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Generation of arylzinc reagents through an iodine–zinc exchange reaction
promoted by a non-metallic organic superbasew

Published on 09 June 2010. Downloaded by Universitat de Barcelona on 15/04/2016 16:19:54.

Hiroshi Naka,*ab Keisuke Ito,a Masahiro Ueno,a Koji Kobayashia and
Yoshinori Kondo*a
Received (in Montpellier, France) 16th March 2010, Accepted 28th April 2010
DOI: 10.1039/c0nj00202j
Functionalized aryl and heteroaryl zinc reagents were prepared from aryl iodides and diethylzinc
through t-Bu-P4 base-promoted iodine–zinc exchange reactions. The scope and limitations of this
protocol, and several applications for the synthesis of oligoaryls and fused aromatics, are
presented.

Introduction
Arylzinc compounds are important reagents for the synthesis
of the functionalized aromatic compounds that are important
constituents of biologically-active compounds.1 Compared to
sister aryllithium or arylmagnesium compounds, arylzinc
compounds display less but chemoselective reactivity.
Accordingly, arylzinc reagents have been widely used for
chemoselective reactions, such as Negishi cross-couplings with
unsaturated organic halides and asymmetric additions to
carbonyl compounds.1,2 The preparation of arylzinc compounds
has been accomplished through transmetalation from aryllithium or arylmagnesium compounds, but this method suffers
from the limited compatibility of the aryllithium or arylmagnesium reagent towards functional groups on the aromatic
ring.3 Recently, several improved methods have been developed
to enable the generation of variously-functionalized aromatic
zinc compounds.4–6 For instance, the use of lithium dialkylamidozincates [R2Zn(tmp)Li] and related zincate complexes,4,5
or simple amidozinc reagents,6 has allowed the direct zincation
of aromatic rings. The LiCl-promoted direct metal insertion of
Zn(0) dust to aryl halides,7 or the halogen–zinc exchange of
aryl halides8 mediated either by lithium zincates (R3ZnLi8b or
R4ZnLi28c–e) or by i-Pr2Zn and 0.1 equiv. Li(acac)8f,g give the
corresponding functionalized organozinc regents. However,
these methods often require extra metallic compounds other
than zinc, such as alkali or transition metals, which, in some
cases, can cause problematic side reactions.9
We have recently reported that phosphazene base t-Bu-P410
dramatically promoted the generation of arylzinc compounds
from aryl iodides 1 through iodine–zinc exchange reactions
(Fig. 1 and Scheme 1).11,12 This method utilizes commercially
available diethylzinc as a zincation reagent. Although diethylzinc is pyrophoric, this protocol does not require any other
a

Graduate School of Pharmaceutical Sciences, Tohoku University,
Aramaki Aza Aoba 6-3, Aoba-ku, Sendai 980-8578, Japan.
E-mail: ykondo@mail.pharm.tohoku.ac.jp; Fax: +81 22-795-6804;
Tel: +81 22-795-6804
b
Research Center for Materials Science, Nagoya University,
Chikusa, Nagoya 464-8602, Japan.
E-mail: naka.hiroshi@a.mbox.nagoya-u.ac.jp;
Fax: +81 52-789-5904; Tel: +81 52-789-5904
w This paper is dedicated to the memory of Professor Pascal Le Floch
and is part of a themed issue on Main Group chemistry.

1700 | New J. Chem., 2010, 34, 1700–1706

This journal is 

c

Fig. 1

Phosphazene bases.

Scheme 1 Zincation of aryl iodide 1a in the presence of a phosphazene base.11

metallic promoters. The resulting salt-free arylzinc reagents
can be functionalized by various electrophiles. In this paper,
we detail the scope and limitations of this arylzinc generation,
and several applications for the synthesis of structurallydefined, multi-functionalized aromatic compounds.

Results and discussion
Chemoselective generation of 2-iodoarylzinc reagents
In our previous conditions (Scheme 1), the reactivity in the
zincation of complex substrates was rather limited. For
instance, the mono-zincation of 1,2-diiodobenzene (1b)
proceeded slowly under the typical reaction conditions and
hydrolysis yielded iodobenzene (2b) in only 54% yield, with
the recovery of 1b in 46% yield (Table 1, entry 1). The selective
preparation of 2-iodoarylzinc species is considered difficult
because of competitive bis-zincation or benzyne generation
through 1,2-elimination.7,13 After re-investigating the reaction
conditions, we found that the use of a polar aprotic solvent
significantly accelerated the reaction rate (Table 1, entries
2–5). Although benzene (3b) was also observed in 3–13%
yield, the yield of 2b was increased up to 72–93%. Dimethylacetamide (DMA) proved to be the best solvent, allowing
mono-zincation at room temperature to yield 2b in 93%
selectively after a methanol quench. Surprisingly, the reaction

