Catalysts for the R-Arylation of Ketones
J. Am. Chem. Soc., Vol. 122, No. 7, 2000 1361
â-tetralone with 2-chloro-5-bromoanisole, for which no yield
was reported.18 Thus, it was of considerable interest when, in
the course of our studies on carbon-oxygen bond formation,22
an R-aryl ketone was formed in small amounts when the sodium
salt of cyclohexanol was combined with an aryl bromide and a
Pd2(DBA)3/Tol-BINAP23 catalyst (eq 1).19
(12) Reagents that produce R-aryl ketones: Diaryliodonium salts: (a)
Varvoglis, A. Synthesis 1984, 709 and references therein. (b) Iwama, T.;
Birman, V. B.; Kozmin, S. A.; Rawal, V. H. Org. Lett. 1999, 1, 673. (c)
Chen, K.; Koser, G. F. J. Org. Chem. 1991, 56, 5764. (d) Ryan, J. H.;
Stang, P. J. Tetrahedron Lett. 1997, 38, 5061. Organobismuth reagents:
(e) Finet, J.-P. Chem. ReV. 1989, 89, 1487 and references therein. (f)
Abramovitch, R. A.; Barton, D. H. R.; Finet, J.-P. Tetrahedron 1988, 44,
3039 and references therein. Organoboron reagents: (g) Brown, H. C.;
Nambu, H.; Rogic, M. M. J. Am. Chem. Soc. 1969, 91, 6852 and references
therein. Tricarbonylcyclohexadienylium iron salts: (h) Kelly, L. F.; Narula,
A. S.; Birch, A. J. Tetrahedron Lett. 1980, 21, 2455. (π-Chlorobenzene)-
chromium tricarbonyl: (i) Mino, T.; Matsuda, T.; Maruhashi, K.; Yamashita,
M. Organometallics 1997, 16, 3241. Copper reagents: (j) Rathke, M. W.;
Vogiazoglou, D. J. Org. Chem. 1987, 52, 3697. (k) Marino, J. P.; Jae´n, J.
C. J. Am. Chem. Soc. 1982, 104, 3165 and references therein. (l) Sacks, C.
E.; Fuchs, P. L. J. Am. Chem. Soc. 1975, 97, 7372. (m) Sakurai, H.;
Shirahata, A.; Araki, Y.; Hosomi, A. Tetrahedron Lett. 1980, 21, 2325.
Aryldiazonium salts with catalytic CuCl: (n) Al Adel, I.; Adeoti Salami,
B.; Levisalles, J.; Rudler, H. Bull. Soc. Chim. Fr. 1976, 930. Aryl lead
reagents: (o) Pinhey, J. T. In ComprehensiVe Organometallic Chemistry
II; McKillop, A., Ed.; Pergamon: Oxford, 1995; Vol. 11, Chapter 11 and
references therein. (p) Pinhey, J. T. Pure Appl. Chem. 1996, 68, 819 and
references therein. (q) Morgan, J.; Pinhey, J. T.; Rowe, B. A. J. Chem.
Soc., Perkin Trans. 1 1997, 1005. π-(2-Methoxyallyl)nickel bromide: (r)
Hegedus, L. S.; Stiverson, R. K. J. Am. Chem. Soc. 1974, 96, 3250. Grignard
reagents with R-bromoketones: (s) Newman, M. S.; Farbman, M. J. Am.
Chem. Soc. 1944, 66, 1550. Organocadmium reagents: (t) Jones, P. R.;
Young, J. R. J. Org. Chem. 1968, 33, 1675.
(13) For reagents that produce 2-aryl-1,3-diketones, R-aryl-â-ketoesters,
R-arylmalonate esters, R-aryl cyanoacetates, and R-aryl malononitriles, see
refs 12a, e, f, o, p, and (a) Lindley, J. Tetrahedron 1984, 40, 1433 and
references therein. In addition, R-aryl acetates: (b) Brown, H. C.; Nambu,
H.; Rogic, M. M. J. Am. Chem. Soc. 1969, 91, 6855. R-aryl malonate
esters: (c) Semmelhack, M. F.; Chong, B. P.; Stauffer, R. D.; Rogerson,
T. D.; Chong, A.; Jones, L. D. J. Am. Chem. Soc. 1975, 97, 2507. (d)
Setsune, J.-I.; Matsukawa, K.; Wakemoto, H.; Kitao, T. Chem. Lett. 1981,
367. R-aryl cyanoacetates: (e) Suzuki, H.; Kobayashi, T.; Yoshida, Y.;
Osuka, A. Chem. Lett. 1983, 193. R-aryl malononitriles: (f) Suzuki, H.;
Kobayashi, T.; Osuka, A. Chem. Lett. 1983, 589. R-aryl phenylsulfonyl-
acetonitriles: (g) Suzuki, H.; Yi, Q.; Inoue, J.; Kusume, K.; Ogawa, T.
