Synergistic iron-and-amine catalysis in carbocyclizations

Article abstract of DOI:10.1055/s-0033-1338612

The fruitful merger of iron catalysis to amine catalysis was successfully applied in the direct intramolecular addition of aldehydes to non-activated alkynes. Accordingly, the carbocyclizations of a range of formyl-alkynes afforded the corresponding cyclo

Full text of DOI:10.1055/s-0033-1338612

1334▌
SPECIAL TOPIC
special topic
Synergistic Iron-and-Amine Catalysis in Carbocyclizations
Synergistic Iron-and-Amine Catalysis in Carbocyclizations
Chandrasekaran Praveen, Sabine Levêque, Maxime R. Vitale, Véronique Michelet,* Virginie Ratovelomanana-Vidal*
Institut de Recherche de Chimie Paris, CNRS – Chimie ParisTech, 11 rue Pierre et Marie Curie, 75005 Paris, France
E-mail: veronique.michelet@chimie-paristech.fr; E-mail: virginie.vidal@chimie-paristech.fr
Received: 08.01.2014; Accepted after revision: 25.02.2014
Dedicated to Professor Max Malacria on the occasion of his 65th birthday
when enamine organocatalysis is combined with π-Lewis
Abstract: The fruitful merger of iron catalysis to amine catalysis
acid metal catalysis, the carbocyclization of formyl-
was successfully applied in the direct intramolecular addition of al-
alkynes may take place.10,11 We wish to report herein the
discovery of an original catalytic system composed of an
dehydes to non-activated alkynes. Accordingly, the carbocycliza-
tions of a range of formyl-alkynes afforded the corresponding
cyclopentanes in good to excellent yields. Experimental evidence iron catalyst and an amine organocatalyst that synergisti-
tends to support a synergistic enamine/π-activation reaction mecha-
nism.
cally promotes the intramolecular α-addition of aldehydes
to non-activated terminal alkynes [Scheme 1 (2)].
Key words: synergistic catalysis, iron, organocatalysis, carbocycli-
zation, alkenylation
Kim, Lee et al. (ref. 6)
alkynyl β-keto esters
O
O
R2O2C
R1OC
FeCl3 (10 mol%)
At present iron catalysis is receiving tremendous attention
as it is a promising alternative to the use of noble metals,
such as palladium, platinum, iridium, or gold.1–4 Indeed,
while iron is an inexpensive, easily available, and bio-
compatible metal, the sustainability of precious metals is
questionable considering their limited supplies and recent
price inflation.1 Numerous achievements have been made
in this field over the last decade, including the remarkable
development of iron-catalyzed cross-coupling,2 reduc-
tion,3 and oxidation reactions.1 Several enantioselective
variants have also been developed.4 Despite the increasing
use of iron complexes in catalytic transformations, it is
noteworthy that many issues remain. For instance, the
iron-catalyzed addition of carbon nucleophiles to alkynes
is mostly restricted to the use of acetylenic moieties acti-
vated by an aromatic group.5 To the best of our knowl-
edge, there are only two reports in which non-activated
alkynes are employed: in the iron-catalyzed Conia-ene re-
action of alkynyl β-keto esters [Scheme 1, (1)]6 and in the
cycloisomerization reaction of enynes.7 Hence, the devel-
opment of new iron-catalyzed functionalization of non-
activated alkynes by carbon-based nucleophiles remains
highly desirable.
R1
OR2
(1)
DCE, r.t. or 70 °C
58–77%
this work
alkynyl aldehydes
O
O
R
Y
[Fe] cat.
amine cat.
R
H
(2)
H
synergistic
catalysis
Y
Y
Y
Scheme 1
The search for an efficient iron-based catalytic system be-
gan with the evaluation of several iron complexes in the
carbocyclization reaction of the model substrate 1. This
screening was initially performed using 50 mol% of vari-
ous iron(II) and iron(III) sources in the presence of 20
mol% cyclohexylamine at 100 °C in 1,2-dichloroethane
(Table 1). Formyl-alkyne 1 was selected due to the pres-
ence of a methyl substituent in the α position of the alde-
hyde moiety, which should prevent internal double bond
isomerization after cyclization.11a In addition, cyclohexyl-
amine was chosen as the amine co-catalyst as primary
amines are suitable organocatalysts for the generation of
enamines from α,α-disubstituted aldehydes.12 The initial
inspection of iron(II) complexes in this transformation,
which included iron(II) nitrate, iron(II) sulfate, iron(II)
oxalate, and iron(II) trifluoromethanesulfonate, gave ei-
ther no product or very low yields of the desired cyclopen-
tane 2 after 16 hours of reaction (entries 1–4). For this
reason, iron(III) sources were subsequently examined.
