Decarbonylative Olefination of Aldehydes to Alkenes

Article abstract of DOI:10.1021/jacs.9b12354

New atom-economical alternatives to Wittig chemistry are needed to construct olefins from carbonyl compounds, but none have been developed to-date. Here we report an atom-economical olefination of carbonyls via aldol-decarbonylative coupling of aldehydes using robust and recyclable supported Pd catalysts, producing only CO and H₂O as waste. The reaction affords homocoupling of aliphatic aldehydes, as well as heterocoupling of aliphatic and aromatic ones. Computations provide insight into the selectivity and thermodynamics of the reaction. The tandem aldol-decarbonylation reaction opens the door to exploration of new carbonyl reactivity to construct olefins.

Full text of DOI:10.1021/jacs.9b12354

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Communication
Decarbonylative olefination of aldehydes to alkenes
Diana Ainembabazi, Christopher Reid, Amanda Chen, Nan An, Jakub Kostal, and Adelina Voutchkova-Kostal
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b12354 • Publication Date (Web): 29 Dec 2019
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Decarbonylative olefination of aldehydes to alkenes
Diana Ainembabazi, Christopher Reid, Amanda Chen, Nan An, Jakub Kostal, Adelina Voutchkova-
Kostal*
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Chemistry Department, the George Washington University, 800 22nd St NW, Washington D.C. 20910
avoutchkova@gwu.edu
Supporting Information Available
Scheme 1.
ABSTRACT: New atom-economical alternatives to
Wittig chemistry are needed to construct olefins from
carbonyl compounds, but none have been developed to-
date. Here we report an atom-economical olefination of
carbonyls via aldol-decarbonylative coupling of
aldehydes using robust and recyclable supported Pd
catalysts, producing only CO and H2O as waste. The
reaction affords homocoupling of aliphatic aldehydes, as
well as heterocoupling of aliphatic and aromatic ones.
Computations provide insight into the selectivity and
thermodynamics of the reaction. The tandem aldol-
decarbonylation reaction opens the door to exploration of
new carbonyl reactivity to construct olefins.
(a) Wittig
R1
R2
O
R1
R3
R2
R4
+ O=PPh3
+
R3
R4
PPh3
Hazardous waste, low
atom economy, high PMI*
(b) This work
R1
R1
[Pd cat]
O
+ CO
R2
+
H2O
+
R3
R3
O
The Wittig carbonyl olefination of ketones or aldehydes
No liquid hazadous waste, high
atom economy, low PMI*
R2
by phosphorous ylids
(Scheme 1a) has been a
*
cornerstone of modern synthesis due to its utility and
reliability.1-2 However, the utility of the chemistry is
hindered by the need to pre-form phosphorous ylids and
by the production of stoichiometric waste, necessitating
the development of more atom-economical alternatives.
Recently, we reported the activity of heterogeneous
catalysts based on Pd-doped hydrotalcites (Pd-HTs) for
selective decarbonylation of aldehydes.3 In the course of
this study we observed that ,-unsaturated aldehydes
decarbonylate faster than aromatic and saturated aliphatic
aldehydes. Furthermore, we noted that the basic sites of
Pd-HTs facilitate aldol condensation of enolizable
aldehydes to form ,-unsaturated aldehydes, which
undergo further decarbonylation to form alkenes
(Schemes 1b and 2). Thus, herein we set out to develop a
practical catalytic process for decarbonylative coupling
of carbonyls to selectively afford alkenes through
decarbonylative homo- and hetero-coupling.
PMI: Process Mass Intensity = mass of materials
mass of isolated product
Given that the aldol condensation can be catalyzed by
acidic or basic sites, we considered hydrotalcites, MgO,
Al2O3, carbon and silica as potential non-innocent
supports that could facilitate this step. However, the
electronic nature of the support also affects the activity of
the Pd phase, which catalyzes the decarbonylation.4-5 In
order to explore the potential of optimizing both steps, we
synthesized and screened Pd-HT, Pd-Al2O3, Pd-SiO2, Pd-
C and Pd-MgO for the reaction in Scheme 2. The catalysts
were fully characterized by ICP-OES, TEM, XPS, surface
analysis
and
PXRD
(ESI
section
Catalyst
Characterization). XPS showed notable electronic
differences in speciation and binding energies of the
immobilized Pd species (ESI Table S3 and Figure S7).
