Catalytic Pauson-Khand Reaction in Ethylene Glycol-Toluene: Activity, Selectivity, and Catalyst Recycling

Article abstract of DOI:10.1055/s-0037-1610441

The use of ethylene glycol (15% v/v in toluene) as additive in the catalytic Pauson-Khand reaction (PKR) is reported. In most cases both the yield and selectivity were enhanced compared to standard protocols. Moreover, the immiscibility of ethylene glycol

Full text of DOI:10.1055/s-0037-1610441

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–F
paper
A
en
A. Cabré et al.
Paper
Synthesis
Catalytic Pauson–Khand Reaction in Ethylene Glycol–Toluene:
Activity, Selectivity, and Catalyst Recycling
Albert Cabréa,b
Xavier Verdaguer*a,b
Antoni Riera*a,b
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5-
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Co2(CO)8
1–5 mol%
toluene
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CO (1 bar)
80 ºC
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a Institute for Research in Biomedicine (IRB Barcelona),
The Barcelona Institute of Science and Technology,
Baldiri Reixac 10, Barcelona 08028, Spain
antoni.riera@irbbarcelona.org
(MEG)
X
- 11 examples
- intramolecular and intermolecular
- biphasic system: catalyst recycling
- gram-scale synthesis
- enhanced yield and selectivity
- low catalyst loading (as low as 1 mol%)
xavier.verdaguer@irbbarcelona.org
b Departament de Química Inorgànica i Orgànica, Secció
Orgànica, Universitat de Barcelona, Martí i Franquès 1,
Barcelona 08028, Spain
Received: 19.04.2018
Accepted after revision: 30.05.2018
Published online: 05.07.2018
hard Lewis bases,16 and sulfides17 are the most relevant.
However, the use of large amounts of additives usually hin-
ders the purification of the product.
DOI: 10.1055/s-0037-1610441; Art ID: ss-2018-z0271-op
Catalyst recycling is clearly desirable. Several heteroge-
neous catalytic systems such as colloidal cobalt nanoparti-
cles (NPs),18 cobalt on charcoal,19 or cobalt Raney20 have
been described for the PKR.21 However, to the best of our
knowledge, there are no precedents of catalyst recycling in
homogenous systems.
Based on a previous methodology developed by Baran
and co-workers,4a our group recently reported that, eth-
ylene glycol (ethane-1,2-diol, MEG) can enhance the alkene
range in the stoichiometric N-oxide promoted intermolecu-
lar PKR (Scheme 1).22 In the present study we report that
this additive also has a positive effect on the cobalt-cata-
lyzed PKR, allowing the reaction to be performed with very
low catalyst loadings, reducing undesired byproducts, facil-
itating the purification of the final product, and permitting
catalyst recycling by simple liquid–liquid separation.
Abstract The use of ethylene glycol (15% v/v in toluene) as additive in
the catalytic Pauson–Khand reaction (PKR) is reported. In most cases
both the yield and selectivity were enhanced compared to standard
protocols. Moreover, the immiscibility of ethylene glycol in toluene al-
lowed recycling of the catalyst (which remained mainly in the ethylene
glycol). The recycling allowed catalyst loading to be reduced to only 3
mol%. A gram-scale reaction was also performed, allowing the use of
only 1 mol% of Co2(CO)8, the lowest amount reported so far in intermo-
lecular cobalt-catalyzed PKR.
Key words Pauson–Khand Reaction, homogeneous catalysis, cycliza-
tion, cobalt, additives, cyclopentenones, cycloaddition, catalyst recycling
The Pauson–Khand reaction (PKR),1,2 a metal-catalyzed
[2+2+1] cycloaddition coupling of an alkyne, an alkene, and
CO, is one of the most powerful synthetic tools with which
to prepare cyclopentenones.3,4 The stoichiometric version
of the reaction uses large amounts of dicobalt octacarbonyl
with the subsequent drawbacks of price, residue disposal,
and difficult purification of the final product. In this regard,
the development of catalytic methodologies to reduce the
amount of metal are required for large-scale preparations.
