LETTER
Preparation of 2-Aminomethylbiphenyls
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a SN2-type mechanism.26 A sp2 trigonal, uncoordinated current methodology provides an efficient way to produce
boron NMR signal and a tetragonal sp3-coordinated signal useful intermediates. We are currently working to exploit
with an amine are approximately d = 30 and 15 ppm, re- this versatile synthetic method to prepare useful biphenyl
spectively.20 As shown in Table 2, the 11B NMR chemical derivatives.
shift of boronic acids 1 and 2 indicates that the boron atom
is tetracoordinated in solution. Boronic acid 1 displays a
Supporting Information for this article is available online at
signal at d = 12.3 ppm, while 2 displays a signals at d = 4.6
ppm.
Table 2 11B NMR Chemical Shift of Boronic Acids 1–4 in CDCl3
Acknowledgment
Compound
11B NMR (d, ppm, 128.34 MHz)
We wish to thank Professor Frederic-Georges Fontaine for his X-
ray crystallography experiments and also Mr. Pierre Audet for his
technical assistance with the NMR experiments. This work was
supported by NSERC of Canada, FQRNT of Quebec, and Universi-
té Laval. PLB and SC thank the NSERC of Canada for postgraduate
sholarships.
1
2
3
4
12.3
4.6
34.4
31.2
References
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chloroform, the presence of a carbamate on the N forbids
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pair is delocalized on the carbonyl group, leaving the
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It is worth noting that the anchimeric participation of
the aminomethyl group in compounds of type 1 and 2
affect the pKa, which influences the activation step of the
Suzuki–Miyaura coupling reaction. The transmetalation
step is known to be facilitated by a base-mediated tetraco-
ordinated boronate anion,27 although its exact role re-
mains unclear.28
Finally, another possible explanation is that the enhanced
reactivity of 3 and 4 in the Suzuki–Miyaura reaction can
be attributed to the fact that the amine protected by an N-
Boc group does not interact with Pd as strongly as in 1 and
2. Hence, the catalytic cycle can proceed smoothly, lead-
ing to increased reaction rates and yields.
In summary, we have demonstrated that properly protect-
ed 2-aminomethylphenylboronic acids are useful syn-
thons for the preparation of functionalized 2-
aminomethylbiphenyl derivatives. The presence of a pro-
tonable N atom adjacent to the boronate was shown to de-
crease the yields and rate of the reaction. Taking into
account the ease of preparation of the boronic acids, the
Synlett 2010, No. 16, 2449–2452 © Thieme Stuttgart · New York