Tandem hydroformylation/aldol condensation reactions: Synthesis of unsaturated ketones from olefins

Article abstract of DOI:10.1016/j.jorganchem.2018.04.031

Platinum-catalysed tandem hydroformylation/aldol condensation reaction of vinyl aromatics and ketones toward the corresponding α,β-unsaturated ketones were performed under syngas atmosphere in the presence of acid co-catalysts. The in situ generated catal

Full text of DOI:10.1016/j.jorganchem.2018.04.031

Journal of Organometallic Chemistry 866 (2018) 184e188
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Tandem hydroformylation/aldol condensation reactions: Synthesis of
unsaturated ketones from olefins
L aꢀ szl oꢀ Koll aꢀ r, P eꢀ ter Pongr aꢀ cz*
Department of Inorganic Chemistry, University of P ꢀe cs and J aꢀ nos Szent aꢀ gothai Research Centre, MTA-PTE Research Group for Selective Chemical Syntheses,
H-7624, P ꢀe cs, P.O. Box 266, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 22 March 2018
Received in revised form
Platinum-catalysed tandem hydroformylation/aldol condensation reaction of vinyl aromatics and ke-
tones toward the corresponding a,b-unsaturated ketones were performed under syngas atmosphere in
the presence of acid co-catalysts. The in situ generated catalysts modified with various ligands proved to
be efficient under applied conditions. The presence of acids promotes side reactions like hydrogenation
of the alkene substrate and that of the aldehyde to the corresponding alkane and alcohol, respectively.
Interestingly, the hydrogenation of the condensed products is not preferred, only trace amounts of
saturated products can be detected by GC-MS. In general, moderate yields can be achieved with several
ketones using styrene and a-methylstyrene as substrate in hydroformylation reaction. Linear aldehydes
proved to be more active in aldol condensation step, furthermore, aromatic and cyclic ketones are also
feasible coupling partners to generate the corresponding unsaturated ketones. Contrary to the preceding
12 April 2018
Accepted 21 April 2018
Available online 23 April 2018
Keywords:
Tandem reaction
Hydroformylation
Aldol condensation
Platinum
literature, ketones possessing
a-methylene group(s) showed exclusive preference for methylene func-
Unsaturated ketone
tionalization in the aldol condensation reaction.
©
2018 Elsevier B.V. All rights reserved.
1. Introduction
function of temperature.
In most cases the aldehydes are not the final products and the
reactivity of these substantial materials allow us to perform
numerous additional reactions even under hydroformylation con-
ditions. Aldehydes can be considered as ideal substrates for further
transformations, like oxidations, reductions or condensation re-
actions. In the presence of N- or O-nucleophiles versatile domino
reactions are known like hydroaminomethylation, cyclo-
hydrocarbonylation, acetalization or aldol condensation [13,14].
The first hydroformylation/aldol condensation reactions were re-
ported by Breit and Eilbracht with rhodium catalysts using proline
organocatalyst [15,16]. Breit described hydroformylation/Knoeve-
nagel condensation reaction in the presence of piperidine base and
acetic acid [17], and further tandem decarboxylative Knoevenagel
Hydroformylation represents an efficient and selective method
for the transformation of alkenes to valuable aldehydes [1e3]. The
reaction discovered accidently by Otto Roelen in 1938, represents
one of the large scale catalytic reactions. It has an especially high
importance among homogenous catalytic reactions in industry
today. Regioselective hydroformylation of propene to n-butyral-
dehyde (basic compound of 2-ethylhexanol used as alcohol
component in the production of diisooctyl phthalate plasticizer), or
the enantioselective hydroformylation of vinylaromatics to 2-
arylpropanals (intermediate of non-steroidal anti-inflammatory
drugs (NSAIDs)) are only two important examples for the process
[
4]. Beside the well-studied cobalt- and rhodium-containing cata-
lysts, platinum-phosphine-tin(II)halide type systems were also
developed focusing on the enantioselective reactions [5e9], and
reaction mechanism. Seminal work by Casey et al. on the kinetics of
enantioselective hydroformylation [10] and asymmetric hydro-
formylations of a set of 4-substituted styrenes by our group [11,12]
were carried out to rationalise the reversal of enantioselectivity as a
reactions, which allowed an efficient one-pot synthesis of a,b-un-
saturated acids and esters [18]. Recently, Beller and co-workers
developed an efficient hydroformylation/aldol condensation/hy-
drogenation protocol using piperidine and benzoic acid cocatalysts
[19,20]. In this study, a set of substrates and ketones proved to be
suitable for the production of normal chain saturated ketones, i.e.,
the consecutive hydrogenation of the unsaturated ketones formed
via condensation was observed. Examples of intramolecular
hydroformylation/aldol reactions of unsaturated ketones were also
*
Corresponding author.
