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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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slide1

Novel stabilized organoboron partners

for the Suzuki-Miyaura

cross-coupling reaction

By Olga Dykhno

slide2

1

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

slide3

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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slide4

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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slide5

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

slide6

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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slide8

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

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Boronic acids. Ed. Hall, D.G, Wiley-VCH. Weinheim, 2005.

slide9

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

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Boronic acids. Ed. Hall, D.G, Wiley-VCH. Weinheim, 2005.

slide10

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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slide11

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.

slide12

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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slide13

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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slide14

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

slide15

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

slide16

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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.

slide19

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.

slide20

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.

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

slide21

Masking Group Requirements

  • Easy installation
  • High stability during coupling and isolation process
  • Easy unmasking

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

slide22

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

slide23

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

slide24

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

slide26

Boron masking strategy

25

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

slide27

26

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

slide28

27

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

slide29

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.

slide30

29

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

slide31

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

slide32

31

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

slide34

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

slide35

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

slide36

Solubility issues are present

  • Unmasking requires harsh conditions
  • Functional group tolerance was not illustrated
  • Expensive protecting group
  • Loss of atom economy

35

slide37

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