A hydroacylation-triggered carbon-carbon triple bond cleavage in alkynes via retro-Mannich type fragmentation

Article abstract of DOI:10.1021/ja034337n

The carbon-carbon triple bond in alkyne is cleaved via hydroacylation followed by retro-Mannich type fragmentation in the presence of aldehyde, which triggers a successive C-C bond cleavage. Copyright

Full text of DOI:10.1021/ja034337n

Published on Web 04/30/2003
A Hydroacylation-Triggered Carbon-Carbon Triple Bond Cleavage in Alkynes
via Retro-Mannich Type Fragmentation
Dae-Yon Lee, Boo-Sun Hong, Eung-Goo Cho, Hyuk Lee, and Chul-Ho Jun*
Department of Chemistry, Yonsei UniVersity, Seoul 120-749, Korea
Received January 25, 2003; E-mail: junch@yonsei.ac.kr
Scheme 1. A Plausible Mechanism for C-C Bond Cleavage of
The carbon-carbon bond activation is one of the most chal-
lenging areas in organometallic chemistry.1 Despite the significant
developments in this field during the past decade, the cleavage of
an alkyne triple bond has remained only as a few examples
including alkyne-ligand scission on transition metal complexes,2
oxidative cleavage,3 alkyne metathesis,4 and so on.5 In the course
of our studies on the chelation-assisted activation of C-H and C-C
bonds in organic molecules,6,7 we found that the reaction of alkynes
and allylamines resulted in the cleavage of the C-C triple bond
through an R,â-unsaturated ketimine intermediate.8 However, an
allylamine as a substrate caused a limitation to its versatile use.
Herein, we describe a new protocol for the cleavage of the carbon-
carbon triple bond in alkyne, which is triggered by a chelation-
assisted hydroacylation.
Alkyne
Table 1. The Reaction of Various Aldehydes (1) and Alkynes (2)
In our reaction, acetaldehyde (1a) reacted with 6-dodecyne (2a)
in the presence of (PPh3)3RhCl (3a, 5 mol % based on 2a),
cyclohexylamine (4), 2-amino-3-picoline (5), and aluminum chloride
(6) to afford 2-octanone (7a) after hydrolysis (eq 1).
isolated yield of
product (7, 7’)
1
2
3
entry
R (1)
R , R (2)
1
2
PhCH2CH2 (1b)
R2 ) R3 ) Me (2b)
R2 ) R3 ) Et (2c)
R2 ) R3 ) Pr (2d)
R2 ) Me, R3 ) t-Bu (2e)
(2d)
90% (7b)
91% (7c)
94% (7d)
33% (7b)
91% (7e)
82% (7f)
54% (7g)
3
4a
5
C5H11 (1c)
PhCH2 (1d)
p-MeOC6H4 (1e)
6
(2b)
(2b)
7b
a A parent R,â-unsaturated ketone 14a remained unreacted (47% yield).
b The unreacted starting material was detected in 35% GC yield. 100 mol
% of 5 was used.
A plausible mechanism for the reaction is depicted in Scheme
1. The first step might be condensation of aldehyde 1a and 5 to
give aldimine 8, which reacts with alkyne 2a to give R,â-unsaturated
ketimine 9a. A conjugate addition of cyclohexylamine 4 into 9a
and subsequent retro-Mannich type fragmentation of the resulting
â-aminoketimine 10 afford aldimine 11 and enamine 12.8,9 Enamine
12 then isomerizes into ketimine 13a, which is hydrolyzed to yield
ketone 7a.
The reaction of various aromatic and aliphatic aldehydes with
alkynes gave corresponding ketones in good to moderate yields
(Table 1). When an internal alkyne bearing different substituents
such as 4,4-dimethyl-2-pentyne (2e) was used for the reaction with
hydrocinnamaldehyde (1b), only 1-phenyl-pentan-3-one (7b) was
obtained in a 33% yield along with R,â-unsaturated ketone 14a
(47%), a hydrolysis product of intermediate ketimine (entry 4). This
result implies that the reactivity and regioselectivity of this reaction
largely depend on the bulkiness of substituents in alkynes. While
two regioisomers of the initial hydroacylation product, that is, 14a
and 14b, are possible from the reaction of 1b and 2e, a bulky tert-
butyl group suppresses the formation of 14b. Furthermore, subse-
quent fragmentation of R,â-unsaturated ketone 14a was inhibited
due to the steric hindrance of the tert-butyl group, which gives
rise to a low yield of 7b as compared to the case of 2-butyne (2b,
entry 1).
It should be noted that an aldehyde, which was generated through
the fragmentation of R,â-unsaturated ketone (Scheme 1), could react
with the remaining alkyne. Therefore, we envisaged a serial
cleavage of alkyne induced by a small amount of external aldehyde,
a hydroacylation-triggered C-C bond cleavage of alkyne. For
example, when 2a was subject to react with a small amount of 1a
