Ru-catalyzed decarbonylative addition of aliphatic aldehydes to terminal alkynes

Article abstract of DOI:10.1021/ol101107w

(Figure Presented) A novel method for the formation of isolated C - C bonds was developed via a ruthenium-catalyzed decarbonylative addition of aliphatic aldehydes and alkynes. An unprecedented complete switch of chemoselectivity from aromatic aldehydes to aliphatic aldehydes was observed simpl y by using tri(2,4,6-trismethoxyphenyl)phosphine as ligand. A synthesis by this method of an insect sex pheromone was demonstrated.

Full text of DOI:10.1021/ol101107w

ORGANIC
LETTERS
2010
Vol. 12, No. 14
3176-3178
Ru-Catalyzed Decarbonylative Addition
of Aliphatic Aldehydes to Terminal
Alkynes
Xiangyu Guo, Jun Wang, and Chao-Jun Li*
Department of Chemistry, McGill UniVersity, 801 Sherbrooke St. West,
Montreal, Quebec H3A 2K6, Canada
cj.li@mcgill.ca
Received May 13, 2010
ABSTRACT
A novel method for the formation of isolated CdC bonds was developed via a ruthenium-catalyzed decarbonylative addition of aliphatic
aldehydes and alkynes. An unprecedented complete switch of chemoselectivity from aromatic aldehydes to aliphatic aldehydes was observed
simply by using tri(2,4,6-trismethoxyphenyl)phosphine as ligand. A synthesis by this method of an insect sex pheromone was demonstrated.
Carbon-carbon double bond forming reactions are vital to
the synthesis of various fine chemicals, pharmaceuticals, and
natural products.1 Many synthetic methodologies have been
developed throughout the history of organic chemistry for
an effective olefination1 such as the Wittig-type reactions,2
the Heck-type reactions,3 and olefin metathesis.4 Alterna-
tively, the Negishi-type addition of various organometallic
reagents to alkynes provided a versatile strategy for alkene
synthesis.5 On the other hand, the cleavage of the C-H bond
in aldehydes promoted by transition metal leads to acyl
hydrido metal intermediates, which could undergo decarbo-
nylation reactions or further reactions to generate carbonyl
compounds.6 Recently, we reported an olefination strategy
via a ruthenium-catalyzed decarbonylative addition reaction
of aldehydes to alkynes, suggesting a new method for CdC
bond formation.7 However, the first generation catalyst was
limited to only aromatic aldehydes (Scheme 1, reaction a).
On the other hand, isolated alkenes are the structural feature
(1) (a) Kolodiazhnyi, O. I. Phosphorus Ylides: Chemistry and Applica-
tions in Organic Chemistry; Wiley-VCH: New York, 1999. (b) Dumeunier,
R.; Marko´, I. E. In Modern Carbonyl Olefination; Takeda, T., Ed.; Wiley-
VCH: Weinheim, 2004.
(5) (a) Negishi, E.; Van Horn, D. E.; Yoshida, T.; Rand, C. L.
Organometallics 1983, 2, 563. (b) Studemann, T.; Ibrahim-Ouali, M.;
Knochel, P. Tetrahedron 1998, 54, 1299. (c) Xie, M.; Gu, X.; Wang, J.;
Zhang, J.; Lin, G.; Wang, S. Appl. Organomet. Chem. 2009, 23, 258.
(6) For recent reviews, see: (a) Garralda, M. A. Dalton Trans. 2009,
3635. (b) Willis, M. C. Chem. ReV. 2010, 110, 725.
(2) For some examples, see: (a) Hoffmann, R. W. Angew. Chem., Int.
Ed. 2001, 40, 1411. (b) Comins, D. L.; Ollinger, C. G. Tetrahedron Lett.
2001, 42, 4115. (c) Jung, M. E.; Pontillo, J. Tetrahedron 2003, 59, 2729.
(d) Huang, J.; Wu, C.; Wulff, W. D. J. Am. Chem. Soc. 2007, 129, 13366.
(e) Aissa, C. Eur. J. Org. Chem. 2009, 12, 1831.
(3) For a recent review, see: Beletskaya, I. P.; Cheprakov, A. V. Chem.
ReV. 2000, 100, 3009.
(7) Guo, X.; Wang, J.; Li, C.-J. J. Am. Chem. Soc. 2009, 131, 15092.
Varela et al. also reported an alternative ruthenium catalyzed formation of
cyclic alkene from aldehyde and alkyne via the cleavage of Ct C bond;
see: Varela, J. A.; Gonzalez-Rodriguez, C.; Rubin, S. G.; Castedo, L.; Saa,
C. J. Am. Chem. Soc. 2006, 128, 9576. Krische and co-workers reported a
direct vinylation of aldehyde and alcohol with alkynes to give allyl alcohols
recently; see: Patman, R. L.; Chaulagin, M. R.; Willams, V. W.; Krische,
M. J. J. Am. Chem. Soc. 2009, 131, 2066.
(4) For some examples, see: (a) Schrock, R. R.; Meakin, P. J. Am. Chem.
Soc. 1974, 96, 5288. (b) Nguyen, S. T.; Johnson, L. K.; Grubbs, R. H.
J. Am. Chem. Soc. 1992, 114, 3975. (c) Trnka, T. M.; Grubbs, R. H. Acc.
Chem. Res. 2001, 34, 18. (d) Vehlow, K.; Wang, D.; Buchmeiser, M. R.;
Blechert, S. Angew. Chem., Int. Ed. 2008, 47, 2615. (e) Alcaide, B.;
Almendros, P.; Luna, A. Chem. ReV. 2009, 109, 3817.
10.1021/ol101107w  2010 American Chemical Society
Published on Web 06/15/2010

