P. Rhonnstad, D. Wensbo / Tetrahedron Letters 43 (2002) 3137–3139
3139
Figure 2. ortho-Directors arranged in the order of increasing strength.
[with or without TMEDA; temperature (−78 to 25°C);
electrophile (MeI and DMF)]. As indicated by the
comparable yields, lithiation of 2b is as effective at
−78°C as it is at −30°C (entries 3 and 4). This was
further confirmed by HPLC-analysis of aliquots, fol-
lowed by methyl iodide quench, taken from a solution
of 2b in THF after the addition of TMEDA and
sec-BuLi. Full conversion of 2b was achieved already at
−78°C in less than 30 min.
stituted, as compared to N-unsubstituted derivatives
(entries 1 and 3, 4 and 5, 7 and 8).
In summary, we have estimated the relative strengths of
the N2-triphenylmethyl substituted, and of the N-
unsubstituted tetrazole nucleus, in comparison to some
commonly employed ortho-lithiation directors through
intramolecular competition experiments. The results are
summarized in Fig. 2, where the tetrazoles are drawn
together with the competing ortho-directors used in this
study in the order of increasing strength. We believe
that this information will serve as a useful guideline in
the design of syntheses of 5-aryltetrazoles carrying
additional substituents on the benzene-ring.
Thereafter, the para-substituted 5-aryltetrazoles 4a–h
were used as substrates in intramolecular competition
experiments (Table 2). The N-unsubstituted tetrazoles
4a–d were conveniently obtained from the correspond-
ing nitriles by treatment with trimethylsilyl azide and
dibutyltin oxide in toluene at 100°C.6 Subsequent trityl-
ation yielded the corresponding N2-triphenylmethyl
substituted derivatives 4e–h. The para-substituents were
chosen from the groups of moderate (OMe; 4a,e) and
strong (OCONEt2; 4d,h>NHCOCMe3; 4c,g, CONEt2;
4b,f) ortho-directors as classified by Snieckus.2 From
the ratio of the regioisomeric products 5a–h and 6a–h,
resulting from ortho-lithiation followed by methyl
iodide trapping of 4a–h, respectively, an estimate of the
ortho-directing strength of the N-(un)substituted tetra-
zole as compared to the para-substituent of the same
molecule, was obtained. Thus, 2-(triphenylmethyl)-2H-
tetrazole was found to be a stronger ortho-director than
OMe and CONEt2 (entries 3 and 4, respectively), but
weaker than NHCOCMe3 and OCONEt2 (entries 8, 9
and 10, respectively), regioselectivities in these cases
being equal to 9:1 or better.
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In the same way, 1H-tetrazole was found to be stronger
than OMe (entries 1 and 2), but weaker than CONEt2
and OCONEt2 (entries 5 and 11, respectively). The
failure of 4c to give more than trace amounts of either
5c or 6c may be due to the reluctance of the molecule
to formally carry three negative charges after ortho-
lithiation (entries 6 and 7). Overall, higher yields and
conversions were obtained for N2-triphenylmethyl sub-
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