCl

3) 120575 719 (1H m) 768 (1H m) 791 (1H m) 999 (1H

d J = 24 Hz)

24 2-Iodo-5-Methoxybenzaldehyde Yield 98 (642 mg245 mmol) Colorless solid mp 113ndash116∘C 1H NMR (400MHz CDCl

3) 120575 384 (3H s) 692 (1H dd J = 84 Hz 32

Hz) 743 (1H d J = 32 Hz) 780 (1H d J = 84 Hz) 1002 (1Hs)

25 41015840-Fluoro-21015840-Iodoacetophenone Yield 98 (647mg 245mmol) Colorless solid mp 45ndash46∘C 1H NMR (400 MHzCDCl

3) 120575 259 (3H s) 711 (1H m) 752 (1H m) 765 (1H m)

26 3-Iodothiophene-2-Carboxaldehyde Yield 99 (589 mg248 mmol) Colorless solid mp 82ndash85∘C 1H NMR (400MHz CDCl

3) 120575 728 (1H d J = 48 Hz) 770 (1H dd J = 48

Hz 12 Hz) 983 (1H d J = 12 Hz)

27 Typical Procedure for the Synthesis of Aryl(iodo)(4-methylphenyl)bismuthane To a round-bottomed flask(50 mL) equipped with a magnetic stir bar were addedbismuth(III) chloride (422 mg 133 mmol) and tris(4-methylphenyl)bismuthane (323 mg 067 mmol) Afterdry diethyl ether (6 mL) was added to the flask at roomtemperature the mixture was stirred for 1 h To anotherround-bottomed flask (50 mL) were added iodoarene (1mmol) zinc powder (262 mg 4 mmol) and dry DMF (5mL) The flask was set in an ultrasonic water bath at roomtemperature (25∘C) and the resulting mixture was sonicatedfor 15ndash4 h during which time the water bath temperaturerose to 48∘C The sonication was stopped and unreactedzinc powder precipitated The resulting supernatant solutioncontaining an arylzinc reagent was slowly transferred to thesuspension of dichloro(4-methylphenyl)bismuthane (ca 2mmol) thus formed and the resulting mixture was stirredfor 35ndash8 h at room temperature The reaction was quenchedwith a saturated aqueous solution of NaI (3 mL) and theresulting mixture was extracted with ethyl acetate (3 times 50

mL) The combined extracts were concentrated to leavean oily residue which was chromatographed on silica gelwith hexanendashethyl acetate (51) to afford the correspondingiodobismuthane

28 (2-Acetylphenyl)iodo(4-methylphenyl)bismuthane 2aYellow crystal Yield 35 (191mg 035mmol) mp 160ndash162∘C1H NMR (400 MHz CDCl

3) 120575 225 (3H s) 269 (3H s)

725 (2H d J = 80 Hz) 771 (1H dt J = 76 Hz 12 Hz) 788(1H dt J = 76 Hz 12 Hz) 807 (2H d J = 80 Hz) 822 (1Hdd J = 76 Hz 12 Hz) 941 (1H dd J = 72 Hz 08 Hz) 13CNMR (100MHz CDCl

3) 120575 2154 2708 12850 13236 13451

13801 13821 13898 14310 14555 16678 17209 20754 IR(KBr) ] 3738 3037 1622 1552 1276 and 761 cmminus1 HRMS(APCI) calcd for C

15H13BiIO [MndashH]minus 5449832 found

5449821

29 (2-Acetyl-5-fluorophenyl)iodo(4-methylphenyl)bismu-thane 5a Yellow crystal Yield 28 (158 mg 028 mmol) mp186ndash188∘C 1H NMR (400 MHz DMSO-d

6) 120575 219 (3H s)

272 (3H s) 729 (2H d J = 76 Hz) 754 (1H dt J = 84 Hz20 Hz) 811 (2H d J = 76 Hz) 855 (1H dd J = 84 Hz 48Hz) 889 (1H br-s) 13CNMR (100MHz DMSO-d