The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2010

6b.2-diiodobenzene in the presence of phosphazene basea Table 2 Phosphazene base-promoted zincation–allylation sequencesa Published on 09 June 2010. 1700–1706 | 1701 . Entry Substrate Entry Solvent Yield of 2b (%) Yield of 3b (%) Recovery of 1b (%) 1 2 3 4 5 6b 7c DMF NMP DMA DMI DMPU DMA DMA 54 72 93 77 85 73 59 o1 7 3 5 13 11 18 46 21 4 18 2 16 23 1 1b Product Yield (%) 91 2b 65 3 71 NMR yield. yielded 2-allyl-iodobenzene (4b) in 91% yield (Table 2. 6 83 7 90 8 97 9 76 10 98 11 77 12c 81 a The trapping of functionalized arylzinc reagents With the improved conditions in hand.. 4 95 5 76 proceeded in DMA using t-Bu-P1 base (5 mol%). This protocol transformed dihaloaromatics 1c–e to mono-allylated products 4c–d in 65–95% yields (Table 2. 2010. entry 6.16e Thus.N 0 dimethylimidazolidinone. Overall.N-dimethylformamide. c Quenched with benzaldehyde instead of allyl bromide.15 The 2-pyridylzinc intermediate was trapped with benzaldehyde instead of allyl bromide because 2-allylpyridine is highly volatile. Aryl and heteroaryl iodides with perfluoroalkyl groups 1j–l also underwent the reaction to yield the corresponding allylated products 4j–l in 76–98% yield (Table 2. we tested the phosphazene base-promoted zincation–allylation sequence for various aromatic iodides (Table 2). ZnEt2 was used. 5m. b t-Bu-P1 (5 mol%) was used instead of t-Bu-P4. Biaryl synthesis through the oxidative coupling of arylzinc reagents Oxidative homo-coupling16 of arylzinc intermediates is a powerful method for the preparation of synthetically useful biphenyls. O-Allyl-2-iodophenyl ether (1g) resisted cyclization and yielded allylated product 4g. and the corresponding alcohol. entry 5. DMA = N. 83%). Zincation of p-cyanoiodobenzene (1f) and allylation proceeded without the loss of the cyano group (Table 2. entry 7). b 0. followed by trapping of the arylzinc intermediate with allyl bromide at room temperature. entries 2–4). Downloaded by Universitat de Barcelona on 15/04/2016 16:19:54. This journal is  c a NMR yield. DMI = N. excluding the formation of radical intermediates (Table 2. entries 6 and 7). 34. as demonstrated in the pioneering reports by Knochel and co-workers. entries 9–11).N 0 -dimethylpropyleneurea. DMPU = N. or even without any base. was obtained in 81% yield (Table 2. entry 12). Zincation at the 3-position of protected indole 1h proceeded at room temperature without thermal migration to the 2-position (Table 2. DMF = N. c Without t-Bu-P4. we next tested the application of this transformation to the arylzinc compounds prepared by the phosphazene-promoted iodine–zinc exchange The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2010 New J. 76%).View Article Online Table 1 The mono-zincation of 1. the t-Bu-P4 base-promoted zincation in DMA proved to be a powerful method for the chemoselective preparation of multi-functionalized aromatic and heteroaromatic zinc reagents. The selective zincation of 1b at room temperature for 24 h. but the product yield and selectivity were lower than the t-Bu-P4 base-promoted system (Table 1. Chem.6 eq. NMP = N-methylpyrrolidone. These products can be easily separated from non-fluorous compounds using so-called fluorous technology. entry 1).14 Pyrazine 1i also underwent zincation– allylation to yield allylated product 4i in 97% yield (Table 2. entry 8).N-dimethylacetamide.

