Application of Rh(l)-Catalyzed C - H Bond Activation to the Ring Opening of 2-Cycloalkenones in the Presence of Amines

Article abstract of DOI:10.1021/ol025816e

(matrix presented) Herein described is the application of the Rh(l)-catalyzed C-H bond activation to the ring-opening of 2-cycloalkenones in the presence of cyclohexylamine. This reaction includes the C-C double bond cleavage of 2-cycloalkenones through the conjugate addition of cyclohexylamine followed by the retro-Mannich-type fragmentation. The resulting ring-opened intermediates subsequently underwent either chelation-assisted hydroacylation to afford a ring-opened dicarbonyl compound or β-alkylation via a ring contraction.

Full text of DOI:10.1021/ol025816e

ORGANIC
LETTERS
2
002
Vol. 4, No. 9
595-1597
Application of Rh(I)-Catalyzed C−H
Bond Activation to the Ring Opening of
1
2-Cycloalkenones in the Presence of
Amines
Chul-Ho Jun,* Choong Woon Moon, Sung-Gon Lim, and Hyuk Lee
Department of Chemistry, Yonsei UniVersity, Seoul 120-749, Korea
junch@yonsei.ac.kr
Received March 5, 2002
ABSTRACT
Herein described is the application of the Rh(I)-catalyzed C−H bond activation to the ring-opening of 2-cycloalkenones in the presence of
cyclohexylamine. This reaction includes the C−C double bond cleavage of 2-cycloalkenones through the conjugate addition of cyclohexylamine
followed by the retro-Mannich-type fragmentation. The resulting ring-opened intermediates subsequently underwent either chelation-assisted
hydroacylation to afford a ring-opened dicarbonyl compound or â-alkylation via a ring contraction.
The activation of C-H bonds by transition metal catalysts
cleavage of a reaction intermediate, R,â-unsaturated ketimine,
by primary amines. Therefore, our Rh(I)-catalyzed C-H
4
is considered to be one of the most efficient tools for a new
1
C-C bond coupling in organic synthesis. By utilizing a
bond activation was applied to 2-cycloalkenones to explore
the scope of the reaction for conjugated carbonyl compounds
and provide new multifunctionalized compounds. Herein, we
present the amine-assisted C-C double bond cleavage of
2-cycloalkenones followed by the Rh(I)-catalyzed C-H bond
activation or hydroiminoacylation.
chelation-assistance strategy, we had successfully developed
a series of catalytic C-H bond activation reactions such as
2
hydroacylation of olefins and ortho-alkylation of aromatic
3
ketones. In our efforts toward C-H bond activation, we
reported the Rh(I)-catalyzed hydroiminoacylation of alkynes
with allylamines, which included the C-C double bond
In our experiment, 2-cycloalkenone (1)5 reacts with
1
-alkene (2) at 130 °C for 1 h in toluene under the cocatalyst
(
1) For reviews, see: (a) Ryabov, D. Chem. ReV. 1990, 90, 403-424.
b) Shilov, A. E.; Shul’pin, G. B. Chem. ReV. 1997, 97, 2879-2932. (c)
Dyker, G. Angew. Chem. 1999, 111, 1808-1822; Angew. Chem., Int. Ed.
999, 38, 1698-1712. (d) Guari, Y.; Sabo-Etienne, S.; Chaudret, B. Eur.
J. Inorg. Chem. 1999, 1047-1055.
2) (a) Jun, C.-H.; Chung, K.-W.; Hong, J.-B. Org. Lett. 2001, 3, 785-
87. (b) Jun, C.-H.; Lee, D.-Y.; Lee, H.; Hong, J.-B. Angew. Chem., Int.
system consisting of (PPh RhCl (3, 3 mol %), 2-amino-
3 3
)
(
3-picoline (4, 20 mol %), cyclohexylamine (5, 100 mol %),
and benzoic acid (6, 5 mol %) to afford a mixture of ketones
7 and 8 in a high yield (Table 1). For example, the reaction
of 2-cyclononenone (1a) and 1-hexene (2a) under the above
1
(
7
Ed. 2000, 39, 3070-3072. (c) Jun, C.-H.; Lee, H.; Park, J.-B.; Lee, D.-Y.
Org. Lett. 1999, 1, 2161-2164. (d) Jun, C.-H.; Hong, J.-B. Org. Lett. 1999,
1
1
1
, 887-889. (e) Jun, C.-H.; Huh, C.-W.; Na, S.-J. Angew. Chem., Int. Ed.
998, 37, 145-147. (f) Jun, C.-H.; Lee, H.; Hong, J.-B. J. Org. Chem.
997, 62, 1200-1201. (g) Jun, C.-H.; Lee, D.-Y.; Hong, J.-B. Tetrahedron
(4) Jun, C.-H.; Lee, H.; Moon, C. W.; Hong, H.-S. J. Am. Chem. Soc.
2001, 123, 8600-8601.
(5) 2-Cycloalkenones larger than 2-cycloheptenone were prepared by the
known procedures as described in Supporting Information. See: (a) Ito,
Y.; Fujii, S.; Nakatsuka, M.; Kawamoto, F.; Saegusa, T. Organic Syntheses;
Wiley: New York, 1988; Collect. Vol. VI, pp 327-333. (b) Nicolaou, K.
C.; Zhong, Y.-L.; Baran, P. S. J. Am. Chem. Soc. 2000, 122, 7596-7597.
Lett. 1997, 38, 6673-6676.
(3) (a) Jun, C.-H.; Hong, J.-B.; Kim, Y.-H.; Chung, K.-W. Angew. Chem.,
Int. Ed. 2000, 39, 3440-3442. (b) Jun, C.-H.; Moon, C. W.; Hong, J.-B.;
Lim, S.-G.; Chung, K.-W.; Kim, Y.-H. Chem. Eur. J. 2002, 8, 485-492.
1
0.1021/ol025816e CCC: $22.00 © 2002 American Chemical Society
Published on Web 04/03/2002