Despite the fact that similar results were obtained with
iron(III) trifluoromethanesulfonate and iron(III) chloride
(entries 5 and 6), we observed a clear improvement in the
yield of cyclopentane 2 when iron(III) acetylacetonate
was used (71% GC yield, entry 7). Attempts to decrease
either reaction time or reaction temperature resulted in a
With respect to this challenge, we have recently consid-
ered that the synergistic use of an iron catalyst with an or-
ganocatalyst could open new perspectives in this area.
Indeed, ‘synergistic metallo-organocatalysis’, by promot-
ing the complementary and orthogonal activation of reac-
tants, has demonstrated its ability to reveal new types of
reactivity that would not occur by catalysis alone.8 In ad-
dition, it has also contributed to the development of some
original iron-catalyzed processes.9 Our past experience in
synergistic catalysis has established that, in some cases,
SYNTHESIS 2014, 46, 1334–1338
Advanced online publication: 19.03.2014
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1338612; Art ID: SS-2014-C0018-OP
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Synergistic Iron-and-Amine Catalysis in Carbocyclizations
1335
significant reduction in the corresponding yields (entries Next, we evaluated the catalytic performance of this iron-
8 and 9). A this point, we decided to progressively de- based synergistic catalytic system for the carbocyclization
crease the iron(III) acetylacetonate catalyst loading. Un- of a wide range of formyl-alkynes 3–12 (Table 2).
der otherwise identical reaction conditions, we were
Table 2 Scope of the Synergistic Fe(acac)3/CyNH2 Catalytic
System
pleased to observe an increase in reaction yield when 20
or 10 mol% of iron(III) acetylacetonate were employed,
which probably resulted from lower degradation within
the reaction mixture. In the latter case, after 16 hours at
100 °C, carbocycle 2 was efficiently obtained in 90% iso-
lated yield (entry 11).
R
Fe(acac)3 (5 mol%)
CyNH2 (20 mol%)
OHC
R
OHC
DCE, 100 °C
16–96 h
Y
Y
Y
Y
13–22
3–12
Table 1 Optimization of a Synergistic Iron-Based Catalytic System
Entry
1
Substrate
Product
Yielda (%)
[Fe] (x mol%)
OHC
OHC
CyNH2 (20 mol%)
DCE, 100 °C
OHC
MeO2C
CO2Me
MeO2C
CO2Me
3
63
1
2
BnO2C
13
CO2Bn
Entry Fe source
mol% of Fe source Time (h) Yielda (%)
OHC
1
Fe(NO3)2
FeSO4
50
50
50
50
50
50
50
50
50
20
10
5
16
16
16
16
16
16
16
7
0
2
17
13
18
0
2
3
4
5
69
44
i-PrO2C
14
CO2i-Pr
3
FeC2O4
Fe(OTf)2
Fe(OTf)3
FeCl3
4
OHC
5
MeO2C
15a/15bb
OHC
6
22
71
63
31
85c
90c
87c
80c
<5
<5
H
7
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
–
8
9b
10
11
12
13
14d
15
16
16
16
24
24
24
24
4
5
6
6
7
8
59
92
AcO
OAc
16
OHC
TBDPSO
OTBDPS
1
17
5
OHC
5
c
–
N
a GC yield using tridecane as external standard.
b Reaction performed at 80 °C.
c Isolated yield.
Ts
18
n-Pr
OHC
d Reaction performed without CyNH2.