Several catalytic versions of the PKR involving the use of
other metals, such as Ti,5 Ru,6 Rh,7 Ni,8 and Ir9 or bimetallic
species, have been described.10 However, the use of cobalt
complexes is probably the most practical and economical
approach. Although the catalytic system can be prepared in
situ by reducing CoBr2 with Zn under CO pressure,11 dico-
balt octacarbonyl continues to be the most common cata-
lyst.12
O
X
R1
R1
R2
Co2(CO)8 (1 equiv)
NMO (6 equiv)
+
OH
HO
R2
O
CH2Cl2
Scheme 1 Previous work of MEG-assisted intermolecular PKR
We chose three standard enynes 1a–c to test the intra-
molecular catalytic PKR (Table 1). As expected the reaction
proceeded smoothly in toluene using 5 mol% of Co2(CO)6 to
afford the corresponding bicyclic cyclopentenones 2a–c in
moderate to good yields. The yield of 2c from the oxygen-
containing enyne 1c was slightly lower than those of 2a and
2b from all-carbon 1a and nitrogen-containing 1b, respec-
tively. Under the same conditions but using 15% MEG/tolu-
Many additives have been described to improve the
yields in the cobalt-catalyzed PKR. Ureas such as tetrameth-
ylthiourea (TMTU),13 phosphites,14 triphenylphosphines,15
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F

B
A. Cabré et al.
Paper
Synthesis
ene instead of pure toluene (Table 1, entries 1–3) the yields
consistently increased by approximately 10% points. Al-
though the increase in yield was moderate, the reaction
crudes were much cleaner in MEG/toluene, thus allowing
easier workup and purification.
Table 2 Catalytic Intermolecular Pauson–Khand Reactiona
Entry Alkyne
Cyclopentenone
Ratio exo/endo Yieldb (%)
O
TMS
TMS
A: 93:7
B: 93:7
A: 75
B: 99
1
Table 1 Catalytic Intramolecular Pauson–Khand Reactiona
1d
2d
2e
2f
Entry
1
Enyne
Cyclopentenone
Yieldb (%)
O
O
NHBoc
A: 83:17
B: 93:7
A: 60
B: 93
2
3
EtOOC
EtOOC
NHBoc
EtOOC
EtOOC
2a
A: 81
B: 90
O
1e
1f
1a
SPh
A: 83
B: 91
TsN
A: 93:7
B: 96:4
A: 79
B: 93
2
3
TsN
O
SPh
1b
2b
O
A: 47
B: 60
O
O
O
A: 98:2
B: >99
A: 89
B: 91
1c
4
2c
a Reaction conditions A: enyne (100 mg, 1.0 equiv), Co2(CO)8 (0.05 equiv, 5
mol%), toluene, 80 °C, under CO (1 bar), overnight. Reaction conditions B:
as A but 15% MEG/toluene was used as the solvent system.
b Isolated yields.
2g
1g
1h
O
O
O
NHTs
OTBS
A: 93:7
B: 95:5
A: 80
B: 85
5
NHTs
OTBS
We then, turned our attention to the intermolecular
version. Terminal alkynes 1d–j were reacted with norborn-
adiene (NBD) or norbornene (Table 2, entries 1–7 and 8, re-
spectively) under CO pressure using dicobalt octacarbonyl
as catalyst affording cyclopentenones 2d–j in good to excel-
lent yields. Except in one case (entry 7) the yields clearly
improved when using the MEG/toluene mixture. Moreover,
a significant improvement in terms exo/endo selectivity
was also achieved in all cases. In entry 4, for instance, only
traces of trimerization of phenylacetylene, a common by-
product in catalytic PKR that is usually avoided by adding
triphenylphosphine, was detected. In addition, no endo ad-
duct was observed. It is worth noting that 2d and 2e are the
most interesting substrates from the synthetic point of
view since they have been used in the synthesis of several
biologically active compounds.4b–d
Apart from the effect of MEG on the yield and exo/endo
selectivity, the addition of this compound to the reaction
mixture also gave a much cleaner crude product. In fact, af-
ter completion of the reaction, two phases were clearly ob-
served: a slightly colored upper toluene layer and a dark
red lower MEG layer (Figure 1). Therefore, when the reac-
tion finished, toluene and MEG formed two immiscible liq-
uid layers. We assumed that most of the product remained
in the organic phase, whereas most of the cobalt species
were trapped in the MEG layer.