Initial findings showed that Pd-HTs facilitate the
conversion of enolizable aldehydes under neat conditions
to the ,-unsaturated carbonyls, which decarbonylate to
afford internal alkenes (Scheme 2). The reactions require
low Pd loading (0.1 mol% Pd) and proceed at 150 C or
above using microwave or conventional heating.
Heptanal thus afforded (E)-tridec-6-ene, an olefin with
Catalysts for tandem aldol condensation-decarbonylation
should be bifunctional, consisting of catalytic sites
effective for both steps. It would ideally be possible to
tune the activity of both sites independently in order to
optimize selectivity for different carbonyl substrates.
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(2n-1) carbons, and small amounts of the intermediate 3
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Thus, the strong basic sites on MgO and HT are more
effective for aldol condensation than the Lewis acidic
sites of Al2O3. At 150 C decarbonylation yields 38 –
78% of 4 in 24 hr, discerning the activity trend for
decarbonylation: Pd-Al2O3 > Pd-HT > Pd-MgO (ESI
Figure S10), while at 180 C decarbonylation is rapid, so
intermediate 3 is quickly consumed (ESI Figure S11). As
a control, we compared the reaction with Pd-Al2O3 to one
with Pd(OAc)2 and Al2O3. The reaction yields 4 but
decarbonylation is significantly slower, resulting in build-
up of 3 (ESI Figure 12). Decarbonylation rate is thus the
rate-determining process, and is sensitive to support and
reaction temperature in the range studied. Further
reactions were explored using Pd-Al2O3 as the most
active catalyst.
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(Scheme 2).
Scheme 2
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Curiously, we observed that the configuration of aldol
intermediate 3 is cis w.r.t. R-groups, while alkene 4 is a
trans alkene (Scheme 2 and ESI Fig. S13). Based on
Zimmerman-Traxler 6-membered transition state for the
alkylation of the enolate, trans configuration of 3
suggests it was derived from a cis enolate. The latter
could be preferred when the acid/base sites are
immobilized on a solid support. The trans geometry of 4
indicates that the catalyst facilitates both isomerization
and decarbonylation of 3. As further evidence for the
latter, we find that α-methylcinnamaldehyde (cis w.r.t. the
R-groups) affords a 1:6 ratio of cis:trans propylbenzene
in 8 hours with Pd-Al2O3, and complete conversion to the
trans product in 24 hours (Scheme 3 and ESI Figure S14).
This is consistent with the assertion that the catalyst
facilitates both decarbonylation and isomerization to the
thermodynamic alkene isomer. No alkene migration was
observed in the substrates.
Figure 1. Product distribution of supported Pd catalysts
and supports in decarbonylative olefination of heptanal.
(Conditions: 0.1 mol% Pd, at 180 C, 8 hr). See ESI Fig.
S8 for profiles at 150 C.
The activity of five supported Pd catalysts were examined
with heptanal as model substrate at 150 and 180 C,
(Figures 1 and S8). The activities of the supports were
compared to distinguish the activity for aldol vs
decarbonylation. Consistent with our initial hypothesis,
all of the supports showed some activity for aldol
condensation, but only the Pd catalysts afforded
decarbonylation products (Figure 1). Use of Pd(OAc)2
alone afforded only minimal yield of aldol intermediate 3
(10%) with no olefin 4.
Scheme 3
At 180 C quantitative yields of alkene 4 could be
obtained with Pd-Al2O3, Pd-HT and Pd-MgO in only 8
hours, while Pd-C and Pd-SiO2 afforded 70 and 82%
respectively (Figure 1). No decarbonylation was observed
with homogeneous Pd(OAc)2 precursor. Catalyst
screening at 150 C (ESI Figure S8) allowed us to
establish activity trends at lower conversions. Pd-Al2O3
still afforded highest yield of olefin 4 (35% in 8 hours
and 98% in 24 hours), followed by Pd-C (20% in 8 hours).
