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4726

J. Org. Chem. 1998, 63, 4726-4731

Palladium-Catalyzed Carbonylative Cross-Coupling Reaction of Arylboronic Acids with Aryl Electrophiles: Synthesis of Biaryl Ketones
Tatsuo Ishiyama, Hiroe Kizaki, Takahiro Hayashi, Akira Suzuki,† and Norio Miyaura*
Division of Molecular Chemistry, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628, Japan
Received March 4, 1998

The carbonylative cross-coupling reaction of arylboronic acids with aryl electrophiles (ArI, ArBr, and ArOTf) to yield unsymmetrical biaryl ketones was carried out in anisole at 80 °C in the presence of a palladium catalyst and a base. The reaction selectively proceeded under an atmospheric pressure of carbon monoxide when PdCl2(PPh3)2 (3 mol %)/K2CO3 (3 equiv) were used for aryl iodides and PdCl2(dppf) (3 mol %)/K2CO3 (3 equiv)/KI (3 equiv) for the bromides or the triflates. The carbonylation of arylboronic acids with benzyl halides gave aryl benzyl ketones. The transition metal-catalyzed three-component crosscoupling reaction between arylmetal reagents, carbon monoxide, and aryl electrophiles is a straightforward and convenient route for the synthesis of unsymmetrical biaryl ketones. Various arylmetal reagents including magnesium,1 aluminum,2 silicon,3 and tin compounds4 have been reported to undergo the carbonylative coupling, but the development of the protocol to electrondeficient aryl electrophiles is severely limited due to a side reaction that gives a direct coupling product without carbon monoxide insertion. We previously reported the palladium-catalyzed crosscoupling reaction5 of organoboron compounds with organic electrophiles and the carbonylative cross-coupling reaction of 9-alkyl-9-borabicyclo[3.3.1]nonane derivatives (9-alkyl-9-BBN) with aryl, 1-alkenyl, benzyl, and alkyl halides.6 In this paper, we wish to report the synthesis of biaryl ketones (3) via the palladium-catalyzed carbonylative cross-coupling of arylboronic acids (1) with aryl iodides, bromides, or triflates (2) (eq 1).7 The use of a
† Current address: Department of Applied Chemistry, Okayama University of Science, Okayama 700, Japan. (1) Yamamoto, T.; Kohara, T.; Yamamoto, A. Chem. Lett. 1976, 1217. (2) Bumagin, N. A.; Ponomaryov, A. B.; Beletskaya, I. P. Tetrahedron Lett. 1985, 26, 4819. (3) (a) Hatanaka, Y.; Fukushima, S.; Hiyama, T. Tetrahedron 1992, 48, 2113. (b) Hatanaka, Y.; Hiyama, T. Synlett 1991, 845. (c) Hatanaka, Y.; Hiyama, T. Chem. Lett. 1989, 2049. (4) (a) Kang, S.-K.; Yamaguchi, T.; Kim, T.-H.; Ho, P.-S. J. Org. Chem. 1996, 61, 9082. (b) Davies, S. G.; Pyatt, D.; Thomson, C. J. Organomet. Chem. 1990, 387, 381. (c) Echavarren, A. M.; Stille, J. K. J. Am. Chem. Soc. 1988, 110, 1557. (d) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. (e) Kikukawa, K.; Idemoto, T.; Katayama, A.; Kono, K.; Wada, F.; Matsuda, T. J. Chem. Soc., Perkin Trans. 1 1987, 1511. (f) Bumagin, N. A.; Bumagina, I. G.; Kashin, A. N.; Beletskaya; I. P. Dokl. Akad. Nauk SSSR 1981, 261, 1141. (g) Tanaka, M. Tetrahedron Lett. 1979, 20, 2601. (5) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457. (b) Suzuki, A. Pure Appl. Chem. 1994, 66, 213. (c) Suzuki, A. Pure Appl. Chem. 1991, 63, 419. (d) Suzuki, A. Pure Appl. Chem. 1985, 57, 1749. (e) Suzuki, A. Acc. Chem. Res. 1982, 15, 178. (6) (a) Ishiyama, T.; Murata, M.; Suzuki, A.; Miyaura, N. J. Chem. Soc., Chem. Commun. 1995, 295. (b) Ishiyama, T.; Miyaura, N.; Suzuki, A. Tetrahedron Lett. 1991, 32, 6923. (c) Ishiyama, T.; Miyaura, N.; Suzuki, A. Bull. Chem. Soc. Jpn. 1991, 64, 1999. (d) Wakita, Y.; Yasunaga, T.; Akita, M.; Kojima, M. J. Organomet. Chem. 1986, 301, C17. (7) The preliminary results were reported in: Ishiyama, T.; Kizaki, H.; Miyaura, N.; Suzuki, A. Tetrahedron Lett. 1993, 34, 7595.