2h
2i
2j
3
A: 93:7
B: 95:5
A: 56
B: 70
6
1l
1j
A: 93:7
B: >99
A: 75
B: 72
7
O
TMS
TMS
A: 86:14
B: >99
A: 94
B: 98
8c
1d
a Reaction conditions A: norbornadiene (5.0 equiv), alkyne (100 mg, 1.0
equiv), Co2(CO)8 (0.05 equiv, 5 mol%), toluene, 80 °C under CO (1 bar), over-
night. B: as A but 15% MEG/toluene was used as the solvent system.
b Isolated yields.
c Norbornene was used as alkene.
To test this assumption, the upper layer was separated
and a solution of alkyne and alkene in toluene was added to
the MEG phase. Heating at 80 °C under CO (1 bar), the PKR
proceeded again thereby proving that the cobalt species
that remain in the MEG phase were catalytically active. This
observation prompted us to use the novel methodology to
test the recycling of Co2(CO)8. For this purpose, 1d and
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F

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A. Cabré et al.
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Synthesis
The MEG-phase containing the cobalt residues degrad-
ed during each catalytic cycle, until it became inactive (Fig-
ure 2). As far as we know, this is the first example of cata-
lyst recycling performed homogeneously by simple liquid–
liquid separation. In this regard, the amount of cobalt cata-
lyst was reduced to 3 mol%.
Figure 1 Reaction crude of 3 after 17 h of heating (Table 2, entry 8);
with MEG as additive (left) and without MEG (right)
N-protected propargylamine acetylenes 1e and 1h were se-
lected as alkynes and norbornadiene as alkene. The reac-
tion was performed using an initial loading of 10 mol% of
Co2(CO)8 in 15% MEG/toluene. The reaction mixture was
stirred at 80 °C overnight under CO (1 bar). Then, the reac-
tor was depressurized and the supernatant organic layer
was separated. A fresh toluene solution of alkyne and NBD
was added to the MEG layer containing the cobalt complex-
es. The second catalytic cycle finished after 36 hours (mon-
itored by TLC) and the operation was repeated. Finally, the
third catalytic cycle lasted 72 hours. Each of the toluene
layers was collected, evaporated, and chromatographed af-
fording the corresponding PK-adducts (Table 3). The overall
yields were excellent and less than 10% of the product was
found in the final MEG layer. Therefore, it was possible to
perform up to three catalytic cycles (Table 3). In this case,
the exo/endo selectivities were similar to those obtained
with the previous methodology.
Figure 2 Catalytic intermolecular PK reaction of 1e with NBD recycling
the catalyst that remains in the MEG phase; after the 1st cycle (left),
after the 2nd cycle (center), and after the 3rd cycle (right)
The process was scaled up to gram scale, and catalyst
loading was reduced to 1 mol% without the need for cata-
lyst recycling (Scheme 2). To the best of our knowledge, this
is the lowest catalyst loading successfully used in the inter-
molecular PKR.
