6394
J. Org. Chem. 1998, 63, 6394-6397
Synthesis of 2-Phenyl-1-(2-thienyl)- and 2-Aryl-1-(2-furyl)ethanones by the SRN1 Mechanism. Relative Reactivities of Enolate Ions of Ketones
Scheme 1
Marı´a T. Baumgartner, Mariana H. Gallego, and Adriana B. Pierini* INFIQC, Departamento de Quı´mica Orga´ nica, Facultad de Ciencias Quı´micas, Universidad Nacional de Co´ rdoba, A.P. 4, C.C. 61, (5000) Co´ rdoba, Argentina Received March 17, 1998
The synthesis of R-aryl ketones has received much attention over the past two decades. Several arylation reactions have been devised with the assistance of transition metal catalysis, although each of them requires special reagents or gives unsatisfactory yields.1 Beside aryl halides other reagents such as aryliodonium salts, aryllead, and arylbismuth reagent have been proposed for this purpose.2 Also the reaction of silyl enol ether with arenediazonium salts in the presence of Pd(0) and tetraphenylborate anion gave R-aryl ketones.3 Recently it has been reported that the arylation of ketone enolate ions with aryl bromides gave good yields of R-aryl ketones by a palladium-catalyzed coupling in the presence of TolBINAP or BINAP as a ligand.4 The SRN1 mechanism is also an important route to achieve the synthesis of this type of compounds.5 Good percentages of substitution are usually obtained with enolate ions of aliphatic ketones, mainly from acetone and pinacolone. These anions react with phenyl halides under photostimulation in liquid ammonia (-33 °C) or in DMSO at room temperature. In DMSO substitution can be achieved without photostimulation with substrates that are very good electron acceptors.6 Aromatic ketones behave somewhat different. For example, the enolate ion of acetophenone reacts with halobenzenes or halonaphthalenes in liquid ammonia under irradiation only under drastic conditions.7 Heteroarylation of the anion can be achieved in this solvent either under irradiation or even in the dark with highly electrophilic substrates.8,9 On the other hand, phenylation as well as heteroarylation of the anion is possible in (1) (a) Semmelhack, M. F.; Stauffer, R. D.; Rogerson, T. D. Tetrahedron Lett. 1973, 4519. Semmelhack, M. F.; Chong, B. P.; Stauffer, R. D.; Rogerson, T. D.; Chong, A.; Jones, L. D. J. Am. Chem. Soc. 1975, 97, 2507. (b) Kalinin, V. N. Synthesis 1992, 413 and references therein. (2) Abramovitch, R. A.; Barton, D. H. R.; Finet, J.-P Tetrahedron 1988, 44, 3039 and references therein cited. (3) Sakakura, T.; Hara, M.; Tanaka, M. J. Chem. Soc., Perkin Trans. 1 1994, 283. (4) Palucki, M.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 11108. Tol-BINAP (2,2′-bis(di-p-tolylphosphino)-1,1′-binaphthyl; BINAP (2,2′bis(diphenylphosphino)-1,1′-binaphthyl. (5) (a) Rossi, R. A.; Pen˜e´n˜ory, A. B.; Pierini, A. B. in The Chemistry of Functional Group; Patai, S., Rappoport, Z., Eds.; Wiley: Chichester; 1995; Supl. D2, Chapter 24, p 1395. (b) Norris, R. K. Comprehensive Organic Synthesis; Trost, B. M., Ed.; Pergamon: New York, 1991; Vol. 4, p 451. (6) Scamehorn, R. G.; Bunnett, J. F. J. Org. Chem. 1977, 42, 1449. Scamehorn, R. G.; Bunnett, J. F. J. Org. Chem. 1979, 44, 2604. Scamehorn, R. G.; Hardacre, J. M.; Lukanich, J. M.; Sharpe, L. R. J. Org. Chem. 1984, 49, 4881. (7) (a) Bunnett, J. F.; Sundberg, J. E. J. Org. Chem. 1976, 41, 1702. (b) Rossi, R. A.; de Rossi, R. H.; Lo´pez, A. F. J. Am. Chem. Soc. 1976, 98, 1252. (c) Semmelhack, M. F.; Bargar, T. M. J. Am. Chem. Soc. 1980, 102, 7765.
