An olefination via ruthenium-catalyzed decarbonylative addition of aldehydes to terminal alkynes

Article abstract of DOI:10.1021/ja906265a

(Chemical Equation Presented) A ruthenium-catalyzed olefination via decarbonylative addition of aldehydes and alkynes has been developed. A strong electronic effect and high chemoselectivity between aromatic and aliphatic aldehydes were observed in this r

Full text of DOI:10.1021/ja906265a

Published on Web 10/07/2009
An Olefination via Ruthenium-Catalyzed Decarbonylative Addition of
Aldehydes to Terminal Alkynes
Xiangyu Guo, Jun Wang, and Chao-Jun Li*
Department of Chemistry, McGill UniVersity, Montreal, QC, Canada H3A 2K6
Received July 26, 2009; E-mail: cj.li@mcgill.ca
Table 1. Decarbonylative Addition under Various Conditionsa
The generation of CdC double bonds, a principal functionality in
organic chemistry, is one of the most important reactions in synthesis.1
Various olefination methodologies have been developed throughout
the history of organic chemistry.1 The well-known Wittig reaction
provides access to CdC bonds with higher efficiency and better regio-
and stereoselectivities over the classical elimination reactions (E1, E2,
% NMR
yieldb
entry
% catalyst
% additive or ligand
E1cB).1,2 Other olefination reactions between nucleophiles and alde-
hydes include the Horner-Wadsworth-Emmons reaction,3 the
Peterson olefination,4 the Julia-Lythgoe olefination,5 and the Tebbe
olefination.6 However, such reactions generally involve highly reactive
carbanions and suffer from lower atom economy.7 The recently
developed olefin metathesis reaction provides an alternative for olefin
synthesis that overcomes some of the limitations of the earlier
methods.8 These reactions are particularly useful in the synthesis of
cyclic alkenes (to avoid homoalkene exchange).8d HoweVer, the
deVelopment of catalytic, more atom-economical, and highly regiose-
lectiVe methods for intermolecular olefination reactions remains an
ongoing synthetic challenge. Herein, we report a novel method for
synthesizing CdC bonds by decarbonylative addition of aldehydes to
alkynes (Scheme 1).
1
2
3
4
5
6
7
8
9
5% RuCl3
5% RuCl3.3H2O
5% [Ru(COD)Cl2]n 4 µL of H2O
5% [Ru(COD)Cl2]n 10% dppp + 4 µL of H2O
5% [Ru(COD)Cl2]n 10% dppe + 4 µL of H2O
5% [Ru(COD)Cl2]n 10% Ph3P + 4 µL of H2O
5% [Ru(COD)Cl2]n 10% ((F3C)2CH)3P + 4 µL of H2O
5% [Ru(COD)Cl2]n 50% 1,5 -COD + 4 µL of H2O
5% [Ru(COD)Cl2]n 30% CuCl2 hydrate
NR
19
35
22
11
23
11
6
48
16
10 5% [Ru(COD)Cl2]n 5 equiv of LiCl
11 5% [Ru(COD)Cl2]n 30% CuCl2 hydrate + 5 equiv of LiCl 59
12 10% [Ru(COD)Cl2]n 30% CuCl2 hydrate + 5 equiv of LiCl 83
13 10% [Ru(COD)Cl2]n 30% CuCl2 hydrate + 5 equiv of LiCl 65c
14 10% [Ru(COD)Cl2]n 30% CuCl2 hydrate + 5 equiv of LiCl 48d
15 10% [Ru(COD)Cl2]n 30% CuCl2 hydrate + 5 equiv of LiCl NRe
16 10% [Ru(COD)Cl2]n 30% CuCl2 hydrate + 5 equiv of LiCl 72f
17 10% [Ru(COD)Cl2]n 30% CuCl2 hydrate + 5 equiv of LiCl 70g
18 10% [Ru(COD)Cl2]n 30% CuCl2 hydrate + 5 equiv of LiCl 50h
Scheme 1. Catalytic Decarbonylative Aldehyde-Alkyne Addition
a Conditions: 1a (0.2 mmol), 2a (0.8 mmol), toluene (1 mL), 120 °C,
16 h under argon, unless otherwise noted. b Determined by 1H NMR
analysis of the crude reaction mixture. c In anisole. d In diglyme. e In
water. f At 130 °C. g At 110 °C. h In air.
Transition-metal-catalyzed decarbonylation reactions of alde-
hydes are an attractive subject that has been studied for decades.9
However, very limited research has focused on decarbonylative
addition reactions, which utilize the decarbonylative intermediate
for addition to an unsaturated system.10 During our studies of C-H
activation of aldehydes, we observed that when an alkyne is added,
an alkene (corresponding to a decarbonylative addition) is generated.
Subsequently, various conditions concerning the catalysts and the
additives were examined to optimize the formation of this decar-
bonylative addition product (Table 1). Water was found to be
beneficial to the reaction (entries 1 and 2). With the use of
[Ru(COD)Cl2]n together with 4 µL of water, the product was
generated in 35% yield (entry 3). The addition of various ligands
reduced the yield (entries 4-8). Complex hydrates were found to
be an alternative to added water: the addition of 30 mol %
CuCl2 ·2H2O increased the product yield to 48% (entry 9).11 We
speculated that chloride ion might serve as a weak coordinating
ligand that could facilitate the reaction by stabilizing the catalyst.
Indeed, in the presence of 5 equiv of LiCl, the product could still
be generated in 16% yield without adding water or CuCl2 ·2H2O
(entry 10). The use of cationic ruthenium catalysts or the combina-
tion of [Ru(COD)Cl2]n with AgOTf reduced the product yield.11
A combination of the catalyst, CuCl2 ·2H2O, and LiCl was
examined:11 an 83% yield of the desired product was achieved with
10 mol % catalyst together with CuCl2 ·2H2O and LiCl (entry 12).
The reaction temperature and solvents were also examined (entries
13-17). The yield was reduced to 50% when the reaction was
conducted under air (entry 18).11 Although a small amount of water
was beneficial for the reaction, no product was generated when the
reaction was conducted in water (entry 15). When D2O instead of H2O
was added,11 no deuterated product was detected and a similar yield
(32%) was obtained. We reasoned that water is not involved in the
catalytic cycle and that a trace amount of water can help the chloride
ion disperse in the reaction system and coordinate to the metal catalyst,
whereas too much water would quench the reaction.
With the optimized reaction conditions in hand, different substrates
were investigated using this reaction (Table 2). Aliphatic aldehydes
failed to react under the current catalytic system, which provides an
Scheme 2. One-Pot Competing Reaction between Aromatic and
Aliphatic Aldehydesa
a Conditions: 1a (0.2 mmol), 1q (0.2 mmol), 2a (0.8 mmol),
[Ru(COD)Cl2]n (0.02 mmol). Yields were determined by 1H NMR analysis.
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15092 J. AM. CHEM. SOC. 2009, 131, 15092–15093
10.1021/ja906265a CCC: $40.75  2009 American Chemical Society

