Oxidative Alkoxycarbonylation of Alkynes by Means of Aryl α-Diimine Palladium(II) Complexes as Catalysts

Article abstract of DOI:10.1002/adsc.201600521

The straightforward in situ synthesized bis(2,6-diisopropyl)acenaphthenequinonediimine palladium triflate catalyst was generally employed for both the mono-alkoxycarbonylation of terminal alkynes, and the bis-alkoxycarbonylation of 1,2-disubstituted alkynes by using mild reaction conditions [carbon monoxide pressure (P_CO)=4 bar, temperature=20 °C]. Utilizing low catalyst loading (down to 0.5 mol%), a variety of propiolic esters were synthesized with good to excellent isolated yields. Most importantly the system was very efficient not only with methanol but also with a range of different alcohols, starting from the less hindered benzyl alcohol to the most hindered ones, such as isopropyl alcohol and tert-butyl alcohol. In addition, aromatic and aliphatic 1,2-disubstituted alkynes were converted into maleic acid derivatives, together with an acid-catalyzed isomerization reaction, showing modest to good selectivity and excellent combined yields. In particular 3-hexyne showed a satisfactory degree of selectivity for the maleic diesters of methanol and benzyl alcohol, obtaining the corresponding products with good isolated yields. (Figure presented.).

Full text of DOI:10.1002/adsc.201600521

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DOI: 10.1002/adsc.201600521
Very Important Publication
Oxidative Alkoxycarbonylation of Alkynes by Means of Aryl
a-Diimine Palladium(II) Complexes as Catalysts
Michela Beltrani,a Carla Carfagna,b,* Barbara Milani,c Raffaella Mancuso,d
Bartolo Gabriele,d and Francesco Finia,*
a
Department of Biomolecular Sciences, University of Urbino “Carlo Bo”, Piazza del Rinascimento 6, 61029 Urbino (PU),
Italy
Fax : (+39) 0722 303306; Tel: (+39) 0722 303302; e-mail: fini_f@libero.it
Department of Industrial Chemistry “T. Montanari”, University of Bologna, Viale Risorgimento 4, 40136 Bologna (BO),
b
Italy
E-mail: carla.carfagna@unibo.it
Department of Chemical and Pharmaceutical Sciences, University of Trieste, Via Licio Giorgieri 1, 34127 Trieste (TS),
c
Italy
d
Department of Chemistry and Chemical Technologies, University of Calabria, Via P. Bucci 12/C, 87036 Arcavacata di
Rende (CS), Italy
Received: May 16, 2016; Revised: July 20, 2016; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201600521.
Abstract: The straightforward in situ synthesized tert-butyl alcohol. In addition, aromatic and aliphatic
bis(2,6-diisopropyl)acenaphthenequinonediimine pal- 1,2-disubstituted alkynes were converted into maleic
ladium triflate catalyst was generally employed for acid derivatives, together with an acid-catalyzed iso-
both the mono-alkoxycarbonylation of terminal al- merization reaction, showing modest to good selec-
kynes, and the bis-alkoxycarbonylation of 1,2-disub- tivity and excellent combined yields. In particular 3-
stituted alkynes by using mild reaction conditions hexyne showed a satisfactory degree of selectivity
[carbon monoxide pressure (PCO)=4 bar, tempera- for the maleic diesters of methanol and benzyl alco-
ture=208C]. Utilizing low catalyst loading (down to hol, obtaining the corresponding products with good
0.5 mol%), a variety of propiolic esters were synthe- isolated yields.