O
NHBoc
Co2(CO)8 (1 mol%)
+
NHBoc
toluene/MEG 5:1
2 bar CO, 80 ºC, overnight
(5.0
equiv)
1e
2e
91% isolated yield
gram scale
Scheme 2 Gram-scale intermolecular PKR using MEG/toluene as solvent
with alkyne 1e (1 g), norbornadiene (5.0 equiv), and Co2(CO)8 (1 mol%)
Table 3 Catalytic Recyclabilitya
Entry Alkyne
Cyclopentenone
Yieldb (%) Overall yieldc (%)
(cycle)
(ratio exo/endo)
In summary, we have demonstrated that the mixture of
15% MEG/toluene enhances the PKR allowing the use 1
mol% of Co2(CO)8 as catalyst under low CO pressure (1 bar).
When the reactions were finished, the toluene and MEG
formed immiscible layers thus facilitating the workup be-
cause the toluene layer contained most of the product.
Since the MEG layer contains most of the cobalt species it
can be reused by adding a fresh solution of alkyne and
alkyne. This new synthetic protocol for catalytic PKR is effi-
cient and practical and has the lowest catalyst loading re-
ported to date in cobalt-catalyzed PKR.
O
TMS
95 (1st)
90 (2nd)
71 (3rd)
TMS
85
(90:10)
1
1d
2d
2e
2h
O
O
NHBoc
99 (1st)
93 (2nd)
85 (3rd)
92
(92:8)
2
3
NHBoc
1e
1h
NHTs
99 (1st)
92 (2nd)
85 (3rd)
92
(95:5)
NHTs
Reactions were carried out under CO in an oven-dried pressure tube.
Anhyd toluene was obtained from commercial suppliers. Reactions
were monitored by TLC analysis using Merck silica gel 60 F-254 thin
layer plates. Solvents were removed under reduced pressure with a
rotary evaporator. Silica gel chromatography was performed using an
automated chromatography system (PuriFlash® 430, Interchim).
NMR at 400 MHz for 1H and at 101 MHz for 13C. Chemical shifts were
a Reaction conditions C. Three cycles of alkyne (200 mg, 1.0 equiv) and nor-
bornadiene (5.0 equiv), were run with Co2(CO)8 (10 mol%), 15% MEG/tolu-
ene, 80 °C under CO (1 bar);
b Yield after each catalytic cycle.
c Isolated overall yield. In parentheses, overall exo/endo ratio.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F

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A. Cabré et al.
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Synthesis
referenced to internal solvent resonances and reported relative to
TMS. HRMS (ESI) were recorded on a LC/MSD-TOF G1969A (Agilent
Technologies). Enynes 1a,7c 1b,7c and 1c23 were prepared following the
literature. Terminal alkynes 1h and 1e were prepared by following
our previously reported procedure.19
The analytical data for this compound were in excellent agreement
with the reported data.7c
6-Methyl-3a,4-dihydro-1H-cyclopenta[c]furan-5(3H)-one (2c)
Starting from alkyne 1c (0.91 mmol) gave 2c as a pale orange oil; iso-
lated yield: 59 mg (47%, GPA); 75 mg (60%, GPB).
Catalytic Pauson–Khand Reaction; General Procedure A (GPA)
1H NMR (400 MHz, CDCl3): δ = 4.63–4.44 (m, 2 H), 4.31 (d, J = 5.0 Hz, 1
H), 3.18 (d, J = 3.8 Hz, 2 H), 2.71–2.62 (m, 1 H), 2.12 (dd, J = 18.0, 2.6
Hz, 1 H), 1.76 (s, 3 H).
In a flame-dried pressure tube containing a magnetic stirrer, the 1,6-
enyne (100 mg, 1.0 equiv) or alkyne (100 mg, 1 equiv) was dissolved
in anhyd toluene (0.3 M). Co2(CO)8 (5 mol% or 1 mol% as indicated)
was added. In the case of intermolecular reactions, norbornadiene or
norbornene (5.0 equiv) was also added. The pressure vessel was first
purged with N2 and then with CO (3 ×). Finally, it was charged with
CO (1–2 bar) and heated to 80 °C; the mixture was stirred overnight.