Table 1.

Carbonylative Coupling of Phenylboronic Acid with 4-Iodoacetophenonea yieldb (%) catalyst PdCl2(PPh3)2 base K2CO3 Cs2CO3 Tl2CO3 K3PO4 K2CO3 solvent anisole 3 84 69 38 43 82 71 74 68 63 6 4 11 23 24 23 9 4 7 11 8 0

entry 1 2 3 4 5 6 7 8 9 10

PdCl2(dppf)c PdCl2(CH3CN)2 Pd(PPh3)4 PdCl2(PPh3)2

toluene dioxane DMF

a Reactions between phenylboronic acid (1.1 mmol), CO (1 atm), and 4-iodoacetophenone (1.0 mmol) were carried out at 80 °C for 5 h in the presence of catalyst (3 mol %), base (3 mmol), and solvent (6 mL). b GLC yields based on 4-iodoacetophenone. c Dppf: 1,1′bis(diphenylphosphino)ferrocene.

dppf ligand for the palladium catalyst and the addition of NaI or KI were requisite to achieve a selective coupling for aryl bromides or triflates, though various palladium complexes were effective for aryl iodides in the absence of metal iodides.

Results and Discussion Reaction Conditions. The reaction of phenylboronic acid (1.1 equiv) with 4-iodoacetophenone was examined at 80 °C for 5 h under an atmospheric pressure of carbon monoxide to optimize the reaction conditions (Table 1).

