The [2 + 2] Cycloaddition-Retroelectrocyclization and [4 + 2] Hetero-Diels-Alder Reactions of 2-(Dicyanomethylene)indan-1,3-dione with Electron-Rich Alkynes: Influence of Lewis Acids on Reactivity

Article abstract of DOI:10.1021/acs.orglett.5b01598

The reaction of electrophilic 2-(dicyanomethylene)indan-1,3-dione (DCID) with substituted, electron-rich alkynes provides two classes of push-pull chromophores with interesting optoelectronic properties. The formal [2 + 2] cycloaddition-retroelectrocycliz

Full text of DOI:10.1021/acs.orglett.5b01598

Letter
pubs.acs.org/OrgLett
The [2 + 2] Cycloaddition−Retroelectrocyclization and [4 + 2] Hetero-
Diels−Alder Reactions of 2‑(Dicyanomethylene)indan-1,3-dione with
Electron-Rich Alkynes: Influence of Lewis Acids on Reactivity
Etienne J. Donckele,† Aaron D. Finke,† Laurent Ruhlmann,‡ Corinne Boudon,‡ Nils Trapp,†
and Franco̧
is Diederich*,†
†Laboratorium fur Organische Chemie, ETH Zurich, Vladimir-Prelog-Weg 3, 8093 Zurich, Switzerland
̈
‡Laboratoire d’ Electrochimie et de Chimie Physique du Corps Solide, Institut de ChimieUMR 7177, C.N.R.S., Universite
́
de
Strasbourg, 4 rue Blaise Pascal, 67081 Strasbourg Cedex, France
S
* Supporting Information
ABSTRACT: The reaction of electrophilic 2-(dicyanomethylene)indan-1,3-dione (DCID) with substituted, electron-rich
alkynes provides two classes of push−pull chromophores with interesting optoelectronic properties. The formal [2 + 2]
cycloaddition−retroelectrocyclization reaction at the exocyclic double bond of DCID gives cyanobuta-1,3-dienes, and the formal
[4 + 2] hetero-Diels−Alder (HDA) reaction at an enone moiety of DCID generates fused 4H-pyran heterocycles. Both products
can be obtained in good yield and excellent selectivity by carefully tuning the reaction conditions; in particular, the use of Lewis
acids dramatically enhances formation of the HDA adduct.
he formal [2 + 2] cycloaddition−retroelectrocyclization
(CA−RE) reaction between electron-rich alkynes and
Herein we show that DCID exhibits two modes of reactivity
with electron-rich alkynes: the expected CA−RE reaction
involving the dicyanovinyl moiety, and a previously unseen
hetero-Diels−Alder (HDA) pathway. The properties of the
resulting two classes of chromophores are reported.
In an initial experiment, the CA−RE reaction of 1 with 1
equiv of N,N-dimethylanilinoacetylene (DMA-acetylene) 2
afforded 3 (85% yield) as the major product and oligoene E-
4 as a minor product (10% yield) (Scheme 1). By mixing 2.1
T
electron-deficient olefins yielding push−pull-substituted buta-
1,3-dienes is a versatile, well-studied transformation.1 It is a
“click”-type reaction2 that is high yielding, atom-economic,
requires no catalyst, proceeds under mild conditions, and
exhibits excellent chemo- and regioselectivity. CA−RE
reactions of electron-rich alkynes with electron-deficient
alkenes, such as tetracyanoethene (TCNE),3a 7,7,8,8-tetracya-
no-p-quinodimethane (TCNQ),3b and others1,3c−e have been
used as a convenient, robust method for preparing nonplanar,
π-conjugated, donor−acceptor (D−A) chromophores that
exhibit intense, low-energy, intramolecular charge-transfer
(CT) bands. Some of them have found application in devices
for all-optical switching.4
Scheme 1. CA−RE Reaction of 1 with 2
To this end, we became interested in 2-(dicyanomethylene)-
indan-1,3-dione (DCID) 1 as an acceptor for the formation of
new push−pull chromophores. DCID was first described in the
literature in 1968,5 but has received little attention as an
electron acceptor because of its facile rearrangement to 2,3-
dicyano-1,4-naphthoquinone upon chemical reduction.6 DCID
can be prepared in good yield as yellow, air-stable crystals by
reaction of ninhydrin with malononitrile in water.5
Received: June 1, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b01598
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Organic Letters
Letter
equiv of 2 with 1 equiv of DCID in CHCl3, E-4 was obtained in
one pot in 83% yield. Only the E-isomer was observed,
confirmed by X-ray analysis (Figure S1, Supporting Information
(SI)), in accordance with our previous work.7
Hall et al. studied the influence of Lewis acids, such as ZnCl2
and LiClO4, on the cycloaddition of cyano- and carbomethoxy-
substituted olefins with donor-substituted alkenes.12 In the
absence of Lewis acids, the [4 + 2] HDA pathway to yield 3,4-
dihydro-2H-pyrans was preferred, whereas Lewis acids
promoted the [2 + 2] cycloaddition pathway. We observed
the same selectivity in the transformation of DCID with 4-
vinylanisole 7 (Scheme 2), yielding cyclobutane ( )-8a and
dihydropyran ( )-8b.