(a) 0.17 Triphenylene derivatives are one of the simplest two-dimensional p-conjugated nanocarbon frameworks and have been used as core chemical building blocks for functional materials. terphenyl 6ns was obtained in 78% yield. we aimed for the programmed and discrete synthesis of non-symmetrical multi-substituted triphenylenes 7 using the presented zincation–functionalization sequence (Scheme 3). 1700–1706 This journal is  c than symmetrically-functionalized frameworks. and the crosscoupling product. 1702 | New J. a reaction that gives only the desired single isomer would be of importance.5 mol% Pd2dba3. followed by the homo-coupling. Scheme 4 The regiocontrolled synthesis of substituted triphenylenes 7. entries 3–5).2 eq. View Article Online reaction (Table 3).5 mol% Pd2dba3. As a typical example. 1r and 1a. 20 mol% PCy3.6 eq. 5 mol% P(2-furyl)3.6 eq. Selective mono-zincation of iodothiophenes 1o–q.) in the presence of t-Bu-P4 base (5 mol%). 5 mol% t-Bu-P4. (d) 2-iodo-4 0 -methoxylbiphenyl (1t). (b) 2-iodo-4 0 methylbiphenyl (1s).19 Because these isomers are not easy to separate. entry 1). (c) 10 mol% Pd(OAc)2. followed by the addition of chloranil. 2. 2010. ZnEt2. The zincation of 1r using 1. MW 300 W.20 As a result.Published on 09 June 2010. In addressing this issue. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2010 . The synthesis of non-symmetrical multi-substituted triphenylenes using functionalized arylzinc reagents The non-symmetrical substitution of p-conjugated nanocarbon frameworks is an important topic in modern synthetic chemistry. As a result. DMA. Scheme 4 shows a phosphazene base-promoted iodine–zinc exchange reaction of 1n followed by a Negishi cross-coupling with 2-iodo-4 0 -methylbiphenyl (1s). 24 h. The Pd-catalyzed annulation Scheme 3 Programmed synthesis of non-symmetrically substituted triphenylenes. DMF. as it often affords higher degrees of functionality Table 3 Oxidative homo-coupling of arylzinc reagents Entry ArI Ar–Ar Yield 6n 57 6h 72 3 6o 92 4 6p 91 5 6q 85 1 2 1h Scheme 2 The oxidative cross-coupling of aryl iodides 1r and 1a. 24 h. gave the corresponding bisthiophenes 6o–q in 85–92% yield (Table 3. 34. but even this method gave a mixture of isomers when non-symmetrical benzynes were used. 2 eq. transition metal-free biaryl synthesis is characteristic of the presented iodine–zinc exchange method. the corresponding biaryl. entry 2). was also tested (Scheme 2). Although the chemical yield of the cross-coupling product was rather low. 6n. K2CO3. aryl iodide 1n was treated with diethylzinc (0. nonsymmetrical construction of these frameworks is considered difficult because classical condensation or functionalization methodologies suffer from the formation of regioisomer side-products. 24 h. The homo-coupling of indole 1h provided bisindole 6h in 72% yield (Table 3. diethylzinc was followed by the successive treatment of 1a and chloranil.. Downloaded by Universitat de Barcelona on 15/04/2016 16:19:54. Chem. was obtained in 57% yield (Table 3. 100 1C. rt. 3 h. the transition metal-free cross-coupling of two aryl iodides. rt. In addition. rt. 6ra.18 However. have reported an efficient method for constructing non-symmetrical triphenylenes using a benzyne annulation strategy. Larock et al. 2. 5 mol% P(2-furyl)3. was obtained in 43% yield.