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but the choice of less polar solvents was essential to achieve high yields (Table 1. The reaction worked well in anisole. Org. 9-Ph9-BBN (3/4 ) 69%/7%). 452. 1.. Representative results are summarized in Table 3. 14. entries 8-10). entries 24 and 25) suffered from low yields due to the exclusive formation of the direct coupling products 4. which.. Org.. Cs2CO3. good yields of ketones were similarly obtained from aryl bromides and triflates.3-propanediol ester (3/4 ) 17%/0%).2 and an analogous reaction with tributyltin hydride resulted in only a 9% yield of 4-nitrobenzaldehyde with an accompanying 84% yield of nitrobenzene. For example. J. 7175. Although the iodide afforded better results in shorter reaction times. K3PO4. J. presumably due to another side reaction leading to 4-acetylbenzoic acid (Table 1. p 348. K. Palenik. and 1. the dppf complex was apparently better than the triphenylphosphine complexes for the bromide and the triflate (Table 2. PdCl2(dppf) was a good catalyst for 2-bromothiophene or 3-bromoquinoline (Table 3. Inorg. 350.. For these two substrates. respectively. Chem.Synthesis of Biaryl Ketones Table 2. entries 24 and 25). Higuchi. L. W. W. V. 1983. the dppf complex. Soc. Pergamon Press: Oxford. The presence of a strong electron-attracting substituent such as NO2 is known to promote the direct coupling giving biaryl 4. suggesting the superiority of boronic acids. De Bernardinis. K. 55. the reaction of phenylboronic acid with 4-iodonitrobenzene with PdCl2(PPh3)2 resulted in 3/4 ) 50%/35%. (b) Baillargeon. 4-acetylbiphenyl (23-24%). J. p 251. The carbonylative cross-coupling reaction between various arylboronic acids and aryl electrophiles was carried out in anisole at 80 °C under an atmospheric pressure of carbon monoxide in the presence of PdCl2(PPh3)2 (3 mol %)/K2CO3 (3 equiv) for the iodides (Table 1. entries 2-5 and 12). thus suggesting the superiority of bidentate phosphine ligands with a large bite angle. Pd(PPh3)4 exceptionally resulted in high yields of ketone (Table 3.. 63. p 1026. Abel. b GLC yields based on aryl electrophiles.1 mmol). 15. G. entry 4) also afforded a similar order of reactivity. K2CO3 (3 equiv) suspended in anisole is very efficient to yield 4-acetylbenzophenone (82-84%) in the presence of PdCl2(PPh3)2 or PdCl2(dppf) (3 mol %). entries 7-10). D. Most of the representative palladium catalysts.4-bis(diphenylphosphino)butane. but the corresponding reaction of 2-bromopyridine or 2-bromofurane (Table 3. Konishi. Ed.. (b) Hayashi. Am. The bases affected the selectivity of the reaction (entries 1-4).9 (8) (a) Soderberg. T. entries 17 and 19). smoothly catalyzed the reaction. Vol. R. M. Hirotsu. CO (1 atm). entries 3-8). Soc. Academic Press: New York. entry 9). Chem. 1976. Chem. A more sterically hindered combination of mesitylboronic acid and iodomesitylene was further decelerated. entry 1). M. W. J.. Chem. The reaction of mesitylboronic acid with 2-iodotoluene and that of o-tolylboronic acid with iodomesitylene took a longer reaction time due to their large steric hindrance (Table 3. The selectivity of ketone decreased in the order of dppf > dppb . (9) (a) Cabri. 12. the carbonylative coupling reaction of triphenylalane with 4-iodonitrobenzene was reported to provide a 41% yield of 4-nitrobenzophenone and a 55% yield of 4-nitrobiphenyl. The bromo group in phenylboronic acid remained intact during the reaction with iodobenzene (Table 3. and 4-bromoacetophenone or 4-acetylphenyl triflate (1. but the reaction still yielded a 35% yield of dimesityl ketone. entries 1-4. dppe. entry 1) or PdCl2(dppf) (3-5 mol %)/K2CO3 (3 equiv)/KI (3 equiv) for the bromides and the triflates (Table 2. Y. K. Penco. dppp > dppe (Table 2. 1998 4727 OTf Pd(dba)2/dppfc Pd(dba)2/dppbc Pd(dba)2/dpppc Pd(dba)2/dppec PdCl2(PPh3)2 PdCl2(dppf)c a Reactions between phenylboronic acid (1... dioxane. entries 21-28). Santi. (b) Thompson.2-bis(diphenylphoshino)ethane. Kobori. C. S. V.5 had a strong tendency to produce a direct coupling product. was still accompanied the biaryl (9∼11%) (Table 1. but the phosphine-free palladium catalyst of PdCl2(MeCN)2 gave a high yield of ketone (3/4 ) 89%/6%) (Table 3. 105. The addition of NaI or KI (3 equiv) and the use of a dppf ligand for the palladium catalyst remarkably enhanced the selectivity of ketone (Table 2. Am. Vol. F. Kumada. Wilkinson. c Dppf. Palladium Reagents in Organic Syntheses. 1990. but these substrates resulted in low yields under the conditions optimized for the iodides. A.10 Indeed. however. and the phosphine-free complex PdCl2(CH3CN)2. J. 2432. Eds. and 12). 1984. and oxygen atoms afforded good yields of the corresponding ketones (Table 3. entry 10). M. Vol.. 1985. P. (c) Heck. (c) Steffen. 1991. S. J. Am. Stone..0 mmol) were carried out at 80 °C for 16 h in the presence of catalyst (3 mol %). entries 4 and 12). F. Francalanci.. J. F. R. The method provides a quite general route for the synthesis of unsymmetrical biaryl ketones having various functionalities.3-bis(diphenylphosphino)propane. or toluene. thus..1′-bis(diphenylphosphino)ferrocene. and dppb: 1. nitrogen. The carbonylative coupling of heteroaromatic halides or triflates containing sulfur. Although various palladium complexes were effective for iodides. J.. . P. A comparison of various phenylboron derivatives in the reaction with 4-iodoacetophenone gave the following order of yields: PhB(OH)2 (3/4 ) 84%/11%). 1995..8 The results prompted us to investigate the reaction of aryl bromides or triflates (Table 2). including the triphenylphosphine complexes. In Comprehensive Organometallic Chemistry II. Soc. G. In Comprehensive Organic Synthesis. and additive (3 mmol) in anisole (6 mL). B. Stille. Other aryl halides and triflates having an electron-withdrawing group were successfully carbonylated and coupled with arylboronic acids with PdCl2(PPh3)2 or PdCl2(dppf) (Table 3. dppp. B. Stille.. Trost. K2CO3 (3 mmol).. the phenylboronic acid 1. Carbonylative Coupling of Phenylboronic Acid with 4-Bromoacetophenone or 4-Acetylphenyl Triflatea yieldb (%) entry 1 2 3 4 5 6 7 8 9 10 11 12 X Br catalyst PdCl2(PPh3)2 PdCl2(dppf)c additive none KI none KI NaI LiI KI KI KI KI none KI 3 55 64 66 81 80 52 73 67 24 16 3 78 4 36 22 18 3 2 1 6 6 6 6 83 8 J. 1. 158. which have been utilized in the cross-coupling reaction of organoboron compounds. Synthesis of Unsymmetrical Biaryl Ketones. Pergamon Press: Oxford. Chem. 106. (10) (a) Baillargeon. Chem. but low yields resulted in polar solvents such as DMF. No. 1986. and Tl2CO3. entries 1 and 5). E. 108. T. 11. 3. and the phenylboronic acid pinacol ester (3/4 ) 3%/0%). The carbonylative coupling of 4-bromoacetophenone with phenylboron derivatives in the presence of KI (Table 2... entries 22 and 28). G.

