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Novel stabilized organoboron partners for the Suzuki-Miyaura cross-coupling reaction

Novel stabilized organoboron partners for the Suzuki-Miyaura cross-coupling reaction. By Olga Dykhno. 1. Metal- Catalyzed Cross- Coupling Reactions . 2nd ed. Ed. De Meijere, A.; Diederich, F. Wiley- VCH. Weinheim, 2004. .

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Novel stabilized organoboron partners for the Suzuki-Miyaura cross-coupling reaction

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  1. Novel stabilized organoboron partners for the Suzuki-Miyaura cross-coupling reaction By Olga Dykhno

  2. 1 Metal- Catalyzed Cross- Coupling Reactions. 2nd ed. Ed. De Meijere, A.; Diederich, F. Wiley- VCH. Weinheim, 2004.

  3. Miyaura, N.; Suzuki, A. J. Chem. Soc., Chem. Commun.1979,866 - 867. Miyaura, N.; Yanagi, T.; Suzuki, A. Synth. Commun. 1981, 11, 513 - 519. 2

  4. Walker, S.D.; Barber, T.W.; Martinelli, J.R.; Buchwald, S.L. Angew. Chem. Int. Ed.2004,43, 1871-1876 – 867; Bhayanna, B.; Fors, B.P.;Buchwald, S.L. Org. Lett., 2009, 11, 3954-3957. 3

  5. 4 Nicolaou, K.C.; Bulger, P.G.; Sarlah, D. Angew. Chem. Int. Ed. 2005, 44, 4442- 4489.

  6. Boronic acids. Ed. Hall, D.G, Wiley-VCH. Weinheim, 2005; Molander, G.A.; Canturk, B. Angew. Chem. Int. Ed., 2009, 48, 9240-9262.; 5

  7. 6

  8. Boronic acids are trivalent boron-containing organic compounds • Mild organic Lewis acids • Low toxicity and degrades into environmentally friendly boric acid • Products of second oxidation of boranes • Formation of boronic esters – loses hydrogen bond donor capabilities • Boronic esters are less polar, easier to handle • Boronic esters are non atom economical 7 Boronic acids. Ed. Hall, D.G, Wiley-VCH. Weinheim, 2005.

  9. Limitations • Boronic acids are not monomeric species, but rather exist as dimeric and cyclic trimeric anhydrides. • Due to easy protodeboronation, excess (20-50%) of boronic acid is needed. • Sensitivity to reagents commonly used in organic synthesis 8 Boronic acids. Ed. Hall, D.G, Wiley-VCH. Weinheim, 2005.

  10. First report of convenient synthesis of organotrifluoroborates using boronic acid and derivatives using KHF2 • First to utilize organotrifluoroborates in coupling reactions with arenediazonium tetrafluoroborates. Vedejs, E.;Chapman, R.W.; Fields, S.C.; Lin, S.; Schrimpf, M.R. J. Org. Chem. 1995, 60, 3020-3027; Darses, S.; Genet, J.P.; Brayer, J.L.; Demoute, J.P. Tetrahedron Lett.1997, 38, 4393-4396. 9

  11. Advantages • Monomeric, crystalline compounds that are easily handled and indefinitely stable to moisture and air. • BF3K moiety is compatible with sensitive functional groups • Tolerant to reaction conditions. 10 Darses,S.; Michaud, G.; Genet, J.-P. Eur.J.Org.Chem.,1999, 1875-1883.

  12. Molander, G.A.; Cooper, D.J. J. Org. Chem. 2007, 72, 3558-3560; Molander, G.A.; Petrillo, D.E. J. Am. Chem. Soc. 2006, 128, 9634-9635. 11

  13. Potassium heteroaryl trifluoroborates with aryl chlorides. • Coupling of vinyl trifluoroborates with aryl triflates • Electron poor aryl bromide with electron-deficient aryltrifluoroborates. Molander, G.A.; Biolatto, B. J. Org. Chem. 2003, 68, 4302-4306; Molander, G. A.;Rivero, M.R. Org. Lett.2002, 4, 107-111; Molander, G.A.; Canturk, B. Org.Lett. 2008,10, 2135-2138; Barber, T.E.; Buckwald, S.L. Org.Lett. 2004, 6, 2649-2652. 12

  14. 13 Molander, G.A.; Canturk, B. Org.Lett. 2008,10, 2135-2138.