HRMS: calc. 1178.43 (m.11 (m.15 (s. Yield: 76%. 914. 2H). J = 7. 1H).40–3. colorless crystals. 1700–1706 | 1703 . 709.9. 1 H NMR (400 MHz. 1639.60 mmol) and dry DMA (0.025 mL. 46. 4. 1148. 1021. colorless oil. 1H). Anal.33 (d.8 Hz.65.9. IR(neat): 2360.7. Furthermore. CDCl3) d (ppm): 39. no other regioisomer was formed. The reaction was carried out using 0. CDCl3/TMS) d (ppm): 3.3 Hz. 1459. m = multiplet.3 Hz. J = 7. on JEOL JMS-DX303 and JMS-700 spectrometers. Low and high resolution mass spectra (LRMS and HRMS) were obtained from Mass Spectrometry Resource.6 eq.6.0 cm1.6.5. J = 8. The spectra were acquired as 32 scans per spectrum at a resolution of four using system ReactIRTM 2. 5. 756. found: 227. 1725.50 MHz for 13C). 8. 6.Published on 09 June 2010. 4i. for C9H9I: 243. 2H).95 (m. Graduate School of Pharmaceutical Sciences.and heteroarylzinc compounds without using alkali or transition metal promoters. diethylzinc. LRMS (EI) m/z: 227 (M+). 7.93%. Chem. and 6 and 7 were easily separated from the minor hydrolyzed side products using silica gel chromatography. Yield: 71%. 7. 127. 1196.9 Hz. for C8H9N2BrO: 227. 7. Infrared (IR) data were recorded on a SensIR ATR (attenuated total reflectance) FT-IR.84–5. found: 243. 1H). J = 6. 1133.1. 2360. Melting points (mp) were determined with a Yazawa micro melting point apparatus and are uncorrected. 0–10% EtOAc or CHCl3 in hexane) to give 4.60 mmol) was added to the reaction mixture and stirred for 24 h at room temperature. 8. The mixture was treated with saturated aq. 4c.97–6.87 (d.30 (m. 2H). View Article Online of 6ns under microwave irradiation afforded non-symmetrical triphenylene 7ns in 81% yield. 1H NMR spectra were referenced to a tetramethylsilane internal standard or to a solvent signal (CDCl3: 7. 1536. 880. 0.2-Diiodobenzene (1b.8 cm1. for C23H17O3S: C. 5. Chemical shifts are expressed in d (parts per million.5. 1273.0623. the zincation– coupling protocol proved to be an efficient and reliable method for constructing terphenyls and non-symmetrical functionalized triphenylenes in a programmed and discrete manner.07–5. 0. IR(neat): 3076. IR(neat): 2950.3 Hz.67. J = 8.21 4d.60 mL.01–5.5.3. 5. NMR data were recorded on a JEOL AL400 spectrometer (395.60 mL. 7. Yield: 97%.5.0300. respectively.0644.96 (m. 7. 5. 1362. In all cases. 39. 899. The extract was washed with brine and dried over MgSO4. Chemoselective zincation of various aromatics and heteroaromatics generated functionalized aryl.0 M solution in n-hexane (0. These arylzinc intermediates underwent allylation and oxidative coupling.96 (d. J = 8. Aryl iodide-bearing trifluoromethyl compound 1u afforded terphenyl 6us in 61% yield and triphenylene 7us in 70% yield. 5.3 Hz.27 (d.8 Hz. 1414. 1562.3 Hz. 5.6 Hz. 2H). 0. found: 692.08 (m. 2H).90.5. Yield: 98%. J = 6.62 (t. Spectral data for 4b. dd = double doublet. 2H). for C23H13F17O3S: 692. 1382. 2H) 13C{1H}NMR (100 MHz. 1H).2.3.4. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2010 New J. 1007. 1063. 1199.02 (t.0 ppm). ppm) values. 130. 99. J = 6. 703. 2H). 1469. 1H).025 mmol) was added to the solution at room temperature and the mixture stirred for 24 h. IR(neat): 2357.63. 7. 2H). O. The same protocol using 2-iodo-4 0 -methoxybiphenyl (1t) instead of 1s gave terphenyl 6nt in 56% yield and triphenylene 7nt in 58% yield. HRMS: calc. 4j.7. 2311. for C20H13F17O2: 608. 1H).20 software. 1638.12–5.88 (d.0314. HRMS: calc. 54. J = 7.75 MHz for 1H.2 cm1. 919.025 mL. 1427. LRMS (EI) m/z: 244 (M+).3.60 mmol) and dry solvents noted in the text (0.and chemoselective synthesis of complex aromatic compounds. 7.89.24 4h8g and 5m25 were identical to those in the literature.9898. 1H). 1169.12 (m. mp 66–70 1C. 136. 5. brown oil. t = triplet. found: C. 135. The mixture was then treated with methanol.07 (m.33 (d. 770. calc.025 mmol) was added to the solution at room temperature and the mixture stirred for 24 h. 39.9 Hz.09 (d.7. 1. d = doublet. The solvent was removed under reduced pressure and the crude product purified by silica gel column chromatography (gradient elution. and coupling constants are expressed in Hertz (Hz). CDCl3) d (ppm): 36. Conclusions The scope and limitations of the phosphazene base-promoted iodine–zinc reaction on aromatic and heteroaromatic iodides were investigated.23 4g.55 (m.89–5.6 Hz. a diethylzinc 1. 5. 1H NMR (400 MHz. 2H).50 mL) were added to a test tube sealed with a septum equipped with a magnetic stirring bar under an argon This journal is  c atmosphere. 1H NMR (400 MHz. 2H). 137. 1612. J = 7. 4. 2010. NH4Cl and the mixture extracted with EtOAc. 2922. dt = double triplet and br = broad. Absorbance frequencies are reported in reciprocal centimetres (cm1). the present protocol was found to be a powerful method for the regio. CDCl3/TMS) d (ppm): 2.22 4e.00 (s. Microwave irradiation was performed on CEM’s DiscoverTM. 1501.. 0. 1290. 3.5 Hz. 133. 1H NMR (400 MHz. To summarize. S. 1.3.2 cm1.50 mmol). 0. 133. 2H). q = quartet. Tohoku University. CDCl3/ TMS) d (ppm): 3.07–5.3 Hz.9751. Allyl bromide (72 mg. LRMS (EI) m/z: 608 (M+).45 (d. F.26 ppm). HRMS: calc. J = 8.53–7. J = 7.21 4f.15 (d. 7. 2H). A t-Bu-P4 1.93. 137. Allylation reactions of arylzinc compounds prepared from aryl iodides using Et2Zn/t-Bu-P4 Aryl iodide 1 (0.91–5. A t-Bu-P4 1. 1H). 94.5. H. 13C NMR spectra were referenced to a tetramethylsilane internal standard or to a solvent signal (CDCl3: 77. 142.9749. 117.72 (t. 0. 6. 1H). Experimental General comments Reactions were carried out under an Ar atmosphere using dry solvents. The following abbreviations are used: s = singlet. 34. recrystallized from hexane. colorless oil. a diethylzinc 1. found: 608.0. 1H).50 mL) were added to a test tube sealed with a septum equipped with a magnetic stirring bar under an argon atmosphere.90 (m. Iodine–zinc exchange reaction using Et2Zn/t-Bu-P4 1.50 mmol). Downloaded by Universitat de Barcelona on 15/04/2016 16:19:54. 1596. CDCl3/TMS) d (ppm): 3. 2H). 157. The yields of 2b and 3b were determined by 1 H NMR. J = 6. 143. 1127. 956. 116.9863. 1H) LRMS (EI) m/z: 692 (M+).18 (m. 13C{1H}NMR (100 MHz. 4. 4k.0 M solution in n-hexane (0.0. 3H).08 (d.0 M solution in n-hexane (0. H.0 M solution in n-hexane (0.

