Preparation of ketones via the palladium-catalyzed cross-coupling of acid chlorides with trialkylboranes

Article abstract of DOI:10.1016/S0040-4039(99)02226-1

Trialkylboranes react with acid chlorides in the presence of palladium to generate alkyl and aryl ketones in good yields. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(99)02226-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 999–1001
Preparation of ketones via the palladium-catalyzed cross-coupling
of acid chlorides with trialkylboranes
George W. Kabalka,∗ Rama R. Malladi, David Tejedor and Shane Kelley
Departments of Chemistry and Radiology, The University of Tennessee, Knoxville, Tennessee 37996-1600, USA
Received 2 November 1999; revised 24 November 1999; accepted 29 November 1999
Abstract
Trialkylboranes react with acid chlorides in the presence of palladium to generate alkyl and aryl ketones in good
yields. © 2000 Elsevier Science Ltd. All rights reserved.
Carbon–carbon bond-formation via organometallic reactions has been extensively studied.1 In recent
years, numerous transition-metal-catalyzed, cross-coupling reactions of organic halides with organomet-
allic reagents such as organotin,2 organoaluminum3 and organoboron4 compounds have been reported.
Of these, the palladium-catalyzed coupling reactions of organoborane derivatives (the Suzuki–Miyaura
Reaction) is playing an ever increasing role in modern organic synthesis.5
We recently reported the first coupling of trialkylboranes with acid chlorides using a Suzuki–Miyaura
coupling sequence to prepare aliphatic and aromatic ketones via the coupling of trialkylboranes with
acyl halides (Scheme 1).6 In an earlier study, Negishi had reported that tetraalkylborates will react with
acid chlorides to form ketones in the absence of catalysts.7 Subsequently, Uemara developed a palladium-
catalyzed reaction involving the use of tetraphenylborates with acid chlorides for preparing aryl ketones.8
The procedure was later modified and improved by Bumagin.9 The preparation of aryl ketones utlizing
aryl boronic acids has also been reported.9,10
Scheme 1.
We carried out a study to elucidate reaction conditions which promote maximum product yields. A
reaction temperature of 65°C results in convenient reaction times although the reaction does proceed
at room temperature (Table 1). The cross-coupling reaction presumably involves an oxidative addition
of the acid halide to the palladium(0) catalyst to generate an acyl palladium(II) halide. Treatment of
∗
Corresponding author. Tel: (865)974-3260; fax: (865)974-2997; e-mail: kabalka@utk.edu (G. W. Kabalka)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02226-1
tetl 16154

1000
the acyl palladium with potassium acetate generates the acyl palladium(II) acetate which undergoes
transmetallation with the organoborane reagent. The resultant acyl organopalladium complex then
undergoes reductive elimination to generate the ketone product.
Table 1
Reaction of benzoyl chloride with tributylborane to generate valerophenonea
Several features of this reaction make it synthetically useful. These include the fact that reactions can
be carried out at moderate temperatures in THF, unlike other transition-metal-catalyzed cross-coupling
reactions involving main group organometallics. Most importantly, the reaction is not limited to aromatic
acid chlorides, aliphatic acid chlorides also undergo the coupling reaction. The reaction is straightforward
and it appears to be generally applicable (Table 2). At present, the reaction involves the transfer of only
one of the three alkyl groups and thus is not as efficient as some of the more recent developments using
arylboron derivatives which also employ smaller quantities of the palladium reagent.9,10 A detailed study
of the scope and limitations of the synthesis is in progress.
The synthesis of 1-phenyl-1-pentanone is representative: Benzoyl chloride (1.0 mmol) is added to
Pd(PPh3)4 (0.2 mmol) and the mixture stirred at room temperature for 10 min. Potassium acetate (2
mmol) and tributylborane (1 mmol) are added to the reaction mixture which is refluxed at 65°C for 3
h. The reaction is quenched with water (10 mL) and the product extracted into ether (3×20 mL). The
combined organic extracts are washed with brine and then dried over anhydrous magnesium sulfate prior
to solvent removal under reduced pressure. The product is purified by column chromatography (silica
gel) using ethyl acetate–hexanes to yield 0.74 mmol (74%) of the desired 1-phenyl-1-pentanone.
Acknowledgements
We thank the US Department of Energy and the Robert H. Cole Foundation for support.
References
1. The Chemistry of Metal–Carbon Bond; Kumar, V. G.; Chu, C. K.; Miginiae, L.; Hartley, F. R.; Patai, S., Eds.; John Wiley &
Sons: New York, 1985; Vol. 3, p. 1.
2. Baillargeon, V. P.; Stille, J. K. J. Am. Chem. Soc. 1983, 105, 7175; ibid. 1986, 108, 452.
3. Alper, H.; Antebi, S.; Woell, J. B. Angew Chem., Int. Ed. Engl. 1984, 23, 732; Bumagin, N. A.; Ponomanyor, A. B.;
Beletskya, I. P. Tetrahedron Lett. 1985, 26, 4819.
4. (a) Negishi, E.; Takahashi, T.; Baba, S.; Van Horn, D. E.; Okikad, N. J. Am. Chem. Soc. 1987, 109, 2393. (b) Hashem, K.
E.; Woell, J. B.; Alper, H. Tetrahedron Lett. 1984, 25, 3791.

1001
Table 2
Reaction of acid chlorides with trialkylboranes to generate ketonesa
5. (a) Miyaura, N.; Yanagi, T.; Suzuki, S. Synth. Commun. 1981, 11, 513. (b) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95,
2457. (c) Suzuki, A. J. Organomet. Chem. 1999, 576, 147.
6. Presented in part at the 215th National Meeting of the American Chemical Society, Dallas, TX, 1998, ORGN 256.
7. Negishi, E.; Chiu, K. W.; Yosida, T. J. Org. Chem. 1975, 40, 1676.
8. Cho, C. S.; Itotani, K.; Uemara, S. J. Organomet. Chem. 1993, 443, 253.
9. Bumagin, N. A.; Koreleve, D. N. Tetrahedron Lett. 1999, 40, 3057.
10. Haddach, M.; McCarthy, J. R. Tetrahedron Lett. 1999, 40, 3109.