sized with good to excellent isolated yields. Most im-
portantly the system was very efficient not only with
methanol but also with a range of different alcohols, Keywords: alkynes; aryl a-diimine ligands; carbony-
starting from the less hindered benzyl alcohol to the lation; maleic acid esters; oxidative carbonylation;
most hindered ones, such as isopropyl alcohol and palladium; propiolic acid esters
Introduction
The oxidative carbonylation of simple, unfunction-
alized alkynes may basically lead to two different
Oxidative carbonylations are among the most impor- kind of products, that are, dicarbonylated products
tant reactions in organometallic and organic chemis- (maleates and/or fumarates) and monocarbonylated
try.[1] These processes enable the direct conversion of products (propiolic esters and 2-ynamides).[2] The first
raw materials, such as olefins and alkynes, into high oxidative carbonylation of alkynes was reported by
value added carbonylated products starting from the Tsuji and co-workers in 1964, who described the con-
simplest C1 unit, that is, carbon monoxide.[1] Depend- version of acetylene into muconyl and maleic acid
ing on the nature of the substrate and reaction condi- chloride by using a stoichiometric amount of PdCl2.[3]
tions, different carbonylated products can be obtained Later on, they synthesized propiolic esters by using
in one step under the promoting action of a metal cat- 5 mol% of PdCl2 in combination with CuCl2 as the
alyst and in the presence of an external oxidant. Ace- oxidant to close the catalytic cycle.[4] During the last
tylenic substrates, in particular, have proved to be four decades various methodologies for the catalytic
very useful and versatile starting materials in oxida- oxidative carbonylation of alkynes to maleates,[5] halo-
tive carbonylation reactions, usually carried out in the
acrylates and alkoxyacrylates,[6] 2-ynoates[7] and 2-yna-
ACHTUNGTRENNUNG
presence of a Pd-based catalytic system.[1]
mides,[8] have been reported, mostly based on the use
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of Pd(II) as the catalytic species and oxygen as the ence of 5 mol% of Pd(TFA)2/1a as catalyst and
external oxidant. These processes have been conven- 1.5 equiv. of BQ as oxidizing agent. With phenylacety-
iently applied to variously functionalized alkynes, af- lene 2a as the substrate, no conversion was observed,
fording a variety of different compounds, such as nu- proving that alkynes are less reactive compared with
merous carbonylated heterocycles.[1,9]
olefins under these conditions (Table 1, entry 1). We
Recently, we developed a novel catalytic system, accordingly tested a potentially more reactive catalyt-
consisting of a palladium source with 1,4-diaryl-2,3-di- ic species, consisting of (PhCN)2Pd(OTf)2/1a, which
azabutadiene (DAB) ligands, able to promote the car- has been generated in situ from (PhCN)2PdCl2,
bonylation of olefins to succinic diesters with high se- 2 equiv. of AgOTf and ligand 1a. This system was
lectivity and efficiency[10] as well as the copolymeriza- indeed very effective, and was able to promote the
tion of styrene with CO to yield a copolymer with smooth conversion of 2a (80%) into the correspond-
a high degree of tacticity.[11] In this paper, we have ing oxidative mono-carbonylation product (methyl
studied the activity of this catalytic system in the oxi- phenylpropiolate, 3a), after 42 h, with a catalyst load-
dative carbonylation reaction of both terminal and in- ing as low as 0.5 mol%, (Table 1, entry 2).
ternal alkynes. We have found that our catalyst, in
On performing the reaction in the absence of the
a suitably modified form, is also able to efficiently ligand, only 55% of conversion was obtained (Table 1,
promote the oxidative monocarbonylation of terminal entry 3). No reaction occurred without AgOTf or in
alkynes to propiolate esters and of internal alkynes to the absence of the palladium source (Table 1, en-
maleic derivatives (diesters and their cyclic isomers) tries 4 and 5). No improved results with respect to
under particularly mild reaction conditions (4 bar CO, that of Table 1, entry 2, were observed using AgPF6
208C) and using benzoquinone (BQ) as external oxi- or AgSO3CH3 as the Ag(I) source (Table 1, entries 6
dant.