Chem. Lett. 1987, 887.
(14) Catalytic reactions that form R-arylesters: Pd- and Ni-catalyzed
couplings of Reformasky reagents with aryl halides: (a) Fauvarque, J. F.;
Jutand, A. J. Organomet. Chem. 1979, 177, 273. (b) Orzini, F.; Pelizzoni,
F.; Vallarino, L. M. J. Organomet. Chem. 1989, 367, 375. Pd-catalyzed
couplings of ethyl-R-tributylstannyl acetate with aryl halides: (c) Kosugi,
M.; Negishi, Y.; Kameyama, M.; Migita, T. Bull. Chem. Soc. Jpn. 1985,
58, 3383. Pd-catalyzed arylations of silylketene acetals with added TlOAc:
(d) Carfagna, C.; Musco, A.; Sallese, G.; Santi, R.; Fiorani, T. J. Org. Chem.
1991, 56, 261. (e) Galarini, R.; Musco, A.; Pontellini, R.; Santi, R. J. Mol.
Catal. 1992, 72, L11. (f) Sakamoto, T.; Kondo, Y.; Masumoto, K.;
Yamanaka, H. J. Chem. Soc., Perkin Trans. 1 1994, 235. (g) Sakamoto,
T.; Kondo, Y.; Masumoto, K.; Yamanaka, H. Heterocycles 1993, 36, 2509.
Pd-catalyzed arylations of silylketene acetals with added Bu3SnF or CuF:
(h) Agnelli, F.; Sulikowski, G. A. Tetrahedon Lett. 1998, 39, 8807. Ni-
catalyzed coupling of aryl-Grignard reagents with R-bromopropionate
esters: (i) Amano, T.; Yoshikawa, K.; Sano, T.; Ohuchi, Y.; Manzo, S.;
Ishiguro, M.; Fujita, Y. Synth. Commun. 1986, 16, 499.
(15) Catalytic reactions that form R-aryl ketones: Pd-catalyzed arylations
of silyl enol ethers with added Bu3SnF: (a) Kuwajima, I.; Urabe, H. J.
Am. Chem. Soc. 1982, 104, 6831. Pd-catalyzed arylations of enol acetates
with added Bu3SnOMe: (b) Kosugi, M.; Hagiwara, I.; Sumiya, T.; Migita,
T. Bull. Chem. Soc. Jpn. 1984, 57, 242. Ni-catalyzed arylations of R-bromo-
silyl enol ethers: (c) Tamao, K.; Zembayashi, M.; Kumada, M. Chem. Lett.
1976, 1239. Ni-catalyzed electrochemical couplings of aryl halides with
R-halo ketones and R-halo esters: (d) Durandetti, M.; Ne´de´lec, J.-Y.;
Pe´richon, J. J. Org. Chem. 1996, 61, 1748 and references therein.
(16) Ni-catalyzed coupling of a lithium ester enolate: (a) Millard, A.
A.; Rathke, M. W. J. Am. Chem. Soc. 1977, 99, 4833. Cu-catalyzed arylation
of â-dicarbonyl compounds with 2-bromobenzoic acids: (b) Bruggink, A.;
McKillop, A. Tetrahedron 1975, 31, 2607 and references therein. Cu-
catalyzed reaction of aryliodides with ethyl cyanoacetate, malononitrile, or
acetylacetone: (c) Okuro, K.; Furuune, M.; Miura, M.; Nomura, M. J. Org.