6) 120575 2113

2748 11562 (d J = 226 Hz) 13094 (br-d) 13208(times2) 1370913845 13885 (d J = 80 Hz) 14051 16952 17212 20785IR (KBr) ] 1620 1575 1558 1358 1299 1262 and 1201 cmminus1HRMS (APCI) calcd for C

15H12BiFIO [MndashH]minus 5629730

found 5629726

210 (2-Formylphenyl)iodo(4-methylphenyl)bismuthane 6aYellow crystal Yield 56 (298 mg 056 mmol) mp143ndash144∘C 1H NMR (400 MHz DMSO-d

6) 120575 221 (3H s)

730 (2H d J = 76 Hz) 786 (1H t J = 72 Hz) 795 (1H t J= 72 Hz) 814 (2H d J = 76 Hz) 844 (1H d J = 72 Hz)902 (1H d J = 72 Hz) 1075 (1H s) 13C NMR (100 MHzCDCl

3) 120575 2155 12865 13247 13758 13823 13844 13963

14366 14616 16599 17092 19950 IR (KBr) ] 3058 28571633 1572 1553 1296 and 1207 cmminus1 HRMS (APCI) calcdfor C14H13BiIO [M+H]+ 5329808 found 5329810

211 (2-Formyl-5-fluorophenyl)iodo(4-methylphenyl)bismu-thane 7a Yellow crystal Yield 29 (195 mg 029 mmol) mp148ndash149∘C 1H NMR (400 MHz DMSO-d

6) 120575 221 (3H s)

732 (2H d J = 76 Hz) 761 (1H dt J = 84 Hz 24 Hz) 818(2H d J = 76 Hz) 852 (1H dd J = 80 Hz 52 Hz) 874 (1Hd J = 64 Hz) 1074 (1H s) 13C NMR (100 MHz DMSO-d

6)


O

H

O

H

Benzene

NLiNOLi 1) BuLi (excess)

N

NMe

Me

6

O

H

Bi

X

Ar

2) NaX2) Ｌ2ＣＦ then （2

ＣＬ2

1) 3∙Ｎ2

Scheme 4 Conventional synthesis of 6 by directed lithiation

120575 2114 11575 (d J = 227 Hz) 13183 (br-s) 13217(times2) 1370513901 14073 (d J = 90 Hz) 14088 16919 17180 19967IR (KBr) ] 3061 2875 1638 1582 1561 1259 and 1204 cmminus1HRMS (APCI) calcd for C


found 5489570

212 (2-Formyl-4-methoxyphenyl)iodo(4-methylphenyl)bis-muthane 8a Yellow crystal Yield 31 (175 mg 031 mmol)mp 146ndash147∘C 1H NMR (400 MHz DMSO-d

6) 120575 222 (3H

s) 387 (3H s) 731 (2H d J = 80 Hz) 748 (1H dd J = 76Hz 28 Hz) 799 (1H d J = 28 Hz) 813 (2H d J = 76 Hz)878 (1H d J = 80 Hz) 1066 (1H s) 13C NMR (100 MHzCDCl

3) 120575 2157 5567 12295 12569 13238 13820 13831

14509 14794 16026 16134 16638 19913 IR (KBr) ] 30272924 2862 1640 1585 1552 1460 1251 and 1044 cmndash1 HRMS(APCI) calcd for C

15H13BiIO2 [MndashH]minus 5609770 found

5609770

213 (2-Formyl-3-thienyl)iodo(4-methylphenyl)bismuthane9a Yellow crystal Yield 53 (287 mg 053 mmol) mp132ndash133∘C 1H NMR (400 MHz CDCl

3) 120575 228 (3H s) 731

(2H d J = 76 Hz) 804 (1H d J = 44 Hz) 809 (1H d J =44 Hz) 814 (2H d J = 76 Hz) 1012 (1H s) 13C NMR (100MHz CDCl

3) 120575 2158 13267 13850 13856 14208 14566

14847 16697 17432 18644 IR (KBr) ] 1586 1483 14501397 1337 1195 853 and 794 cmminus1 HRMS (APCI) calcd forC12H11BiIOS [M+H]+ 5389374 found 5389374