Table 1. Ring Opening/Hydroacylation of 2-Cycloalkenones
Scheme 1 Mechanism for Reaction of 1a-e via Hydroacylation
a
(1)
product
isolated
entry
1
R of 2
ratio (7/8)
yield (%)
1
2
3
4
5
6
7
8
9
1a (n ) 3)
nC4H9 (2a )
nC6H13 (2b)
tC4H9 (2c)
Me3Si (2d )
Cy (2e)
nC4H9 (2a )
2a
87/13 (7a /8a )
70/30 (7b/8b)
74/26 (7c/8c)
88/12 (7d /8d )
72/28 (7e/8e)
87/13 (7f/8a )
85/15 (7g/8a )
85/15 (7h /8a )
80/20 (7i/8a )
86
96
99
99
67
1b (n ) 4)
1c (n ) 5)
1d (n ) 6)
1e (n ) 9)
86b
68b
61b,c
89b,c
enyl)-ethanone (16a), and 1-(2-methyl-cyclopent-1-enyl)-
heptan-1-one (17a) was obtained in a 27%, 14%, and 43%
yield, respectively (entry 1 in Table 2). It is interesting that
2a
2a
a
The reaction was carried out with 1 (0.216 mmol) and 2 (0.648 mmol)
as starting materials. 5 mol % of 3 was used based upon 1. c 100 mol %
b
of 4 and 1000 mol % of 2 were used.
Table 2. Ring Cleavage/â-Alkylation of 1f and 1g
reaction condition gave a 87:13 mixture of pentadecane-2,9-
dione (7a) and tridecan-7-one (8a) in a 86% yield after
chromatographic purification (entry 1). Other olefins (2b-
e) were also examined for this reaction, which led to fairly
good yields of corresponding 2,9-diones (7b-e) and sym-
metric dialkyl ketones (8b-e) (entries 2-5). 2-Cyclo-
alkenones (1b-e) with a ring size larger than that of 1a
reacted with 2a to give the corresponding 2,10-, 2,11-, 2,
12-, 2,15-dione (7f-i), respectively, as well as 8a in fairly
2a a
4b
entry
1
product (% yield)
good yields (entries 6-9).
1
2
3
1f (n ) 1)
5
5
0
0
20
0
0
15a (27) 16a (14) 17a (43)
15a (60) 16a (11) 17a (8)
The mechanism of this reaction was speculated as shown
in Scheme 1. The conjugate addition of cyclohexylamine (5)
to enone 1 and the subsequent retro-Mannich-type fragmen-
tation of 9 in the presence of an acid would generate the
c
14a (100)
14b (100)
c
4
1g (n ) 2)
0
a
Equivalents based upon 1. b Mole percent based upon 1. c 200 mol %
of 5 was used. The reaction time was 1 h.
6,7
ring-opened imine 10. Hydroiminoacylation of 1-alkene
2) with aldimine 10 by the cocatalyst system of 3 and 4
(
might lead to ketimine 11. This transimination/hydroimino-
this reaction afforded, even in the absence of 2-amino-3-
picoline (4), the same mixture of products in a fairly good
yield with 15a predominate (entry 2). Without 1-hexene (2a)
and 2-amino-3-picoline (4) in entry 3, the reaction of 1f gave
simply a ring-contracted product, 1-cyclopent-1-enyl-etha-
none (14a), in a quantitative yield. From these results, it
could be inferred that 15a and 16a were produced by an
initial skeletal rearrangement of 1f into 14a, via the amine-
assisted ring cleavage and the subsequent â-alkylation of 14a
with 2a under the Rh(I) catalyst (3). When 2-cyclooctenone
acylation protocol was well established for the efficient
2
conversion of aldimines to ketimines. Further chelation-
assisted C-C bond activation of 11 with 2 in the presence
of 3 and 4 could provide a symmetric dialkyl ketimine 12
and 13. Hydrolysis of ketimine 11 and 12 would produce
ketone 7 and 8. When this reaction was performed with
2-cycloheptenone (1f) and 1-hexene (2a) under the identical
reaction condition, an isomeric mixture of 1-(2-hexyl-
cyclopent-1-enyl)-ethanone (15a), 1-(2-hexyl-cyclopent-2-
(
(
1g) was examined without 2a, 1-cyclohex-1-enyl-ethanone
14b) was also obtained in 100% yield by GC anaylsis.8
The proposed mechanism for the reaction of 1f and 1g is
(
6) For the C-C double bond cleavage of conjugated enones by amines,
see: (a) Eisch, J. J.; Sanchez, R. J. Org. Chem. 1986, 51, 1848-1852. (b)
Yamagami, C.; Weisbuch, F.; Dana, G. Tetrahedron 1971, 27, 2967-2975.
(
7) For other examples to cleave the C-C double bond of cyclic enones,
depicted in Scheme 2. After the ring opening of 1f to 10,
the subsequent intramolecular Mannich reaction to 19 seems
see: Kondo, Y.; Kon-I, K.; Iwasaki, A.; Ooi, T.; Maruoka, K. Angew.
Chem., Int. Ed. 2000, 39, 414-417.
1596
Org. Lett., Vol. 4, No. 9, 2002