E-mail address: pongracz@gamma.ttk.pte.hu (P. Pongr aꢀ cz).
https://doi.org/10.1016/j.jorganchem.2018.04.031
022-328X/© 2018 Elsevier B.V. All rights reserved.
0

L. Koll aꢀ r, P. Pongr aꢀ cz / Journal of Organometallic Chemistry 866 (2018) 184e188
185
reported, which afforded the corresponding cyclic aldol adducts in
good yields [21].
Herein, we present the application of platinum(II)-phosphine
complexes and para-toluenesulfonic acid as efficient catalyst sys-
tems for domino hydroformylation/aldol condensation reactions.
2.3.4. 3-Methyl-5-phenyl-3-hexene-2-one (4an)
(500 MHz, CDCl ): 7.34e7.22 (5H, m, Ph), 6.67 (1H, t, 7.0 Hz,
CH), 2.82 (2H, t, 7.5 Hz, PhCH ), 2.60 (2H, td, 7.4 Hz, 7.5 Hz, CH CH),
2.30 (3H, s, COCH ), 1.76 (3H, s, CCH ); (125.7 MHz, CDCl ): 199.7,
d
H
3
2
2
3
3
d
C
3
142.1, 141.0, 138.2, 128.6, 128.5, 126.2, 34.8, 30.8, 25.4, 11.1. MS m/z
Styrene and
a
-methylstyrene as model substrates are transformed
(rel int. %): 188 (4), 173 (4), 145 (5), 116 (20), 91 (100), 65 (12).
to unsaturated ketones under moderate conditions in the presence
of various ketones used as solvents or reactants.
.3.5. 2-Methyl-7-phenyl-5-octene-4-one (4bi)
2
MS m/z (rel int. %): 216 (8), 159 (100), 131 (92), 118 (46), 91 (71),
7 (28), 57 (24). (NMR characterization of the analytically pure
2
. Experimental
7
sample was failed due to low yield. Using iBu-Me-ketone both
2
.1. General
condensed products and branched aldehyde were obtained in low
n
yield. Therefore, only the condensation product 4b ) obtained from
2 2
The PtCl (PhCN) [22] precursor was synthesized as described
the normal aldehyde was isolated in analytically pure form.)
earlier. Toluene was distilled and purified by standard methods [23]
and stored under argon. Styrene, tin(II) chloride (anhydrous) and
ketones were used as obtained from Sigma-Aldrich without any
further purification. All reactions were carried out under argon
atmosphere using standard Schlenk technique.
2
.3.6. 2-Methyl-8-phenyl-5-octene-4-one (4bn)
(500 MHz, CDCl ): 7.34e7.20 (5H, m, Ph), 6.86 (1H, td, 6.8 Hz,
5.6 Hz, CHCO), 6.13 (1H, d, 15.6 Hz CH CH), 2.82 (2H, t, 7.5 Hz,
PhCH ), 2.59e2.54 (2H, m, CH CH), 2.41 (2H, d, 7.0 Hz, COCH ),
.19e2.13 (1H, m, CH(CH ), 0.95 (6H, d, 6.6 Hz CH );
(125.7 MHz, CDCl ): 200.4, 145.9, 140.8, 131.2, 128.5, 128.4, 126.2,
9.2, 34.5, 34.1, 25.2, 22.7. MS m/z (rel int. %): 216 (1), 158 (29), 130
13), 91 (100), 65 (13).
d
H
3
1
2
2
2
2
The GC and chiral GC measurements were run on a Chrom-Card
Trace GC-Focus GC gas-chromatograph. The enantiomeric excesses
2
3
)
2
3
d
C
1
13
3
were determined on a capillary Cyclodex-column. The H and
C
4
(
NMR spectra were recorded on a Bruker Avance III 500 spectrom-
eter. Chemical shifts are reported in ppm relative to TMS (down-
1
13
field) for H and C NMR spectroscopy.
