B. Vaz et al. / Tetrahedron Letters 42 (2001) 7409–7412
7411
aldehydes and pyrrole.16 Excess pyrrole is required to
maximize formation of dipyrromethane and to avoid
appearance of higher oligomers and polymers. After
completion, unreacted pyrrole is recovered by distilla-
tion and can be recycled.
of tetrasubstituted porphyrins. The process leads to
functionalized A2B2 porphyrin scaffolds in high yields
and under mild conditions. The additional formyl func-
tionality makes it possible to connect bidirectional
other components to construct complex supramolecular
assemblies. Work along these lines is in progress bi-
directionally and will be reported in due course.
For the coupling step, we explored different reaction
conditions, changing the nature of the base, solvent and
catalyst within the range of temperatures required for
the coupling to take place. Although Therien reported
the use of strongly basic conditions [Pd(PPh3)4,
Ba(OH)2·8H2O, DME/H2O, 80°C, 6–12 h] to couple
Zn(II)-porphyrinato boronic acids,12b a more polar sol-
vent and a weaker base ensured good coupling rates
when the porphyrin was functionalized as electrophile.
Reaction conditions involving the use of Pd(PPh3)4 as
catalyst, DMF as solvent, and solid Na2CO3 as base at
60°C proved optimal. Excess boronic acid was required
to compensate for adventitious hydrolytic prot-
iodeboronation. Rigorous exclusion of oxygen in the
reaction flasks and solvents (through freeze–thaw
cycles) was also required. Under those optimized condi-
tions,17 the meso-A2B2 porphyrins were obtained in
virtually quantitative yields. The results are collected in
Table 1. The nature of selected arylboronic acids ranges
from the phenyl to the 4-formyl derivative, as well as
the formylthiophene isomers. Previously, it had been
reported that boronic acids with electron-withdrawing
groups at the ortho position of the aryl ring or boronic
acids derived from strongly electron-deficient hetero-
cycles, gave no coupling to octabromotetraarylporphy-
rins.18 However, 2-formylthiophene-3-boronic acid cou-
pled to 3 and 4 in excellent yield, perhaps as a result of
the activating effect of the formyl group. We could
corroborate the lack of reactivity of 3-formyl-thio-
phene-2-boronic acid, even after heating to 90°C for 8
h, thus confirming the dependence of the Suzuki reac-
tion to the electronic effects of the boronic acids. Due
to the tedious separation of the excess boronic acid and
free base A2B2 porphyrins containing formyl groups
upon attempted purification by column chromatogra-
phy, their isolation as the corresponding Zn(II)–por-
phyrinato complexes was more convenient, and these
compounds released the free base upon treatment with
TFA. It has been claimed that the use of free-base
porphyrins should ensure milder reaction conditions
when used as electrophiles in metal-catalyzed cross-coup-
ling reactions, in metal-catalyzed cross-coupling reac-
tions due to their reduced electron density compared to
the electron-rich metalloporphyrins. However, the
direct use of the more electron-rich dibromo-Zn(II)-
porphyrinato derived from 6 led to a faster Suzuki
reaction, which was complete in only 1 h at 60°C (95%).
For the orthoformylthiophene derivatives 12 and 9, two
isomers were obtained, which differed in the orienta-
tions of the formyl group relative to the porphyrin ring.
We could isolate and characterize both isomers of 12
(a,a and a,b; 12a and 12b), but all attempts at charac-
terizing 9 after the separation of its components led to
their rapid interconversion at room temperature.
Acknowledgements
This work was supported by the Xunta de Galicia
(Grant XGIDT99PXI30105B) and the Spanish Ministe-
rio de Educacio´n y Cultura (Grant SAF98-0143, Fel-
lowship to B.V.).
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In conclusion, the results reported here illustrate the
utility of the Suzuki coupling reaction for the synthesis