Vol. Chem. No.4728 J. Org. 63. 14. .. 1998 Table 3. Synthesis of Unsymmetrical Biaryl Ketonesa Ishiyama et al.

Chem. (f) Garrou. The carbonylative crosscoupling of arylboronic acid with aryl electrophile may proceed through a catalytic cycle analogous to that proposed for other metal reagents (cycle A in Figure 1). Abel. In Comprehensive Organometallic Chemistry II. W. Wilkinson.1-4 Oxidative addition of ArX to a palladium(0) complex provides Ar-Pd-X (6). S. R. Since 6 is a common intermediate for the carbonylation (cycle A) and the direct coupling giving biaryls (cycle B).. P. 1998 4729 a Reactions between arylboronic acids (1.and (12) The carbonylation of Ar-M-X complexes (M ) Pd. Chem. Dixon. J. In Comprehensive Organometallic Chemistry II.. G. and 3-bromo-2phenyl-1-propene.. Abel. Heck. (d) Cross. a large amount of biaryls is often yielded when the carbon monoxide insertion (6 f 7) is slower than the transmetalation (6 f 9)... F. 1981. Soc. Under the conditions used for aryl iodides.. Minkiewicz.. R. The subsequent coupling with the remaining p-tolylboronic acid gave a 90% yield of biaryl monoketone.b) were obtained in 76% and 78% yields in the reaction of benzyl bromide with phenylboronic acid or [2-(methoxymethoxy)phenyl]boronic acid. C. 9. Am. d 5 mol % of catalyst was used. J.11 (11) Bass. 2809. Gemmill. The carbon monoxide insertion into 6 is fast in electronrich aryls. G. Commun. The reaction failed in other organic electrophiles such as 1-iodo-1hexene. 78. E. 1-iodohexane. J. Eds. 2. b Isolated yields based on the halides or triflates. K.. (c) Alexander. J. Soc. The ketone 5b thus obtained is a useful synthetic intermediate readily convertible to isoflavone (79%) (eq 5). the carbonylation of 4-bromoiodobenzene selectively occurred at the C-I bond in the presence of 2 equiv of p-tolylboronic acid (eq 3). On the other hand. Chem. but the carbonylation of diiodobenzene with 2 equiv of p-tolylboronic acid provided the diketone in 82% yield after 5 h. 1976. 1995. J. R.1 mmol). 1976. Eds.. Vol. Eds. W. The reaction was very slow for the bromide. G. low yields and low selectivity resulted in the reaction of electron-deficient substrates. Vol. but benzyl halides readily participated in the carbonylative cross-coupling reaction (eq 4). A. CO (1 atm). 14. p 349. 1985.. R. R. and aryl electrophiles (1. Pt): (a) Dixon. Pergamon Press: Oxford. G. Dalton Trans. Vol. Stone. F. Iodo. 17. Thus. especially for the bromides and the triflates. Inorg. No. 9. 3 4 2 A one-pot synthesis of diketone via the sequential double carbonylation is shown in eq 2. F. In The Chemistry of the Metal-Carbon Bond.. F. Hartley. p 460. Wiley: New York.. Chem. Org. 1-iodo-1-hexyne. Subsequent transmetalation between 7 and arylboronic acid with the aid of K2CO3 and reductive elimination of ketone 3 from ArCO-Pd-Ar′ (8) reproduce the palladium(0) species. e Pd(PPh ) was used as the catalyst in place of PdCl (dppf). J. which is followed by migratory insertion of carbon monoxide giving ArCO-Pd-X (7). J.. the corresponding aryl benzyl ketones (5a. N. and the electron-withdrawing groups slow the insertion12 by reversely accelerating the rate of transmetalation (6 f 9). (e) Sugita. A. Synthesis of Aryl Benzyl Ketones... Soc. Wilkinson..0 mmol) were conducted at 80 °C in the presence of K2CO3 (3 mmol) in anisole (6 mL) by using PdCl2(PPh3)2 (3 mol %) for iodides and PdCl2(dppf) (3 mol %) with KI (3 mmol) for bromides or triflates. Heck. Stone. p 208. V. 1995. 98. Vol.Synthesis of Biaryl Ketones Table 3 (Continued) J. G. 4115. (b) Anderson.. .. Patai. J. 1978. E. Chem. R. K. 63. 2317. E. A. c PdCl2(MeCN)2 was used as catalyst... Reaction Mechanism. Chem. Pergamon Press: Oxford. F. J.