The CO was removed using a vacuum line and the biphasic solution
was concentrated under reduced pressure. The crude was purified by
column chromatography (hexanes/EtOAc mixtures of increasing po-
larity).
The analytical data for this compound were in excellent agreement
with the reported data.24
(4S,7R)-2-(Trimethylsilyl)-3a,4,7,7a-tetrahydro-1H-4,7-methano-
inden-1-one (2d)
Starting from alkyne 1d (1.02 mmol) gave 2d as an off-white solid;
isolated yield: 167 mg (75%, GPA); 220 mg (99%, GPB). GPC: 1st cycle:
421 mg (95%); 2nd cycle: 400 mg (90%); 3rd cycle: 315 mg (71%).
1H NMR (400 MHz, CDCl3): δ = 7.59 (dd, J = 2.5, 0.5 Hz, 1 H), 6.28–6.23
(m, 1 H), 6.22–6.16 (m, 1 H), 2.91 (d, J = 2.1 Hz, 1 H), 2.84 (ddt, J = 5.2,
2.3, 1.1 Hz, 1 H), 2.69 (dtt, J = 3.1, 1.6, 0.8 Hz, 1 H), 2.28 (ddd, J = 5.2,
1.6, 1.1 Hz, 1 H), 1.39–1.36 (m, 1 H), 1.20–1.16 (m, 1 H), 0.17 (s, 9 H).
Catalytic Pauson–Khand Reaction; General Procedure B (GPB)
As for GPA but MEG (15% v/v) was added to the mixture.
Catalyst Recycling in the Catalytic Ethylene Glycol Assisted
Pauson–Khand Reaction; General Procedure C (GPC)
The analytical data for this compound were in excellent agreement
with the reported data.22
In a flame-dried pressure tube containing a magnetic stirrer, the
alkyne (200 mg, 1.0 equiv) and alkene (5.0 equiv) were dissolved in
anhyd toluene (0.3 M). Then, MEG (15% v/v) and Co2(CO)8 (10 mol%)
were added. The pressure vessel was first purged with N2 and then
with CO (3 ×). Finally, it was charged with 1–2 bar of CO and heated to
80 °C; the mixture was stirred overnight. The CO was removed in the
vacuum line. The biphasic solution was separated and the superna-
tant phase was collected. The MEG-containing phase was kept in the
pressure tube and alkyne (200 mg, 1.0 equiv), alkene (5.0 equiv), and
freshly anhyd toluene were added. The same procedure as above was
carried out and the mixture was stirred for 36 h (second cycle). For
the third cycle, the methodology was repeated again and the mixture
was stirred for 48–72 h. Finally, each organic phase was concentrated
under reduced pressure and purified by column chromatography
(hexane/EtOAc mixtures of increasing polarity).
tert-Butyl {[(4S,7R)-1-Oxo-3a,4,7,7a-tetrahydro-1H-4,7-methano-
inden-2-yl]methyl}carbamate (2e)
Starting from alkyne 1e (0.64 mmol) gave 2e as a pale orange oil; iso-
lated yield: 106 mg (60%, GPA); 164 mg (93%, GPB). GPC: 1st cycle:
349 mg (99%); 2nd cycle: 318 mg (93%); 3rd cycle: 300 mg (85%).