Intriguingly, Lewis acids have the opposite effect on DCID
reactivity with donor-substituted alkynes. In this case, the
addition of 1.0 equiv of different Lewis acids activates the
enone moiety of DCID for the HDA reaction. We tested the
efficiency of various Lewis acids to promote the HDA reaction
of DCID with alkyne 5 (Table 1). The best selectivity (6a/6b =
5:95) was obtained with LiClO4 in the presence of a mixed-
solvent system at 80 °C (Table 1, entry 10). In the absence of
Lewis acid, the CA−RE pathway dominates. Putative
mechanisms for the formal [2 + 2] and [4 + 2] reactions of
DCID with donor-substituted alkynes are presented in section
S4 in the SI. There, the difference in the effect of Lewis acids on
cycloadditions with donor-activated alkenes and alkynes is also
briefly discussed.
When DCID was reacted with bis-DMA-acetylene 5,
oligoene formation was suppressed and the expected CA−RE
product 6a was isolated as the major product (90% yield),
along with the unexpected, fused 4H-pyran 6b (10% yield), the
product of an inverse electron demand HDA reaction (Scheme
2).8 In view of the interest in 4H-pyran derivatives in natural
products and biologically active compounds9 as well as in
optoelectronics,10 we investigated ways to control the
selectivity of this transformation to bias formation of 4H-
pyran 6b.11
Scheme 2. Differences in the Reactivity of Electron-
Donating Olefins and Alkynes with DCID
With optimized conditions in hand, we evaluated the scope
of the reaction with a series of different donor-substituted
alkynes 9−21 (Table 2).
In general, good to excellent yields and chemoselectivities
were obtained starting from anilino-substituted alkynes. The
CA−RE transformation was consistently preferred in the
absence of Lewis acid, providing buta-1,3-dienes 22a−30a,
while addition of LiClO4 afforded 4H-pyrans 22b−30b with
excellent selectivity. In contrast, the use of alkynes with less
activating donor substitutents, such as anisyl7 or ferrocenyl,13
led to no reaction. The reaction of DCID with asymmetric
alkynes 20 and 21 gave mixtures of regioisomers that were
inseparable by either chromatography or recrystallization.
The majority of the new products described herein were
characterized by X-ray crystallographic analysis. Figure 1 shows
Table 1. Selected Results for the Chemoselectivity in the Reaction of DCID with Bis-DMA-acetylene
a
entry
additive
solvent
ratio
yield (%) 6a
yield (%) 6b
1
2
−
−
−
DCM
MeCN
DCE
75:25
85:15
90:10
28:72
34:66
35:65
20:80
14:86
10:90
75
82
90
27
32
33
19
14
10
5
25
14
10
70
63
61
76
86
90
95
3
4
TiCl4
AlCl3
BF3·Et2O
ZnCl2
LiClO4
LiClO4
LiClO4
DCE
5
DCE
6
DCE
7
DCE
8
DCE
b
9
DCE
b
10
DCE/MeCN (98:2)
5:95
a
All reactions were conducted using 1.0 equiv of 1, 1.05 equiv of 5, and 1.0 equiv of additive on 0.15 mmol scale at 0.1 M concentration, 3 h at 25
°C. DCM = dichloromethane; DCE = 1,2-dichloroethane. Ratio and yield determined by 1H NMR using dibromomethane as the internal standard.
b
Reaction conducted at 80 °C.
B
DOI: 10.1021/acs.orglett.5b01598
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Organic Letters
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Table 2. CA−RE and HDA Reaction of DCID with Various
a
Donor-Substituted Alkynes
Figure 2. UV−vis spectra of selected CA−RE products in CH2Cl2 at
25 °C.