and 7, respectively) or increasing the temperature to
608C (Table 1, entry 8) and the pressure of CO to
8 bar (Table 1, entry 9). A possible optimization of
the nature of the ligand was also taken into consider-
ation (Table 1, entries 10–13, ligands 1b–e). Ligands
Results and Discussion
To begin with, an extensive optimization study has 1b and 1d were less effective than ligand 1a, although
been carried out testing common sources of palladium 1b was the best ligand tested for the bis-alkoxycarbo-
such as Pd(TFA)2 and (PhCN)2PdCl2 and DAB li- nylation of olefins.[10] (Table 1, entries 10 and 12, re-
gands 1a–e (Scheme 1).[12]
spectively). On the other hand, ligands 1c and 1e
The initial reaction conditions were similar to those turned out to be quite effective, bringing the reaction
previously reported for the bis-alkoxycarbonylation of to completion, probably due to the high steric hin-
olefins,[10] consisting of 4 bar of CO at 208C in THF/ drance at the ortho positions of the aryl moiety
MeOH (1:1, v/v) as the reaction medium, in the pres- (Table 1, entries 11 and 13, respectively). By lowering
the catalyst loading down to 0.1 mol%, the efficiency
of the process was further tested with both ligands 1c
and 1e (Table 1 entries 14 and 15). In these cases the
two results were quite different, and only the catalytic
species bearing the bis(2,6-diisopropyl)acenaphthene-
quinonediimine (diaryl-BIAN) ligand 1e retained
most of its activity by converting 2a into 3a in 80%
yield, with a TON of 800 and TOF of 9.5 hÀ1,
(entry 15).[13] We finally tested our system at atmos-
pheric pressure of CO; as can be seen from the results
reported in Table 1, entry 16, a certain degree of reac-
tivity was preserved by using 0.5 mol% of catalyst
loading (65% conversion), meanwhile complete con-
version of the starting material was achieved by
slightly increasing the loading of the in situ synthe-
sized catalyst (PhCN)2Pd(OTf)2/1e up to 2 mol%
(entry 17). This latter result show that our system is
significantly efficient even under an atmospheric pres-
sure of CO, allowing the use of simple Schlenk tube
equipped with a balloon as a CO reservoir (Table 1,
entries 15–17).
With these data in hand, we extended the process
to several aromatic (2a–e) and aliphatic (2f) alkynes
Scheme 1. N,N-Diaryldimine ligands tested in the reaction
optimization process 1a–e.
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Table 1. Optimization study for the oxidative carbonylation of the phenylacetylene 2a.
Entry[a]
Pd(II) [mol%]
Ligand 1a–e [mol%]
Ag(I) [mol%]
Conversion [%][b]
1
2
3
4
5
6
7
Pd(TFA)2 [5]
1a [5.5]
1a [0.55]
–
–
<5
80
55
<5
<5
10
70
40
80
45
>95
30
>95
25
80
65
(PhCN)2PdCl2 [0.5]
(PhCN)2PdCl2 [0.5]
(PhCN)2PdCl2 [0.5]
–
AgOTf [1.1]
AgOTf [1.1]
–
1a [0.55]
1a [0.55]
1a [0.55]
1a [0.55]
1a [0.55]
1a [0.55]
1b [0.55]
1c [0.55]
1d [0.55]
1e [0.55]
1c [0.11]
1e [0.11]
1e [0.55]
1e [2.2]
AgOTf [1.1]
AgPF6 [1.1]
AgSO3CH3 [1.1]
AgOTf [1.1]
AgOTf [1.1]
AgOTf [1.1]
AgOTf [1.1]
AgOTf [1.1]
AgOTf [1.1]
AgOTf [0.22]
AgOTf [0.22]
AgOTf [1.1]
AgOTf [4.5]
(PhCN)2PdCl2 [0.5]
(PhCN)2PdCl2 [0.5]
(PhCN)2PdCl2 [0.5]
(PhCN)2PdCl2 [0.5]
(PhCN)2PdCl2 [0.5]
(PhCN)2PdCl2 [0.5]
(PhCN)2PdCl2 [0.5]
(PhCN)2PdCl2 [0.5]
(PhCN)2PdCl2 [0.1]
(PhCN)2PdCl2 [0.1]
(PhCN)2PdCl2 [0.5]
(PhCN)2PdCl2 [2]
8[c]
9[d]
10
11
12
13
14
15
16[e]
17[f]
>95
[a]
Reaction performed in an autoclave at PCO =4 bar, with phenylacetylene 2a (2-mmol scale, 0.5M), Pd(II) (5 mol%,
0.5 mol% or 0.1 mol%, 0.10 mmol, 0.01 mmol or 0.002 mmol), ligand 1a–e (5.5 mol%, 0.55 mol% or 0.11 mol%,
0.11 mmol, 0.011 mmol or 0.0022 mmol), Ag(I) (1.1 mol% or 0.22 mol%, 0.022 mmol or 0.0044 mmol) and 1.5 equiv. of
BQ (3 mmol) with THF/MeOH 1:1 (4 mL) as reaction medium at 208C, for 42 h.