1H NMR (400 MHz, CDCl3): δ = 7.34 (s, 1 H), 6.29 (dd, J = 5.6, 3.1 Hz,
1 H), 6.20 (dd, J = 5.7, 3.0 Hz, 1 H), 5.01 (s, 1 H), 3.87 (d, J = 6.0 Hz, 2 H),
2.91 (s, 1 H), 2.78–2.72 (m, 1 H), 2.72–2.66 (m, 1 H), 2.31 (dt, J = 5.0,
1.4 Hz, 1 H), 1.43 (s, 9 H), 1.30–1.18 (m, 2 H).
The analytical data for this compound were in excellent agreement
with the reported data.22
(4S,7R)-2-[(Phenylthio)methyl]-3a,4,7,7a-tetrahydro-1H-4,7-
methanoinden-1-one (2f)
Diethyl 6-Methyl-5-oxo-3,3a,4,5-tetrahydropentalene-2,2(1H)-di-
Starting from alkyne 1f (0.67 mmol) gave 2f as a pale orange oil; iso-
carboxylate (2a)
lated yield: 142 mg (79%, GPA); 167 mg (93%, GPB).
1H NMR (400 MHz, CDCl3): δ = 7.37–7.21 (m, 5 H), 7.20–7.16 (m, 1 H),
6.25 (dd, J = 5.6, 3.1 Hz, 1 H), 6.18 (dd, J = 5.6, 3.0 Hz, 1 H), 3.73–3.56
(m, 2 H), 2.91 (d, J = 2.9 Hz, 1 H), 2.70–2.65 (m, 1 H), 2.58 (d, J = 2.9 Hz,
1 H), 2.31 (dq, J = 5.0, 1.2 Hz, 1 H), 1.31 (dd, J = 9.5, 2.1 Hz, 1 H), 1.08
(d, J = 9.4 Hz, 1 H).
Starting from alkyne 1a (0.40 mmol) gave 2a as a colorless oil; isolat-
ed yield: 91 mg (81%, GPA); 101 mg (90%, GPB).
1H NMR (400 MHz, CDCl3): δ = 4.23 (dq, J = 15.8, 7.1 Hz, 4 H), 3.28–
3.13 (m, 2 H), 2.97 (s, 1 H), 2.78 (dd, J = 12.7, 7.4 Hz, 1 H), 2.65 (ddd,
J = 17.9, 6.3, 0.8 Hz, 1 H), 2.08 (dd, J = 17.9, 3.1 Hz, 1 H), 1.72 (ddd,
J = 2.5, 1.7, 1.0 Hz, 3 H), 1.65 (t, J = 12.6 Hz, 1 H), 1.27 (dt, J = 9.8, 7.1
Hz, 6 H).
The analytical data for this compound were in excellent agreement
with the reported data.22
The analytical data for this compound were in excellent agreement
with the reported data.7c
(4S,7R)-2-Phenyl-3a,4,7,7a-tetrahydro-1H-4,7-methanoinden-1-
one (2g)
6-Methyl-2-tosyl-2,3,3a,4-tetrahydrocyclopenta[c]pyrrol-5(1H)-
Starting from alkyne 1g (0.98 mmol) gave 2g as an off-white solid;
one (2b)
isolated yield: 194 mg (89%, GPA); 198 mg (91%, GPB).
1H NMR (400 MHz, CDCl3): δ = 7.73–7.67 (m, 3 H), 7.41–7.32 (m, 3 H),
6.34 (dd, J = 5.6, 3.1 Hz, 1 H), 6.26 (dd, J = 5.6, 2.9 Hz, 1 H), 3.03 (s,
1 H), 2.87–2.82 (m, 1 H), 2.79 (s, 1 H), 2.48 (dt, J = 5.1, 1.4 Hz, 1 H),
1.43 (dt, J = 9.4, 1.6 Hz, 1 H), 1.35 (d, J = 9.7 Hz, 1 H).
Starting from alkyne 1b (0.38 mmol) gave 2b as an off-white solid;
isolated yield: 92 mg (83%, GPA); 101 mg (91%, GPB).
