facile removal of silicone and iridium residues from the
product can be achieved by the use of PMHS; the product
can be isolated from the reaction mixture by simple extraction.
Since the reaction is generally applicable to a variety of
carboxamides containing other functional groups, this paper
should stimulate studies on aldenamines as important
synthetic intermediates. Detailed mechanistic studies on the
present catalyst system are now under way.
Scheme 1 Enamine formation followed by cyclopropanation.
This work was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science and Technology, Japan.
Notes and references
z To a 0.02 M solution of IrCl(CO)(PPh3)2 in toluene (0.5 mL;
0.01 mmol of [Ir]) was added the substrate (1 mmol) and PMHS
(266 mg, Si–H = 4.0 mmol) at 25 1C. Immediately, hydrogen gas
evolved and the homogeneous solution turned to a gel after 15 min.
After it was allowed to stand for 15 min, the resultant residue was
washed ten times with ether (30 mL total), and the combined organic
solution was filtered through a pad of Celite and the filtrate was
evaporated under reduced pressure to afford the essentially pure
enamine.
Scheme 2 A plausible reaction mechanism.
procedure can be applicable to the reaction of various
carboxamides, and both p-stabilized and non-p-stabilized
enamines were obtained in good to high yields.z The following
points highlight differences from the results obtained in the
reaction with TMDS: (1) a small amount of amine is formed as
a by-product in the reaction of amides with sterically less bulky
N-substituents such as PhCH2CONEt2 1a (entry 1); (2)
the reaction of bromo-substituted carboxamide 1e gave the
enamine 2e in moderate yield due to formation of unidentified
by-products (entry 5); (3) in the reaction of the amido ketone
1g, no organic compound was detectable in the extracts. This is
presumably due to the concomitant occurrence of the
hydrosilylation of the CQO bond in 1g with PMHS, which
results in immobilization of the product to the silicone resin via
Si–O bonds (entry 7). The present procedure is adaptable to a
large quantity of reaction material; 2.74 g of (E,E)-2i was
obtained from 3.00 g (13.3 mmol) of 1i (entry 10). Finally, we
successfully extended our method to the stereospecific syn-
thesis of the trans-aminocyclopropane. The (E)-2b obtained
in Table 3, entry 2 was subjected to the Simmons–Smith
cyclopropanation to afford trans-N-(2-phenylcyclopropyl)-
N-methylaniline (4) as a single product (Scheme 1).
1 (a) G. Stork, A. Brizzolara, H. Landesman, J. Szmuszkovcz and
R. Terrell, J. Am. Chem. Soc., 1963, 85, 207; (b) P. W. Hickmott,
Tetrahedron, 1982, 38, 1975; (c) P. W. Hickmott, in The Chemistry
of Enamines, ed. Z. Rappoport, John Wiley & Sons, New York,
1994.
2 (a) Enamines: Synthesis, Structure and Reactions, ed. A. G. Cook,
Marcel Dekker, New York, 2nd edn, 1987; (b) R. L. Larock, in
Comprehensive Organic Transformations: A Guide to Functional
Group Preparations, Wiley-VCH, New York, 2nd edn, 1999,
pp. 1507; (c) T. E. Muller and M. Beller, Chem. Rev., 1998, 98, 675.
¨
3 (a) C. R. V. Reddy, S. Urgaonkar and J. G. Verkade, Org. Lett.,
2005, 7, 4427; (b) J. R. Dehli, J. Legros and C. Bolm, Chem.
Commun., 2005, 973; (c) X. Zhang, A. Fried, S. Knapp and
A. S. Goldman, Chem. Commun., 2003, 2060; (d) Y. Fukumoto,
H. Asai, M. Shimizu and N. Chatani, J. Am. Chem. Soc., 2007, 129,
13792; (e) A. R. Shaffer and J. A. R. Schmidt, Organometallics,
2008, 27, 1259. Also see: (f) M. Ahmed, A. M. Seayad, R. Jackstell
and M. Beller, Angew. Chem., Int. Ed., 2003, 42, 5615.
4 G. Belanger, M. Dore, F. Menard and V. Darsigny, J. Org. Chem.,
´ ´ ´
2006, 71, 7481.
5 (a) K. Matsubara, T. Iura, T. Maki and H. Nagashima, J. Org.
Chem., 2002, 67, 4985; (b) Y. Motoyama, C. Itonaga, T. Ishida,
M. Takasaki and H. Nagashima, Org. Synth., 2005, 82, 188;
(c) S. Hanada, Y. Motoyama and H. Nagashima, Tetrahedron Lett.,
2006, 47, 6173; (d) S. Hanada, T. Ishida, Y. Motoyama and
H. Nagashima, J. Org. Chem., 2007, 72, 7551.
A plausible mechanism is shown in Scheme 2. The hydride-
reduction first proceeds at the CQO bond of the amide and
subsequent elimination of siloxane forms an iminium inter-
mediate. Then deprotonation of an a-proton of the iminium
intermediate with hydride takes place much faster than
the hydride reduction, resulting in the formation of the
aldenamine and H2.
6 R. J. P. Corriu, J. J. E. Moreau and M. Pataud-Sat, J. Organomet.
Chem., 1982, 228, 301.
7 Buchwald and co-workers reported a stoichiometric amount of
(i-PrO)4Ti promoted the formation of aldenamines from carboxamides,
which proceeds under mild conditions and tolerates various functional
groups. The aldenamines formed were hydrolyzed to the corresponding
aldehydes without isolation. S. Bower, K. A. Kreutzer and
S. L. Buchwald, Angew. Chem., Int. Ed. Engl., 1996, 35, 1515.
8 Y. Motoyama, K. Mitsui, T. Ishida and H. Nagashima, J. Am.
Chem. Soc., 2005, 127, 13150.
In summary, we have developed an efficient catalyst system
for the preparation of enamines by IrCl(CO)(PPh3)2-catalyzed
silane-reduction/dehydration of carboxamides. The reaction
proceeds under mild conditions in high turnover frequency
with other functional groups remaining intact. Furthermore,
9 Dioumaev and Bullock reported the pioneering work on the
‘‘catalyst self-separation’’, see: V. K. Dioumaev and
R. M. Bullock, Nature, 2003, 424, 530.
ꢁc
This journal is The Royal Society of Chemistry 2009
1576 | Chem. Commun., 2009, 1574–1576