2,2′-DIIODOBIPHENYL 1

2,2′-Diiodobiphenyl

I I

[2236-52-4] C12H8I2 (MW 405.87)InChI = 1S/C12H8I2/c13-11-7-3-1-5-9(11)10-6-2-4-8-12(10)

14/h1-8HInChIKey = OZVRXSGTNWILMN-UHFFFAOYSA-N

(reagent used for preparation of dibenzoannulated heterocycles byfunctionalization of dinucleophiles and hypervalent iodine(III)-

based reagents)

Alternate Names: 1,1′-biphenyl, 2,2′-diiodo-; 2,2′-Diiodo-1,1′-biphenyl.

Physical Data: mp 107–108 ◦C (from methanol),1 solid.Preparative Method: mostly prepared through bromine-lithium

exchange in 2,2′-dibromobiphenyl followed by iodination us-ing molecular iodine or diazotization of 2,2′-diaminobiphenylfollowed by iodination.

Purification: recrystallization from methanol,1 columnchromatography.

Methods of Preparation. Several different strategies havebeen used for the synthesis of 2,2′-diiodobiphenyl. Initial pro-cedures involved the use of a n-BuLi-mediated coupling of 1,2-dibromobenzene to give 2,2′-dibromobiphenyl that was further re-acted with n-BuLi to generate the corresponding lithiated species.The corresponding adduct was quenched with molecular iodineto give 2,2′-diiodobiphenyl (eq 1).1

Br

Br

1. nBuLi (2.2 equiv)

THF, –78 ºC to 25 ºC

2. I2 (2.2 equiv)

Et2O, 0 ºC

85%

I

I

Br

Br

1. nBuLi (0.5 equiv)

THF, –78 ºC

(1)

81%

In a different approach, the synthesis was completed in athree-step reaction sequence starting with the oxidation of 2-iodobiphenyl using mild oxidizing agents such as Koser’s reagent2

or peracetic acid3 to form the corresponding diphenyliodiniumsalts (eqs 2 and 3). In the next step, these salts were converted intodiphenyliodinium iodide through metathesis with KI, followed bypyrolysis at 200 ◦C to obtain 2,2′-diiodobiphenyl.

In a parallel approach, 2,2′-diiodobiphenyl has also beenprepared through a two-step procedure starting from 2,2′-diaminobiphenyl. Here, the two amino groups were diazo-tized with a HCl/NaNO2 mixture, followed by complexationwith potassium iodomercurate. The intermediate is subsequently

decomposed through pyrolysis to obtain diiodobiphenyl in 50%yield (eq 4).4

I

I1. Koser's reagent (1 equiv)

CH3CN, rt, 4 day

I 2. KI

3. 200 ºC

41%

(2)

I

1. CH3CO3H, (CH3CO)2O

conc. H2SO4, < 10 ºC

2. KI

3. 200 ºCI

I(3)

NH2

H2N

1. HCl, NaNO2, Urea

0 ºC, 15 min

2. HgI2, KI

H2O, 15 min

50%

I

I

(4)

Isoamyl nitrite has also been used as the diazotizing agent inthe presence of diiodomethane as the iodine source to obtain 2,2′-diiodobiphenyl in 60% yield (eq 5).5

NH2

H2N

Isoamyl nitrite (10 equiv)

CH2I2, rt to 80 ºC

60%

I

I

(5)

An iodine–magnesium exchange procedure was utilized toachieve a direct synthesis of 2,2′-diiodobiphenyl starting from1,2-diiodobenzene using CuBr·Me2S in the presence of a 1,3-dinitrobenzene-derived oxidant (eq 6).6

I

I

1. iPrMgCl (1 equiv)

THF, –20 ºC

2. CuBr·Me2S (0.5 equiv)

3. Oxidant (1 equiv), THF

I

I66%

O2N

NO2

N

O

N

Oxidant

(6)

In an alternative approach, using Pd(II) as the catalyst, arynesunderwent dimerization and subsequent distannylation withhexamethyldistannane to give 2,2′-bis(trimethylstannyl)biphenyl.This reagent can be readily converted into 2,2′-diiodobiphenylsimply by stirring in DCM in the presence of I2 at 20 ◦C (eq 7).7

2 2,2′-DIIODOBIPHENYL

TMS

OTf

KF, 18-crown-6

Pd(OAc)2 (2 mol %)

I2 (2.1 equiv), CH2Cl2

55%

I

I

OPO

OEt

Ligand

+

SnMe3

SnMe3

(7)SnMe3

Me3Sn

Ligand (10 mol %)

THF, 20 ºC

In a transition metal-free approach, a methodology was de-veloped based on the homocoupling of 2-iodophenyl Grignardreagent to obtain the required compound directly in the presenceof substoichiometric amounts of an organic oxidant (eq 8).8 It wasfound that by using the corresponding organomagnesium reagent,the yield of the homocoupling product can be improved to 80%.