7
8
9
70
The iron(III) acetylacetonate loading could be further re-
duced to 5 or 1 mol%, although the reaction time increase
to 24 hours for full conversion of the starting formyl-
alkyne 1 (entries 12 and 13). Considering that a lower
yield was obtained when 1 mol% of this iron complex was
used, we decided to explore the scope of the reaction us-
ing 5 mol% iron(III) acetylacetonate and 20 mol% cyclo-
hexylamine. Notably, control experiments, in the absence
of the amine organocatalyst or in the absence of the iron
catalyst, gave only traces of carbocyclized product 2,
which conclusively supported a synergistic catalytic pro-
cess (entries 14 and 15).
i-PrO2C
CO2i-Pr
19
i-Pr
OHC
d
10
–
MeO2C
CO2Me
20
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1334–1338

1336
C. Praveen et al.
SPECIAL TOPIC
Table 2 Scope of the Synergistic Fe(acac)3/CyNH2 Catalytic System
(continued)
and 92% yields, respectively (entries 4 and 5). This differ-
ence in the yield was attributed to the superior stability of
silyl ethers compared to the acetate moiety under the reac-
tion conditions. It is worth noticing that starting from the
N-tosyl-tethered substrate 8, the synergistic iron-based
catalytic system led to the formation of N-tosylpropargyl-
amine, as a result of a competitive retro-Michael reaction
pathway (entry 6). The impact of the substitution pattern
in the α-position of the aldehyde residue was then studied.
Employing α-propyl- and α-isopropyl-substituted formyl-
alkynes 9 and 10, resulted in divergent results. Whereas
the propylcyclopentane 19 was synthesized in 70% yield
after 19 hours, after four days only 20% conversion of the
starting formyl-alkyne 10 was observed (entries 7 and 8).
Thus, the presence of a bulky secondary alkyl group in the
α-position of the aldehyde generates enhanced steric
strains that probably hampered cyclization. Despite this
limitation, we demonstrated that larger primary alkyl
groups in the same position such as butyl or 4-methoxy-
benzyl were tolerated, the corresponding carbocycles 21
and 22 were isolated in good 78% and 75% yields, respec-
tively (entries 9 and 10).
R
Fe(acac)3 (5 mol%)
CyNH2 (20 mol%)
OHC
R
OHC
DCE, 100 °C
16–96 h
Y
Y
Y
Y
13–22
3–12
Entry
9
Substrate
Product
Yielda (%)
n-Bu
OHC
11
78
i-PrO2C
CO2i-Pr
21
PMB
OHC
10
12
75
i-PrO2C
CO2i-Pr
22
a Isolated yield.
b Major diastereomer is shown (85:15 dr).
Concerning the reaction mechanism involved in such an
iron-and-amine catalytic process, the fact that two cata-
lysts were required for the reaction to take place supported
a synergistic catalytic pathway. Nevertheless, the actual
role of each catalyst was not clear. At the outset of this
project, we postulated that the α-addition of aldehydes to
non-activated alkynes could arise from the formation, un-
der organocatalysis, of an intermediary enamine, which
would be sufficiently nucleophilic to undergo addition to
the triple bond activated by an iron complex (Scheme 2,
catalytic cycle A). Nevertheless, due to the basic character
of amines and the Lewis acidic properties of iron(III)
complexes, we could not rule out the possibility that both
catalysts could favor the formation of an iron enolate,
c N-Tosylpropargylamine was formed after 16 h of reaction.
d Reaction conversion was lower than 20% after 96 h of reaction.