.2. Tandem hydroformylation/aldol condensation experiments
In a typical experiment, PtCl (PhCN) (4.7 mg, 0.01 mmol),
2
.3.7. 4-Methyl-6-phenyl-4-heptene-3-one (4ci)
(500 MHz, CDCl ): 7.38e7.19 (5H, m, Ph), 6.72 (1H, d, 9.5 Hz,
CHC), 3.90 (1H, dq, 6.9 Hz, 9.5 Hz, CH CH), 2.72 (2H, q, 7.4 Hz,
CH CH ), 1.90 (3H, s, CCH ), 1.46 (3H, d, 7.0 Hz, CHCH ), 1.11 (3H, t,
.3 Hz, CH CH ); (125.7 MHz, CDCl ): 202.0, 144.5, 143.0, 135.5,
128.8, 127.0, 126.6, 38.9, 30.5, 21.1, 11.6, 8.8. MS m/z (rel int. %): 202
29), 173 (67), 145 (100), 128 (34), 105 (81), 77 (39), 57 (22).
2
d
H
3
3
2
3
3
3
2
2
7
2
3
d
C
3
diphosphine (0.01 mmol), and tin(II) chloride (3.8 mg, 0.02 mmol),
para-toluenesulfonic acid (17.2 mg, 0.1 mmol) and 0.115 mL
(
(
1.0 mmol) of styrene was transferred under argon into a 100 mL
stainless steel autoclave. Either 10 mL of ketone (Method A) or a
mixture of 8 mL of toluene and 2 mL of the appropriate ketone
2.3.8. 4-Methyl-7-phenyl-4-heptene-3-one (4cn)
(500 MHz, CDCl ): 7.34e7.22 (5H, m, Ph), 6.67 (1H, t, 7.1 Hz,
(
Method B) was added as solvent. The reaction vessel was pres-
d
H
3
surized to 80 bar total pressure (CO/H
2
¼ 1/1) and placed in an oil
CH), 2.81 (2H, t, 7.5 Hz, PhCH ), 2.70e2.66 (2H, m, CH CH), 2.59 (2H,
2
2
bath of appropriate temperature and the mixture was stirred with a
magnetic stirrer. Sample was taken from the mixture and the
pressure was monitored throughout the reaction. After cooling and
venting of the autoclave, the pale yellow solution was removed and
immediately analysed by GC.
q, 7.3 Hz, CH
2
CH
3
), 1.77 (3H, s, CCH
3
2 3 C
), 1.11 (3H, t, 7.3 Hz, CH CH ); d
(125.7 MHz, CDCl ); 202.5, 141.0, 140.6, 137.5, 128.6, 128.4, 126.2,
3
34.8, 30.8, 30.4, 11.4, 8.8. MS m/z (rel int. %): 202 (1), 173 (29), 145
(10), 116 (13), 91 (100), 65 (13).
2
.3.9. 1,4-Diphenyl-2-pentene-1-one (4di)
(500 MHz, CDCl ): 7.91e7.24 (10H, m, Ph), 7.21 (1H, dd, 6.8 Hz,
5.5 Hz, CHCO), 6.86e6.80 (1H, m, CHCHCO), 3.77e3.72 (1H, m,
PhCH), 1.51 (3H, d, 7.1 Hz, CH ); (125.7 MHz, CDCl ): 191.1, 153.1,
43.4, 137.9, 132.6, 128.7, 128.5, 128.4, 127.4, 126.7, 124.4, 42.5, 20.5.
MS m/z (rel int. %): 238 (11), 133 (32),120 (83), 105 (100), 91 (39), 77
75), 51 (19).
2.3. Characterization of the products
d
H
3
1
2
.3.1. 5-Phenyl-3-hexene-2-one (2i)
3
d
C
3
d
H
(500 MHz, CDCl
6.5 Hz, CHCHCH), 6.06 (1H, d, 16.5 Hz, COCH), 3.63e3.59 (1H, m,
PhCH), 2.23 (3H, s, COCH ),1.43 (3H, d, 7 Hz, CHCH ); (125.7 MHz,
CDCl ): 199.2, 151.9, 143.5, 129.9, 129.0, 127.6, 127.1, 42.5, 27.2, 20.4.
MS m/z (rel int. %): 176 (3), 116 (20), 91 (100), 65 (13).
