C O M M U N I C A T I O N S
Scheme 1. Postulated Mechanism for the Formation of Ketones
from Aldehydes and RBF3K
We have thus described for the first time the cross-coupling
reaction of organometallic reagents with aldehydes to access ketones
directly under mild conditions. Deuterium labeling studies suggest
that this efficient reaction occurs via a Heck-type mechanism
followed by unusual hydrogen transfer thanks to inexpensive
acetone playing the part of hydride acceptor.
Acknowledgment. M.P. thanks the Ministe`re de l’Education
et de la Recherche for a grant.
Supporting Information Available: Experimental procedures and
description of compounds. This material is available free of charge
rhodium(I): the first one would involve C-H bond activation1
followed by reductive elimination of ketone. The second pathway
would imply insertion of the carbonyl bond into an arylrhodium(I)
species, followed by â-hydrogen elimination to form a ketone
(Heck-type mechanism). The first mechanism seems to be highly
improbable not only from Hartwig’s mechanistic studies of alde-
hydes insertion into arylrhodium(I)15 but also because we never
observed any traces of decarbonylation product, a commonly
observed byproduct in reactions involving this C-H activation.3
Even if aldehyde C-H activation may not be completely ruled out,
we strongly favor a mechanism involving insertion/â-hydrogen
elimination.
Whatever the initial steps of the mechanism are, a rhodium
hydride species should be generated in the reaction. To understand
the subsequent transformations of the putative rhodium hydride and
the crucial role of acetone in this reaction, labeling studies were
conducted (eq 3).
References
(1) For some reviews on C-H bond activation, see: (a) Dyker, G. Angew.
Chem., Int. Ed. 1999, 38, 1698. (b) Ritleng, V.; Sirlin, C.; Pfeffer, M.
Chem. ReV. 2002, 102, 1731.
(2) Sakai, K.; Ides, J.; Oda, O.; Nakamura, N. Tetrahedron Lett. 1972, 13,
1287.
(3) See: (a) Vora, K. P.; Lochow, C. F.; Miller, R. G. J. Organomet. Chem.
1980, 192, 257. (b) Marder, T. B.; Roe, D. C.; Milstein, D. Organome-
tallics 1988, 7, 1451. (c) Fairlie, D. P.; Bosnich, B. Organometallics 1988,
7, 936. (d) Legens, C. P.; White, P. S.; Brookhart, M. J. Am. Chem. Soc.
1998, 120, 6965. (e) Kondo, T.; Hiraishi, N.; Morisaki, Y.; Wada, K.;
Watanabe, Y.; Mitsudo, T. Organometallics 1998, 17, 2131 and references
therein.
(4) See: (a) Lee, H.; Jun, C.-H. Bull. Korean Chem. Soc. 1995, 16, 1135. (b)
Kokubo, K.; Matsumasa, K.; Miura, M.; Nomura, M. J. Org. Chem. 1997,
62, 4564. (c) Jun, C.-H.; Huh, C.-W.; Na S.-J. Angew. Chem., Int. Ed.
1998, 37, 145. (d) Ko, S.; Na, Y.; Chang, S. J. Am. Chem. Soc. 2002,
124, 750. (e) Chang, D.-H.; Lee, D.-Y.; Hong, B.-S.; Choi, J.-H.; Jun,
C.-H. J. Am. Chem. Soc. 2004, 126, 424 and references therein.
(5) Satoh, T.; Itaya, T.; Miura, M.; Nomura, M. Chem. Lett. 1996, 823.
(6) Ishiyama, T.; Hartwig, J. J. Am. Chem. Soc. 2000, 122, 12043.
(7) Huang, Y.-C.; Majumdar, K. K.; Cheng, C.-H. J. Org. Chem. 2002, 67,
1682.
(8) For some examples, see: (a) Oi, S.; Moro, M.; Inoue, Y. Chem. Commun.
1997, 1621. (b) Sakai, M.; Ueda, M.; Miyaura, N. Angew. Chem., Int.
Ed. 1998, 37, 3279. (c) Batey, R. A.; Thadani, A. N.; Smil, D. V. Org.
Lett. 1999, 1, 1683. (d) Ueda, M.; Miyaura, N. J. Org. Chem. 2000, 65,
4450. (e) Li, C.-J.; Meng, Y. J. Am. Chem. Soc. 2000, 122, 9538. (f)
Fu¨rstner, A.; Krause, H. AdV. Synth. Catal. 2001, 4, 343. (g) Huang, T.;
Meng, Y.; Venkatraman, S.; Wang, D.; Li, C.-J. J. Am. Chem. Soc. 2001,
123, 7451.