DMSO under photostimulation.10,11 A similar behavior has been observed with the enolate ions of 2-acetylnaphthalene12 and other aromatic ketones such as 2-acetylfuran8b,11 and 2-acetylthiophene. The latter carbanion has been reported to afford the substitution product only by reaction with phenyl azosulfides,13 which are very good electron acceptors that react spontaneously or under laboratory light with different nucleophiles. The difference in reactivity between enolate anions of aromatic and aliphatic ketones toward phenyl halides in liquid ammonia has been attributed to the lower efficiency of the former in the photoinitiation step of the proposed mechanism (Scheme 1).5 This situation can be overcome by employing other methods of initiation like solvated electrons from alkali metals, electrochemically, favoring the initial electron transfer at higher temperatures (DMSO, rt), or performing the reaction in the presence of added nucleophiles that are less reactive than the enolate anion of the aromatic ketone toward phenyl radicals (eq 3) but are better electron donors to initiate the chain (eq 1) (entrainment reaction). On this basis, we studied the reaction of the enolate ions of 2-acetylthiophene and 2-acetylfuran with different aryl halides to determine their reactivity, the initiation conditions that favor the substitution reaction, and the possibility of increasing their synthetic scope. Photoinitiation and initiation by ferrous ion were carried out. Ferrous ion (usually FeSO4 in liquid ammonia and FeCl2 or FeBr2 in DMSO)14 can provide an alternative and efficient method to initiate the reaction of carbanions with iodobenzene and other aryl halides. The relative reactivities of the enolate ions of 2-acetylthiophene and 2-acetylfuran with respect to the enolate ions of acetophenone and 2-acetylnaphthalene were determined. (8) (a) Oostvee, E. A.; van der Plas, H. C. Recl. Trav. Chim. PaysBas 1979, 98, 441. (b) Nair, V.; Chamberlain, S. D. J. Am. Chem. Soc. 1985, 107, 2183. (9) (a) Hay, J. V.; Wolfe, J. F. J. Am. Chem. Soc. 1975, 97, 3702. Hay, V. J.; Hudlicky, T.; Wolfe, J. F. J. Am. Chem. Soc. 1975, 97, 374. (b) Carver, D. R.; Komin, A. P.; Hubbard, J. S.; Wolfe, J. F. J. Org. Chem. 1981, 46, 294. (10) Borosky, G. L.; Pierini, A. B.; Rossi, R. A. J. Org. Chem. 1992, 57, 247. (11) Beugelmans, R.; Bois-Choussy, M. Heterocycles 1987, 26, 1863. (12) Beugelmans, R.; Bois-Choussy, M.; Tang, Q. J. Org. Chem. 1987, 52, 3880. (13) Dell’Erba, C.; Novi, M.; Petrillo, G.; Tavani, C. Tetrahedron 1993, 49, 235. Dell’Erba, C.; Novi, M.; Petrillo, G.; Tavani, C. Phosphorus, Sulfur and Silicon 1993, 74, 409. (14) (a) Galli, C.; Bunnett, J. F. J. Org. Chem. 1984, 49, 3041. (b) van Leeuwen, M.; Mckillop, A. J. Chem. Soc., Perkin Trans. 1 1993, 2433. (c) Galli, C.; Gentili, P. J. Chem. Soc., Perkin Trans. 2 1993, 1135. (d) Murguı´a, M. C.; Rossi, R. A. Tetrahedron Lett. 1997, 38, 1355.
S0022-3263(98)00499-X CCC: $15.00 © 1998 American Chemical Society Published on Web 08/15/1998
Notes
J. Org. Chem., Vol. 63, No. 18, 1998 6395
Table 1. Reaction of Aryl Halides with the Carbanions from 2-Acetylthiophene (1) and 2-Acetylfuran (2) in DMSOa expt
Nu-, M × 103
ArX, M × 103
t-BuOK, M × 103
% X- b
1d 2 3e 4h 5 6e 7h 8e,i 9 10i 11k 12l 13 14l 15l,m 16n 17 18l 19n 20k
1, 15.4 1, 123.3 1, 69.5 1, 123.3 2, 74.8 2, 74.8 2, 99.7 2, 74.8 2, 74.8 2, 74.8 2, 74.8 2, 74.8 2, 74.8 2, 74.8 2, 74.8 2, 74.8 2, 74.8 2, 74.8 2, 74.8 2, 74.8
3, 5.1 3, 44.8 3, 22.3 3, 44.9 3, 26.4 3, 22.3 3, 35.7 3, 22.3 6a, 24.0 6a, 27.4 6a, 27.4 6a, 27.4 6b, 25.0 6b, 25.5 6b, 25.0 6b, 22.0 6c, 25.9 6c, 26.7 6c, 26.8 6c, 25.7
20.6 133 185 173 103 177 156 216 148 154 162 157 150 165 155 165 165 150 144 147
3 6 53 11 82