3
): 7.34e7.20 (5H, m, Ph), 6.92 (1H, dd, 7.0 Hz,
1
1
3
3
d
C
(
3
2
.3.10. 1,5-Diphenyl-2-pentene-1-one (4dn)
(500 MHz, CDCl ): 7.89e7.20 (10H, m, Ph), 7.09e7.04 (1H, m,
.3.2. 6-Phenyl-3-hexene-2-one (2n)
d
H
3
2
CH
PhCH
2
CH), 6.87 (1H, d, 15.0 Hz, CHCO), 2.86e2.81 (2H, t, 7.0 Hz,
), 2.66e2.62 (2H, m, CH CH ); (125.7 MHz, CDCl ): 190.8,
48.8, 140.7, 137.8, 132.6, 128.5, 128.5, 129.5, 128.3, 126.5, 126.1 34.5,
d
H
(500 MHz, CDCl
6.0 Hz, CH CH), 6.12 (1H, d, 16.0 Hz, CHCO), 2.82 (2H, t, 7.5 Hz,
PhCH ), 2.58 (2H, td, 7,5 Hz, CH CH), 2.25 (3H, s, CH );
125.7 MHz, CDCl ): 198.4, 146.9, 140.7, 131.7, 128.5, 128.3, 126.2,
4.5, 34.1, 26.9. MS m/z (rel int. %): 176 (34), 118 (65), 91 (100), 65
3
): 7.34e7.20 (5H, m, Ph), 6.84 (1H, dt, 6.7 Hz,
2
2
2
d
C
3
1
2
1
3
7
2
2
3
d
C
4.4. MS m/z (rel int. %): 236 (5), 145 (4), 116 (25), 105 (26), 91 (100),
7 (22), 65 (12), 51 (10).
(
3
3
(
24).
2
.3.11. 1,4-Diphenyl-2-methyl-2-pentene-1-one (4ei)
2
.3.3. 3-Methyl-6-phenyl-3-hexene-2-one (4ai)
d
H
(500 MHz, CDCl
CHC), 3.96 (1H, qd, 7.2 Hz, 9.5 Hz, PhCH), 2.08 (3H, s, CCH
(3H, d, 7.0 Hz, CHCH ); (125.7 MHz, CDCl ): 199.0, 147.4, 140.3,
137.5, 131.5, 129.8, 129.4, 128.7, 128.4, 128.0, 127.9, 39.2, 22.7, 14.1.
MS m/z (rel int. %): 250 (49), 235 (37), 145 (51), 128 (31), 105 (100),
77 (96), 51 (25).
3
) 7.66e7.21 (10H, m, Ph), 6.42 (1H, d, 9.6 Hz,
d
H
(500 MHz, CDCl ): 7.34e7.22 (5H, m, Ph), 6.14 (1H, d, 7.0 Hz,
CHC), 3.92e3.86 (1H, m, PhCH), 2.19 (3H, s, COCH ), 1.89 (3H, s,
CCH ), 1.46 (3H, d, 6.9 Hz, CHCH ); (125.7 MHz, CDCl ) 199.8,
47.2, 141.0, 133.1, 128.8, 128.6, 126.9, 39.0, 28.2, 21.1, 11.3; MS m/z
rel int. %): 188 (1), 159 (29), 116 (18), 91 (100), 65 (12).
3
3
), 1.44
3
3
d
C
3
3
3
d
C
3
1
(

186
L. Koll aꢀ r, P. Pongr aꢀ cz / Journal of Organometallic Chemistry 866 (2018) 184e188
2
.3.12. 1,5-Diphenyl-2-methyl-2-pentene-1-one (4en)
(500 MHz, CDCl ): 7.58e7.21 (10H, m, Ph), 6.32 (1H, t, 7.5 Hz,
CH), 2.80 (2H, t, 7.3 Hz, PhCH ), 2.70e2.66 (2H, m, CH CH), 1.95 (3H,
s, CH ); (125.7 MHz, CDCl ): 198.8,145.0,141.0,138.6,131.4,129.4,
29.3, 128.5, 128.4, 128.0, 127.9, 34.7, 21.3, 12.5. MS m/z (rel int. %):
2.3.19. 1,5-Biphenyl-2-methyl-2-hexene-1-one (5e)
(500 MHz, CDCl ): 7.54e7.19 (10H, m, Ph), 6.22 (1H, t, 7.2 Hz,
CHC), 2.96e2.91 (1H, m, PhCH), 2.62e2.59 (2H, m, CHCH ),1.95 (3H,
s, CHCH ), 1.36 (3H, d, 6,9 Hz, CCH ); (125.7 MHz, CDCl ): 198.9,
146.2, 138.5, 137.0, 131.4, 129.4, 128.6, 128.4, 127.9, 126.9, 126.4, 39.7,
37.8, 22.0, 12.7. MS m/z (rel int. %): 254 (1), 160 (47), 105 (100), 77
d
H
3
d
H
3
2
2
2
3
d
C
3
3
3
d
C
3
1
2
50 (7), 159 (13), 116 (19), 91 (100), 77 (33), 51 (10).