1H NMR (400 MHz, CDCl3): δ = 7.78–7.69 (m, 2 H), 7.40–7.33 (m, 2 H),
4.24 (d, J = 16.1 Hz, 1 H), 4.00 (dd, J = 6.8, 2.5 Hz, 1 H), 3.97 (d, J = 2.7
Hz, 1 H), 3.01 (s, 1 H), 2.65–2.54 (m, 2 H), 2.44 (s, 3 H), 2.07–1.98 (m,
1 H), 1.68 (ddd, J = 2.5, 1.7, 0.9 Hz, 3 H).
The analytical data for this compound were in excellent agreement
with the reported data.25
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F

E
A. Cabré et al.
Paper
Synthesis
4-Methyl-N-{[(4S,7R)-1-oxo-3a,4,7,7a-tetrahydro-1H-4,7-methano-
of the Catalan Government. IRB Barcelona is the recipient of a Severo
inden-2-yl]methyl}benzenesulfonamide (2h)
Ochoa Award of Excellence from MINECO (Government of Spain).
M
neistri
o
de
E
co
n
o
ma
í
y
C
o
m
pvdteiat
d
C(
T
Q
2
0
1
7-8
7
8
4
0-P)
Starting from alkyne 1h (0.48 mmol) gave 2h as a pale orange oil; iso-
lated yield: 126 mg (80%, GPA); 134 mg (85%, GPB). GPC: 1st cycle:
312 mg (99%); 2nd cycle: 291 mg (92%); 3rd cycle: 268 mg (85%).
Acknowledgment
IR (ATR-FTIR): 3270, 2977, 2371, 2256, 1692, 1325, 1160 cm–1
.
A.C. thanks Ministerio de Economia y Competividad (MINECO) for a
1H NMR (400 MHz, CDCl3): δ = 7.71 (dd, J = 8.3, 2.0 Hz, 2 H), 7.31 (d,
J = 8.8 Hz, 1 H), 7.29–7.27 (m, 2 H), 6.26 (dd, J = 5.6, 3.0 Hz, 1 H), 6.17
(dd, J = 5.6, 3.0 Hz, 1 H), 5.10–5.02 (m, 1 H), 3.76 (d, J = 5.9 Hz, 2 H),
2.85–2.80 (m, 1 H), 2.65–2.62 (m, 2 H), 2.41 (s, 3 H), 2.18 (dt, J = 4.9,
1.4 Hz, 1 H), 1.32 (dt, J = 9.6, 1.5 Hz, 1 H), 1.06–0.99 (m, 1 H).
predoctoral fellowship (FPU).
References
(1) The Pauson–Khand Reaction: Scope, Variations and Applications;
Rios, R., Ed.; Wiley: Chichester, 2012.
13C NMR (101 MHz, CDCl3): δ = 209.07, 161.35, 144.81, 143.55,
138.43, 136.99, 136.78, 129.70, 127.19, 52.83, 48.16, 43.55, 42.76,
41.13, 39.16, 21.49.
HRMS (ESI): m/z [M + H]+ calcd for C18H20NO3S: 330.1158; found:
330.1165.
(2) Selected reviews: (a) Ricker, J. D.; Geary, L. M. Top. Catal. 2017,
60, 609. (b) Evans, P. Appl. Organomet. Chem. 2013, 27, 261.
(c) Strübing, D.; Beller, M. In Catalytic Carbonylation Reactions;
Beller, M., Ed.; Springer: Heidelberg, 2006, 165. (d) Omae, I.
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J. Org. Chem. 1996, 61, 9016.
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6670.
(4S,7R)-2-[(tert-Butyldimethylsiloxy)methyl]-3a,4,7,7a-tetrahy-
dro-1H-4,7-methanoinden-1-one (2i)
Starting from alkyne 1i (0.59 mmol) gave 2i as a colorless oil; isolated
yield: 96 mg (56%, GPA); 120 mg (70%, GPB).