214 (2-Ethoxycarbonylphenyl)iodo(4-methylphenyl)bismu-thane 10a Yellow crystal Yield 61 (351 mg 061 mmol)mp 125ndash126∘C 1H NMR (400 MHz CDCl

3) 120575 140 (3H t

J = 72 Hz) 226 (3H s) 443 (2H m) 726 (2H d J = 76Hz) 736 (1H dt J = 76 Hz 08 Hz) 784 (1H dt J = 76 Hz12 Hz) 809 (2H d J = 76 Hz) 822 (1H dd J = 76 Hz 12Hz) 943 (1H d J = 72 Hz) 13C NMR (100 MHz CDCl

3)

120575 1409 2154 6331 12829 13228 13277 13435 1379613827 13870 14383 16684 16952 17585 IR (KBr) ] 29901634 1573 1373 1311 1005 785 and 733 cmminus1 Anal Calc forC16H16BiIO2 C 3335 H 280 Found C 3332 H 303

3 Results and Discussion

Initially we tried the one-pot synthesis of 10a by the zincationof ethyl 2-iodobenzoate The arylzinc was prepared by usingthe method reported by Takagi and coworkers [20] whotreated iodoarenes containing an electron-withdrawing sub-stituent such as a methoxycarbonyl or an acetyl substituent

at the ortho position in the presence of zinc powder underultrasonication at 30∘C

When a mixture obtained by sonicating ethyl 2-iodobenzoate with zinc powder (1 equiv) at 25∘C in DMFwas allowed to react with TolBiCl

2(1 equiv) 10a was

obtained in only 4 yield (Table 1 Entry 1) The pooryield was attributed to the incomplete conversion of thestarting iodoarene to the arylzinc The yield of 10a wasincreased by increasing the equivalents of zinc powderand TolBiCl

2(Entries 2 and 3) Furthermore an increase

in the temperature from 25 to 48∘C during the sonicationaccelerated the zincation reaction (Entries 4ndash9)The reactionmixture turned dark yellow during the zincation which wasa good indicator for the completion of the reaction Theyield of 10a was sensitive to the zinc powder loading and thebest result was obtained when 4 equiv zinc powder and 2equiv TolBiCl

2were used (Entry 7) Higher zinc powder or

TolBiCl2loadings decreased the yield of 10a (Entries 8 and

9)Encouraged by the success of the one-pot synthesis of 10a

we performed the one-pot syntheses of 2a and 5a which havean acetophenone scaffold using the reaction conditions usedin the synthesis of 10a (Table 1 Entry 7) After the zincationreaction mixtures had turned dark yellow the arylzinc wasallowed to react with TolBiCl

2 followed by quenching with a

saturated aqueous solution of NaI to give 2a and 5a in 35and 28 yields respectively despite the presence of acidicacetyl protons (Table 2 Entries 1 and 2) We have previouslyreported that the synthesis of 5a from the correspondingsilyl enol ether by conventional directed lithiation failed(Scheme 1) [14] We explained the failure by the presence ofthe fluoro substituent which can act as a directing groupThesuccess in obtaining 5a demonstrates the usefulness of thezincation method

Furthermore we used this method to synthesize 6andash9awhich have a formyl substituent (Entries 3ndash6) We havepreviously reported the synthesis of 6 by the directed ortho-lithiation of lithium 120572-amino alkoxide (Scheme 4) [13] Thismethod required excess BuLi which often caused the lossof Ar2BiCl or decomposition of the product by overreaction

with unreacted BuLi In addition the lithium alkoxide moi-ety could form an undesired bismuth alkoxide by reactingwith Ar

2BiCl Hence the present zincation overcomes these

drawbacks In particular 7a 8a and 9a were obtained inacceptable yields by the zincation if conventional directedlithiation was used the fluoro and methoxy substituents in7a and 8a respectively would act as directing groups and thethienyl ring proton 120572 to the sulfur atom in 9a would undergoundesired lithiation