MgCl.LiCl

Oxidant (0.5 equiv)

–40 °C, 12 h

I

I

I

40%

Mg

I

2

Oxidant (0.5 equiv)

–40 °C, 12 h80%

(8)

O

O

Oxidant

Synthesis of Biphenylene. An elegant synthesis of bipheny-lene was reported using a one-pot strategy. 2,2′-Diiodobiphenylwas treated with n-BuLi to generate dilithiobiphenyl followedby reaction with 1.1 equiv of ZnCl2 to form dibenzozincacy-clopentadiene. This reactive zinc species were treated with 3 equivof CuCl2 to obtain biphenylene in 81% yield along with smallamounts of tetraphenylene (eq 9).9

Synthesis of Spiro[cyclopentene-1,9′-[9H]fluorene]. In animproved procedure for the synthesis of 9,9′-spirofluorene,2,2′diiodobiphenyl was coupled with a cyclopentenyl zinc chlo-ride reagent in the presence of Pd(0) as the catalyst to give thecorresponding product (eqs 10 and 11).10 This method is moreefficient than the classical reaction sequence11 applied in the syn-thesis of this class of compounds.

I I

1. n-BuLi (2.2 equiv), THF

2. ZnCl2 (1.1 equiv)

+

81% 5%

(9)

3. CuCl2 (3 equiv)

Zn

Br

1. Li wire, THF

rt, 1 h

2. ZnCl2, THF

0 ºC to rt, 1 h

ZnCl

+

I

I

Pd(PPh3)2Cl2 (5 mol %)

(i-Bu)2AlH (10 mol %)

THF, 66 ºC, 10 h

85%

(10)

Br

1. Li wire, THF

rt, 1 h

2. ZnCl2, THF

0 ºC to rt, 1 h

ZnCl

+

I

I

1. Pd(PPh3)4 (1 mol %)

THF, 66 ºC, 10 hOO

OO

O

2. HCl/H2O

34%

(11)

Suzuki coupling was applied to the synthesis of spirofluo-rene compound; therefore, 2,2′-diiodobiphenyl was treated with 2equiv of 2-indenylboronic acid to give the corresponding productin 58% yield (eq 12).12

2,2′-DIIODOBIPHENYL 3

I

I

Pd(PPh3)4 (2 mol %)

K2CO3 (2.5 equiv)+ 2 B(OH)2

DME/H2O, reflux

58%

(12)

Synthesis of 1,1′-Dibenzo-n-butylaluminum. 2,2′-Diiodo-biphenyl upon treatment with t-BuLi in xylene followed by sub-sequent reaction with n-BuLi and AlBr3 gave 1,1′-dibenzo-n-butylaluminum that was used efficiently to prepare 9,9′-diphenyl-fluorene in 83% yield (eq 13).13

I I

1. t-BuLi (4.0 equiv)

Xylene, –78 ºC

2. n-BuLi (1 equiv)

AlBr3 (0.9 equiv)

25 ºC

Al

nBu

FF

83%

(13)

Synthesis of Dibenzosiloles and Dibenzogermoles. A cyclicdouble intramolecular arylation of a secondary silane and ger-mane with 2,2′-diiodobiphenyl was carried out in the presenceof [Pd(P(t-Bu)3)2] as catalyst and DIPEA as the base to obtaindibenzosiloles and dibenzogermoles in excellent yields (eq 14).14

I I

[Pd(P(tBu)3)2] (5 mol %)

(iPr)2EtN (3 equiv), rt, 3 day

ER

E H (2 equiv)H

R

R

R

E = SiR = Et , 88% = Ph, 89%E = GeR = Et, 88% = Ph, 87%

(14)

Spiro[silacyclobutane-1,9′-[9H-9]silafluorene] was ob-tained by reaction of 1,1′-dichlorosilacyclobutane with 2,2′-dilithiobiphenyl that was generated from the title compound viatreatment with 4 equiv of lithium (eq 15).15

I I

Si

Li (4 equiv), Et2O

SiCl Cl

75%+

(15)