Z. M..17 and trans-PdI(4-MeCOC6H4)(PPh3)218 were prepared. 73. (h) Cabri. Buijs. phenylboronic acid and trans-PdX(4-MeCOC6H4)(PPh3)2 (X ) I. Subramanian.. Acc. J.15 The superiority of the palladium iodides over the bromides was demonstrated by a stoichiometric reaction between (13) The effect of phosphine ligands on the CO insertion of R-Pd-X complexes: (a) Yu. C. Collect. W. Vrieze. Org. (f) Dekker. P. Dalton Trans. J. p 407.. N. H. Wilkinson. J. P. Figure 1. J. C.. J. 5796.21 4-iodo-N.1 mmol). Candiani. Chem. G. Penco. E.. 65. A. C. R. C. W. Candiani. 1980. E. M. 977. In Comprehensive Organometallic Chemistry II. 1991. B. 35.03 (16) Ukai. 74.. Bedeschi... Vol. Org. Kooijman.1 mmol). Cross. Organometallics 1992. 1975. (d) Takagi. J. 4950. C. I. 5521. 191. C. 1992. J. S. PdCl2(dppf). The yields based on 4-iodoacetophenone were determined by GLC using pentadecane as an internal standard. T. van Leeuwen. K. J. North-Holland: Amsterdam. 56. E. 7076. M. Organomet.. W. J.. Br) (eq 7). (c) Stang. Vol. A.-Y. Chem.. van Leeuwen. W. No. K. Chem. P.16 trans-PdBr(4-MeCOC6H4)(PPh3)2. Pt): (a) Cross. The palladium-dppf complex is highly effective for the carbonylative coupling of aryl bromides and triflates. E. C.. Chem... 1974.. 430.. Palladium catalyst (0. P. T. (23) Gaertner. (19) (a) Nesmeyanov. 3711.. and 4-acetylphenyl bromide and triflate (1. Am. Soc. H. The effect of phosphine ligands on the alkene insertion: (g) Cabri. G. Chem. J. R.... Chem.0 mmol) were added to a flask fitted with a reflux condenser. Jpn. N.. J. A.. H. a septum inlet. Organometallics 1992. 1992. p 59.. Turnquest. K. The synthesis of 4-acetylbenzophenone25 is representative. I. Chem. V.. (21) Janssen. M. 3654. 57.. C. Alper. 1995. Chem. Hanack. G. Pergamon Press: Oxford. 712.. Chem. K2CO3 (3 mmol)..23 and aryl triflates24 were prepared by the literature procedures. F. 1951. 57.. A. Organoboron Compounds in Organic Synthesis. (22) Potts.. K. 114. S. entries 1 and 2) indeed exhibited a strong tendency to produce the direct coupling products. 11. M. F. 52. 1953. N. Elsevier. D. A. R. Y. 4-Iodo-1. Goubitz. E. Eds. Martin. K. Vol. which facilitates the CO insertion.. Cheng. the reaction between phenylboronic acid (1. Bedeschi. 287.. Vol. S.9b Pd(dba)2. Chem. and a reflux condenser was charged with PdCl2(PPh3)2 (0. S.. Chem. 9. Santi. A. (d) Anderson. p 56. J. Indeed. van ¨ Leeuwen. F.. N. (24) Stang.. M. 691. (c) van Asselt. Soc... H. Rick. 6053. Reaction Conditions (Tables 1 and 2). base (3 mmol).. Roobeek. van Leeuwen. R. P. and 4-iodoacetophenone (1. J. A flask equipped with a magnetic stirring bar. Org. W.2-(methylenedioxy)benzene. P. 1992. Bull.0 mmol) was carried out in anisole (6 mL) at 80 °C for 16 h in the presence of palladium catalyst (0. Stam. F. The reaction of phenylboronic acid with diols in the presence of MgSO4 in benzene gave phenylboronates. Elsevier. 9. 1987.. H. A. T. Santi. R. Chem. Chem. 4-bromonitrobenzene (Table 3. Santi.. J.: Amsterdam. F. 1967. H. A. 1481. N. W. R. J.. C. p 547. Organometallics 1992. G. Am. J. 11.. Hayama. Y. R. Chem. A. Wilson. R... 1995. Y. Organomet. Wiley: New York. 1937. W. P. 53. M. and dried over MgSO4. Zhong. and powdered KI or NaI (3 mmol).. C. E. 3558. Wang.22 2-iodopyridine. The flask was flushed with carbon monoxide and then charged with solvent (6 mL). I.. Soc. B. C. R. L. Synthesis 1982. Vrieze. K.. J. The carbon monoxide insertion to the Ar-Pd-I complexes (6. Francalanci..9 The rate of carbon monoxide insertion is accelerated by bidentate phosphine ligands having a large bite angle. C. R. G. R.. 1984. E... Cross. Table 2. 