C O M M U N I C A T I O N S
Scheme 3. Tentative Mechanism for the Ruthenium-Catalyzed
Decarbonylative Addition Reaction
interesting chemoselectivity. A competition experiment involving both
aromatic and aliphatic aldehydes led to the olefination product
corresponding exclusively to the reaction of the aromatic aldehyde
(Scheme 2).
Table 2. Substrate Scope of the Decarbonylative Addition
Reactiona
In summary, we have developed a novel method of olefination
using aldehydes and alkynes via a decarbonylative addition. Various
substrates were examined, and a strong electronic effect and high
chemoselectivity between aromatic and aliphatic aldehydes were
observed in this reaction. Further efforts to expand the scope of
such an olefination based on decarbonylative addition are currently
underway in our laboratory.
Acknowledgment. We are grateful to the Canada Research
Chair (Tier I) Foundation (to C.-J.L.), CFI, and NSERC for support
of our research.
a Conditions: 1a (0.2 mmol), 2a (0.8 mmol), toluene (1 mL), 120 °C,
16 h under argon, unless otherwise noted. b At 150 °C. c Total yield of
both the E and Z isomers; the E/Z ratio was determined by 1H NMR
analysis.
Supporting Information Available: Experimental procedures,
1
characterization data of new compounds, and H and 13C NMR data.
This material is available free of charge via the Internet at http://
pubs.acs.org.
Electronic effects played an important role in this reaction.
Aromatic aldehydes with more electron-donating groups on the
phenyl ring gave much better yields than those with electron-
withdrawing groups (Table 2). The yield decreased when an ester
group was the substituent (3k). Other substrates (aldehyde and
alkyne) containing ester groups, such as methyl 4-formylbenzoate,
methyl propiolate, and propargyl propionate, also gave low yields,
and the corresponding acids, resulting from decomposition of the
esters, were found after the reaction. An unprotected hydroxyl group
could also be tolerated by the reaction (3l). Both aromatic and
aliphatic alkynes can be used as the alkyne substrate. Phenylacety-
lenes bearing electron-withdrawing groups gave better yields than
those having electron-donating groups (3l-3n). It is worth noting
that a conjugated aldehyde could also participate in the reaction,
generating a 1,3-butadiene product (3p). Trans alkenes were
generated as major products in all cases, and aliphatic alkynes
showed better stereoselectivity than aromatic alkynes (Table 2).
No product was obtained when the terminal alkynes were replaced
with internal alkynes such as 2-hexyne and biphenylethyne.
A tentative mechanism to rationalize the decarbonylative addition
reaction is illustrated in Scheme 3. The catalyst polymer first forms
the monomer, which coordinates with the alkyne to generate inter-
mediate B. A control experiment showed that no corresponding
decarbonylative product was formed in the absence of alkyne.
Oxidative addition with the aldehyde generates intermediate D, which
subsequently undergoes a decarbonylative process to form intermediate
E. Finally, reductive elimination affords the decarbonylative addition
product and CO and regenerates the active ruthenium complex A. An
IR study of the reaction residue revealed that a ruthenium carbonyl
complex was formed after the reaction, which led to the termination
of the catalytic cycle. The chloride ion serves as a weak coordinating
ligand shuttle to facilitate these steps.
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