Starting with α-methyl-substituted substrates, the influ-
ence of the tether that connects the aldehyde and the al-
kyne moieties was evaluated. Bulkier dibenzyl and
diisopropyl malonate linkages induced a small decrease in
the yield in the corresponding cyclopentanes 13 and 14
(Table 2, entries 1 and 2). The replacement of the dimeth-
yl malonate linkage by a monomethyl ester group led to
carbocycles 15a/15b in 44% yield and a good 85:15 dia-
stereomeric ratio (entry 3). With gem-bis(acetoxymethyl)
or gem-bis[(tert-butyldiphenylsiloxy)methyl] compounds
6 and 7, cyclopentanes 16 and 17 were obtained in 59%
O
R
H2O
H
O
CyNH2
[Fe]
O
R
Cy
H
R
Z
N
H
H
cat. 1 cat. 2
R
H
CyNH2
cat. 1
Z
O
Z
R
Z
H
and/or
Cy
Z
[Fe]
N
CyNH3
R
cat. 2
H
[Fe]
R
[Fe]
O
O
R
Z
[Fe]
R
H
H
H2O
Cy
H
N
Z
R
Z
[Fe]
Z
Cy
N
H
H
Z
B) Brønsted base/
iron enolate rearrangement
A) enamine/π-activation pathway
Scheme 2 Mechanistic considerations
Synthesis 2014, 46, 1334–1338
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Synergistic Iron-and-Amine Catalysis in Carbocyclizations
1337
material. At r.t., an aqueous solution of 50% AcOH (1 mL) was add-
ed and the resulting biphasic mixture was vigorously stirred for 10
min and then transferred to a separating funnel. The aqueous layer
was extracted with CH2Cl2 (3 × 5 mL), and the combined organic
layers were dried (MgSO4), filtered, and concentrated under re-
duced pressure. To remove traces of iron complexes, the residue
was filtered through a small plug of silica gel (i.d. 1 cm, h = 2 cm,
cyclohexane–EtOAc, 7:3) followed by concentration under reduced
pressure of the filtrate. The crude material was purified by flash
chromatography (silica gel) to afford the desired carbocyclized
product.
which in turn would rearrange itself to an alkenyl–ironate
complex (Scheme 2, catalytic cycle B).13 For this reason,
starting from our model substrate 1, we performed two
control experiments in which cyclohexylamine was re-
placed by either N,N-diisopropylethylamine (Hünig’s
base) or N-isopropylcyclohexylamine. Under otherwise
identical reaction conditions, the use of these stronger
Brønsted bases led, in both cases, to incomplete conver-
sion of the starting formyl-alkyne 1 and poor yields of cy-
clization product 2 (Scheme 3).
Dimethyl 3-Formyl-3-methyl-4-methylene-cyclopentane-1,1-di-
carboxylate (2)
Using 1 (240 mg, 1 mmol) for 24 h gave 2 (224 mg, 87%) as a pale
yellow oil. Spectral data were in agreement with those reported in
the literature.11a
1H NMR (300 MHz, CDCl3): δ = 9.29 (s, 1 H), 5.23 (t, J = 2.1 Hz,
1 H), 4.95 (t, J = 2.0 Hz, 1 H), 3.75 (s, 3 H), 3.74 (s, 3 H), 3.07–2.92
(m, 2 H), 2.95 (d, J = 14.4 Hz, 1 H), 2.27 (d, J = 14.4 Hz, 1 H), 1.27
(s, 3 H).
O
Fe(acac)3 (5 mol%)
OHC
H
amine (20 mol%)
DCE, 100 °C
24 h
MeO2C
CO2Me
MeO2C
CO2Me
1
2
CyNHi-Pr
(i-Pr)2NEt
13% GC yield
28% GC yield
Dibenzyl 3-Formyl-3-methyl-4-methylenecyclopentane-1,1-di-
carboxylate (13)
Using 3 (118 mg, 0.3 mmol) for 17 h gave 13 (74 mg, 63%) as a pale
yellow oil. Spectral data were in agreement with those reported in
the literature.10d
1H NMR (300 MHz, CDCl3): δ = 9.19 (s, 1 H), 7.37–6.99 (m, 10 H),
5.12 (t, J = 2.0 Hz, 1 H), 5.03 (s, 4 H), 4.85 (t, J = 2.2 Hz, 1 H),
3.04–2.81 (m, 3 H), 2.21 (d, J = 14.1 Hz, 1 H), 1.15 (s, 3 H).
Scheme 3 Control experiments employing secondary and tertiary
amines
The fact that the non-nucleophilic N,N-diisopropylethyl-
amine, which is unable to form an enamine, induced some
cyclized product formation indicated that a reaction
mechanism involving an iron enolate may take place.