Synthesis of Carbazoles. 2,2′-Diiodobiphenyl has been usedvery efficiently in metal-catalyzed reactions for the synthesis ofvarious carbazole derivatives. Various amides have been appliedas the source of nitrogen. When reacted with 2,2′-diiodobiphenylin the presence of Cu(I) as the catalyst and N,N′-dimethylethane-1,2-diamine as the ligand, an Ullmann-type coupling to obtaina variety of carbazoles in good to excellent yields is achieved(eq 16).15

I I

+H2N

O

R

CuI (20 mol %)

HNNH (20 mol %)

K2CO3 (2 equiv), Toluene, Reflux

N

O R

R = Bu, Bn, OEt, 4-OMePh, 4-NH2Ph 58–85% Yield

(16)

It was later demonstrated that aniline derivatives can also beused as the source of nitrogen under similar reaction conditions togive corresponding N-aryl carbazoles.17 Later, the combination ofsome primary amines along with 2,2′-diiodobiphenyl was used ina Pd(0)-catalyzed coupling reaction to obtain different carbazoles(eq 17).18

I I

+ R NH2

Pd2(dba)3 (0.5 mol %)

Ligand (2 mol %)

NaO-t-Bu (3 equiv)

Toluene, 80 ºC

N

R

R = n-Oct, 34% Bn, 84% 4-NO2Ph, 94%

P

NN

N

N

(17)

Synthesis of 5-Phenyl-5H-benzo[b]phosphindole The titlecompound was heated with Li wire in ether to obtain thecorresponding dilithiated compound that was quenched withphenyldichlorophosphine to obtain phenyldiphenylphosphine in6.6% yield (eq 18).19

4 2,2′-DIIODOBIPHENYL

I I

1. Li wire, Ether

2. C6H5PCl2 (1.0 equiv)

Ether, reflux P

Ph

(18)

Synthesis of Spirophosphonium Salts. At least two sepa-rate classes of spirophosphonium salts have been prepared fromdilithiated biphenyl and different phosphates (eqs 19 and 20). Bis-biphenylspirophosphonium salt can be subsequently reduced us-ing LiAlH4 to form the corresponding phosphorane (eq 20).20

Li

Li+

Et2O

HX

90%

P+

X–P

O

Ph (19)

Li

Li + PO

R

P+ X–

Et2O

HX

(20)LiAlH4

P

H

Synthesis of Dibenzothiophene. 2,2′-Diiodobiphenyl hasbeen used in a Cu(I)-catalyzed C–S coupling reaction to directlyobtain dibenzothiophene. Potassium sulfide was used as sulfursource to obtain the product in 89% yield (eq 21).21 In anotherrather lengthy procedure, 2,2′-diiodobiphenyl was treated with 1equiv of i-PrMgCl·LiCl followed by quenching with thiosulfonateto obtain the corresponding monothiolated product. This productupon further iodine–magnesium exchange and treatment with t-BuOLi gives dibenzothiophene (eq 22).22

I

IS

CuI (10 mol %)

K2S (3 equiv)

CH3CN, 140 ºC

89%

(21)

Synthesis of Dibenzotellurophene. 2,2′-Diiodobiphenyl hasbeen used in a coupling with Te–Cu bimetallic reagent to givedibenzotellurophene in 42% yield. The bimetallic reagent wasobtained by mixing disodium telluride and CuI in 1:2 molar ratioin NMP (eq 23).23

Synthesis of Dibenzo-fused 1,2-Dihydro-1,2-diborin Dian-ions. Dibenzo-fused 1,2-diborin dianion was synthesized by thereaction of dilithiated biphenyl with a bisboron compound that

gave dibenzo-fused bisborone compound as the major product thatwas reduced with KC8. The resulting diarene-fused 1,2-dihydro-1,2-diborin dianion was trapped by [2,2,2]cryptand (eq 24).24

I

I

1. i-PrMgCl.LiCl (1.1 equiv)

THF, –50 ºC, 1.5 h

2. PhSO2SCH2Ar (1.0 equiv)

THF, –50 ºC to –20 ºC, 2 h

S

I

Ar1. i-PrMgCl.LiCl (1.1 equiv)

THF, –50 ºC, 1.5 h

2. t-BuOLi, THF

–20 ºC, 20 h

S

(22)+

Ar MgX

X = Cl, OtBu

I

ITe

150 ºC

42%

Te-Cu , NMP(23)

