A. Mirloup et al. / Tetrahedron Letters 54 (2013) 4456–4462
4457
targets for the synthesis of precursors to multi-Bodipy species
involving conjugated linkers, the two molecules shown in Chart 1
were chosen.
I
2, HgO
PCC
DCM
S
1
OH
toluene
I
S
OH
I
S
O
2
3
41 %
In a first attempt to obtain the thienyl-aldehyde-Bodipy, iodin-
ation of 2-hydroxymethylthiophen 117 was used to provide 2,
which was oxidised to aldehyde 3 with PCC (Scheme 1). Condensa-
tion of 3 with 2,4-dimethylpyrrole afforded the dipyrromethane
intermediate 4, which was then oxidised with DDQ and complexed
I
I
N
H
TFA
1
) DDQ
S
S
2
) Et
3
N, BF .OEt
3
2
DCM
32 %
with BF
3
ÁOEt
2
under basic conditions to give the thienyl-Bodipy
DCM
N
N
NH HN
dye 5 in 32% yield. Formylation of the thienyl group in 5 failed,
B
8
7 %
1
8
F
F
however, using Pd-catalysed carboformylation conditions in-
stead de-iodination occurred, leading to the unsubstituted deriva-
tive 6. While 6 underwent ready reaction19 with the appropriate
Grignard reagent to provide the substituted di-ethynyl-Bodipy 7
in good yield and 7 could be formylated under Vilsmeier–Haack
5
4
CO
O
[
Pd(PPh ) Cl ]
3 2 2
S
N
S
N
2
0
O
conditions, the site of formylation proved to be on one pyrrole
1
and not the thienyl ring, as in 8. The H NMR spectrum of 8 shows
three thienyl-H signals at 6.33, 6.64, and 6.90 ppm, one b-pyrrolic
proton at 5.77 ppm and a formyl-H signal at 10.04 ppm. Note that,
as for related compounds,21 8 is inert under standard Knoevenagel
conditions.
H
ONa
N
DMF
N
B
B
F
F
35 %
F
F
6
EtMgBr
After the failure of numerous variations on the above ap-
proaches to obtain the (thienylaldehyde)-Bodipy, a new strategy
was adopted based on a protected aldehyde and stepwise con-
struction of the Bodipy dye as in Scheme 2. As expected from ear-
O
O
81 %
THF
2
2
lier work, protection of 2-formylthiophene 9 as in the dioxolan
0 enabled the introduction of a nonprotected formyl group by a
S
N
S
N
1
two-step procedure based on metallation at low temperature and
formylation with anhydrous DMF, giving 11. Bodipy 13 was ob-
tained in a manner similar to Bodipy 5, with a condensation step,
an oxidation with Chloranil instead of DDQ and introduction of
the B(III) (Scheme 2). Subsequent alkynylation at boron and hydro-
N
O
N
B
B
O
POCl
3
DMF
3 %
3
O
O
O
23
lysis of the dioxolane provided the pivotal aldehyde 15 in 52%
1
yield. The H NMR spectrum of 15 shows thienyl-H signals at
7
8
O
O
O
O
7
.15 (1H) and 7.80 (1H) ppm, a b-pyrrolic-H signal at 6.04
(
2H) ppm and a formyl-H signal at 9.97 (1H) ppm.
With this unusual thienylformyl-Bodipy in hand, we first tested
Scheme 1. Synthetic routes for the preparation of thienyl substituted Bodipys.
the reactivity of dye 15 towards the tetramethyl-Bodipy 16 under
standard Knoevenagel reactions. This provided the monostyryl
derivative 17 but in a low yield of 12% (Scheme 3). Mono-substitu-
tion was confirmed by the magenta colour (kabs = 581 nm) and the
indirect indication that the phenylaldehyde is more stable than
the thienylaldehyde (Scheme 4).
The X-ray molecular structure and selected geometrical param-
eters of 5 are shown in Figure 1. The compound crystallised in the
1
H NMR spectrum which exhibited three b-pyrrolic signals at 6.19
(
1H), 6.22 (2H), and 6.88 (1H) ppm and two vinylic protons at 7.30
1
orthorhombic space group, Ccm2 , and the crystallographically im-
and 7.49 ppm, with a coupling constant of 16.1 Hz confirming the E
conformation of the double bonds. The low yield of 17 is probably
due to the low stability of aldehyde 15 in the forcing conditions
posed mirror symmetry involves the atoms of the iodothiophene
group lying on the mirror plane bisecting the boradiazaindacene
unit. The C and N atoms of the Bodipy unit lie very close to the
one plane, with an rms deviation of 0.052 Å, and with the boron
displaced from this plane by only 0.177 Å. The boron centre dis-
plays a very nearly regular tetrahedral geometry with angles rang-
ing from 109.3(6)° to 110.4(4)°.
One molecule at the general position x, y, z, with the thiophene
lying in the crystallographic mirror (100) and the Bodipy parallel
to the (034) plane is surrounded in the (100) plane by four neigh-
bours with their Bodipy parallel to the (0-34) plane making a dihe-
dral angle of 80.3° with the former one, through Cthio–H. . .F and
2
4
used.
When 15 was condensed with the already monocondensed
Bodipy 18, the green distyryl derivative 19 was, like 17, obtained
in only rather low yield (23%). Proton NMR was diagnostic for
the double substitution, showing two different b-pyrrolic protons
at 6.06 (2H) and 6.61 (2H) ppm and two different vinyl protons
at 7.36 and 7.41 ppm.
In order to compare the efficiency in the synthesis with that of a
phenyl bridged formyl derivative, compound 20 was allowed to re-
act with dyes 16 and 18 under similar conditions, providing the hy-
brid dyes 21 and 22 in respectively, 31% and 61% yield. This is an
Cthio–H. . .S nonconventional hydrogen bond interactions (distance
of 2.39 and 2.86 Å, respectively) and also through I. . .F interactions
O
O
O
O
O
N
N
O
O
N
N
O
H
S
H
B
B
O
O
Chart 1. Molecular structures of the pivotal carbaldehyde molecules.