However, considering the low 13% cyclization yield that
was observed, it also seemed to show that this reaction
pathway is rather poorly efficient. Similarly, the use of the
highly hindered N-isopropylcyclohexylamine impeded
product formation as a probable consequence of low lev-
els of enamine formation. In this context, we concluded
that cyclohexylamine favors an apparently more produc-
tive enamine/π-activation pathway (Scheme 2, catalytic
cycle A).14
Diisopropyl 3-Formyl-3-methyl-4-methylenecyclopentane-1,1-
dicarboxylate (14)
Using 4 (118 mg, 0.4 mmol) for 22 h gave 14 (82 mg, 69%) as a pale
yellow oil. Spectral data were in agreement with those reported in
the literature.10d
1H NMR (300 MHz, C6D6): δ = 9.16 (s, 1 H), 4.99 (m, 2 H), 4.92 (t,
J = 1.9 Hz, 1 H), 4.66 (t, J = 2.2 Hz, 1 H), 3.23–3.03 (m, 2 H), 2.92
(d, J = 16.5 Hz, 1 H), 2.35 (d, J = 14.0 Hz, 1 H), 1.07 (d, J = 6.3 Hz,
3 H), 1.04–0.90 (m, 12 H).
Methyl 3-Formyl-3-methyl-4-methylenecyclopentanecarboxyl-
ate (15a/15b)
Using 5 (91 mg, 0.5 mmol) for 16 h gave diastereomers 15a/15b (40
mg, 44%) as a pale yellow oil; 85:15 dr. Spectral data were in agree-
ment with those reported in the literature.10f
Altogether, the fruitful merger of iron catalysis with
amine catalysis allows the addition of aldehyde nucleo-
philes to non-activated alkynes. A simple synergistic cat-
alytic system composed of cyclohexylamine and iron(III)
acetylacetonate leads to the carbocyclization of formyl-
alkynes in good yields. Experimental evidence tends to
support an enamine/π-activation pathway, which would
account for the efficiency of the C–C bond formation.
This work further demonstrates that synergistic catalysis
may open some new perspectives for the development of
new iron-catalyzed processes.
15a
1H NMR (300 MHz, CDCl3): δ = 9.36 (s, 1 H), 5.17 (t, J = 1.9 Hz,
1 H), 4.85 (dd, J = 2.7, 2.0 Hz, 1 H), 3.71 (s, 3 H), 2.99 (tt, J = 10.1,
7.4 Hz, 1 H), 2.82–2.60 (m, 2 H), 2.47 (dd, J = 13.1, 10.1 Hz, 1 H),
1.86 (dd, J = 13.0, 6.3 Hz, 1 H), 1.23 (s, 3 H).
15b
1H NMR (300 MHz, CDCl3): δ = 9.26 (d, J = 1.1 Hz, 1 H), 5.22 (t,
J = 1.9 Hz, 1 H), 4.96 (t, J = 2.3 Hz, 1 H), 3.70 (s, 3 H), 2.93–2.81
(m, 1 H), 2.76–2.64 (m, 2 H), 2.59 (dd, J = 12.9, 7.0 Hz, 1 H), 1.85–
1.70 (m, 1 H), 1.29 (s, 3 H).
Formyl-alkynes 1 and 3–12 were prepared according to published
procedures.10 Iron complexes (+99% grade) were purchased and di-
rectly used. Amines and DCE were distilled over CaH2 prior use.
4,4-Bis(acetoxymethyl)-1-methyl-2-methylenecyclopentane-
carbaldehyde (16)
Using 6 (107 mg, 0.4 mmol) for 22 h gave 16 (63 mg, 59%) as a pale
yellow oil. Spectral data were in agreement with those reported in
the literature.10a
1H NMR (300 MHz, CDCl3): δ = 9.29 (s, 1 H), 5.18 (t, J = 1.9 Hz,
1 H), 4.97 (dd, J = 2.3, 1.7 Hz, 1 H), 4.12–3.80 (m, 4 H), 2.55–2.16
(m, 3 H), 2.06 (d, J = 1.4 Hz, 6 H), 1.43 (d, J = 14.3 Hz, 1 H), 1.29
(s, 3 H).