Determined by direct H NMR analysis of a sample of the reaction mixture.
Reaction performed at 8 bar of CO.
[b]
[c]
[d]
[e]
[f]
1
Reaction performed at 608C.
Reaction performed in a Schlenk tube at atmospheric pressure of CO (balloon).
Reaction performed in a Schlenk tube at atmospheric pressure of CO (balloon) with 2a (2 mmol, 0.5M), (PhCN)2PdCl2
(2 mol%, 0.04 mmol), ligand 1e (2.2 mol%, 0.044 mmol) and AgOTf (4.5 mol%, 0.09 mmol) with the stated time, oxidant,
solvent and temperature.
by performing the reaction under conditions able to hexynoate 3f in 72% yield, although in a mixture with
guarantee full conversion of the substrates (0.5– methyl (E)-3-methoxy-2-heptenoate (12% yield,
2 mol% of catalyst, under 4 bar of CO at 208C, for Table 2, entry 6).[14] Our method could also be suc-
42 h; Table 2).
cessfully applied to higher alcohols (including benzyl
As can be seen from Table 2, good to excellent re- alcohol isopropyl alcohol, cyclopentanol, sec-butyl al-
sults were obtained in terms of isolated yields of the cohol, sec-phenethanol, as well as a hindered tertiary
corresponding propiolate methyl esters 3a–f, the best alcohol such as tert-butyl alcohol) using phenylacety-
outcome being achieved with phenylacetylene 2a (af- lene 2a as model substrate (Table 2, entries 7–12).
fording 90% yield of 3a, Table 2 entry 1). Arylacety- Indeed the corresponding propiolates 3g–l were at-
lenes 2b–d, bearing electron-donating (p-OMe) or tained in good to excellent yields, demonstrating the
electron-withdrawing (o-CF3, p-F) groups, were com- broadness of this methodology (Table 2, entries 7–12).
patible with the catalytic system, with the correspond-
Encouraged by these results, we went further to ex-
ing products 3b–d obtained in fair to good isolated plore the reactivity of internal alkynes. We started
yields (62–82%, entries 2–4). The reaction could also our investigation with inexpensive and readily avail-
be applied to a substrate bearing a strong electron- able 1-phenyl-1-butyne 4a. Considering the expected
withdrawing group, such as p-NO2 (2e), which was lower reactivity of an internal alkyne with respect to
converted into 3e in 55% isolated yield working with a 1-alkyne, the experiments were performed with
a catalyst loading of 2 mol% (Table 2, entry 5). An 2 mol% of the in situ generated (PhCN)2Pd(OTf)2/1a
aliphatic alkyne, such as 1-hexyne, was also reactive catalyst; the obtained results are shown in Table 3.[15]
under the standard conditions and led to methyl 2-
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Table 2. Substrate scope of the mono-alkoxycarbonylation of alkynes 2a–f.