Chem. 1993, 58, 7606. Pd-catalyzed reactions of aryl bromides or aryl
iodides with alkyl cyanoacetates or malononitrile: (d) Uno, M.; Seto, K.;
Takahashi, S. J. Chem. Soc., Chem. Commun. 1984, 932. (e) Sakamoto,
T.; Katoh, E.; Kondo, Y.; Yamanaka, H. Chem. Pharm. Bull. 1988, 36,
1664 and references therein.
Presumably, in the reaction shown in eq 1, cyclohexanone is
formed by a Pd-catalyzed oxidation, deprotonated by unreacted
sodium alkoxide, and subsequently transformed to 1 by a Pd-
catalyzed arylation. It was hoped that, if cyclohexanone was
used instead of cyclohexanol and its enolate was formed in situ,
conditions otherwise similar to those in eq 1 would produce 1
efficiently. Indeed, this goal was achieved, and a simple protocol
was developed that produced a variety of R-aryl ketones by
simply heating a THF solution of an aryl bromide and a ketone
with sodium tert-butoxide, Pd2(DBA)3, and Tol-BINAP or
BINAP23 (eq 2)19
An important feature of this reaction is the selectivity that is
observed for ketones with two enolizable positions. Thus, for
2-methyl-3-pentanone, arylation occurs exclusively at the meth-
ylene carbon. For 2-hexanone, arylation at the methyl carbon
is preferred, with only very minor amounts of arylation at the
methylene (selectivity g16:1). Also noteworthy is that, for the
12 substrate combinations reported, diarylation was only
observed in five cases, and in no case was the ratio of mono:
diarylation less than 7:1.
Nearly concurrent with this work, Hamann and Hartwig
reported that Pd(DBA)2 and 1,1′-bis(di-o-tolylphosphino)ferro-
cene catalyzed the reaction of aryl bromides or iodobenzene
with aromatic ketones or pinacolone,20 and Miura and co-
workers reported that PdCl2 and Cs2CO3 converted 1,3 diphenyl-
acetone and iodobenzene to 1,1,3,3-tetraphenylacetone.21a
A
subsequent report by the latter group showed that their procedure
was useful for the reactions of aryl iodides or bromobenzene
with benzyl ketones, but that arylations of 3-pentanone failed.21b,24
An extension of these methods was recently reported by
Shaughnessy, Hamann, and Hartwig, who found that conditions
(17) For catalytic, intramolecular arylations of ketones and 1,3-diketones,
see ref 13c and (a) Ciufolini, M. A.; Qi, H.-B.; Browne, M. E. J. Org.
Chem. 1988, 53, 4151. (b) Muratake, H.; Natsume, M. Tetrahedron Lett.
1997, 38, 7577. (c) Muratake, H.; Hayakawa, A.; Natsume, M. Tetrahedron
Lett. 1997, 38, 7581. For a catalytic intramolecular vinylation of a ketone,
see: (d) Piers, E.; Renaud, J. J. Org. Chem. 1993, 58, 11.
(18) Hou, D.; Mas, J. L. U.S. Patent 4,992,591, 1991; Chem. Abstr. 1991,
115, 28927z.
(19) Palucki, M.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 11108.
(20) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1997, 119, 12382.
(21) (a) Satoh, T.; Kawamura, Y.; Miura, M.; Nomura, M. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 1740. (b) Satoh, T.; Inoh, J.-I.; Kawamura, Y.;
Kawamura, Y.; Miura, M.; Nomura, M. Bull. Chem. Soc. Jpn. 1998, 71,
2239.
(22) (a) Palucki, M. P.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc.
1996, 118, 10333. (b) Palucki, M. P.; Wolfe, J. P.; Buchwald, S. L. J. Am.
Chem. Soc. 1997, 19, 3395.
(23) DBA ) dibenzylidene acetone. Tol-BINAP ) 2,2′-bis(di-p-tolyl-
phosphino)-1,1′-binaphthyl. BINAP ) 2,2′-bis(diphenylphosphino)-1,1′-
binaphthyl.
(24) Related work by Miura and co-workers: (a) Terao, Y.; Satoh, T.;
Miura, M.; Nomura, M. Tetrahedron Lett. 1998, 39, 6203. (b) Satoh, T.;
Kametani, Y.; Terao, Y.; Miura, M.; Nomura, M. Tetrahedron Lett. 1999,
40, 5345.