A. S. Harisha et al. / Tetrahedron Letters 56 (2015) 1427–1431
1429
Ar = 2-methoxy phenyl), mp 148–149 °C; MS m/z 305.1 (negative
mode) were identified with products obtained by treating isoquin-
oline-1,3-dione with cinnamaldehyde and 2-methoxycinnamalde-
hyde, respectively. 1H NMR spectrum of the complex product
from 27 (Ar = phenyl) did show the presence of significant quanti-
ties of a reduced species but this was different from 29.11 This
was also noted in the other two cases.
Probing the structural requirements further it was found that an
amide 20 (instead of ester) was essentially unaffected, so also ethyl
cinnamate and b-nitro styrene (with one EWG on the double bond)
and benzaldehyde. Interestingly phenazine was also unaffected by
triethylamine in ethanol at 70–75 °C in contrast to the observation
under irradiation.12 Products got by replacement of the ester group
in 16 and 21 with a nitrile group underwent reduction almost up to
50% with significant formation of aldehydes. Arylidene derivatives
of 2, 4-pentanedione, ethyl acetoacetate and ethyl methylsulfony-
lacetate were also studied.
While probing the origin of the vinyl fragment in the butadiene,
we noted that diethylamide instead of an ester was not responsible
(20, no reaction) and the ethyl ester was not a contributor (methyl
ester 19, 38% dihydro, 13% butadiene), nor ethanol (no reaction in
the absence of triethylamine) thus pointing to the triethylamine
being the vinyl donor. The reaction of 16 with triethylamine has
been carried out in various solvents, results indicating that it is
favored by protic (EtOH, MeOH) or aprotic, polar (dioxane, acetoni-
trile) solvents and was sluggish in non-polar solvents (toluene,
xylene). Among various amines studied (diethylamine, di-isopro-
pylethylamine, N,N-dimethylisopropylamine, piperidine, dimeth-
ylcyclohexylamine, N,N-diethylaniline, N-benzyldimethylamine)
di-isopropylethylamine uniquely led to the formation of the dihy-
dro derivative.
Figure 1. ORTEP diagram of 18.
(d, J = 15.2 Hz, 1H) and a third proton at 8.01 (d, J = 10.6 Hz, 1H) in
addition to 3 aryl protons at 7.11 (d), 8.28 (dd) and 8.43 (d). The
structure of the butadiene product 18 was confirmed by single crys-
tal X-ray studies (Fig. 1)7 Reaction of 16 with acetaldehyde in tolu-
ene afforded 18 in 55% yield.
The reaction was found to be mostly general with subtle to
gross variations in the amounts of unchanged starting material,
dihydro derivatives and butadienes. The early precursor alde-
hydes8 to such substrates were also observed in the NMR of some
crude product (Table 1). Yields are based upon semi quantitative
NMR analysis of peaks diagnostic for the products. Authentic dihy-
dro compounds were obtained by borohydride reduction of start-
ing materials and butadiene 21 was identified with the product
form condensation of 2-methoxycinnamaldehyde with ethyl
cyanoacetate.
Analogous 2-thienyl derivative was largely unchanged expect
for the formation of about 5% dihydro compound, while the 3-pyr-
idyl derivative decomposed to the aldehyde to 50% and the 2-pyr-
idyl derivative gave a complex mixture. The 4-pyridyl analogue
behaved like the 4-nitrophenyl analogue in getting reduced largely
to the dihydro derivative.10 This was identical with the product
obtained from sodium borohydride reduction. Another analogue
of 16 having a NO2 group at position 2 gave complex mixtures,
wherein 2-amino derivatives were suspected be present (ArH sig-
nals in the NMR at 6.5 ppm).
We like to speculate that there is an initial electron transfer
from triethylamine to 16, creating triethylamine cation radical
which then transfers a proton to form 17 and N-vinyldiethylamine
30.1b,2a,b
C2H5
N
CH
CH2
C2H5
As an extension of the study, we investigated cyclic scaffolds 26
and 27 mimicking the conjugated system in 16.
30
Ar
O
Ph
Ar
O
O
4
CN
NH
NH
NH
O
O
O
O
O
27
28
29
26
Both 3-cyano coumarin 26 and arylidene isoquinoline-1, 3-dione 27
gave complex mixtures. However in the case of the latter, the vinyl-
ogated products 28 could be isolated by chromatography (Ar = phe-
nyl 58%, 4-methoxyphenyl 40%, mp 229–231 °C; MS m/z 305.1
(negative mode), 2-methoxyphenyl 30%). cinnamyldeneisoquino-
line-1, 3-dione (28, Ar = phenyl), mp 228–230 °C; MS m/z 275.1
(negative mode) and 4-(2-methoxycinnamylidene)-1, 3-dione (28,
A speculative mechanism for the formation of the butadiene is
offered below (Scheme 4). A [2+2] addition of the cyanoacrylic ester
with 30 is not ruled out.
In keeping with the hypothesis of a radical mediation, the reac-
tion of 16 with triethylamine was suppressed by addition of