I I

1. n-BuLi (5 equiv) Toluene, rt

B BBr

NMe2Me2N

Br

B BMe2N NMe2

1. KC8, THF

2. [2.2.2]cryptand

PentaneB B

Me2N NMe2

2–

2[K+([2.2.2]cryptand)]

(24)

Synthesis of Phenanthrene Derivative. In a Pd-catalyzedcoupling of 2,2′-diiodobiphenyl with indenyl tin reagent, a fusedphenanthrene derivative was obtained in modest yield (eq 25).10

I

I

PdCl2(PPh3)2 (5 mol %)+ 2

SnBu3

26%

(25)

2,2′-DIIODOBIPHENYL 5

Synthesis of 9,10-Dihydrophenanthrenes. An aryl-substituted analog was synthesized from 2,2′-diiodobiphenylthrough a four-step reaction sequence in good yield (eq 26).25

I I

1. n-BuLi (2.2 equiv), THF

2. Ar2C=O, Xanthone

3. HBF4/(EtCO)2O

4. SmI2

81% O

ArAr

(26)

Synthesis of Imidazo[1,2-f]phenanthridine. 2,2′-Diiodo-biphenyl was used in copper-catalyzed domino N-arylation and C-arylation with imidazole to form a nitrogen heterocycle (eq 27).27

I

I

CuI (10 mol %)

Cs2CO3 (3 equiv)

DMF, 160 ºC

29%

+NH

N

N

N

(1.5 equiv)

(27)

Synthesis of Seven-membered Cyclic Systems Derived from2,2′-Diiodobiphenyl.

Synthesis of Dibenzocycloheptatriene Derivative. Tricyan-odibenzocycloheptatriene can be prepared in one step from di-iodobiphenyl and malonitrile through a Pd(0)-catalyzed reaction(eq 28).25

I

I+ NC CN

(4 equiv)

Pd(PPh3)4 (10 mol %)

THF, reflux

56%

NH2

NC CNCN (28)

Synthesis of Acyclic Systems Derived from 2,2′-Diiodo-biphenyl. 2,2′-Diiodobiphenyl, upon dilithiation by n-BuLi andsubsequent treatment with B(OMe)3, gave 2,2′-biphenyldiboronicacid after hydrolysis. This was demonstrated to effectively partic-ipate in a Suzuki-coupling protocol with 2-bromoindene to forma 2,2′-diindenebiphenyl (eq 29).12

The title compound has been used to prepare 2,2′-dialkylbiphenyl as well. In a Pd(II)-catalyzed reaction, [(3-dimethylamino)propyl]dimethylaluminum was used as the alky-lating agent to obtain 2,2′-dimethylbiphenyl in almost quantita-tive yield (eq 30).27 In a different approach toward alkylation,2,2′-diiodobiphenyl was first treated with Zn·LiCl to generate thecorresponding zinc reagent followed by coupling with allylbro-mide in a Cu(I)-catalyzed step to form 2,2′-diallylbiphenyl in 49%overall yield (eq 31).28

I I

1. n-BuLi (2.7 equiv), TMEDA

2. B(OMe)3, HCl, H2O

(HO)2B

B(OH)2

Br

Pd(PPh3)4 (7 mol %)

K2CO3 (3 equiv)

DME–H2O

79%

(29)

I

I+

Al

N

PdCl2(PPh3)2 (2 mol %)

(0.505 equiv)

C6H6, 50–80 ºC

99%

(30)

I

I

1. Zn·LiCl (5 equiv)

50 ºC, 6 h

2. CuCN·2LiCl (2 mol %)

Allylbromide (2.4 equiv)

(31)

49%

2,2′-Diiodobiphenyl has been applied in the synthesis of chiral,configurationally stable biphenyl-bridged metallocenes.29 In thefirst synthesis, the ferrocenyl zinc chloride was coupled with 2,2′-diiodobiphenyl in a Pd(0)-catalyzed process to obtain the corre-sponding 2,2′-diferrocenylbiphenyl in 71% overall yield (eq 32).In the synthesis of biphenyl-bridged ansa-ferrocene, zinc chlo-ride salt of dilithioferrocene was coupled with 2,2′-diiodobiphenylthrough the same Pd(0) procedure as in the previous case (eq 33).

Fe

ZnCl Pd(PPh3)2 (5 mol %)

THF, 65 ºC

Fe

Fe

71%I

I +

(32)

6 2,2′-DIIODOBIPHENYL

Fe

ZnCl

ZnCl

I

I

Pd(PPh3)2 (5 mol %)

THF, 65 ºC

Fe

20%+

(33)

Synthesis of Hypervalent Imidoiodine(III) Reagents. Thetitle reagent has been used to generate a dinuclear bisimidoio-dine(III) reagent upon oxidation with selectfluor followed byaminolysis using HNTs2.30 This hypervalent reagent was shown tosuccessfully carry out the diamination of various alkenes (eq 34).