However, Pd-C showed lowest overall conversion,
suggesting it is a poor catalyst for aldol condensation. In
contrast, Pd-MgO and Pd-HT afforded full conversion in
8 hours, but only 10-15% yield of the alkene. These
results establish the following trend for activity for aldol
condensation: MgO > HT > Al2O3 > activated carbon >
SiO2; and for decarbonylation: Pd-Al2O3 > Pd-C > Pd-
HT > Pd-MgO > Pd-SiO2.
We briefly explored the relative thermodynamics of the
intermediates and products in the reaction with heptanal
(Scheme 2 and Figure 2). Calculations were carried out
with the PM7 semiempirical method in gas phase using
the Gaussian 16 software.6 Geometries were fully
optimized, and all minima were verified to have to
imaginary vibrational frequencies. Free energies,
evaluated at 298 K, show that while initial aldol addition
is 2.9 kcal/mol uphill, the aldol condensation is
thermodynamically favorable (Grxn = -3.9 and -4.0
kcal/mol respectively for trans and cis ,-unsaturated
carbonyls)
w.r.t.
heptanal.
The
subsequent
Reaction time courses of the three most promising
catalysts revealed further details about the relative aldol
vs decarbonylation activity. At 100 C, no
decarbonylation is observed, and aldol activity follows
the trend Pd-MgO~ Pd-HT >> Pd-Al2O3 (ESI Figure S9).
decarbonylation to the cis-olefin is near thermoneutral,
but the isomerization to the trans-olefin (4) drives Grxn
to be slightly more favorable (-1.3 kcal/mol), bringing the
overall Grxn of the two-step process to -5.2 kcal/mol (vs.
-4.4 kcal/mol for the cis-olefin, Figure 1). These
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calculations are consistent with the experimental
observation of the trans-olefin product. Furthermore, the
thermodynamics suggest that decarbonylation is close
enough to thermoneutral to potentially allow for
reaction was performed using the conditions optimized
for homocoupling, selectivity for the desired
heterocoupled olefin was low due to rapid
decarbonylation of the non-enolizable (aromatic)
aldehyde relative to aldol condensation. To increase
selectivity for the cross-aldol condensation we introduced
hydrotalcite (HT) as a more effective aldol catalyst than
alumina. Initial reaction with only HT pre-forms the
hetero-aldol product, and subsequent addition of Pd-
Al2O3 affords decarbonylation. This protocol
significantly improved the selectivity and yield of the
desired olefin (79% yield in 8 hours for furfural and
heptanal).
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reversibility under appropriate conditions.
O
4
5
OH
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- H2O
2
O
4
0
0
-1
-2
-3
-4
-5
-6
O
Further exploration of heterocoupling for a selection of
substrates is summarized in Table 2. Similar to the Wittig
reaction, the aldol condensation does not tolerate
electrophilic and nucleophilic groups (e.g. unprotected
amines, alcohols, alkyl halides), and thus these were
excluded. Substrates shown in Table 2 afforded full
conversion, and good to excellent yields of desired olefin,
but some competing homocoupling of heptanal was still
observed in select cases. Since selectivity for
heterocoupling is affected by the aldol step, it can be
related to the reactivity of the non-enolizable aldehydes:
e.g. furfural carbonyl carbon is more electrophilic than
that of benzaldehyde, and thus more reactive.
Computationally, the latter can be approximated by the
Mulliken charges, which reflect the same trend (ESI
Table S4). Since selectivity issues are primarily related to
the aldol step, synthetic conditions can be further
modified to optimize selectivity and yields for the desired
intermediate. The second limitation on substrate scope is
functionality that is susceptible to Pd-catalyzed
processes: e.g., aryl halides susceptible to C-X oxidative
addition. The latter is responsible for the low yields of
3,4-dichlorobenzaldehyde (12%) as well as iodo and
bromobenzaldehyde (< 5%) due to aryl-aryl by-products.
As expected, this is not an issue for C-F bonds, and 3,4-
difluorobenzaldehyde affords good yields and selectivity.
5
5
4
-3.9
-4.0
5
4
- CO
-4.4
-5.2
5
4
O
4
Figure 2. Free energy diagram for decarbonylative
olefination of heptanal (see reaction in Scheme 2).
We briefly explored the substrate scope of the
decarbonylative olefination. Enolizable aldehydes with
no -branching afford excellent yields (Table 1, entries
1-3), while those with -branching react more slowly
(entries 4 and 5) due to slower aldol condensation. The
latter is evidenced by the low conversion in the latter
cases. Thus, optimization of olefin selectively requires
balancing rates of three independent reactions: aldol
condensation, decarbonylation of aldol product and
undesired decarbonylation of initial substrate.