Scheme 2 Proposed Mechanism for Reaction of 1f and 1g
Scheme 3. Direct â-Alkylation of 14a with 2a
mechanism was supported by the direct â-alkylation of 14a
with 2a in the presence of catalyst 3 and cyclohexylamine
(5), which resulted in the identical mixture of products in a
good yield (Scheme 3). Direct â-alkylation of 14a with 2a
is another possibility, which does not need a chelation-
9
assistant auxiliary. However, when the reaction of 14a with
2
a was carried out in the presence of 3 and 6 without
cyclohexylamine (5), no â-alkylation proceeded. This result
implies that the imine 20, generated from 14a and 5, is a
prerequisite intermediate for the â-alkylation. Compound 4
seems to play the same role in part with 5 in this reaction
since the ratio of 17a increased in the presence of both 4
and 5, whereas low yield of 17a was obtained with only 5
(entries 1 and 2 in Table 2).
In conclusion, we have demonstrated the application of
the Rh(I)-catalyzed C-H bond activation to the ring opening
of 2-cycloalkenones in the presence of cyclohexylamine. This
reaction includes the C-C double bond cleavage of 2-cyclo-
alkenones through the conjugate addition of cyclohexylamine
followed by the retro-Mannich-type fragmentation. Such ring
cleavage of 2-cycloalkenones could generate intermediates
that would undergo either the chelation-assisted hydro-
acylation of olefins (e.g., 2-cyclononenone) to afford a ring-
opened dicarbonyl compound or â-alkylation (e.g., 2-cyclo-
heptenone) to provide an alkylated ring-contraction product.
to be facilitated by the five- or six-membered ring closure.
Deamination of 19 gives R,â-unsaturated ketone product 14,
and the condensation of 14 with cyclohexylamine generates
R,â-unsaturated ketimine 20. Then, the chelation-assisted
â-alkylation of 20 with 1-hexene can take place to produce
2
3 via â C-H bond cleavage by the Rh(I) catalyst.
Acknowledgment. This work was supported by the
National Research Laboratory (2000-N-NL-01-C-271) Pro-
gram administered by Ministry of Science and Technology.
Authors acknowledge the Brain Korea 21 project.
Hydrolysis of 23 furnishes a mixture of 15 and 16. On the
other hand, the other product 17 can be generated from 23
by the following reaction sequence: (i) the conjugate addition
of cyclohexylamine (5) into 23; (ii) the retro-Mannich-type
fragmentation of the resulting â-amino ketimine 24 to give
a ring-opened compound 25; (iii) the intramolecular Mannich
condensation of 26 to produce 28 through intermediate 27;
Supporting Information Available: Full experimental
details and characterization data for all compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(iv) the hydrolysis of the resulting ketimine 28. This proposed
OL025816E
(8) When the reaction was carried out with 5 equiv of 2a, 1-acetylcy-
clohexene (14b) was obtained as a major product along with a trace amount
of â-alkylated compounds that were characterized as 1-(2-hexyl-cyclohexyl)-
ethanone, a hydrogenated compound of 15b and 16b, by H2 under Pd/C;
see Supporting Information. This result shows that 14b is not a good
substrate for â-alkylation.
(9) The Ru-catalyzed direct â-alkylation is only applicable to the vinyl
silane or vinyl siloxane. For example, see: (a) Trost, B. M.; Imi, K.; Davies,
I. W. J. Am. Chem. Soc. 1995, 117, 5371-5372. (b) Sato, T.; Kakiuchi, F.;
Chatani, N.; Murai, S. Chem. Lett. 1998, 893-894.
Org. Lett., Vol. 4, No. 9, 2002
1597