(5 mol % based on 2a) in the presence of [(C8H14)2RhCl]2 (3b),
4-diphenylphosphinobenzoic acid (15) as an external ligand, 4, 5,
and 6, 6-dodecanone (16a), as well as 2-octanone (7a, 4% GC yield)
were obtained in an 87% yield after hydrolysis (eq 2).10
A possible mechanism of this reaction is depicted in Scheme 2.
The initial step might be chelation-assisted hydroacylation of 2a
with 1a to give R,â-unsaturated ketimine 9a, which undergoes
fragmentation to afford aldimine 11 and ketone 7a. The reaction
of the resulting aldimine 11 and remaining alkyne 2a gives another
R,â-unsaturated ketimine 9b, and then ketone 16a through the
subsequent fragmentation of 9b and hydrolysis. A newly generated
aldimine 11 could react with 2a along the catalytic cycle.
9
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J. AM. CHEM. SOC. 2003, 125, 6372-6373
10.1021/ja034337n CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
Scheme 2. A Proposed Mechanism for the
Hydroacylation-Triggered C-C Bond Cleavage of Alkyne
Scheme 3. A Crossover Experiment
Figure 1. ESI-MS spectrum of polyketones 18.
lowed by retro-Mannich type fragmentation of the resulting R,â-
unsaturated ketone under the catalyst system of Rh(I) complex,
2-amino-3-picoline, cyclohexylamine, and Lewis acid. This one-
pot protocol was also applied to the ring-opening oligomerization
of cycloalkyne.
Acknowledgment. This work was supported by the National
Research Laboratory (NRL) (2000-N-NL-01-C-271) program ad-
ministered by the Ministry of Science and Technology, and the
Korea Basic Science Institute for obtaining ESI-MS spectrum.
Scheme 4. A Ring-Opening Oligomerization of Cyclododecyne
(2g)
Supporting Information Available: Experimental details and
characterization data for the compounds (PDF). This material is
available free of charge via the Internet at http://pubs.acs.org.
References
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A direct hydroamination of 2a is also a possible mechanism for
the formation of 16a.11 Therefore, the crossover experiment was
performed using two different alkynes, 2a and diphenylacetylene
(2f) as shown in Scheme 3. In this reaction, crossover products,
17a and 17b, were obtained as well as noncrossover products, 16a
and 16b, in a ratio of 50/50 (33% for 16a and 16b, 33% for 17a
and 17b, determined by GC analysis). This result indicates that
the mechanism for the formation of 16 is a chelation-assisted hydro-
acylation-triggered mechanism rather than the direct hydroamination
of alkyne where crossover products could not be formed.12
Encouraged by the results, we attempted to apply the protocol
of alkyne cleavage to the ring opening of strain-free cycloalkyne,
where consecutive hydroacylation and fragmentation would result
in the ring-opening oligomerization of cycloalkyne to yield polyke-
tone. For example, cyclododecyne (2g) was reacted in the presence
of 20 mol % of 1d under the catalyst system of 3a, 4, 5, and 15 at
100 °C for 72 h to give polyketones 18 in a 30% isolated yield
(based on total amount of all starting materials, Scheme 4). In this
reaction, R,â-unsaturated ketimine 19a is an imine of the initial
hydroacylation product, which is identified as 18a after hydrolysis.
Successive retro-Mannich fragmentation and hydroacylation gave
polyketones 18 after hydrolysis. The degree of oligomerization was
determined by ESI-MS, which showed that polyketones 18b-e (n
) 1-4) as well as 18a were formed in this one-pot reaction, and
among them polyketone 18c (n ) 2) was a major component (Figure
1).
(10) Various amines and phosphines were examined, and cyclohexylamine and
4-diphenylphosphinobenzoic acid turned out to be the most effective.
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2001, 66, 6339. (b) Johnson, J. S.; Bergman, R. G. J. Am. Chem. Soc.
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Chem., Int. Ed. 1999, 38, 3222. (d) Haak, E.; Bytschkov, I.; Doyes, S.
Angew. Chem., Int. Ed. 1999, 38, 3389.
(12) Furthermore, when the reaction of 2a (eq 2) was performed without 1a,
only a small amount of 16a (3% isolated yield) was obtained.
In conclusion, we demonstrated the cleavage of the C-C triple
bond in alkyne, utilizing a chelation-assisted hydroacylation fol-
JA034337N
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