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

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

References

• 1a Review: Stanforth SP. Tetrahedron  1998,  54:  263 
• 1b Suzuki A. In Metal-Catalyzed Cross-Coupling Reactions   Diederich F. Stang PJ. Wiley-VCH; Weinheim: 1998.  Chap. 2.
• 2 Miyaura N. Suzuki A. Chem. Rev.  1995,  95:  2457 
• For examples see
• 3a Mitchell MB. Wallbank PJ. Tetrahedron Lett.  1991,  32:  2273 
• 3b Zhang H. Chan KS. Tetrahedron Lett.  1996,  37:  1043 
• 3c Wang C. Kilitziraki M. MacBride JAH. Bryce MR. Horsburgh LE. Sheridan AK. Monkman AP. Samuel IDW. Adv. Mater.  2000,  12:  217 
• 3d Ng S.-C. Lu H.-F. Chan HSO. Fujii A. Laga T. Yoshino K. Adv. Mater.  2000,  12:  1122 
• 3e Wang C. Kilitziraki M. Palsson L.-O. Bryce MR. Monkman AP. Samuel IDW. Adv. Funct. Mater.  2001,  11:  47 
• 3f Feuerstein M. Laurenti D. Bougeant C. Doucet H. Santelli M. Chem. Commun.  2001,  325 
• 3g Monkman AP. Palsson L.-O. Higgins RWT. Wang C. Bryce MR. Batsanov AS. Howard JAK. J. Am. Chem. Soc.  2002,  124:  6049 
• 4a Thompson WJ. Jones JH. Lyle PA. Thies JE. J. Org. Chem.  1988,  53:  2052 
• 4b Oh-e T. Miyaura N. Suzuki A. J. Org. Chem.  1993,  58:  2201 
• 4c Li JJ. Yue WS. Tetrahedron Lett.  1999,  40:  4507 
• 4d Lehmann U. Henze O. Schlüter AD. Chem.-Eur. J.  1999,  5:  854 
• 5 Fischer FC. Havinger E. Recl. Trav. Chim. Pays-Bas  1965,  84:  439 
• 6 Fischer FC. Havinger E. Recueil  1974,  93:  21 
• 7a Cai D. Larsen RD. Reider PJ. Tetrahedron Lett.  2002,  43:  4285 
• 7b Li W. Nelson DJ. Jensen MS. Hoerrner RS. Cai D. Larsen RD. Reider PJ. J. Org. Chem.  2002,  67:  5394 
• 7c Matondo H. Ouhaja N. Souirti S. Baboulène M. Main Group Metal Chem.  2002,  25:  163 ; this article states that 2-pyridylboronic acid and 3-pyridylboronic acid have been obtained from the corresponding pyridyl Grignard reagent and trimethylsilylborate although details are not given
• 8 Droes R. Nardin G. Randaccio L. Tauzher G. Vuano S. Inorg. Chem.  1997,  36:  2463 
• 9 Dreos R. Nardin G. Randaccio L. Siega P. Tauzher G. Vrdoljak V. Inorg. Chem.  2001,  40:  5536 
• 10 Bouillon A. Lancelot J.-C. Collot V. Bovy PR. Rault S. Tetrahedron  2002,  58:  2885 
• 11 Bouillon A. Lancelot J.-C. Collot V. Bovy PR. Rault S. Tetrahedron  2002,  58:  3323 
• 12 Bouillon A. Lancelot J.-C. Collot V. Bovy PR. Rault S. Tetrahedron  2002,  58:  4368 
• 13 Parry PR. Wang C. Batsanov AS. Bryce MR. Tarbit B. J. Org. Chem.  2002,  67:  7541 
• Reviews:
• 14a Marsais F. Quéguiner G. Snieckus V. Epsztajn J. Adv. Heterocycl. Chem.  1991,  52:  187 
• 14b Anctil EJ.-G. Snieckus V. J. Organomet. Chem.  2002,  653:  150 
• 15 Comins DL. LaMunyon DH. Tetrahedron Lett.  1998,  29:  773 
• 16 Leeson PD. Emmett JC. J. Chem. Soc., Perkin Trans. 1  1988,  3085 
• 18 Shirota Y. J. Mater. Chem.  2000,  10:  1 

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.