(28), 51 (8).
2
.3.13. 2-(2-phenylpropylidene)-cyclopentanone (4fi)
2
.3.20. 2-(2-Phenyl-butylidene)-cyclopentanone (5f)
(500 MHz, CDCl ) 7.33e7.21 (5H, m, Ph), 6.55 (1H, t, 7.5 Hz,
CHC), 2.94 (1H, m, PhCH), 2.45 (4H, overlapping COCH and CCH ),
.89 (4H, overlapping COCH CH , and CCH CH ), 1.33 (3H, d, 7.0 Hz,
CH ); (125.7 MHz, CDCl ) 206.9, 146.2, 138.3, 134.0, 128.4, 127.0,
26.2, 39.8, 38.6, 34.3, 29.5, 21.6, 19.8.; MS m/z (rel int. %): 214 (2),
30 (10), 110 (32), 105 (100), 91 (5), 77 (14), 51 (10).
d
H
(500 MHz, CDCl
CHC), 3.68e3.61 (1H, m, PhCH), 2.65 (2H, m, CCH
m, COCH ), 2.00e1.93 (2H, m, CH CH ), 1.45 (3H, d, 7.0 Hz, CH
125.7 MHz, CDCl ): 204.1, 139.5, 128.7, 128.5, 128.3, 127.0, 126.6,
0.1, 38.6, 26.7, 21.5, 19.8. MS m/z (rel int. %): 200 (65), 185 (21), 144
3
): 7.35e7.20 (5H, m, Ph), 6.72e6.69 (1H, m,
), 2.38e2.32 (2H,
);
d
H
3
2
2
2
2
3
d
C
2
2
1
2
2
2
2
(
4
3
3
d
C
3
1
1
(
43), 129 (100), 105 (38), 91 (32), 77 (31), 51 (16).
2
.3.14. 2-(3-phenylpropylidene)-cyclopentanone (4fn)
(500 MHz, CDCl ): 7.33e7.20 (5H, m, Ph), 6.61 (1H, t, 7.5 Hz,
CH), 2.80 (2H, t, 7.5 Hz, PhCH ), 2.58e2.55 (2H, m, CH CH),
.52e2.47 (2H, m, CCH ), 2.35e2.31 (2H, m, COCH ), 1.98e1.93 (2H,
m, COCH CH ); (125.7 MHz, CDCl ): 207.0, 141.1, 138.0, 134.7,
28.4, 128.4, 126.1, 39.8, 34.6, 31.6, 26.7, 19.8. MS m/z (rel int. %): 200
5), 182 (2), 141 (3), 116 (20), 91 (100), 65 (18).
3
. Results
d
H
3
2
2
To develop the catalytic system for a general synthesis of un-
2
2
2
saturated ketones, the reaction of phenylpropanal regioisomers,
obtained in the hydroformylation of styrene, and acetone to give 5-
phenyl-3-hexene-2-one (2 ) or 6-phenyl-3-hexene-2-one (2 ) was
chosen as model system (Scheme 1). In general, the catalytic ex-
periments were carried out at 100 C, under 80 bar pressure of
‘syngas’, with catalyst to substrate ratio of 1/100. We decided to
perform the initial optimisation attempts in the presence of an
effective chiral catalyst system obtained in situ from PtCl (PhCN) ,
2
2
d
C
3
1
(
i
n
ꢀ
2
.3.15. 2-(2-phenylpropylidene)-cyclohexanone (4gi)
(500 MHz, CDCl ): 7.33e7.20 (5H, m, Ph), 6.77 (1H, d, 10.0 Hz,
CHC), 3.74e3.71 (1H, m, PhCH), 2.66e2.61 (4H, overlapping COCH
and CCH ), 1.79e1.76 (4H, overlapping COCH CH , and CCH CH ),
.42 (3H, d, 6.9 Hz, CH ); (125.7 MHz, CDCl ): 201.7, 141.3, 138.0,
30.2, 129.3, 128.5, 127.8, 36.2, 34.3, 29.7, 26.3, 23.4, 21.0. MS m/z
d
H
3
2
2
2
2
2
2
2
2
(R)-BINAP and SnCl2.