1745.4 Hz.1 mg.8 mg. 7.025 mL. 0. Ethyl 4-iodobenzoate (138.7 Hz. 7. CDCl3/TMS) d (ppm): 2. The mixture was treated with saturated aq.0 mg.60 mmol).50 mmol). 818.5 Hz. a diethylzinc 1. J = 8. 3. 127. 5. mp 83–84 1C.38–7. 1015. 6.1.5 Hz. 2-Iodo-4 0 -methylbiphenyl 1s (176 mg. 1H NMR (400 MHz. 145. Synthesis of non-symmetrically substituted triphenylenes (7ns) To a test tube equipped with a magnetic stirring bar containing 6ns (95.67 (m.14–7. 112. J = 8. HRMS: calc. 0. 43%) of 2 0 -methoxy-biphenyl-4-carboxylic acid ethyl ester (6ra) as a 1704 | New J. CDCl3/TMS) d (ppm): 7. 2H).99 (d. 117. found: 390.3. CDCl3/ TMS) d (ppm): 3. 130. 2343. 130.54 (d.025 mmol) was added to the solution at room temperature and the mixture stirred for 24 h.9.3.0 M solution in n-hexane (0. IR(neat): 3058. 13C{1H}NMR (100 MHz. 2H).4. Downloaded by Universitat de Barcelona on 15/04/2016 16:19:54. 3H).17. for C25H14NO2F17S: 715.21 (t. 2H). 146. 1H NMR (400 MHz.40–7. 1130.0231. calc. IR(neat): 1378.58 (m. 1609. 126. 2H).5. 0. CDCl3) d (ppm): 113. 2H).50 mL) were added to a test tube sealed with a septum equipped with a magnetic stirring bar under argon atmosphere.04 (m.67 (d. 139. H. 137. 129.3. 126. Recrystallized from chloroform. CDCl3/TMS) d (ppm): 3. 1272.7 Hz. 6.32 (t. 129. 34. 2834. IR(neat): 2969.2. 7. 1437. 124. 1567. LRMS (EI) m/z: 512 (M+). 124. 0. IR(neat): 3000.3. 125.0 Hz. 158. CDCl3) d (ppm): 55.66 (m.4 cm1. 123. 909. J = 7. 117.54–7.09 (d.6 eq.5 Hz. 1318.1.5.7 Hz. 760.26%. 55. 2010. 4. J = 7.98–8.44 (m.9. 3H).7 Hz. 731 cm1. 126. 114.3. NH4Cl and the mixture was extracted with EtOAc. 0. 745.4 mg.0 M solution in n-hexane (0. HRMS: calc. 711. 1H). 3. 138.6 mg. 139. 130. 0. 2H). for C20H17BrO2: 368.33 (m. 7. 1216. LRMS (EI) m/z: 715 (M+). S.0. 7.025 mL. F. The extract was washed with brine and dried over MgSO4. O. 1. 7.6.3.0.1.1. 7. 7.9 cm1.0864. 1.1. 1H NMR (400 MHz. LRMS (EI) m/z: 352 (M+).6. 132. 1590.8. 120.2. 129.0. 2359.27 6p28 and 6q29 were identical to those in the literature.025 mL. J = 4. 5H). 142. 2H). 0.7 Hz.8 mg (yield.75.97.47. colorless oil. J = 8. Yield: 77%.63–6. 0. The resulting mixture was stirred at 100 1C under microwave irradiation for 3 h.5.025 mmol) in DMA (0.. Yield: 70%. 138. found: C. 128. 2H). 2H). 1383. J = 6. 158.2 Hz). 2. 6H).5 Hz. 129. HRMS: calc.054 mmol) was added dry DMF (0.7.47 (m. mp 273 1C.2 eq. The solvent was removed under reduced pressure and the crude product purified by silica gel column chromatography (gradient elution.07–5. 7.9. 1H).1.0412.4. a diethylzinc 1.76 (s.4. Pd2dba3 (11. 1067.025 mmol) was added to the solution at room temperature and the mixture stirred for 24 h. 143. LRMS (EI) m/z: 390 (M+). 1028.50 mmol). 966. 41. colorless oil. 1145. HRMS: calc.4.2. 7. 114.4. 130. 1472. 1175.) and dry DMA (0. 1H).8. 133. 1027.94 (d. 1700–1706 This journal is  c 6us. 138. 128. J = 8.9. 130. 128.99 (m.0.2 Hz). for C28H20N2O4S2: 512. 754.30 mmol) and dry DMA (0. 115. 0.2 cm1. 78%) of 6ns as colorless oil.10 (s. 1735.05 (d. 1371. 134. 6nt. LRMS (EI) m/z: 368 (M+). 132. 2H). 2923.2. J = 7.0. 0.9 cm1.6.027 mmol) and PCy3 (15.1.27 mmol). 6h. 123.0. 1H). 0.6 (q. 0. A t-Bu-P4 1. Anal.39 (d.2. 1H). colorless needles.0456.9. 