Scheme 1
.
Decarbonylative Addition of Aldehyde to Alkynes
Table 1. Decarbonylative Aliphatic Aldehyde-Alkyne Addition
Reactions under Various Conditionsa
entry
additive
ligand
solvent
toluene
toluene
toluene
% yieldb
0c
0
0
0
52
0
1
2
3
4
5
6
7
8
9
30% CuCl2·2H2O
30% CuCl2
30% CuCl2
30% CuCl2
30% CuCl2
30% CuCl2
30% CuCl2
30% CuCl2
20% (tBu)3P toluene
20% (iPrO)3P toluene
20% Cy3P
20% (Me2N)3P toluene
toluene
of a wide range of chemical products such as insect pheromones
(Figure 1), which are greatly important in the agricultural
industry. A simple and direct generation of isolated alkenes from
readily available basic functionalities will be highly desirable
in alkene synthesis. Herein, we report a new catalyst with which
a highly efficient decarbonylative addition of simple aliphatic
aldehydes to terminal alkynes was achieved to give isolated
alkenes, enabling an astonishing complete switch of chemose-
lectivity from completely aromatic to completely aliphatic
aldehydes (Scheme 1, reaction b).
0
5
20% Ph3P
20% L
30% L
10% L
20% L
20% L
20% L
20% L
20% L
20% L
20% L
20% L
20% L
toluene
toluene
toluene
toluene
toluene
toluene
toluene
70d
23
38
0
10 30% CuCl2
11 30% CuCl2
12
13 20% CuCl2
14 50% CuCl2
15 30% CuCl2
16 30% CuCl2
17 30% CuCl2
18 30% CuCl2
19 30% CuCl2
20 30% CuCl2
27
44
CH2Cl2 + toluene 95e
CH2Cl2 + toluene
dioxane
DCE
CH2Cl2 + toluene
CH2Cl2 + toluene
tracef
55
0
e g
,
36
e h
,
trace
a Conditions: the reaction was prestirred with 10% [Ru(COD)Cl2]n, 30%
CuCl2, 20% ligand in 0.2 mL of solvent under argon at rt for 24 h. Then, 1a
(0.2 mmol), 2a (0.8 mmol), and solvent (0.8 mL) were added under argon and
heated to 120 °C for 24 h, unless otherwise noted. b Determined by 1HNMR
of the crude reaction mixture. c 5 equiv of LiCl was added. d L )
tri(2,4,6-trismethoxyphenyl)phosphine. e 0.2 mL of CH2Cl2 was added first
at rt; 0.8 mL toluene was added when heated to 120 °C. f Without prestirring.
g 150 °C. h 100 °C.
formed during the prestirring in toluene. Different solvents
were examined to facilitate the formation of the active
catalyst in situ by dissolving the residue, and it was found
that a combination of methylene chloride (0.2 mL) and
toluene (0.8 mL) gave the best yield at 120 °C (Table 1,
entries 15-18). Either increase or decrease of the reaction
temperature decreased the product yield (Table 1, entries 19
and 20). With the optimized conditions, we then examined
the scope of this reaction (Table 2).
The reaction worked well for various aliphatic aldehydes
and alkynes. Excellent yields could be obtained for aliphatic
alkynes with a high boiling point (Table 2, entries 1 and 2),
while 1-hexyne gave a 75% yield (Table 2, entry 3).
Aromatic alkynes also worked in this reaction system but
gave only moderate yield (Table 2, entries 4 and 5).
Functional groups, such as halides, ester and methoxyl
groups, could well be tolerated by the reaction (Table 2,
entries 6-9), and all these substrates gave excellent yields
of the olefination products. Phenylacetaldehyde derivatives
led to a moderate yield, (Table 2, entries 10 and 11), possibly
due to the increased steric hindrance on the reacting carbon
centers. In a sharp contrast to our previous reports, aromatic
aldehydes remain virtually unreactive under the present
conditions (Table 2, entry 12). Triisopropylsilyl acetylene
also failed to react under this catalytic conditions (Table 2,
entry 13), most likely due to steric effect. To further explore
this complete switch of chemoselectivity, we run a competi-
tion experiment involving both aliphatic and aromatic
Figure 1. Examples of insect pheromones.
We chose hydrocinnamaldehyde (1a) and 1-decyne (2a)
as the standard substrates for the optimization of the reaction
conditions. Under our previously reported conditions for
aromatic compounds, no reaction was observed (Table 1,
entry 1). We postulated that a bulky ligand is necessary to
form a stabilized catalyst center while still maintaining free
coordination sites for the decarbonylation and additions.
Thus, triisopropyl phosphite and tri(2,4,6-trismethoxyphen-
ly)phosphine were found to be effective in this reaction,
producing the desired compound (3a) in 52% and 70% yield,
respectively, whereas no products or low yields were
obtained with other ligands (Table 1, entries 3-9). When
more ligands were used, the yield dropped dramatically to
23%, possibly because of the dwindling of free-coordination
sites for decarbonylation to occur. On the other hand, lesser
amounts of ligands led to an unstabilized catalyst, which also
reduced the yield to 38% (Table 1, entries 10 and 11). Copper
chloride was also found to be essential in the reaction (Table
1, entries 12-14).
Prestirring was found to be essential for the reaction: only
a trace amount of the product could be formed when all the
chemicals were added at the same time and heated directly
to 120 °C (Table 1, entry 16). A black residue was noticeably
Org. Lett., Vol. 12, No. 14, 2010
3177