Table 1 Optimization of the reaction conditions for the synthesis of 10a

2) NaI (aq)10aO

OEt

I

Zn

UltrasoundDMF

O

OEt

ZnI

1) ４ＩＦＣＦ2 8 h rt

Entry Zn TolBiCl2

Ultrasound Ultrasound Yield ()(equiv) (equiv) Temp (∘C) Time (h) 10a

1 10 10 25 6 42 15 10 25 6 93 20 15 25 5 144 25 15 25ndash48 3 185 30 20 25ndash48 4 286 35 20 25ndash48 4 417 40 20 25ndash48 4 618 45 20 25ndash48 5 609 40 30 25ndash48 5 55

Table 2 Synthesis of iodobismuthanes

Zn

Ultrasound DMF ArI ArZnI ArBi(Tol)I

NaI (aq )

25minus48∘C

４ＩＦＣＦ2

Entry ArI Ultrasound TolBiCl2 ArBi(Tol)I Yield ()

Time (h) Time (h)

1 O

Me

I

20 35 2a 35

2 O

IF

Me

15 60 5a 28

3 O

I

H

35 80 6a 56

4 O

IF

H

30 80 7a 29

5 O

I

MeOH

35 80 8a 31

6 O

I

SH

40 80 9a 53


The molecular structure of 2 (Ar = Tol X = Br) hasbeen characterized by X-ray structure analysis and 13C NMRand IR spectra which reveals the formation of a hypervalentOndashBindashBr bond by the intramolecular coordination of thecarbonyl group with the bismuth atom [13] The hypervalentbond formation was also detected in the 1H NMR spectraThe 1H NMR spectrum of 2a in CDCl

3shows anisotropic

deshielding (120575 941 ppm) of the ortho proton adjacent to thebismuth atom in the arylcarbonyl scaffold because of its closeproximity to the electronegative iodine atom owing to thehypervalent OndashBindashI bond formation [14] Compound 10ashowed a similar deshielding of the ortho proton signal at120575 943 ppm in CDCl

3 which is consistent with hypervalent

bond formation In contrast no large deshielding of thearomatic proton was observed in the thienyl ring proton of9a This may be attributed to the signal for the 120572-proton ofthe thienyl ring being shifted downfield because of the effectof the sulfur atom As a result the signal due to the 120573-protonis apparently not affected by anisotropic deshielding by theiodine atom

4 Conclusions

Hypervalent iodobismuthanes bearing a carbonyl groupweresynthesized easily with a one-pot reaction using arylzincreagents The zinc reagents tolerated carbonyl group acetylprotons and ring protons adjacent to fluoro methoxy andsulfur functional groups This indicates that the zincationreaction may be suitable for synthesizing a wide range ofhypervalent antifungal bismuth(III) compoundswith variousmolecular scaffolds

Data Availability

The 1H and 13C NMR spectral data used to support thefindings of this study are included within the supplementaryinformation file

Conflicts of Interest

The authors declare that there are no conflicts of interestregarding the publication of this paper

Acknowledgments

We are grateful to the Center of Instrumental AnalysisYamaguchi University and the Tokiwa InstrumentationAnal-ysis Center Yamaguchi University This work was supportedby JSPS KAKENHI Grant Number 16K05697 to ToshihiroMurafuji

Supplementary Materials

See Figures S1ndashS5 [the 1H NMR spectra of o-carbonyl iodoarenes] and Figures S6ndashS19 [the 1H and13C NMR spectra of compounds 2a and 5andash10a](Supplementary Materials)

References

[1] X Chen Y Yamamoto and K-Y Akiba ldquoHypervalent tetra-coordinate organobismuth compounds (10-Bi-4)rdquo HeteroatomChemistry vol 6 no 4 pp 293ndash303 1995

[2] K Ohkata S Takemoto M Ohnishi and K-Y AkibaldquoSynthesis and chemical behaviors of 12-substituteddibenz[cf][15]azastibocine and dibenz[cf][15]azabismocinederivatives Evidences of 10-Pn-4 type hypervalent interactionrdquoTetrahedron Letters vol 30 no 36 pp 4841ndash4844 1989

[3] C I Rat C Silvestru and H J Breunig ldquoHypervalentorganoantimony and -bismuth compounds with pendant armligandsrdquo Coordination Chemistry Reviews vol 257 no 5-6 pp818ndash879 2013