[a]
Reaction performed in an autoclave at PCO =4 bar, with alkynes 2a–f (2-mmol scale, 0.5M), (PhCN)2PdCl2 (0.5 mol%,
0.01 mmol), ligand 1e (0.55 mol%, 0.011 mmol), AgOTf (1.1 mol%, 0.022 mmol) and 1.5 equiv. of BQ (3 mmol) with
THF/R3OH 1:1 (4 mL) as reaction medium at 208C, for 42 h.
Isolated yields after column chromatography. Unless otherwise noted, substrate conversion was quantitative.
Reaction performed with 2 mol% of catalyst loading.
Conversion of the alkyne 2e was 60%.
Isolated yield of the main product 3f is reported.
Reaction performed by using i-PrOH in place of methanol.
Reaction performed by using t-BuOH in place of methanol.
Reaction performed by using BnOH in place of methanol.
[b]
[c]
[d]
[e]
[f]
[g]
[h]
[i]
Reaction performed by using c-C5H9OH in place of methanol.
Reaction performed by using s-BuOH in place of methanol.
Reaction performed by using s-phenethanol in place of methanol.
[j]
[k]
Under 4 bar of CO, the oxidative carbonylation of of 85/15 (Table 3).[5g,16] They were detected only by
1
4a gave a conversion of the starting material of 80% 13C NMR due to a partial overlap of the H NMR sig-
into a mixture of isomeric products. In particular to- nals. The ratio between the mixture of cyclic re-
gether with the maleic diesters 6a, two regioisomeric gioisomers 5a/5a’ and the maleic diester 6a was 2/
cyclic products 5a and 5a’ were obtained with a ratio 1 (Table 3, entry 2). Conversely the reaction per-
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Table 3. Representative results for the optimization of the
bis-alkoxycarbonylation of 1-phenyl-1-butyne 4a.
served with ligand 1e, by using 2 mol% of catalyst
loading, at 4 bar of CO (Table 3, entries 10 and 11).
Under the optimized conditions, an isolated yield of
48% and of 41% for the regioisomeric mixture 5a/5a’
and for the maleic esters 6a could be respectively ach-
ieved (Table 4, entry 1).
It is worth noting that, as already reported for an
analogous compound by some of us,[5g] the mixture
5a/5a’ can be easily converted into 6a in 91% isolated
yield by acid-catalyzed isomerization in MeOH
(Scheme 2, top).
Thus, the combined carbonylation/isomerization
process allowed the selective synthesis of the maleic
diester 6a in 85% overall yield (Table 4, entry 1).
Moreover the bis-alkoxycarbonylation of 4a with
other alcohols, such as i-PrOH and BnOH was also
successful, in both cases the ratio between the ob-
tained cyclic regioisomers 5b/5b’ and 5c/5c’ was 75:25
(Table 4, entries 2 and 3), meanwhile the ratios be-
tween the mixture of cyclic isomers and the maleic
diesters 5b/5b’:6b and 5c/5c’:6c were of 1:1, with good
isolated yields of 40%, 43%, 41% and 38% respec-
tively (Table 4 entries 2 and 3). Mixtures of re-
gioisomers 5b/5b’ and 5c/5c’ were isomerized under
acid-catalyzed conditions (Scheme 2). Since the iso-
merization condition used for 5a/5a’ was not suitable,
an optimization of the process was carried out
(Scheme 2). By replacing concentrated sulfuric acid
with p-TSA and choosing carefully the reaction
medium, the transformation of cyclic regioisomers 5b/
5b’, 5c/5c’ were brought to completion with good iso-
Entry[a] Ligand PCO [bar] Conv.[b] [%] 5a/5a’:6a ratio[b]
1a–1e
1
2
–
1a
–
4
4
1
1
8
4
4
4
8
4
4
<5
80
<5
40
>98
83
87
–
2:1
–
3[c]
4[c]
5[d]
6
1a
1a
1b
1c
1d
1d
1e
1e
1:1
1:1
1:1
1:1
2:1
3:2
4:3
1:1
7
8
9
82
>98
>98
44
10
11[e]
[a]
Reaction performed in an autoclave at PCO =4 bar, with
alkyne 4a (2-mmol scale, 0.5M), (PhCN)2PdCl2 (2 mol%,
0.04 mmol), ligands 1a–e (2.2 mol%, 0.044 mmol),
AgOTf (4.5 mol%, 0.09 mmol) and 1.5 equiv. of BQ
(3 mmol) with THF/MeOH 1:1 (4 mL) as reaction
medium at 208C, for 44 h.