11. N.. C. K. M. In Comprehensive Organometallic Chemistry II. the reaction of trans-PdBr(4MeCOC6H4)(PPh3)2 with a large excess of KI gave transPdI(4-MeCOC6H4)(PPh3)2 in a yield of 70% (eq 6).. S. K. Sokolik.. L. 253. Soc. entries 7-10).. F. a septum inlet. K. Organometallics 1996. W. J. Santi. Jutand. Abel. Vankoten. (i) Cabri. Harwood Academic Pub. Arylboronic acids19 and 9-phenyl-9-BBN20 were synthesized by the reported procedures. K. Chem. 55. (c) Takagi. C. dppp > dppe. Abel. DeBernardinis. The order of yields and selectivity observed during the reaction of 4-bromoacetophenone is parallel to the bond angles of P-Pd-P (dppf > dppb . Stone. J... Vol. E. 1998 Ishiyama et al.. (20) Brown. M. Experimental Section Reagents. Inokawa. Rulke.14 Thus. 1994. 3691.. J. R. CO (1 atm).. W. Eds. Khalil. (b) Mikhailov.. 1. Pergamon Press: Oxford. 67.. In a similar way.. (j) Cabri. Spek. G. Organomet. Org. Inorg. The product was extracted with benzene (20 mL). IV. (25) Zelinski. A. A. P.. Am. J. Gielens. Chem. 668. 116. 1980. 1963. . G. 1992. A. D. Am. Wiley: New York... Org. G. J. I. Arif. Kaasjager. Candiani. Bedeschi. L. R.. Soc. Organic Syntheses. M. (18) Fitton.. P. M.. T. Res. E. Chem.03 mmol). H. W. Okamoto. (17) Amatore. the high catalytic efficiency and selectivity of PdCl2(dppf) for the bromides and triflates can be attributed to its large P-Pd-P angle. J. (15) The halogen exchange of Ar-Ni-Br: (a) Smith. G. 5684. Li. Chem. V. Vrieze. 14.. K. 63. Synthesis of Unsymmetrical Biaryl Ketones (Table 3). (14) The effect of halogen ligand on the carbonylation of R-M-X complexes (M ) Pd. C. Lett. Vrieze.15d 3-iodobenzothiophene.. (d) Dekker. A.N-dimethylaniline. (e) Dekker. Elsevier. Witte. Catalytic cycle. significant improvement of the yields and selectivity was observed by the addition of NaI or KI for aryl bromides and triflates. Nielsen.. washed with water..4730 J.. Elsevier. Hayama. 1996. F. P. 1952.. The mixture was stirred at 80 °C for 5 h under an atmospheric pressure of carbon monoxide. N. Stone. W. ¨ K. Methods of ElementoOrganic Chemistry. 17. K. Soc. C. Candiani. C. 1598. Soc. (b) Ankersmit.. Ishii. G. A. E. G. Kliphuis. T. Vrieze.. 1017. Elsevier. 1990. Org. A. Penco. P.13 thus.. (b) Rulke. W. Kawazura.. Bubnov.. M. 28. 1971. J. The nickel-catalyzed halogen exchange reaction of aryl halides: (b) Yang. Wilkinson. 1983. (e) Anderson. K. Lakin. The carbonylative coupling of the Pd-I complex with phenylboronic acid resulted in a higher yield and selectivity (3/4 ) 76%/8%) than that of the PdBr complex (3/4 ) 60%/19%) in accordance with the selectivity of the catalytic reaction.03 mmol). S. 85. Spek. W. X ) I) proceeds more readily than that into the corresponding Ar-Pd-Br complexes. Org. Vrieze. J. and a magnetic stirring bar. phenylboronic acid (1. R.. P. 357. 1978. Smeets. 15. J. Chem. J. 1997. Chem. H. Goubitz. N. In Organic Syntheses via Boranes.. 62.