[4] S Shimada ldquoRecent advances in the synthesis and application ofbismuth-containing heterocyclic compoundsrdquo Current OrganicChemistry vol 15 no 5 pp 601ndash620 2011

[5] C Silvestru H J Breunig and H Althaus ldquoStructural chem-istry of bismuth compounds I Organobismuth derivativesrdquoChemical Reviews vol 99 no 11 pp 3277ndash3327 1999

[6] A M Toma A Pop A Silvestru T Ruffer H Lang and MMehring ldquoBismuthsdot sdot sdot 120587 arene versus bismuthsdot sdot sdot halide coordi-nation in heterocyclic diorganobismuth(III) compounds withtransannular N997888rarrBi interactionrdquo Dalton Transactions vol 46no 12 pp 3953ndash3962 2017

[7] Y-P Liu J Lei L-W Tang et al ldquoStudies on the cytotoxicity andanticancer performance of heterocyclic hypervalent organobis-muth(III) compoundsrdquo European Journal of Medicinal Chem-istry vol 139 pp 826ndash835 2017

[8] M Olaru M G Nema A Soran H J Breunig and C Sil-vestru ldquoMixed triorganobismuthines RAr

2Bi [Ar = C

6F5 246-

(C6F5)3C6H2] and hypervalent racemic Bi-chiral diorganobis-

muth(III) bromides RArBiBr (Ar = C6F5 Mes Ph) with the

ligand R = 2-(Me2NCH

2)C6H4 Influences of the organic

substituentrdquoDalton Transactions vol 45 no 23 pp 9419ndash94282016

[9] X Zhang S Yin R Qiu et al ldquoSynthesis and structure of anair-stable hypervalent organobismuth (III) perfluorooctanesul-fonate and its use as high-efficiency catalyst for Mannich-typereactions in waterrdquo Journal of Organometallic Chemistry vol694 no 22 pp 3559ndash3564 2009

[10] S-F Yin and S Shimada ldquoSynthesis and structure of bismuthcompounds bearing a sulfur-bridged bis(phenolato) ligandand their catalytic application to the solvent-free synthesis ofpropylene carbonate from CO

2and propylene oxiderdquo Chemical

Communications no 9 pp 1136ndash1138 2009[11] Y Yamamoto X Chen S Kojima et al ldquoExperimental inves-

tigation on Edge inversion at trivalent bismuth and antimonyGreat acceleration by intra- and intermolecular nucleophiliccoordinationrdquo Journal of the AmericanChemical Society vol 117no 14 pp 3922ndash3932 1995

[12] Y Matano Y Aratani T Miyamatsu et al ldquoWater-solublenon-ionic triarylbismuthanes First synthesis and propertiesrdquoJournal of the Chemical Society Perkin Transactions 1 no 16 pp2511ndash2518 1998

[13] T Murafuji T Mutoh K Satoh K Tsunenari N Azumaand H Suzuki ldquoHypervalent bond formation in halogeno(2-acylphenyl)bismuthanesrdquo Organometallics vol 14 no 8 pp3848ndash3854 1995

[14] T Murafuji M Tomura K Ishiguro and I Miyakawa ldquoActivityof antifungal organobismuth(III) compounds derived fromalkyl aryl ketones against S cerevisiae Comparison with a


heterocyclic bismuth scaffold consisting of a diphenyl sulfonerdquoMolecules vol 19 no 8 pp 11077ndash11095 2014

[15] A F M Hafizur Rahman T Murafuji K Yamashita et alldquoSynthesis and antifungal activities of pyridine bioisosteres ofa bismuth heterocycle derived from diphenyl sulfonerdquo Hetero-cycles vol 96 no 6 pp 1037ndash1052 2018

[16] T Murafuji K Nishio M Nagasue A Tanabe M Aono andY Sugihara ldquoSynthesis of triarylbismuthanes fully substitutedwith arenes each bearing a 120587-accepting substituentrdquo Synthesisno 9 pp 1208ndash1210 2000

[17] M Urano S Wada and H Suzuki ldquoA novel dry route to ortho-functionalized triarylbismuthanes that are difficult to access byconventional wet routesrdquo Chemical Communications vol 3 no10 pp 1202-1203 2003