6.83 (s.29–7. The solvent was removed under reduced pressure and the crude product purified by silica gel column chromatography (3.5. J = 4. 1177.0474.50 mmol). 13C{1H}NMR (100 MHz. diethylzinc 1. 137. found: 368.025 mmol) was added to the solution at room temperature and the mixture was stirred for 24 h. 13C{1H}NMR (100 MHz.48 (m. 7.5. 113. 129. The solvent was removed under reduced pressure and the crude product was purified by silica gel column chromatography (1% EtOAc–hexane) to give 135. 7.35 (s. NH4Cl and the mixture extracted with EtOAc. 129.Published on 09 June 2010. 2H). Pd(OAc)2 (6. 140. 5. 1169. 41. HRMS: calc. 7. J = 6. 4H).4. 2H). 125. The extract was washed with brine and dried over MgSO4. Chloranil (129.2. 8.50 mL) were added to a test tube sealed with a septum equipped with a magnetic stirring bar under an argon atmosphere. 7.28 (s.4.14.74 (d. 1H NMR (400 MHz. The extract was washed with brine and dried over MgSO4. 1H). 924. 756. 143. 3H). 1463.0 M solution in n-hexane (0. for C20H14BrF3: 390.7. 1H).525 mmol) in DMA (0. 2H). colorless oil. found: 512. Yield: 61%. 140. IR(neat): 2958 (br).5 (q. 6.96. 124.1 mg. 1H NMR (400 MHz.46 (d.30 mL.0.0 M solution in n-hexane (0.50 mL) were added to a test tube sealed with a septum equipped with a magnetic stirring bar under an argon atmosphere.50 mmol) was added to the reaction mixture and stirred for 15 h at room temperature. 1079.0. 140.0.63 (s. 1.3.1. N. The mixture was treated with saturated aq.7.48. 129. 9H). 114. 129.0 mg. 7. 1125. 45. CDCl3/ TMS) d (ppm): 2.3. 136.97.0 (2C). 13C{1H}NMR (100 MHz.0853.0233. 4. 831. 4H). 0.8.5. 2H). 0.28 (m. for C20H17BrO: 352. 1241. 1463. H. found: 352.50 mL) under an argon atmosphere.1. 0.48 (m. colorless crystals. A t-Bu-P4 1.1. 127.9.) and dry DMA (0.0463.34 (m.92–5.26 6o. 0. 129.5. The mixture was treated with saturated aq. Spectral data for 6n.7 Hz. 130.3% EtOAc–hexane) to give 54. 7.3. N.0471. J = 6.2.50 mL) was added to the reaction mixture and stirred for 20–24 h at room temperature. 2-Bromo-5-methoxy-iodobenzene (1n) (156. CDCl3) d (ppm): 21. 130. found: 715.09 (d. 129. 700. Oxidative homo-coupling Oxidative cross-coupling (6ra) 2-Iodoanisole (117. 121.0.4. 2.7 mg (yield. J = 7.2.0381. 0–10% EtOAc in hexane) to give 6. The mixture was then cooled The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2010 . 1217. for C20H16O2: C. View Article Online 4l. NH4Cl and the mixture extracted with EtOAc.0. Chem. recrystallized from hexane–chloroform.8. 1089. J = 7.6.4.5 mg.3.5.30–7.0. 0. 683. 3H).8. 3H).8.0 M solution in n-hexane (0.0. 1005. t-Bu-P4 base 1.63–6.6 Hz. 1197.28–7. 55.7. CDCl3) d (ppm): 21. Chloranil (129 mg. 2H).64 (s.0125 mmol) and P(2-furyl)3 (5. 802.60 mL. K2CO3 (74.3. 128. Yield: 56%. J = 7.30 Synthesis of terphenyls (6ns) Aryl iodide (0. 158. 7.0 M solution in n-hexane (0. 114. 7.54 mmol). 133.6.3.12 (m.50 mL) was added to the reaction mixture and stirred for 24 h at room temperature.0 mg. 1590. 126. The spectral data obtained were identical to those in the literature. 135.39–7. 8.71 (d.8. 818. 129.5. 128. 2H).3 mL. 136.525 mmol) was added to the reaction mixture at 0 1C and stirred for 12 h at room temperature.4 mg.