[b]
[c]
1
Determined by direct H NMR analysis of a sample of
the reaction mixture.
Reaction performed in a Schlenk tube at atmospheric
pressure of CO (balloon).
Reaction performed at 608C and 8 bar of CO.
Reaction performed with (PhCN)2PdCl2 (0.5 mol%,
0.01 mmol), ligand 1e (0.55 mol%, 0.011 mmol) and
AgOTf (1.1 mol%, 0.022 mmol).
[d]
[e]
formed without the ligand 1a gave no reaction at all
(Table 3, entries 1 and 3). Under the atmospheric
pressure of CO, the system was poorly active and 4a
was converted only for 40% with a 5a/5a’:6a ratio of
1:1 (Table 3, entry 4). The increase of the temperature
up to 608C and the pressure of CO up to 8 bar in-
creased the conversion of the alkyne 4a with a con-
comitant effect on the 5a/5a’:6a ratio (Table 3, entry 5,
to be compared with entry 2). We then changed the
nature of the ligand, as can be seen from the results
reported in Table 3, entries 6–10. All the other tested
ligands 1b–e were more active than 1a (entry 2): in
Scheme 2. Isomerization of 5a/5a’–5c/5c’ and 5e into maleic
particular, a quantitative conversion of 4a was ob- acid esters 6a–c, 6e by means of Brçnsted acid catalysis.
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Table 4. Bis-alkoxycarbonylation of 4a and 4b by using different alcohols.
[a]
Reaction performed in an autoclave at PCO =4 bar, with alkynes 4a or 4b (2-mmol scale, 0.5M), (PhCN)2PdCl2 (2 mol%,
0.04 mmol), ligand 1e (2.2 mol%, 0.044 mmol), AgOTf (4.5 mol%, 0.09 mmol) and 1.5 equiv. of BQ (3 mmol) with THF/
R3OH 1:1 (4 mL) as reaction medium at 208C, for 44 h.
Isolated yields after column chromatography.
Overall yield after carbonylation of 4a and 4b followed by acid-catalyzed isomerization of 5a/5a’–5c/5c’, 5e into 6a–c, 6e.
[b]
[c]
lated yield (89% and 85%, Scheme 2, center), attain- tries 4 and 6). Conversely the bis-alkoxycarbonylation
ing the maleic diesters 6b and 6c with good overall of 4b, with the more sterically demanding i-PrOH as
isolated yields (79% and 73%, Table 4, entries 2 and alcohol, produced a mixture of 5e and 6e with a ca.
3). Interestingly, the carbonylation of the aliphatic in- 1:1 ratio and isolated yields of 41% and 50%, respec-
ternal alkyne 3-hexyne 4b, was more selective towards tively (Table 4, entry 5). The isomerization of 5e, by
the formation of the alkyl maleates 6 with respect to using p-TSA, brought about the formation of maleic
the analogous reactions with 4a (compare entries 4 diester 6e with 93% isolated yield (Scheme 2, bottom)
and 6 with entries 1–3, Table 4). By using MeOH and and an overall carbonylation/isomerization yield of
BnOH as alcohols, 4b was converted into maleic 88% (Table 4, entry 5).