1H NMR (400 MHz, CDCl3): δ = 7.38 (q, J = 2.2 Hz, 1 H), 6.29 (dd, J = 5.6,
3.1 Hz, 1 H), 6.20 (dd, J = 5.6, 3.0 Hz, 1 H), 4.35 (td, J = 2.1, 0.9 Hz, 2 H),
2.91 (s, 1 H), 2.77 (s, 1 H), 2.71 (s, 1 H), 2.35–2.30 (m, 1 H), 1.40 (d,
J = 9.3 Hz, 1 H), 1.27–1.24 (m, 1 H), 0.92 (s, 9 H), 0.08 (s, 6 H).
The analytical data for this compound were in excellent agreement
with the reported data.23
(4S,7R)-2-Cyclopropyl-3a,4,7,7a-tetrahydro-1H-4,7-methanoin-
den-1-one (2j)
Starting from alkyne 1j (1.51 mmol) gave 2j as a colorless oil; isolated
yield: 211 mg (75%, GPA); 203 mg (72%, GPB).
1H NMR (400 MHz, CDCl3): δ = 6.85 (d, J = 2.8 Hz, 1 H), 6.26 (dd, J = 5.6,
3.0 Hz, 1 H), 6.19 (dd, J = 5.6, 3.0 Hz, 1 H), 2.90 (p, J = 1.5 Hz, 1 H),
2.69–2.57 (m, 2 H), 2.29 (dt, J = 5.0, 1.4 Hz, 1 H), 1.56 (dddt, J = 9.4, 8.5,
5.2, 1.0 Hz, 1 H), 1.35 (dp, J = 9.2, 1.6 Hz, 1 H), 1.19 (dt, J = 9.3, 1.6 Hz,
1 H), 0.86–0.77 (m, 2 H), 0.60 (ddt, J = 6.6, 3.8, 1.3 Hz, 2 H).
The analytical data for this compound were in excellent agreement
with the reported data.24
(4R,7S)-2-(Trimethylsilyl)-3a,4,5,6,7,7a-hexahydro-1H-4,7-methano-
inden-1-one (3)
Starting from alkyne 1d (1.02 mmol) gave 3 as a colorless oil; isolated
yield: 211 mg (94%, GPA); 220 mg (98%, GPB).
1H NMR (400 MHz, CDCl3): δ = 7.56 (d, J = 2.6 Hz, 1 H), 2.65 (dd, J = 5.4,
2.5 Hz, 1 H), 2.38 (s, 1 H), 2.17 (d, J = 4.2 Hz, 1 H), 2.12 (d, J = 5.3 Hz,
1 H), 1.70–1.54 (m, 2 H), 1.32–1.20 (m, 2 H), 0.93–0.91 (m, 2 H), 0.17
(s, 9 H).
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11688. (b) Sturla, S. J.; Buchwald, S. L. J. Org. Chem. 1999, 64,
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Soc. 1997, 119, 6187. (b) Morimoto, T.; Chatani, N.; Fukumoto,
Y.; Murai, S. J. Org. Chem. 1997, 62, 3762.
The analytical data for this compound were in excellent agreement
with the reported data.26
(7) (a) Kwong, F. Y.; Lee, H. W.; Qiu, L.; Lam, W. H.; Li, Y.-M.; Kwong,
H. L.; Chan, A. S. C. Adv. Synth. Catal. 2005, 347, 1750. (b) Jeong,
N.; Sung, B. K.; Choi, Y. K. J. Am. Chem. Soc. 2000, 122, 6771.
(c) Cristóbal-Lecina, E.; Constantino, A. R.; Grabulosa, A.; Riera,
A.; Verdaguer, X. Organometallics 2015, 34, 4989.
Funding Information
(8) Zhang, M.; Buchwald, S. L. J. Org. Chem. 1996, 61, 4498.
(9) Shibata, T.; Takagi, K. J. Am. Chem. Soc. 2000, 122, 9852.
We gratefully acknowledge institutional funding from the Spanish
Ministry of Economy, Industry and Competitiveness (MINECO,
CTQ2017-87840-P) and IRB Barcelona trough the CERCA Programme
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F

F
A. Cabré et al.
Paper
Synthesis
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F