85 (d. Am. Walsh. Armstrong.6.6. 128.8. 8. F. 129.9. 2H). Schlemper. M. W. found: 310. Mulvey. M. Uchiyama and T. 127. 7. 3H). 4. Am.. 2450. 1422. 1700–1706 | 1705 . 69. 77. Culture. E. Yamaguchi and K. Anal. Y. 7. 128. L. H. 47. Y.5. colorless needles.1201. The extract was washed with brine and dried over MgSO4.0. 4175. 1507. 1987. Synlett. M.. 126. J = 8. (b) S. 2006. 8404. found: C. Tetrahedron. 2006. Kajihara.70. 105. 1725. 8. R. J. Imahori.7. 2004. Int. 46. 326. Schlemper. (d) C. 267. 1990. 1999. for C20H16O: C. Yonehara. T. (f) F. 158. Y. 2005.20–7. T. 59. 55. 10348. 7. Y. Singer. H. 808.94 (d.6. 130. Soc. CDCl3/TMS) d (ppm): 2. Schwesinger. 88. Lett. Miyoshi. 105.3 cm1. Honeyman and R. lithium chloride. 5. 8. Kondo. A. IR(neat): 2923. 2007. E. Kajihara. (b) R. 77.1. 1994.65 (m.03 (s. 706. Mulvey. 93. H. S. 4. J. 702. G. 1H). CDCl3/TMS) d (ppm): 2.5. J. 19790003) and by Grants-in-Aid for Scientific Research on Priority Areas ‘‘Advanced Molecular Transformation of Carbon Resources’’.1178. 123. 1H). Chem. Hevia.2. 762.28 (d. IR(neat): 2989. 8. A.7 Hz. Angew. S. Clegg.37.69 (m. 2 P.. Jones.5 Hz. 43. S. 7. and this protocol enabled the asymmetric arylation of aldehydes with high enantioselectivity without filtration of the lithium salt (J.41. Kobayashi. Y. Seggio. (c) M. Jeon.. Engl. Org. 7434. Organozinc Reagents. J. Chem. 4934. no. Anal. for C20H16O2: C. 2H). Mulvey. Singer. C. N. E. Science. 83.. 2007. Miyoshi.4.. S. Anal. 2009. caused background reactions. recrystallized from hexane–chloroform. Liu.87. Uchiyama and Y. Am. 1H) 7. 11. Kameda. C.0. H. Chem.. E..1129.. 1173. Nobuto. C. 34. T. F. 123. CDCl3) d (ppm): 21. G. C... 26. 18. Ohwada and Y.4.. 1992. 127. Int.. Seebach.42 (s. P.20.24%.. Am. 2004. Naka.2. 2009. 3H). Otani. 124.7. 1H NMR (400 MHz. 9 (a) For instance.. 7. 13C{1H}NMR (100 MHz.0969. 1034. 123. Kondo. 8. 2007. Uchiyama. Y. Gong and P. S. ‘‘Synergistic Effects for Creation of Functional Molecules’’ (to Y. Chem. N. Knochel.05 (d. D. 123. Furuyama. Am. 121.80%. E. Fritz.66 (m. Angew. Oxford University Press. 7473). H.1 (2C).92. 7nt.. M. Org. M. CDCl3) d (ppm): 55. for C20H16O2: C.7. Sase. 132.6. 1181. 1H). Schwab. J.. CDCl3/TMS) d (ppm): 4. 45. 129. 1993.-Z.9. Yield: 58%. Ed. 55. 81%) of 7ns.-Y. J. C.8 Hz. 10 (a) R. Hagadorn. T. Am. (h) M. 1117.6. 472. Ottaway. 13C{1H}NMR (100 MHz. 1320. Nobuto and M.–Eur. Bolm. 158. Chem.. 2374. 1H). Metzger. Honeyman and R. 128. (g) L. Harrington.01 (s. Int. J.5. 2005. Honeyman and R. Kondo. H. Chevallier. Ed. Breuer. 123. T.1. 127. T. (d) D. 2009. 105. M.9. 128. (f) W. B. Sakamoto. H. H. Chem. 131. 45. 698.1. S. 1998. H. E. Chem. H.9.0979.31.64 (m. McCall. Russo and R.6. J = 2. D.3 cm1. Dochnahl and P. 128. D. J. Wright. (c) A. D. 93. F.7 Hz. Furuyama. J.1150. Mongin. 2006. Bailey and R.7. C. 8. Angew.35 (s. Soc. 83. 1993. M. Knochel. J. Koike. 8.9. Uchiyama and A. K.. found: 272. 2H). O. J. R.. J. 14. 13106. Chem. (c) W.5 Hz. 123. 4. 131. 55. Kneisel.. Liu. (b) Removal of these metal salts was not easy because arylzinc species are air and moisture sensitive (J. recrystallized from hexane–chloroform. Malakhov and P. H. 2008.9. 137. Yamazaki and T. Conway. Mishima.4 (2C). Knochel.. calc. Rev. 120. J. Am. Chem. Uchiyama. 45. Soc. 7us. 746. 128. H. P. X. for C20H16O: 272.. 2007.6. 128. Dale.. Honeyman and R. Tanaka. Hevia.7 Hz..–Eur. Dambacher. 88.21%. (c) A. 4.42 (d. 7685. 2010. Chem. 7380.7. N. Punzalan. Downloaded by Universitat de Barcelona on 15/04/2016 16:19:54. 16. Am. Chem. Org. 120. Fleischer and J... (d) M. Hermanns and C.Published on 09 June 2010. Takazawa. Chem.. J. 8748. 127. 7. Chem. Soc. Hlavinka and J. Uchiyama.03 (s. Ed. 2375. 4H). Mulvey. Wunderlich and P. T. Hevia. 1999.7. 