esters 6d and 6f with a minimum amount of cyclic
With all these data in hand,[17] and according to the
compounds 5d and 5f (isolated yields of 9%). Esters existing knowledge on Pd-catalyzed oxidative carbon-
6d and 6f were directly obtained by the carbonylation ylation of alkynes,[1–9] we propose the catalytic cycles
process, with 79% and 73% of isolated yields (en- shown in Scheme 3 to justify the mono- and the bis-
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Scheme 3. Proposed catalytic cycle.
alkoxycarbonylation outcomes of terminal and 1,2- N)Pd(PhCN)2]2+[TfOÀ]2 (Scheme 3, A).[17] The subse-
disubstituted alkynes under our conditions (in particu- quent intervention of the alcohol R3OH forms com-
lar, pathway a refers to the monocarbonylation reac- plex B, which is the catalytically active species for ter-
tion, pathway b to the dicarbonylation process). minal and internal alkynes.[17,18] Upon sequential in-
Ligand 1e and (PhCN)2PdCl2, in combination with sertion of carbon monoxide and the alkynes 2 or 4
2 equiv. of AgOTf, in situ generate [(N- into B, the key intermediates D and E (pathway a) or
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AgOTf (5.8 mg, 0.022 mmol) was added in one portion and
the catalyst mixture turned to a light orange color with the
development of a yellowish solid. The preformed catalyst
(PhCN)2Pd(OTf)2/1e was then injected in a nitrogen-flushed
autoclave containing benzoquinone (325 mg, 3 mmol) in the
stated alcohol R3OH (2 mL). After 10 min the respective
alkyne 2a–f (2 mmol) was added in one portion in the reac-
tion mixture by using a syringe. The autoclave was flushed
three times with CO and pressurized with 4 bar of carbon
monoxide. The reaction mixture was vigorously stirred at
room temperature (208C) for 42 h. After the stated time the
autoclave was vented off, flushed with nitrogen and the re-
G (pathway b) are formed. Five-membered palladacy-
cle complex D[11,16,18] could easily isomerize towards
E,[19] which withstands a fast syn-coplanar b-hydrogen
elimination, generating the propiolate ester 3 and the
palladium hydride complex F (pathway a). On the
other hand palladacycle intermediate G[11,16,18] under-
goes a second carbon monoxide addition to give com-
plex H followed by nucleophilic attack by the alcohol
to the carbonyl of the acylpalladium moiety. Displace-
ment of palladium would then lead to the maleate
product 6 and palladium hydride F. Alternatively an
intramolecular rearrangement/cyclization, after a CO
insertion in the 5 position of G, can lead to the h3-al-
lylpalladium intermediate I.[16] The regioselective nu-
cleophilic attack of the alcohol R3OH to the C-5 of I
eventually results in the formation of dialkoxyfura-
nones 5 and 5’ and palladium hydride F.
1
action mixture was directly analyzed by H NMR to deter-
mine the conversion of the starting alkyne. The crude mate-
rial was then dried under reduced pressure and filtered off
a plug of silica gel, washing with CH2Cl2 (100 mL). Finally
the solution was evaporated to dryness under vacuum. Prod-
ucts 3a–l were finally obtained after flash column chroma-
tography on silica gel (petroleum ether/CH2Cl2 50:50 then
30:70).
In both pathways a and b, the reconversion of F
into the catalytically active species B occurs upon the
intervention of the oxidant (BQ, which is reduced to
H2BQ, Scheme 3).[20] Theoretical studies concerning
both mechanisms are currently underway and will be
reported in due course.