I

I

1. Selectfluor

AcOH/CH3CN

rt

2. HNTs2 (4 equiv)

C6H5Cl/CHCl3

50 °C

I(NTs2)2

I(NTs2)2

90%

(34)R′

R

CH2Cl2, rt R′R

NTs2

NTs2

2,2′-Diiodo-4,4′,6,6′-tetramethylbiphenyl, a derivative of 2,2′-diiodobiphenyl, has been used in combination with peracetic acidas the organocatalytic system to carry out intramolecular andintermolecular oxidative C–H bond amination. A variety of 2-acetaminobiphenyls were efficiently converted into correspondingcarbazoles under these organocatalytic conditions (eq 35).31 In theintermolecular version of this reaction, a range of amides was cou-pled with various arenes under mild reaction conditions (eq 35).32

NHAc

R1

R2 Catalyst (10 mol %)

AcOOH (2 equiv)

CH2Cl2/HFIP (1:1), rtNAc

R1

R2

R1

N

H

O

X+ R

2

Catalyst (10 mol %)

AcOOH (2.2 equiv)

DCE, TFA (5 equiv), rt

R1

N

O

X

R2

(35)

I

I

Catalyst

1. Dougherty, T. K.; Lau, K. S. Y.; Hedberg, F. L., J. Org. Chem. 1983, 48,5273.

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5. Smith, W. B.; Ho, O. C., J. Org. Chem. 1990, 55, 2543.

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7. Yoshida, H.; Tanino, K.; Ohshita, J.; Kunai, A., Chem. Commun. 2005,5678.

8. Krasovskiy, A.; Tishkov, A.; del Amo, V.; Mayr, H.; Knochel, P., Angew.Chem., Int. Ed. 2006, 45, 5010.

9. Iyoda, M.; Kabir, S. M. H.; Vorasingha, A.; Kuwatani, Y.; Yoshida, M.,Tetrahedron Lett. 1998, 39, 5393.

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13. Terao, J.; Nakamura, M.; Kambe, N., Chem. Commun. 2009, 6011.

14. Yabusaki, Y.; Ohshima, N.; Kondo, H.; Kusamoto, T.; Yamanoi, Y.;Nishihara, H., Chem. Eur. J. 2010, 16, 5581.

15. Terunuma, D.; Nakamura, M.; Miyazawa, E.; Nohira, H., Bull. Chem.Soc. Jpn. 1987, 60, 2263.

16. Li, E.; Xu, X.; Li, H.; Zhang, H.; Xu, X.; Yuan, X.; Li, Y., Tetrahedron2009, 65, 8961.

17. Liao, Q.; Zhang, L.; Wang, F.; Li, S.; Xi, C., Eur. J. Org. Chem. 2010,5426.

18. Zhou, Y.; Verkade, J. G., Adv. Synth. Catal. 2010, 352, 616.

19. Wittig, G.; Geissler, G., Liebigs. Ann. Chemie. 1953, 44.

20. Turnblom, E. W.; Hellwinkel, D., J. Chem. Soc., Chem. Commun. 1972,404.

21. You, W.; Yan, X.; Liao, Q.; Xi, C., Org. Lett. 2010, 12, 3930.

22. Stoll, A. H.; Krasovskiy, A.; Knochel, P., Angew. Chem., Int. Ed. 2006,45, 606.

23. Suzuki, H.; Nakamura, T., J. Org. Chem. 1995, 60, 5274.

24. Araki, T.; Wakamiya, A.; Mori, K.; Yamaguchi, S., Chem. Asian J. 2012,7, 1594.

25. Suzuki, T.; Ono, K.; Nishida, J.; Takahashi, H.; Tsuji, T., J. Org. Chem.2000, 65, 4944.

26. Liao, Q.; Zhang, L.; Li, S.; Xi, C., Org. Lett. 2011, 13, 228.

27. Blum, J.; Gelman, D.; Baidossi, W.; Shakh, E.; Rosenfeld, A.;Aizenshtat, Z., J. Org. Chem. 1997, 62, 8681.

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Rishikesh Narayan & Andrey P. AntonchickMax-Planck-Institut für Molekulare Physiologie,

Dortmund, Germany