Novel stabilized organoboron partners
for the Suzuki-Miyaura
cross-coupling reaction
By Olga Dykhno
Metal- Catalyzed Cross- Coupling Reactions. 2nd ed. Ed. De Meijere, A.; Diederich, F. Wiley- VCH. Weinheim, 2004.
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Miyaura, N.; Suzuki, A. J. Chem. Soc., Chem. Commun. 1979, 866 - 867.
Miyaura, N.; Yanagi, T.; Suzuki, A. Synth. Commun. 1981, 11, 513 - 519.
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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.
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Nicolaou, K.C.; Bulger, P.G.; Sarlah, D. Angew. Chem. Int. Ed. 2005, 44, 4442- 4489.
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Boronic acids. Ed. Hall, D.G, Wiley-VCH. Weinheim, 2005;
Molander, G.A.; Canturk, B. Angew. Chem. Int. Ed., 2009, 48, 9240-9262.;
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• 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
Boronic acids. Ed. Hall, D.G, Wiley-VCH. Weinheim, 2005.
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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
Boronic acids. Ed. Hall, D.G, Wiley-VCH. Weinheim, 2005.
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• 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.
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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.
Darses,S.; Michaud, G.; Genet, J.-P. Eur.J.Org.Chem., 1999, 1875-1883.
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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.
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• 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.
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Molander, G.A.; Canturk, B. Org.Lett. 2008,10, 2135-2138.
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Molander, G.A.; Canturk, B. Org.Lett. 2008,10, 2135-2138.
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Molander, G.A.; Sandrock, D.L. J. Am. Chem. Soc. 2008,130,15792-15793.
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Molander, G.A.; Sandrock, D.L. J. Am. Chem. Soc. 2008,130,15792-15793.
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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
Madabe, K.; Ishikawa, S. Chem.Comm 2008, 3829-3838.
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• 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.
Noguchi, H.; Hojo, Kosho.; Suginome, M. J. Am. Chem. Soc. 2007,129,758-759.
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Masking Group Requirements
• Easy installation
• High stability during coupling and isolation process
• Easy unmasking
Noguchi, H.; Hojo, Kosho.; Suginome, M. J. Am. Chem. Soc. 2007,129,758-759.
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Noguchi, H.; Hojo, Kosho.; Suginome, M. J. Am. Chem. Soc. 2007,129,758-759.
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Noguchi, H.; Shioda, T.; Chou, C.-M.;Suginome, M. Org.Lett. 2008, 10, 377-380..
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Noguchi, H.; Shioda, T.; Chou, C.-M.;Suginome, M. Org.Lett. 2008, 10, 377-380..
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Boron masking strategy
Gillis, E.P.; Burke, M.D. J. Am. Chem. Soc. 2007, 129, 6716-6717.
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Gillis, E.P.; Burke, M.D. J. Am. Chem. Soc. 2007, 129, 6716-6717.
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Gillis, E.P.; Burke, M.D. J. Am. Chem. Soc. 2007, 129, 6716-6717.
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•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
Gillis, E.P.; Burke, M.D. J. Am. Chem. Soc. 2008, 130, 14084-14085.
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Gillis, E.P.; Burke, M.D. J. Am. Chem. Soc. 2008, 130, 14084-14085.
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Knapp, D.M.; Gillis, E.P.; Burke, M.D. J. Am. Chem. Soc. 2009, 131, 6961- 6963.
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Knapp, D.M.; Gillis, E.P.; Burke, M.D. J. Am. Chem. Soc. 2009, 131, 6961- 6963.
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Gillis, E.P.; Burke, M.D. J. Am. Chem. Soc. 2007, 129, 6716-6717.
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Gillis, E.P.; Burke, M.D. J. Am. Chem. Soc. 2007, 129, 6716-6717.
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• Solubility issues are present
• Unmasking requires harsh conditions
• Functional group tolerance was not illustrated
• Expensive protecting group
• Loss of atom economy
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Professor Tehshik Yoon
Additional practice talk attendees
Kat Myhre
Teresa Beary
J.P. Gerdt
Brad Ryland
Nicky Stephenson
Adam Weinstein
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
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