Table 1. Substrate scope for decarboxylative olefination of
aliphatic aldehydes.
No. Substrate
Olefin product
% Yield
97
Table 2. Substrate scope for heterocoupling of aldehydes
with heptanal.
O
4
1
5
4
O
3
4
2
3
88
82
3
O
O
4
5
45
36
O
Conditions: 14 mmol substrate (neat), 0.1 mol% Pd-Al2O3,
180 C, 8 h, under air.
We also explored whether this reaction can be optimized
in the heterocoupling reactions of two aldehydes.
Selectivity for heterocoupling was favored by coupling
enolizable with non-enolizable aldehydes. When the
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Conditions: 1. 7 mmol heptanal, 10 mmol aldehyde, 50 mg
Page 4 of 5
decarbonylative coupling of aldehydes using robust and
recyclable supported Pd catalysts, producing only CO and
H2O as waste. Computations suggest the reaction is
thermodynamically favorable, with the decarbonylation
step near thermo-neutral. Decarbonylation is rate-
determining, and is sensitive to temperature in the range
100 – 180 C. The tandem reaction is most effectively
facilitated by multifunctional Pd catalysts, such as Pd-
Al2O3, Pd-HT and Pd-MgO, where the relative rates of
the two steps is dependent on catalytic support. The
process can be used to obtain olefins from both
homocoupling and heterocoupling of aldehydes. The
most effective catalyst, Pd-Al2O3, retains activity for at
least 9 cycles with minor decrease in selectivity.
Poisoning experiments implicate involvement of surface-
bound and soluble Pd species.
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HT, 180 C, 2 h; 2. Add 0.3 mol%, Pd-Al2O3, 180 C, 6 h.
aReaction polymerized 2 hours after adding Pd-Al2O3.
The recyclability of the Pd-Al2O3 was explored with
heptanal as substrate. The catalyst was reused after
separation from reaction by centrifugation, washing and
drying. The yields of products obtained over 9 cycles, all
of which below full conversion, indicate that the catalyst
retaines activity (Figure 3), with a small decrease in
selectivity 93% - 98% after cycle 4. Elemental analysis of
the spent catalyst shows negligible loss of Al amd Pd
(within the standard error of the as-prepared catalysts),
suggesting the small drop in selectivity is likely attributed
to factors other than leaching. TEM images of the used
catalyst do not indicate notable morphological changes or
agglomeration of Pd nanoparticles (ESI Figure S15).
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ASSOCIATED CONTENT
Supporting Information is available detailing catalyst
synthesis, characterization, additional figures and tables
related to reaction and NMR characterization of products.
This material is available free of charge via the Internet
at http://pubs.acs.org.
80
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20
0
Funding Sources
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9
Cycle
JK and AV-K thank NSF CBET for support of this work
(award 1805080).
Figure 3.
Recyclability of Pd-Al2O3 in the
decarbonylative olefination of heptanal.
ACKNOWLEDGMENT
To investigate whether Pd-Al2O3 was operationally
heterogeneous in this reaction, we performed hot
filtration, selective poisoning, and mercury poisoning
tests. Hot filtration was performed by sampling a portion
of the reaction mixture after 3 h of reaction and passing
the mixture through a hot frit (2 µm). After 5 h further
reaction, the concentration of olefin 4 did not change
significantly from the time of filtration (ESI Figure S16a),
suggesting that the catalytic species are absent from the
filtrate. This result was consistent with the fact that
decarbonylation activity was completely quenched by
mercury poisoning, which amalgamates with supported
palladium.7 (ESI Figure S16b). However, catalytic
We thank the Material Institute at GWU and Surface
Analysis Center at University of Maryland for use of
instrumentation in catalyst characterization.
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In sum, this preliminary report documents a new, atom-
economical olefination of carbonyls via aldol-
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SYNOPSIS TOC (Word Style “SN_Synopsis_TOC”).
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R1
R3
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Pd
O
+
+ CO
+
H2O
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R2
R2
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High atom economy
R1
R3
Pd
O
CO
R2
H2O
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