1
1
3
d
C
3
In order to improve the yield of the condensation step, several
acid or base co-catalysts were tested (Table 1, entries 1e5). In the
presence of benzoic acid and tBuOK the hydroformylation reaction
was blocked. Using HCl or trichloroacetic acid (TCA) low yield of the
desired ketones and lots of by-products (ethylbenzene and alco-
hols) were observed. The application of para-toluenesulfonic acid
(
(
rel int. %): 214 (56),171 (33), 129 (100), 118 (60), 91 (56), 77 (32), 55
16).
.3.16. 2-(3-phenylpropylidene)-cyclohexanone (4gn)
2
(PTSA) seemed to be satisfactory for further optimisation reactions,
d
H
(500 MHz, CDCl
CH), 2.79 (2H, t, 7.6 Hz, PhCH
CH CH, COCH and CCH )), 1.87e1.82 (2H, m, COCH
2H, m, CCH CH ); (125.7 MHz, CDCl ): 201.1, 141.2, 137.9, 136.9,
3
) 7.33e7.20 (5H, m, Ph), 6.68 (1H, t, 7.4 Hz,
), 2.47e2.40 (6H, m, overlapping
CH ), 1.71e1.67
since the condensation step was slightly increased and the by-
product formation was suppressed in the presence of PTSA (entry
2
2
2
2
2
2
5).
(
2
2
d
C
3
Decreasing the reaction temperature the yield of target products
128.9, 128.4, 126.0, 40.2, 34.7, 29.8, 26.7, 23.5, 23.3.; MS m/z (rel int.
is low, while at higher temperatures the hydrogenation of the C¼C
double bond of the substrate and reduction of the formyl func-
tionality to the corresponding alcohol prevailed (entry 7 and 9,
respectively). The distribution of the side products clearly shows,
that hydrogenation of the styrene was preferential compared to
aldehyde reduction. Increased temperature and acid concentration
facilitates the reduction reaction (entries 9,19 and 11), furthermore,
significantly higher alcohol formation occurred using (S,S)-BDPP as
ligand (entry 10).
%
): 214 (6), 116 (20), 91 (100), 65 (23).
2.3.17. 3-Methyl-6-phenyl-3-heptene-2-one (5a)
MS m/z (rel int. %): 202 (1), 130 (3), 105 (100), 98 (26), 91 (4), 77
(
13), 51 (4).
2
.3.18. 4-Methyl-7-phenyl-4-heptene-3-one (5c)
(500 MHz, CDCl ): 7.36e7.23 (5H, m, Ph), 6.57 (1H, t, 6.9 Hz,
CHC), 2.98.2.91 (1H, m, PhCH), 2.64e2.60 (2H, m, CHCH ),
.57e2.53 (2H, m, CH CH ), 1.77 (3H, s, CCH ), 1.35 (3H, d, 6.9 Hz,
CHCH ), 1.08 (3H, t, 7.3 Hz, CH CH ); (125.7 MHz, CDCl ): 202.5,
46.2, 140.2, 137.6, 128.5, 126.8, 126.3, 39.6, 37.7, 30.4, 21.7, 11.5, 8.9.
MS m/z (rel int. %): 216 (3), 187 (2), 159 (26), 144 (11), 131 (19), 117
100), 112 (91), 105 (66), 91 (39), 77 (10), 57 (90).
d
H
3
2
Next, we planned to examine the efficiency of in situ generated
platinum catalysts incorporated with a series of chiral and achiral
bidentate ligands (entries 10e17). All the tested ligands proved to
be effective under acidic conditions, only dipamp and josiphos gave
lower yields of aldehydes. The ratio of the formed aldehyde
2
3
2
3
3
2
3
d
C
3
1
i
n
(
regioisomers (1 /1 ) are varied in the range of 20/80 to 59/41
Scheme 1. Tandem hydroformylation/aldol condensation reactions with acetone.