4,4-Disubstituted 1-Methyl-2-methylenecyclopentanecarbalde-
hydes 2, 13–17, 19, 21, 22; General Procedure
In a screw cap vial under an argon atmosphere, a freshly prepared
solution of 0.8 M CyNH2 in DCE (100 μL, 0.08 mmol, 0.2 equiv)
was added to freshly purified formyl-alkyne (0.4 mmol, 1 equiv) in
DCE (100 μL). Fe(acac)3 (7.1 mg, 0.02 mmol, 0.05 equiv) was add-
ed followed by DCE (200 μL). The vial was capped and heated at
100 °C until TLC analysis indicated full conversion of the starting
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1334–1338

1338
C. Praveen et al.
SPECIAL TOPIC
4,4-Bis[(tert-butyldiphenylsiloxy)methyl]-1-methyl-2-meth-
ylenecyclopentanecarbaldehyde (17)
Using 7 (132 mg, 0.2 mmol) for 16 h gave 17 (121 mg, 92%) as a
colorless oil. Spectral data were in agreement with those reported in
the literature.10a
1H NMR (300 MHz, CDCl3): δ = 9.16 (s, 1 H), 7.67–7.62 (m, 8 H),
7.52–7.28 (m, 12 H), 5.02 (t, J = 1.7 Hz, 1 H), 4.76 (t, J = 1.9 Hz, 1
H), 3.72–3.47 (m, 4 H), 2.43 (d, J = 15.8 Hz, 1 H), 2.30–2.23 (m, 2
H), 1.46 (d, J = 14.6 Hz, 1 H), 1.11 (s, 3 H), 1.05 (d, J = 1.1 Hz, 18
H).
(b) Sherry, B. D.; Fürstner, A. Acc. Chem. Res. 2008, 41,
1500. (c) Czaplik, W. M.; Mayer, M.; Cvengros, J.; von
Wangelin, A. J. ChemSusChem 2009, 2, 396.
(3) For reviews on iron-catalyzed reduction reactions, see:
(a) Gaillard, S.; Renaud, J.-L. ChemSusChem 2008, 1, 505.
(b) Morris, R. H. Chem. Soc. Rev. 2009, 38, 2282. (c) Le
Bailly, B. A. F.; Thomas, S. P. RSC Adv. 2011, 1, 1435.
(d) Darwish, M.; Wills, M. Catal. Sci. Technol. 2012, 2, 243.
(4) For a review on asymmetric iron catalysis, see: Gopalaiah,
K. Chem. Rev. 2013, 113, 3248.
(5) For hydroarylation reactions, see: (a) Li, R.; Wang, S. R.;
Lu, W. Org. Lett. 2007, 9, 2219. (b) Dal Zotto, C.; Wehbe,
J.; Virieux, D.; Campagne, J.-M. Synlett 2008, 2033.
(c) Komeyama, K.; Igawa, R.; Takaki, K. Chem. Commun.
2010, 46, 1748. For carbometalation reactions, see:
(d) Yamagami, T.; Shintani, R.; Shirakawa, E.; Hayashi, T.
Org. Lett. 2007, 9, 1045.
(6) Chan, L. Y.; Kim, S.; Park, Y.; Lee, P. H. J. Org. Chem.
2012, 77, 5239.
(7) Fürstner, A.; Majima, K.; Martín, R.; Krause, H.; Kattnig,
E.; Goddard, R.; Lehmann, C. W. J. Am. Chem. Soc. 2008,
130, 1992.
Diisopropyl 3-Formyl-3-propyl-4-methylenecyclopentane-1,1-
dicarboxylate (19)
Using 9 (162 mg, 0.5 mmol) for 19 h gave 19 (114 mg, 70%) as a
colorless oil. Spectral data were in agreement with those reported in
the literature.10e
1H NMR (300 MHz, CDCl3): δ = 9.20 (s, 1 H), 5.29–5.09 (m, 1 H),
5.08–4.79 (m, 3 H), 3.08–2.60 (m, 3 H), 2.27 (d, J = 14.1 Hz, 1 H),
1.82–1.62 (m, 1 H), 1.54–1.32 (m, 1 H), 1.30–0.97 (m, 14 H), 0.84
(t, J = 7.2 Hz, 3 H).
Diisopropyl 3-Butyl-3-formyl-4-methylenecyclopentane-1,1-di-
carboxylate (21)
(8) For reviews on synergistic metallo-organocatalysis, see:
(a) Du, Z.; Shao, Z. Chem. Soc. Rev. 2013, 42, 1337.
(b) Allen, A. E.; MacMillan, D. W. C. Chem. Sci. 2012, 3,
633. (c) Patil, N. T.; Shinde, V. S.; Gajula, B. Org. Biomol.