Table 2. Substrate Scope of the Decarbonylative
Aldehyde-Alkyne Addition Reactiona
Scheme 2
.
Competition Experiment between Aliphatic and
Aromatic Aldehydesa
a Conditions: 1a (0.2 mmol), 1o (0.2 mmol), 2a (0.8 mmol),
[Ru(COD)Cl2]n 0.02 mmol; conversions and yields were determined by 1H
NMR.
Sabulodes caberata Guene´e. The reaction provided the alkene
in a 55% NMR yield in one step, albeit as a mixture of Z and
E isomers (Scheme 3).8
Scheme 3. Synthesis of (Z)-9-Nonadecenea
a Z:E ) 1:1, determined by GC-MS analysis.
In summary, we have discovered a novel method of CdC
double bond formation, specifically for aliphatic aldehydes
and alkynes via a decarbonylative addition reaction. Different
functionalized substrates were examined, and good to excel-
lent yields were obained. An unprecedented complete switch
of aromatic-aliphatic selective reactivity was observed. A
tentative mechanism similar to the one in our earlier paper7
is proposed also for this reation. The role of copper may be
either to assist the departure of CO from the ruthenium
catalyst center or to alter the nature of the phosphine ligand,
which are ongoing investigations. Further efforts to charac-
terize the active catalyst and to optimize the stereoselectivity
based on decarbonylative addition in terms of reaction
temperature and functional group tolerance are currently
underway in our laboratory.
a Conditions: the reaction was prestirred with 10% [Ru(COD)Cl2]n, 30%
CuCl2, 20% tri(2,4,6-trismethoxyphenyl)phosphine in 0.2 mL of CH2Cl2
under argon at rt for 24 h. Then 1 (0.2 mmol), 2 (0.8 mmol), and toluene
(0.8 mL) were added under argon and heated to 120 °C for 24 h. b Total
isolated yield of both the E and Z isomers. c The E/Z ratio was determined
by 13C NMR analysis.
aldehydes. The product (3a) generated from aliphatic alde-
hyde was formed in a 90% NMR yield, while less than 1%
corresponding aromatic alkene was observed (Scheme 2),
which provided an exclusive chemoselectivity.
Acknowledgment. We are grateful to the Canada Re-
search Chair (Tier I) Foundation (to C.J.L.), CFI, and NSERC
for support of our research.
As a simple test of the potential utility of this novel olefination
reaction, we applied this reaction in the synthesis of (Z)-9-
nonadecene, an extract of sex pheromone glands of female
Supporting Information Available: Typical experimental
procedure and characterization data for all products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(8) Koike, K.; Takaiwa, M.; Kimura, Y.; Inoue, S.; Ito, S. Biosci.
Biotechnol. Biochem. 2000, 64, 1064.
OL101107W
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Org. Lett., Vol. 12, No. 14, 2010