[18] V Stavila J H Thurston D Prieto-Centurion and K HWhitmire ldquoA new methodology for synthesis of aryl bismuthcompounds Arylation of bismuth(III) carboxylates by sodiumtetraarylborate saltsrdquoOrganometallics vol 26 no 27 pp 6864ndash6866 2007

[19] K Urgin C Aube C Pichon et al ldquoAdvanced preparationof functionalized triarylbismuths and triheteroaryl-bismuthsNew scope and alternativesrdquo Tetrahedron Letters vol 53 no 15pp 1894ndash1896 2012

[20] K Takagi ldquoUltrasound-promoted synthesis of arylzinccompounds using zinc powder and their application topalladium(0)-catalyzed synthesis of multifunctional biarylsrdquoChemistry Letters vol 22 no 3 pp 469ndash472 1993

[21] H Takahashi S Inagaki Y Nishihara T Shibata and K TakagildquoNovel Rh catalysis in cross-coupling between alkyl halides andarylzinc compounds possessing ortho-COX (X = OR NMe

2 or

Ph) groupsrdquoOrganic Letters vol 8 no 14 pp 3037ndash3040 2006[22] A Krasovskiy V Malakhov A Gavryushin and P Knochel

ldquoEfficient synthesis of functionalized organozinc compounds bythe direct insertion of zinc into organic iodides and bromidesrdquoAngewandte Chemie International Edition vol 45 no 36 pp6040ndash6044 2006

[23] A Klapars and S L Buchwald ldquoCopper-catalyzed halogenexchange in aryl halides An aromatic Finkelstein reactionrdquoJournal of the American Chemical Society vol 124 no 50 pp14844-14845 2002

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S1) BuLi or LTMP

S

BiTol

S

BiI

Ar Ar ArAr =

O

Me

1

BuLi (excess)TMEDA

HexaneO

Me

Bi

X

Ar

2

O

Me

MeCN

N NN

NMeMe

MeMe

LTMP =

2) NaX

Li

2 2 2

2) ４ＩＦＣＦ2

Tol = 4-－6（4

）2

－3３ＣＦ

Ｎ3 NaI1) Ｌ2ＣＦ

2) （2

1) 3∙Ｎ2

－3３Ｃ

ＣＬ2

Scheme 1 Synthesis of 1 and 2 by directed lithiation

BiH

O 3

3

BiOEt

O 3

4

INPr-i

H

i-PrMgBr

IOEt

O

i-PrMgBr

THF 25 ∘C

THF minus40 ∘C

ＣＦ3 then （2

ＣＦ3 then （2

Scheme 2 Synthesis of 3 and 4

Several mild bismuthndashcarbon bond forming reactionshave been reported which include the treatment of aryliodides with bismuth shot in the presence of Cu and CuI byball milling [17] the arylation of bismuth(III) carboxylatesby sodium tetraarylborate [18] and the reaction of BiCl

3

with organozinc reagents [19] To achieve wide functionalgroup tolerance we chose organozinc reagents because theyare compatible with carbonyl functionalities such as esteracetyl and even formyl substituents and the chemistryof these reagents is well established [20ndash22] Herein wereport the synthesis of hypervalent iodobismuthanes 2a and5andash10a which contain a carbonyl group by zincation ofthe corresponding iodoarenes (Scheme 3) The organozincmethod was superior to our previously reported organo-lithium and Grignard methods owing to the high functionalgroup tolerance short synthesis mild reaction conditionsand acceptable yields

2 Materials and Methods

All of the reactions were carried out under argon unlessotherwise noted NN-Dimethylformamide (DMF) was dis-tilled from calcium hydride under reduced pressure 14-Dioxane was distilled from calcium hydride Diethyl etherwas distilled from benzophenone ketyl before use 1H and13C NMR spectra were recorded in CDCl

3or DMSO-

d6 on a BRUKER AVANCE 400S spectrometer Chemicalshifts were referenced to residual solvent peak chloroform