L. Koll aꢀ r, P. Pongr aꢀ cz / Journal of Organometallic Chemistry 866 (2018) 184e188
187
Table 1
Tandem hydroformylation/aldol condensation reactions using acetone as ketone reactant.a
o
Conv.b [% ]
other(A/B)c
Entry
Ligand
Cocatalyst
Temperature [ C]
Reaction time [h]
1 (iso/n)
2 (iso/n)
1
2
3
4
5
6
7
8
9
(R)-binap
(R)-binap
(R)-binap
(R)-binap
(R)-binap
(R)-binap
(R)-binap
(R)-binap
(R)-binap
(S,S)-bdpp
(R)-diop
(S,S)-dipamp
(R,S)-josiphos
(R)-segphos
(R)-dm-segphos
dppp
Benzoic acid
tBuOK
HCl
100
100
100
100
100
100
60
120
120
100
100
100
100
100
100
100
100
100
120
48
24
24
24
24
24
48
2
24
24
24
24
24
24
24
24
24
24
24
0
0
81
90
>99
80
60
5 (20/80)
e
e
e
e
e
44 (36/64)
65 (37/63)
74 (41/59)
44 (43/57)
56 (41/59)
19 (32/68)
39 (38/62)
50 (36/64)
71 (38/62)
9 (44/56)
35 (26/74)
52 (37/63)
49 (33/67)
51 (49/51)
29 (55/45)
68 (49/51)
44 (59/41)
7 (29/71)
7 (37/63)
21 (43/57)
18 (33/67)
2 (n.d.)
1 (15/85)
11 (64/36)
19 (84/16)
4 (50/50)
1 (n.d.)
4 (25/75)
12 (49/51)
10 (60/40)
12 (33/67)
21 (14/86)
9 (44/56)
18 (83/17)
30 (93/7)
18 (61/39)
5 (80/20)
18 (39/61)
2 (99/1)
16 (88/12)
50 (80/20)
31 (52/48)
21 (81/19)
18 (94/6)
9 (89/11)
36 (81/19)
29 (86/14)
37 (95/5)
50 (90/10)
20 (75/25)
38 (61/39)
TCA
PTSA
2 PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
36
>99
>99
96
28
48
>99
88
>99
>99
97
10
11
12
13
14
15
16
17
18
19
dppb
(R)-binap
(R)-binap
d
d
>99
a
b
c
Reaction conditions: 0.01 mmol of PtCl
2
(PhCN)
2
, 0.01 mmol ligand, 0.02 mmol SnCl
2
, 1 mmol styrene, 0.1 mmol co-catalyst, pCO ¼ pH
2
¼ 40 bar.
Styrene converted (to aldehydes (1), to condensation products (2) via aldehydes and to side products).
Hydrogenated by-products: ethyl benzene (A) and alcohols (B) (due to aldehyde reduction); the ratio of the by-products in brackets.
Method B was used (see experimental).
d
depending on the catalyst. As expected from platinum-containing
hydroformylation catalysts, generally the linear aldehyde was
formed in excess, that is, in general, the regioselectivity toward
linear products varied between 51 and 68%. The only exception is
the achiral dppb and the high temperature experiment with binap
using method B (entries 17 and 19 respectively). The aldol
condensation step cannot be enhanced by the variation of the P-
ligands. The best results can be achieved by using binap with yields
n
of 21%. Comparing the regioselectivity toward linear aldehyde (1 )
and the regioselectivity toward the formed unsaturated ketone
n
(
2 ), it can be stated that the latter is generally higher. It means, that
the condensation of the linear aldehydes are preferred to the
branched ones. Interestingly, the opposite tendency can be
observed using bdpp and segphos type ligands (entries 10, 14 and
15), where linear selectivity of the ketones decreased during the
aldol condensation step. The same phenomena can be observed at
elevated temperatures.
Under regular hydroformylation conditions only ethylbenzene
can be found as by-product in the product mixture. Unfortunately,
the presence of the acid co-catalyst facilitates the reduction of the
formed aldehydes to alcohols, especially at higher temperatures,
therefore lower chemoselectivities can be achieved compared to
experiments performed in the absence of acids [24].
Most of the experiments were carried out in acetone, used as
reactant in the aldol condensation step and solvent as well (method
A). Another method was also developed, when toluene was used as
solvent and lower amounts of acetone was present in the reaction
mixture (method B, details in experimental section) (entries 18, 19).
The comparable result provided by the latter process, allows us to
extend the scope of the ketones applied in tandem hydro-
formylation/aldol condensation reactions.
In majority, the reactions were carried out using enantiomeri-
cally pure ligands. The enantioselectivity of the hydroformylation
step conducted in the presence of acetone and PTSA was compa-
rable to experiments performed earlier in toluene [24]. The e.e of
the condensed products was not determined, but we cannot as-
sume significant differences to the aldehyde stereoisomers.
Although the optical yield of the aldehydes was moderate (varied in
the range of 5e25%), the application of (R)-BINAP was still
reasonable for further experiments in the view of conversion and
the lack of side products (entry 5).