(9) Direct formation of ketone via such reaction has been observed as a
byproduct (Fujii, T.; Koike, T.; Mori, A.; Osakada, K. Synlett 2002, 298)
or via an isomerization mechanism in the reaction with alkenylboronic
acids (Takezawa, A.; Yamaguchi, K.; Ohmura, T.; Yamamoto, Y.;
Miyaura, N. Synlett. 2002, 1733).
(10) During the preparation of this manuscript, Zou et al. reported direct
coupling of cinnamaldehydes with arylboronic acids under Rh catalysis
with concomitant CdC reduction: Wang, Z.; Zou, G.; Tang, J. Chem.
Commun. 2004, 1192.
(11) Review: Darses, S.; Genet, J.-P. Eur. J. Org. Chem. 2003, 4313.
(12) (a) Pucheault, M.; Darses, S.; Genet, J.-P. Tetrahedron Lett. 2002, 43,
6155. (b) Pucheault, M.; Darses, S.; Genet, J.-P. Eur. J. Org. Chem. 2002,
3552. (c) Pucheault, M.; Darses, S.; Genet, J.-P. Tetrahedron Lett. 2004,
45, 4729. (d) Navarre, L.; Darses, S.; Genet, J.-P. Chem. Commun. 2004,
1108.
(13) (a) Navarre, L.; Darses, S.; Genet, J.-P. Eur. J. Org. Chem. 2004, 69. (b)
Navarre, L.; Darses, S.; Genet, J.-P. Angew. Chem., Int. Ed. 2004, 43,
719.
(14) P(tBu)3 has proven to be highly suited in rhodium-catalyzed 1,2-additions
of boronic acids to aldehydes: see ref 8d.
(15) Hartwig et al. reported that the reaction between isolated arylrhodium(I)
complexes and aldehydes resulted in the formation of ketone upon heating
at 80 °C via the intermediate formation of a rhodium alkoxide complexes,
see: Krug, C.; Hartwig, J. F. J. Am. Chem. Soc. 2002, 124, 1674. Krug,
C.; Hartwig, J. F. Organometallics 2004, 23, 4594.
(16) Review: Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457.
(17) Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am. Chem.
Soc. 2002, 124, 5052.
The reaction of benzaldehyde-d1 (1i) with 2a under conditions
B afforded the expected benzophenone (3b) in 65% yield, together
with 23% (determined by GC) of diphenylmethanol-d1 (6). 2H NMR
spectra of the reaction mixture revealed the formation of 2-deute-
riopropan-2-ol (7, δ ) 3.64 ppm, 64%), diphenylmethanol-d1 (6,
δ ) 5.53 ppm, 23%), and 1,1-dideuteriophenylmethanol (8, δ )
4.35 ppm, 13%) as the sole observable deuterated compounds. From
these results it appeared that equal amounts of benzophenone and
propan-2-ol-d2 were formed during the reaction, indicating that
formation of benzophenone is linked to the reduction of acetone.
Formation of 1,1-dideuteriophenylmethanol may originate from
insertion of rhodium hydride into the starting benzaldehyde.
The overall mechanism is believed to involve a transmetalation
of the organometallic reagent to rhodium(I) complex, followed by
insertion of the aldehyde into the arylrhodium(I) (Scheme 1).
â-Hydride elimination from the generated alkoxorhodium(I) com-
plex15 would release diaryl ketone and a rhodium(I) hydride species.
The latter reacts with acetone to afford an alkoxorhodium(I)
complex, which is suited for transmetalation with the boron reagent.
Transmetalation of organoboron compounds to alkoxo or hydroxo
complexes of palladium,16 rhodium,17 or ruthenium18 have been
described, allowing the regeneration of arylmetal species. It is not
clear at present why the starting aldehyde does not react (or to a
minor extent) with rhodium hydride in the same way as acetone
does.
(18) (a) Kakiuchi, F.; Kan, S.; Igi, K.; Chatani, N.; Murai, S. J. Am. Chem.
Soc. 2003, 125, 1698. (b) Kakiuchi, F.; Usui, M.; Ueno, S.; Chatani, N.;
Murai, S. J. Am. Chem. Soc. 2004, 126, 2706.
JA044749B
9
J. AM. CHEM. SOC. VOL. 126, NO. 47, 2004 15357