3H). Krasovskiy and P. F. 5.8 Hz. Ed. Oxford. Soc. 2006. Schwesinger and H. LRMS (EI) m/z: 272 (M+). Soc. J. (g) D. (g) A. L. The solvent was removed under reduced pressure and the crude product purified by silica gel column chromatography (2% EtOAc–hexane) to give 59. Chem. Soc.60 (s. 5. Kondo. Mulvey and D. Mosrin and P. Uchiyama and Y. L. 3983.03 (d. (b) W. Morokuma and M. 3802. 130. M. 1837. Am. 1611. Salvi. Clegg.55 (m. 5 (a) E. 1H). Weber and D. Clegg. J. Willaredt. 2009. S. Clegg. Sakamoto. Klett. Org. Soc. HRMS: calc. Hasenfratz. (e) T. E.88 (s. 114. 114. 2117 and references therein. References 1 P. 1233. Muranaka. 1H NMR (400 MHz.2.. J. J. M. 2007. Sakamoto. Vaultier and F. 2008. 115. E. 1H). 73. S. 127. Angew.9. Am. 8. Knochel. 122. colorless needles. T. W.1. 1301. 16119).. Wang. Kondo. Soc. N.. G. 72. 15. Recrystallized from hexane–chloroform. 3997. J. Soc. M. M. 2117. 1H). Hevia.6. E.10.5. 15592.5. mp 126 1C. Am. 2007. 2009. (f) Y. Carroll and P. 2008. forming racemic products. Hogg. Boudet. J.3. Angew. Chem. Chem. 5. Ed. R. (e) R. E. M. 123. Morey. 129. V.. Japan (to H. J. treated with saturated aq. formed en route to arylzinc reagents. 1H). 4 (a) Y. Knochel and R. Krasovskiy. calc.2. J. 1017. Chem. Hevia. J.2. J.-Y. Commun. 131. 6 (a) M. G. 73. J = 8. 8 (a) P. J.50–8. 6602. 2010.1. R. J = 2. J = 2. Kobayashi. Knochel and R. Kennedy. Chem. J = 8.2 123. Yokoyama. Morokuma. Kondo.55 (d. C. Org.58–7.). 126. 717. G. 3H). Sakamoto. 124. R. Knochel and P. (e) M. W.. H. Int.5 Hz. Sinha. 6.4 mg (yield. Chem. Y. 5404. Mongin. 1057. 122. Boele. Nobuto. D. J.65 (s.. Rev. K. Putzas. Uchiyama. Uchiyama.5. Tucker.. 2006. 126. T.2. Mulvey. Kondo and K. 1H). Am. T. Sports. for C20H13F3: 310. Yield: 70%. Dale. J. Chem. T.. W. 1994. E.-J.6. Knochel. 1111. Chem. 130. J = 2. (e) M.3. 124. 131. HRMS: calc. 7 (a) N. Soc.54 (d.6. M.2. A. 2H). Furuyama. S... F. Org. J. J. 1042.3. Org. Majid and P.7. M. J. Sakamoto. Drummond.2.3. 131. Kim and P.. Chem. Mosrin and P. Chem. 158. Shilai. 443. 124. E. Chem. 2H) 7. Angew. 1210. Ed. This journal is  c 3 (a) F. E. CDCl3) d (ppm): 22. 1613.73 (d. 812. 2912. mp 180–181 1C. 1081. O. 3775. V. Chem.. 130. 1468. 123.8 (2C).63 (m. Knochel. J = 8. Wheatley. Chem. W.–Eur.. 1780. Morgan. E.. Chem. 1H). 5049. 128. 67. 2006. Kobayashi. 3539. 8. B. Int. in the catalytic asymmetric arylation of aldehydes using arylzinc reagents developed by Walsh et al. Angew.6. Chem. 123. Dale. Am.24. Tetrahedron Lett. Chem. Chem. mp 105 1C. H. IR(neat): 2923. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2010 New J. 115.47–8. Soc. (b) T. M. 2008. Mulvey. 3H). 758. 4717. 2002.3. 46. (b) E. J. found: 288. 1279. 136. Morokuma.22. found: C.. 2006. 125. Chem. Y. Nakamura.4. Org. O. LRMS (EI) m/z: 310 (M+). 2002.5 cm1.2. Ed. 129. 13C{1H}NMR (100 MHz. Matsumoto. They found that the addition of tetraethylenediamine (TEEDA) to the reaction mixture was effective for suppressing the background reaction promoted by the lithium salt.59. L. 8514. P. J. Y.. 120. Fisher. NH4Cl and extracted with EtOAc. Furuyama. L. (d) M. H. K. 1206. Matsumoto and K. 1H NMR (400 MHz. Chem. D. Raithby. 122.. Rudolph. Yasuike. Uchiyama. Soc.27 (m. Acknowledgements This work was partly supported by a Grant-in-Aid for Young Scientists (B) from the Ministry of Education. W. 7. Uchiyama. J = 8.7 Hz. colorless needles. Chem.7. Furuyama. 12734. LRMS (EI) m/z: 288 (M+). 8. Am. Walsh.4. 1449. (d) M. found: C. Sase. N. 1725. (c) P. calc. M. 850. Int. (b) Y. F. 1H). Lipshutz. 11. Arimoto. 128.62–8. Knochel. T. View Article Online down to room temperature. 50. HRMS: calc. H. for C20H16O2: 288. Jaric. Chem. H.19.. Uchiyama. 1167.8. (b) S. 4H). Fletscinger. Chem. Soc.60–7. 12358. 129. R. Michl. Duplais and B. Knochel. W. Kondo and T. Int. A. Matsumoto and M. 2001. Science and Technology.

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