(726 ppm 770 ppm) and DMSO (250 ppm 4045 ppm)IR spectra were obtained as KBr pellets on a Nico-let FT-IR Impact 410 spectrophotometer Melting pointswere determined on a YANAGIMOTO melting pointapparatus without correction Elemental analysis was per-formed on a MICRO CORDER JM10 apparatus (J-SCIENCELAB Co) HRMS were recorded on a Bruker Dalton-ics micrOTOF II (APCI) instrument 21015840-Iodoacetophenoneand ethyl 2-iodobenzoate were commercially available 2-Iodobenzaldehyde 4-fluoro-2-iodobenzaldehyde 2-iodo-5-methoxybenzaldehyde 41015840-fluoro-21015840-iodoacetophenone and3-iodothiophene-2-carboxaldehyde were prepared in highyields by Finkelstein reaction of the corresponding bro-moarenes in accordance with the literature [23]

21 Typical Procedure for the Finkelstein Reaction of Bro-moarenes To a round-bottomed flask (50mL) equippedwitha magnetic stir bar were added bromoarene (25 mmol)CuI (5 mol) NaI (5 mmol) and 13-diaminopropane (10mol) After dry 14-dioxane (25 mL) was added to theflask the mixture was refluxed for 24 h The reaction wasquenched with water (30 mL) at room temperature and theresulting mixture was extracted with ethyl acetate (3 times 30mL)The organic layer was dried (Na

2SO4) and concentrated

to leave a residue which was chromatographed on silica gelwith hexanendashethyl acetate (51) to give the correspondingiodoarene which was used in the next step without furtherpurification


O

H

Bi

I

Tol

O

Me

Bi

I

Tol

O

OEt

Bi

I

Tol

10a

X

O

H

Bi

I

Tol

8a

MeO

X

S

O

H

Bi

I

Tol

9a2a X = H5a X = F

6a X = H7a X = F



3)



3) 120575 719 (1H m) 768 (1H m) 791 (1H m) 999 (1H

d J = 24 Hz)


3) 120575 384 (3H s) 692 (1H dd J = 84 Hz 32

Hz) 743 (1H d J = 32 Hz) 780 (1H d J = 84 Hz) 1002 (1Hs)


3) 120575 259 (3H s) 711 (1H m) 752 (1H m) 765 (1H m)


3) 120575 728 (1H d J = 48 Hz) 770 (1H dd J = 48

Hz 12 Hz) 983 (1H d J = 12 Hz)




3) 120575 225 (3H s) 269 (3H s)


3) 120575 2154 2708 12850 13236 13451



5449821


6) 120575 219 (3H s)


6) 120575 2113



found 5629726


6) 120575 221 (3H s)


3) 120575 2155 12865 13247 13758 13823 13844 13963



6) 120575 221 (3H s)


6)


O

H

O

H

Benzene


N

NMe

Me

6

O

H

Bi

X

Ar


ＣＬ2

1) 3∙Ｎ2




found 5489570


6) 120575 222 (3H


3) 120575 2157 5567 12295 12569 13238 13820 13831



5609770


3) 120575 228 (3H s) 731


3) 120575 2158 13267 13850 13856 14208 14566



3) 120575 140 (3H t


3)






2(1 equiv) 10a was
















2) NaI (aq)10aO

OEt

I

Zn

UltrasoundDMF

O

OEt

ZnI


Entry Zn TolBiCl2




Zn


NaI (aq )

25minus48∘C

４ＩＦＣＦ2


Time (h) Time (h)

1 O

Me

I

20 35 2a 35

2 O

IF

Me

15 60 5a 28

3 O

I

H

35 80 6a 56

4 O

IF

H

30 80 7a 29

5 O

I

MeOH

35 80 8a 31

6 O

I

SH

40 80 9a 53



3shows anisotropic




4 Conclusions


Data Availability




Acknowledgments




References









2Bi [Ar = C

6F5 246-























2 or









Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls





O

H

Bi

I

Tol

O

Me

Bi

I

Tol

O

OEt

Bi

I

Tol

10a

X

O

H

Bi

I

Tol

8a

MeO

X

S

O

H

Bi

I

Tol

9a2a X = H5a X = F

6a X = H7a X = F



3)