Scheme 2. Tandem hydroformylation/aldol condensation reactions of styrene with
different ketone. (Reaction conditions: 0.01 mmol of PtCl (PhCN) , 0.01 mmol (R)-
2
2
BINAP, 0.02 mmol SnCl
2
,
1 mmol styrene, 0.1 mmol PTSA, p(CO) ¼ p(H ) ¼ 40 bar,
2
ꢀ
1
00 C, 24 h).

188
L. Koll aꢀ r, P. Pongr aꢀ cz / Journal of Organometallic Chemistry 866 (2018) 184e188
takes part and lower conversions can be obtained with a-methyl-
styrene. After all, in the presence of propiophenone the best yield
can be achieved in platinum catalysed tandem hydroformylation/
aldol condensation reactions (69%).
4. Summary
Tandem hydroformylation/aldol condensation reactions were
carried out in the presence of platinum catalysts and acid co-
catalysts to synthesize unsaturated ketones with moderate yield.
The application of various ligands and ketones led to the target
products under optimised reaction conditions.
a-Methylene
group of the tested ketones proved to be more reactive in aldol
condensation step than their methyl group adjacent to the
carbonyl functionality. Unlike previous results obtained with
different catalytic systems, hydrogenation of the a,b-unsaturated
ketones took place to a very low extent, i.e., the saturated ketones
could be detected in traces only. Therefore, a potential new
methodology for the synthesis of
described.
a,b-unsaturated ketones was
Acknowledgement
Scheme 3. Tandem hydroformylation/aldol condensation reactions of
ene with different ketones (Reaction conditions: 0.01 mmol of PtCl
a
-methylstyr-
(PhCN)
-methylstyrene, 0.1 mmol PTSA,
2
2
,
0
.01 mmol (R)-BINAP, 0.02 mmol SnCl
2
,
1 mmol
a
This work was supported by the ÚNKP-17-4-II New National
Excellence Program of the Ministry of Human „Capacities”. The
authors thank the Hungarian Research Fund (K113177) for the
financial support. This work was supported by the GINOP-2.3.2-
p(CO) ¼ p(H
2
) ¼ 40 bar, 100 ꢀC, 24 h).
To determine the scope, compatibility and limitations of the
reaction, domino hydroformylation/aldol condensation reactions
were conducted in the presence of various ketones and in situ
15-2016-00049 grant. The project has been supported by the
European Union, co-financed by the European Social Fund Grant
no.: EFOP-3.6.1.-16-2016-00004 entitled by Comprehensive
Development for Implementing Smart Specialization Strategies at
the University of P eꢀ cs. The present scientific contribution is
dedicated to the 650 anniversary of the foundation of the Uni-
versity of P eꢀ cs, Hungary.
2 2 2
system formed from PtCl (PhCN) , (R)-BINAP and SnCl under
optimised conditions (Scheme 2).
It can be stated, that various aliphatic and aromatic ketones
underwent transformation to the corresponding unsaturated ke-
tones in moderate yield and selectivity. Using 2-butanone (3a) we
observed that the functionalization takes place on the methylene
group almost exclusively. Generally, only trace amount of products
due to condensation via the methyl group and similar amount of
saturated ketones can be detected in the following experiments.
The yield of the desired products can be increased to 63% in the
presence of 3-pentanone (3c) with excellent chemoselectivity.
Double functionalization reaction is detected neither on methyl nor
on the methylene group of the applied ketones. Methyl function-
alization takes place in the case of sterically hindered isobutyl-
methyl-ketone (3b), however low amount of condensed product
was achieved. Transformation of aromatic ketones like acetophe-
none (3d) and propiophenone (3e) is favoured compared to
aliphatic analogues. Similarly, cyclic aliphatic ketones are also
suitable coupling partners for the synthesis of corresponding un-
saturated ketones in moderate yield (41% and 39%, respectively).
The linear aldehyde regioisomer, formed in the hydro-
formylation reaction proved to be more reactive in the aldol
condensation step in all cases. The only exception was observed in
the presence of acetophenone, where the branched ketone (4d )
selectivity of 65% was achieved.
In order to eliminate one of the two regioisomers, another set of
experiments was conducted in the presence of a-methylstyrene. As
it was expected, only the linear (‘less branched’) aldehyde can be
found as hydroformylation product. The formed 3-phenylbutanal
proved to be also feasible partner to generate the corresponding
ketones in low to moderate yields (Scheme 3).
Comparing the results with previous experiments (summarised
in Table 1), it can be seen that only the methylene functionalization
th
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