Chem. 2012, 10, 211. (d) Zhong, C.; Shi, X. Eur. J. Org.
Chem. 2010, 2999. (e) Shao, Z.; Zhang, H. Chem. Soc. Rev.
2009, 38, 2745.
(9) For representative examples, see: (a) Zhou, S.; Fleischer, S.;
Junge, K.; Beller, M. Angew. Chem. Int. Ed. 2011, 50, 5120.
(b) Motoyama, K.; Ikeda, M.; Miyake, Y.; Nishibayashi, Y.
Eur. J. Org. Chem. 2011, 2239.
Using 11 (101 mg, 0.3 mmol) for 24 h gave 21 (79 mg, 78%) as a
colorless oil. Spectral data were in agreement with those reported in
the literature.10e
1H NMR (300 MHz, CDCl3): δ = 9.27 (s, 1 H), 5.21 (d, J = 12.8 Hz,
1 H), 5.13–4.88 (m, 3 H), 3.10–2.65 (m, 3 H), 2.33 (d, J = 14.1 Hz,
1 H), 1.89–1.68 (m, 1 H), 1.66–1.43 (m, 1 H), 1.37–1.05 (m, 16 H),
0.88 (t, J = 7.1 Hz, 3 H).
Diisopropyl 3-Formyl-3-(4-methoxybenzyl)-4-methylenecyclo-
pentane-1,1-dicarboxylate (22)
Using 12 (120 mg, 0.3 mmol) for 17 h gave 22 (90 mg, 75%) as a
pale yellow oil. Spectral data were in agreement with those reported
in the literature.10e
1H NMR (300 MHz, CDCl3): δ = 9.45 (s, 1 H), 7.06 (d, J = 8.7 Hz,
2 H), 6.79 (d, J = 8.7 Hz, 2 H), 5.29 (s, 1 H), 5.13–4.90 (m, 3 H),
3.77 (s, 3 H), 3.12 (d, J = 14.0 Hz, 1 H), 3.00–2.89 (m, 1 H), 2.83
(d, J = 14.0 Hz, 1 H), 2.74–2.63 (m, 2 H), 2.42 (d, J = 14.3 Hz, 1 H),
1.25–1.14 (m, 12 H).
(10) (a) Montaignac, B.; Vitale, M. R.; Michelet, V.;
Ratovelomanana-Vidal, V. Org. Lett. 2010, 12, 2582.
(b) Montaignac, B.; Vitale, M. R.; Ratovelomanana-Vidal,
V.; Michelet, V. J. Org. Chem. 2010, 75, 8322.
(c) Montaignac, B.; Vitale, M. R.; Ratovelomanana-Vidal,
V.; Michelet, V. Eur. J. Org. Chem. 2011, 3723.
(d) Montaignac, B.; Östlund, V.; Vitale, M. R.;
Ratovelomanana-Vidal, V.; Michelet, V. Org. Biomol.
Chem. 2012, 10, 2300. (e) Montaignac, B.; Praveen, C.;
Vitale, M. R.; Michelet, V.; Ratovelomanana-Vidal, V.
Chem. Commun. 2012, 48, 6559. (f) Praveen, C.;
Montaignac, B.; Vitale, M. R.; Ratovelomanana-Vidal, V.;
Michelet, V. ChemCatChem 2013, 5, 2395.
Acknowledgment
This work was supported by the Centre National de la Recherche
Scientifique (CNRS) and ENSCP Chimie ParisTech. C.P. is grate-
ful to Ville de Paris for a postdoctoral fellowship.
(11) For seminal examples, see: (a) Binder, J. T.; Crone, B.;
Haug, T. T.; Menz, H.; Kirsch, S. F. Org. Lett. 2008, 10,
1025. (b) Yang, T.; Ferrali, A.; Campbell, L.; Dixon, D. J.
Chem. Commun. 2008, 2923. For related metallo-
organocatalyzed cyclization reactions, see: (c) Bihelovic,
F.; Matovic, R.; Vulovic, B.; Saicic, R. N. Org. Lett. 2007,
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(13) Several metal-enolates are known to undergo this type of
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Synthesis 2014, 46, 1334–1338
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