Typical Procedure for the Bis-Alkoxycarbonylation
Reaction of 1,2-Disubstituted Alkynes 4a and 4b
In a nitrogen-flushed Schlenk tube equipped with a magnetic
stirring bar were added in sequence the (PhCN)2PdCl2
(15.3 mg, 0.04 mmol) and THF (2 mL). After the mixture
had turned to a red/brown color (20 min), the ligand 1e
(22.0 mg, 0.044 mmol) was added and the mixture was left
stirring for 10 min, turning to a dark orange color. AgOTf
(23.1 mg, 0.09 mmol) was added in one portion and the cata-
lyst mixture turned to a light orange color with the develop-
ment of a yellowish solid. The preformed catalyst was inject-
ed in a nitrogen-flushed autoclave containing benzoquinone
(325 mg, 3 mmol) in the stated alcohol R3OH (2 mL). After
10 min the alkyne 4a or 4b (2 mmol) was added in one por-
tion in the reaction mixture by using a syringe. The auto-
clave was flushed three times with CO and pressurized with
4 bar of carbon monoxide. The reaction mixture was vigo-
rously stirred at room temperature (208C) for 44 h. After
the stated time the autoclave was vented off, flushed with
nitrogen and the reaction mixture was directly analyzed by
1H NMR to determine the conversion of 4a and 4b and the
ratio 5b:5b’, 5c:5c’ and 5a/5a’–5c/5c’:6a–c, 5d–5f:6d–f (the
ratio 5a:5a’ was determined by 13C NMR on the purified
mixture). The crude material was then dried under reduced
pressure, then NaOH 1M (30 mL) was added and the solu-
tion was extracted with CH2Cl2 (3ꢁ30 mL). The combined
organic solution was dried over Na2SO4 and the solvent was
removed under reduced pressure. The mixtures 5a/5a’–5c/5c’
and products 5d–5f, 6a–f were finally obtained after flash
column chromatography on silica gel (petroleum ether/
CH2Cl2 50:50 then 30:70). 5a/5a’–5c/5c’ were used for the
acid-catalyzed isomerization without further purification.
Conclusions
We have found that the complex generated in situ
from (PhCN)2PdCl2 with the ligand bis(2,6-diisopro-
pyl)acenaphthenequinonediimine 1e is an excellent
catalytic precursor for realizing the oxidative mono-
alkoxycarbonylation of terminal alkynes 2 to propio-
late esters 3 as well as the oxidative bis-alkoxycarbo-
nylation of internal alkynes 4 to maleic diesters 6 in
combination with an acid-catalyzed isomerization re-
action. Eventually both propiolic esters 3 and maleic
diesters 6 have been obtained with good overall iso-
lated yields from inexpensive alkynes 2 and 4. The
carbonylation processes occur under particularly mild
conditions (4 bar CO, 208C) in the presence of an al-
cohol as nucleophile, including MeOH, benzyl alco-
hol, secondary alcohols or sterically hindered tertiary
alcohols, and benzoquinone as oxidant, demonstrating
the broadness of the process towards the synthesis of
several esters of propiolic and maleic acids.
Experimental Section
Typical Procedure for the Mono-Alkoxycarbonylation
Reaction of Terminal Alkynes
In a nitrogen-flushed dried Schlenk tube equipped with
a
magnetic stirring bar were added in sequence the
Acknowledgements
(PhCN)2PdCl2 (3.8 mg, 0.01 mmol) and THF (2 mL). After
the mixture has turned to a red/brown color (20 min), the
ligand 1e (5.5 mg, 0.011 mmol) was added and the mixture
was left stirring for 10 min, turning to a dark orange color.
This work was supported by Ministero dell’Universitꢀ e della
Ricerca (PRIN n. 2008A7P7YJ)
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8
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first reaction of the sequence has been carried out as
usual: 2a (2 mmol), 0.5 mol% (PhCN)2Pd(OTf)2/1e,
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attributable
to
the
precatalyst
[(N-
N)Pd(PhCN)2]2+[TfOÀ]2. Unfortunately the sequential
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Oxidative Alkoxycarbonylation of Alkynes by Means of
11
Aryl a-Diimine Palladium(II) Complexes as Catalysts
Adv. Synth. Catal. 2016, 358, 1 – 11
Michela Beltrani, Carla Carfagna,* Barbara Milani,
Raffaella Mancuso, Bartolo Gabriele, Francesco Fini*
Adv. Synth. Catal. 0000, 000, 0 – 0
11
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These are not the final page numbers!