195.13. 4 H. phenylboronic acid (1. 129. 131.96. 119 (67).1 Hz).63. 197.51. T. 13C NMR δ 26. 67.1307.45 (s. 7. 198. No.3 Hz).2 Hz). 7. 2 H). Supporting Information Available: Spectral data and copies of 1H NMR spectra of biaryl ketones (18 pages).1 Hz).3 Hz). 130. 128.40. 132. W. 1H NMR δ 7. 91 (38).. 31P NMR (CDCl3. After being stirred at 80 °C for 5 h under CO (1 atm). KI (6 mmol).21. J ) 8.65.30 (t.28 (s. The carbonylative coupling between p-tolylboronic acid (2.32 (t.62. 13C NMR δ 21. A mixture of trans-PdBr(4-MeCOC6H4)(PPh3)2 (0. Synthesis of Isoflavone (Eq 5). 130.4-Bis(4-methylbenzoyl)benzene (Eq 2).5 Hz). 7. 2 H. 121. 3 H). diluted with benzene. 2 H.30.06 mmol). MS m/e 77 (9).93. 314 (M+. 1H NMR δ 2. MS m/e 65 (11). After removal of KI by filtration. 7. washed with water. E.86 (d.46. J ) 8. 2041. K2CO3 (6 mmol).03 mmol).92. 126. 2 H. 8.55 (d. 8.65 (t.69 (t. 222 (M+. J ) 8. and 4-bromoiodobenzene (1.97. 271 (16). 7. J ) 7.66. 1988. 3 H). 130.52 (dd. 2 H. 53.0 mmol) was conducted in anisole (12 mL) at 80 °C for 1.86 (s.-Q. K2CO3 (3 mmol).82 (t. The reaction of arylboronic acids (1.5 Hz). 138.30 (d.90. and KI (6 mmol): IR (Nujol) 1650 cm-1. 94. J ) 7. 63 (56). MS m/e 45 (87). J ) 6. J.67. 7. 1 H. Am. 165 (17). 127. J ) 6.47. 2 H. 6 H). J ) 8.49. the product was extracted with benzene.26 The double carbonylative coupling was carried out in anisole (12 mL) at 80 °C for 5 h under CO (1 atm) by the use of PdCl2(PPh3)2 (0. 128.8 Hz). 65 (8). 137. The reaction of phenylboronic acid (0. Chem. J ) 8. 31).2 mmol).64 (d.0680. 1945. 126.02. 13C NMR δ 21. J ) 7. 7.10.46.63 (t.07. 224 (M+.1 Hz). A similar reaction between p-tolylboronic acid (2.1358. 30).15. and anisole (12 mL) was stirred at 80 °C for 3 h under N2. J ) 7. C. 195.4-diiodobenzene (1. and KI (3 mmol). The flask was flushed with carbon monoxide.11. 172. 92 (51). 4-Methyl-4′-(p-tolyl)benzophenone (Eq 3).06. 1. J ) 7. J ) 7.1 Hz).4 Hz). 7. see any current masthead page for ordering information.7 Hz). 7.96. 12.61.24 (t. 196.1 mmol). 120 (21). Effect of Halogen Ligands (Eq 7).09. 133. 1H NMR δ 3.5 Hz). 125. 3 H). J. 77 (5). 128. 7. 128. 2 H. 129.1099. 135.14.45. J ) 8. 129. 91 (33).16. 1H NMR δ 2. 200. 125. 152 (27). 135.26 (s.46 (s. 136. Gu.2 mmol).8 Hz).83.90. 8.86. 13C NMR δ 50.60.84.32. 1H NMR δ 2.5 h in the presence of PdCl2(PPh3)2 (0. 140. 13C NMR δ 26. 165 (100). 127. 1 H.82. 7. Org.10.4). Vol. J ) 8. J ) 6. exact mass calcd for C15H12O2 224. 3 H). the reaction mixture was cooled to room temperature. 223 (21). 135. J ) 7.4-dibromobenzene (1. JO980417B (27) Brady. 50 (24). 153 (15). 2 H. 136. Chem. After being cooled to room temperature.23 (t. J ) 8. J ) 7. 12 H. Y.1380. 124. J ) 7. and can be ordered from the ACS. 7.5 Hz). 7. J ) 7.. J ) 5.10.67 (s. CO (1 atm). J ) 7. 256 (M+. exact mass calcd for C22H18O2 314.32. exact mass calcd for C16H16O3 256. 286 (M+. 