COMMUNICATION
DOI: 10.1002/asia.201100298
Double Hydroacylation Reactions of Acyclic and Cyclic a,b-Unsaturated
Aldehydes
Kyung-Mi Cha, Hyejeong Lee, Jung-Woo Park, Yura Lee, Eun-Ae Jo, and
Chul-Ho Jun*[a]
Dedicated to Professor Eun Lee on the occasion of his retirement and 65th birthday
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C H bond activation has attracted great attention in the
field of catalytic organic synthesis because it can be em-
[1]
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ployed in atom economical C C bond-forming reactions.
In particular, hydroacylation has emerged as a prominent
example of novel C H bond-activation reactions. Among
these processes, the chelation-assisted hydroacylation of al-
kenes with aldehydes has received great interest because de-
carbonylation can be avoided by using chelation-assistance
by 2-aminopyridine.[3]
[2]
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Scheme 1. Double hydroacylation reactions of a,b-unsaturated aldehydes.
a,b-Unsaturated aldehydes, which have not been explored
fully in the context of hydroacylation, are an interesting sub-
strate family, because their hydroacylation reactions with al-
kenes could lead to the formation of two different ketones
via a pathway involving retro-Mannich type C=C double-
bond cleavage of initially generated b-aminoketimine inter-
turated cyclic aldehydes, enantiomers are generated in an
enantiospecific manner by controlling the order of addition
of two different alkenes.
mediates.[4] It should be noted that some examples of C C
Reactions of a,b-unsaturated aldehydes with 1-alkenes
are promoted by a mixture of catalysts that bring about che-
lation-assisted hydroacylation and retro-Mannich-type frag-
mentation. These processes yield two ketone products aris-
ing by the hydrolysis of the intermediate ketimines. For ex-
ample, treatment of (E)-2-methyl-3-phenylacrylaldehyde
(1a, 0.2 mmol) with 3,3-dimethylbut-1-ene (2a, 1.0 mmol) in
the presence of chlorotris(triphenylphosphine)rhodium(I)
(3, 5 mol% based on 1a), 2-amino-3-picoline (4, 50 mol%),
4-trifluoromethylbenzoic acid (5, 10 mol%), and cyclohexyl-
amine (6a, 100 mol%) at 1308C for 12 hours, followed by
hydrolysis, leads to the generation of ketones 7a and 8a that
were isolated in 99% and 78% yields, respectively (Table 1,
entry 1). Reactions of other acyclic a,b-unsaturated alde-
hydes 1b and 1c with 1-alkenes 2b and 2c also take place in
good yields to form the corresponding ketones, 7 and 8
(Table 1, entries 2–7).
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triple-bond cleavage of alkynes and double-bond cleavage
of a,b-unsaturated ketones, using retro-Mannich type cleav-
age procedures, have been reported.[5] In this manner, a,b-
unsaturated aldehydes act as masked forms of two different
aldehydes in the hydroacylation process (Scheme 1). Our
recent studies leading to the development of a double hy-
droacylation reaction of acyclic and cyclic a,b-unsaturated
aldehydes are described below. Herein, we report that these
processes take place through a mechanistic pathway that in-
volves 1,4-addition of a primary amine to the a,b-enone sub-
strates and retro-Mannich-type fragmentation of resulting b-
aminoketimine intermediates. In the case of chiral a,b-unsa-
[a] K.-M. Cha, H. Lee, J.-W. Park, Y. Lee, E.-A. Jo, Prof. Dr. C.-H. Jun
Department of Chemistry and Centre
for Bioactive Molecular Hybrid (CBMH)
Yonsei University, 50 Yonsei-ro, Seodaemun-gu
Seoul 120-749 (Korea)
Two possible reaction mechanisms, shown in Scheme 2,
can be used to explain this process. In the first (Scheme 2a),
initial chelation-assisted hydroacylation between 1a and 2b
affords the corresponding a,b-unsaturated ketone 9a, which
undergoes conjugate addition and condensation with cyclo-
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Chem. Asian J. 2011, 6, 1926 – 1930