  15. 14 Molander, G.A.; Canturk, B. Org.Lett. 2008,10, 2135-2138.

  16. 15 Molander, G.A.; Sandrock, D.L. J. Am. Chem. Soc. 2008,130,15792-15793.

  17. 16 Molander, G.A.; Sandrock, D.L. J. Am. Chem. Soc. 2008,130,15792-15793.

  18. 17

  19. Iterative Cross-Coupling criteria • Building blocks are readily available and inexpensive • Coupling and Protection/deprotection are high yielding, functional group tolerant and • do not produce toxic by-products • Handling, separation, and purification are facile 18 Madabe, K.; Ishikawa, S. Chem.Comm 2008, 3829-3838.

  20. Coupling of arylboronic acid A with haloboronic acid C – no desired product. • Formation of mixture of oligoarenes • Coupling of arylboronic acid A with “masked” haloboronic acid C’- desired product. 19 Noguchi, H.; Hojo, Kosho.; Suginome, M. J. Am. Chem. Soc. 2007,129,758-759.

  21. Masking Group Requirements • Easy installation • High stability during coupling and isolation process • Easy unmasking 20 Noguchi, H.; Hojo, Kosho.; Suginome, M. J. Am. Chem. Soc. 2007,129,758-759.

  22. 21 Noguchi, H.; Hojo, Kosho.; Suginome, M. J. Am. Chem. Soc. 2007,129,758-759.

  23. 22 Noguchi, H.; Shioda, T.; Chou, C.-M.;Suginome, M. Org.Lett. 2008, 10, 377-380..

  24. 23 Noguchi, H.; Shioda, T.; Chou, C.-M.;Suginome, M. Org.Lett. 2008, 10, 377-380..

  25. 24

  26. Boron masking strategy 25 Gillis, E.P.; Burke, M.D. J. Am. Chem. Soc. 2007, 129, 6716-6717.

  27. 26 Gillis, E.P.; Burke, M.D. J. Am. Chem. Soc. 2007, 129, 6716-6717.

  28. 27 Gillis, E.P.; Burke, M.D. J. Am. Chem. Soc. 2007, 129, 6716-6717.

  29. MIDA boronate functional group is stable to a wide range of common synthetic reagents • Further elaboration or increase in molecular complexity is possible with MIDA boronates 28 Gillis, E.P.; Burke, M.D. J. Am. Chem. Soc. 2008, 130, 14084-14085.

  30. 29 Gillis, E.P.; Burke, M.D. J. Am. Chem. Soc. 2008, 130, 14084-14085.

  31. 30 Knapp, D.M.; Gillis, E.P.; Burke, M.D. J. Am. Chem. Soc. 2009, 131, 6961- 6963.

  32. 31 Knapp, D.M.; Gillis, E.P.; Burke, M.D. J. Am. Chem. Soc. 2009, 131, 6961- 6963.

  33. 32

  34. 33 Gillis, E.P.; Burke, M.D. J. Am. Chem. Soc. 2007, 129, 6716-6717.

  35. 34 Gillis, E.P.; Burke, M.D. J. Am. Chem. Soc. 2007, 129, 6716-6717.

  36. Solubility issues are present • Unmasking requires harsh conditions • Functional group tolerance was not illustrated • Expensive protecting group • Loss of atom economy 35

  37. Additional practice talk attendees Teresa Beary J.P. Gerdt Brad Ryland Nicky Stephenson Adam Weinstein Professor Tehshik Yoon Kat Myhre Steve Burke Yoon Group Kevin Williamson Tamas Benkovics Juana Du Elliot Farney Michael Ischay Shishi Lin Dr. Zic Lu Dr. David Michaelis Dr. Katie Partridge Jon Parrish Laura Ruiz Espelt Liz Tyson 36

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