129 (10).45 (t.10 mmol) was carried out in the presence of K2CO3 (0. J ) 8. 7. 7. 1 H. 1 H). J ) 8.68 (d.04. 7. 1 H. and anisole (6 mL) was then added. 1 H.18 (d.3 Hz). 131.0 mmol).82 (t.1 Hz). 102 (18). 4 H).03 (s. 1660 cm-1. J ) 8.3 Hz).44.61.27 5b (0. 7. immediately follows this article in the microfilm version of the journal.55.2 mmol). J.52.33 (d. The procedure is the same as that employed for the reaction of aryl iodides. 129. Benzyl 2-hydroxyphenyl ketone thus obtained was directly subjected to the further transformation:11 IR (Nujol) 1640 cm-1.6. 2 H).23 (d.0 mmol).11 mmol) with trans-PdX(4-MeCOC6H4)(PPh3)2 (X ) I.29 (d.50. 56. Chem. 7. J ) 4. 119 (100).4 Hz).76 (s. 135 (25). and 1. 4 H). Benzyl 2-(methoxymethoxy)phenyl ketone (5b): IR (film) 1680 cm-1.06 mmol). 7. found 222. J ) 7.06 mmol).21. 176. 2 H. CO (1 atm).29 (d. 21. 1 H. 100). 1H NMR δ 2. 76 (24). 91 (15). and finally dried over MgSO4. 14. trans-PdI(4-MeCOC6H4)(PPh3)2 (Eq 6). J ) 7. Bryan. 2 H. 1 H.0 mmol) was carried out in anisole (6 mL) at 80 °C for 16 h under CO (1 atm) in the presence of PdCl2(dppf) (0.47 (s. 181 (14).87 (d. found 224.0 mmol) with aryl bromides or triflates (1. 7.Synthesis of Biaryl Ketones mmol). 1 H. 7.4 Hz). 130.9 Hz).84.1 Hz). F.0826.38.39 (t. 143. 155.0838. Org. the flask was flushed with nitrogen and charged with H2O (2 mL). 13C NMR δ 118.1280.51 (t. 153. and 1.11.1124. 130. 2 H. 1998 4731 Synthesis of Aryl Benzyl Ketones (Eq 4).3 Hz). H3PO4) δ 23.31. 130.3 Hz). 7..49 (d. 2 H.2 Hz). 128.06 (d.47 mmol) was treated with 10% HCl in MeOH (5 mL) at room temperature for 13 h. 141.55. 63. MS m/e 39 (20). GC analysis revealed the formation of a 84% yield of 4-acetylbenzophenone.6 Hz). J ) 7.1 Hz). 4 H. 3 H). 144. J ) 23. 86). 126. J ) 8. 1 H.0 mmol) was carried out at 80 °C for 16 h in anisole (12 mL) by using of PdCl2(dppf) (0. 7.42 (t. 7. J ) 7. 1353.3 Hz). 129.02.14.43 (t. 5. 156. 0. 139.87. 133. Br) (0. Soc.7 Hz).74.87.75 (d. The resulting mixture was stirred at 80 °C for 16 h under N2: IR (Nujol) 1650 cm-1. p-tolylboronic acid (2. 4. 6. 2 H.23. 2. 129.3 mmol) in anisole (1 mL) at 80 °C for 3 h under CO (1 atm). washed with water.0681.3 Hz).3 Hz). 7. K2CO3 (6 mmol). The isolation by chromatography over silica gel gave a pure compound: IR (Nujol) 1700. 7.81 (d. K2CO3 (3 mmol). 7. J ) 8.25. C. 128. 1 H.33. 195 (100). 126.13. 195 (7).75 (d. MS m/e 65 (14). (26) Koelsch. 134. 1 H. 165 (9).4 Hz). found 256.80 (t. . and purified by recrystallization from benzene: IR (Nujol) 1680 cm-1. exact mass calcd for C21H18O 286.7 Hz). 111 (7).6 Hz). and 4-iodoacetophenone (1. 7. J ) 5. 7. 134. 6 H.66. 143. 209 (100). 128.43.23. 105 (9). 1 H.31 (s. 2 H.31 (d. found 314. 1 H.21. 12 H.2 Hz). exact mass calcd for C15H10O2 222.42 (s. This material is contained in libraries on microfiche.03 (t.06 mmol) and K2CO3 (6 mmol). 114. found 286.31.58 (d.