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Synthesis 2003(7): 1035-1038
DOI: 10.1055/s-2003-39158
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

New Shelf-Stable Halo- and Alkoxy-Substituted Pyridylboronic Acids and their Suzuki Cross-Coupling Reactions to Yield Heteroarylpyridines

Paul R. Parrya, Martin R. Bryce*a, Brian Tarbitb
a Department of Chemistry, University of Durham, Durham, DH1 3LE, England
e-Mail: m.r.bryce@durham.ac.uk;
b Seal Sands Chemicals Ltd., Seal Sands, Middlesbrough, Cleveland, TS2 1UB, England
Further Information

Publication History

Received 6 January 2003
Publication Date:
09 May 2003 (online)

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Abstract

New shelf-stable pyridylboronic acids have been synthesized: bromine-lithium exchange followed by reaction with triisopropylborate (TIPB) yielded 2-fluoro-5-pyridylboronic acid (4), 3-bromo-5-pyridylboronic acid (5) and 2-ethoxy-5-pyridylboronic acid (6); directed lithiation followed by reaction with trimethylborate (TMB) or TIPB afforded 2-methoxy-3-pyridylboronic acid (8), 3-bromo-6-methoxy-4-pyridylboronic acid (11) and 3-bromo-6-ethoxy-4-pyridylboronic acid (12). Cross-coupling of pyridylboronic acids 4, 6, 8, and 11 with 3-bromoquinoline [Cs2CO3, Pd(PPh3)2Cl2, 1,4-dioxane, 95 °C] gave pyridinylquinoline derivatives 13, 15-17 in 50-77% yields: the analogous reaction of 5 was low yielding due to further in situ reactions of the product 14. Cross-coupling of 12 with 2-bromo-5-nitrothiophene gave 3-bromo-4-(5-nitro-2-thienyl)-6-ethoxypyridine (18).

Key words

pyridine - boronic acids - cross-coupling - Suzuki reaction - heterobiaryl

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17

Compounds 5 and 12 could not be obtained analytically pure. As noted by other workers, [7] [9] it is not unusual for arylboronic acids to give unsatisfactory elemental analysis. This can arise if they are hygroscopic or exist as a mixture of the free acid and the anhydride.