Figure 3. UV−vis spectra of selected HDA products in CH2Cl2 at 25
°C.
which reconstituted the initial transition (Figures S18−S49 in
the SI)
The redox properties of compounds 3, E-4, 6a/b, and 22−
30a/b were studied by cyclic voltammetry (CV) and rotating-
disc voltammetry (RDV) in CH2Cl2 + 0.1 M nBu4NPF6. All
potentials are given versus ferrocene, used as internal standard
reference (for details, see section S9 in the SI).
a
Condition A: 1.05 equiv of alkyne and 1.0 equiv of 1 on 0.15 mmol
scale in 0.1 M MeCN for 3 h at 25 °C. Condition B: 1.05 equiv of
alkyne, 1.0 equiv of 1, and 1.0 equiv of LiClO4 on 0.15 mmol scale in
0.1 M DCE/MeCN 98:2 at 80 °C for 2 h. Fc = ferrocenyl. Ratios
b
determined by yields of isolated compounds. No reaction.
c
Regioisomers observed.
By CV, compounds commonly exhibit one or two, usually
reversible oxidation waves corresponding to the oxidation of
the anilino moieties. At least two, mostly reversible reduction
waves are observed, corresponding to the electron transfer to
the extended DCID acceptor in the CA−RE products and the
tricyclic acceptor moiety in the HDA products. The reduction
the crystal structures of 6a, 23a, 24b, and 30b. Crystallographic
data are summarized in section S5 in the SI.
of the CA−RE products is more facile, with Eo
occurring
red,1
between −0.53 and −1.17 V, than the reduction of the HDA
adducts, with Eored,1 occurring between −0.84 and −1.50 V. On
the other hand, the HDA adducts (Eo between +0.34 and
ox,1
+0.78 V) are easier to oxidize than the CA−RE products (Eo
ox,1
Figure 1. ORTEP representation of the molecular structures of CA−
RE adducts 6a (a) and 23a (b) and HDA adducts 24b (c) and 30b
(d). Thermal ellipsoids are shown at the 50% probability level.
Hydrogen atoms not shown. T = 100 K.
between +0.63 and +0.88 V; Table S27). From the CV data
(Tables S26 and S27 in the SI), we calculated a highest
occupied−lowest unoccupied molecular orbital (HOMO−
LUMO) energy gap of 1.80 and 1.84 eV for 26a and 26b,
respectively, in agreement with the optical gaps obtained from
the lowest-energy absorption maximum or the end-absorption
in the UV−vis spectra (for the optical gaps of other
chromophores, see Table S27 in the SI). Both CA−RE and
HDA products feature positive solvatochromism (Figures S16
and S17).
Figures 2 and 3 depict the UV−vis spectra of selected CA−
RE and HDA products, recorded in CH2Cl2 at 25 °C. The
CA−RE products feature intense intramolecular charge transfer
(ICT) bands with λmax values in the range of 450−545 nm (ε =
22500 to 49000 M−1 cm−1). The ICT bands of the HDA
The vertical optical transitions of the optimized structures of
3, 4, 6a−30a and 6b−30b were calculated by time-dependent
density functional theory (TD-DFT) using the software
package Gaussian 09 (see section S8 in the SI).14 In all cases,
the computed transition energies are slightly larger than the
experimental values (Tables S12−S25 in the SI). Differences
products are hypsochromically shifted and less intense (λmax
≈
290−487 nm, ε = 10000−26000 M−1 cm−1; see Figures S12
and S13 in the SI). The ICT nature of these bands was
confirmed by protonation with CF3COOH, leading to
attenuation of the band, followed by neutralization with NEt3,
C
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ASSOCIATED CONTENT
* Supporting Information
Synthesis, NMR spectra, X-ray crystallography details, CIF files,
electrochemical data, UV−vis spectra, and DFT calculations.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.5b01598.
■
S
AUTHOR INFORMATION
Corresponding Author
́
1995; Vol. 5, pp 469−490. (c) Kumar, R. R.; Perumal, S.; Menendez, J.
C.; Yogeeswari, P.; Sriram, D. Bioorg. Med. Chem. 2011, 19, 3444−
3450.
■
*E-mail: diederich@org.chem.ethz.ch.
Notes
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H.; Tian, H. Chem. Commun. 2012, 48, 6073−6084.
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Khavasi, H. R. Catal. Commun. 2008, 9, 1082−1086. (b) Li, P.; Luo,
L.-L.; Li, X.-S.; Xie, J.-W. Tetrahedron 2010, 66, 7590−7594. (c) Chen,
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The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the ERC Advanced Grant No.
246637 (“OPTELOMAC”) and the Swiss National Science
Foundation. We thank Dr. Bruno Bernet and Cagatay Dengiz
for help with the manuscript and Michael Solar (ETH Zurich)
for collecting X-ray structures.
̈
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DOI: 10.1021/acs.orglett.5b01598
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