3) 120575 719 (1H m) 768 (1H m) 791 (1H m) 999 (1H

d J = 24 Hz)


3) 120575 384 (3H s) 692 (1H dd J = 84 Hz 32

Hz) 743 (1H d J = 32 Hz) 780 (1H d J = 84 Hz) 1002 (1Hs)


3) 120575 259 (3H s) 711 (1H m) 752 (1H m) 765 (1H m)


3) 120575 728 (1H d J = 48 Hz) 770 (1H dd J = 48

Hz 12 Hz) 983 (1H d J = 12 Hz)




3) 120575 225 (3H s) 269 (3H s)


3) 120575 2154 2708 12850 13236 13451



5449821


6) 120575 219 (3H s)


6) 120575 2113



found 5629726


6) 120575 221 (3H s)


3) 120575 2155 12865 13247 13758 13823 13844 13963



6) 120575 221 (3H s)


6)


O

H

O

H

Benzene


N

NMe

Me

6

O

H

Bi

X

Ar


ＣＬ2

1) 3∙Ｎ2




found 5489570


6) 120575 222 (3H


3) 120575 2157 5567 12295 12569 13238 13820 13831



5609770


3) 120575 228 (3H s) 731


3) 120575 2158 13267 13850 13856 14208 14566



3) 120575 140 (3H t


3)






2(1 equiv) 10a was
















2) NaI (aq)10aO

OEt

I

Zn

UltrasoundDMF

O

OEt

ZnI


Entry Zn TolBiCl2




Zn


NaI (aq )

25minus48∘C

４ＩＦＣＦ2


Time (h) Time (h)

1 O

Me

I

20 35 2a 35

2 O

IF

Me

15 60 5a 28

3 O

I

H

35 80 6a 56

4 O

IF

H

30 80 7a 29

5 O

I

MeOH

35 80 8a 31

6 O

I

SH

40 80 9a 53



3shows anisotropic




4 Conclusions


Data Availability




Acknowledgments




References









2Bi [Ar = C

6F5 246-























2 or









Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls





O

H

O

H

Benzene


N

NMe

Me

6

O

H

Bi

X

Ar


ＣＬ2

1) 3∙Ｎ2




found 5489570


6) 120575 222 (3H


3) 120575 2157 5567 12295 12569 13238 13820 13831



5609770


3) 120575 228 (3H s) 731


3) 120575 2158 13267 13850 13856 14208 14566



3) 120575 140 (3H t


3)






2(1 equiv) 10a was
















2) NaI (aq)10aO

OEt

I

Zn

UltrasoundDMF

O

OEt

ZnI


Entry Zn TolBiCl2




Zn


NaI (aq )

25minus48∘C

４ＩＦＣＦ2


Time (h) Time (h)

1 O

Me

I

20 35 2a 35

2 O

IF

Me

15 60 5a 28

3 O

I

H

35 80 6a 56

4 O

IF

H

30 80 7a 29

5 O

I

MeOH

35 80 8a 31

6 O

I

SH

40 80 9a 53



3shows anisotropic




4 Conclusions


Data Availability




Acknowledgments




References









2Bi [Ar = C

6F5 246-























2 or









Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls






2) NaI (aq)10aO

OEt

I

Zn

UltrasoundDMF

O

OEt

ZnI


Entry Zn TolBiCl2




Zn


NaI (aq )

25minus48∘C

４ＩＦＣＦ2


Time (h) Time (h)

1 O

Me

I

20 35 2a 35

2 O

IF

Me

15 60 5a 28

3 O

I

H

35 80 6a 56

4 O

IF

H

30 80 7a 29

5 O

I

MeOH

35 80 8a 31

6 O

I

SH

40 80 9a 53



3shows anisotropic




4 Conclusions


Data Availability




Acknowledgments




References









2Bi [Ar = C

6F5 246-























2 or









Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls






3shows anisotropic




4 Conclusions


Data Availability




Acknowledgments




References









2Bi [Ar = C

6F5 246-























2 or









Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls













2 or









Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls









Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls




one-pot synthesis of hypervalent diaryl(iodo)bismuthanes from...

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