Suzuki clutch

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The Suzuki coupling or Suzuki-Miyaura reaction is a name reaction in organic chemistry for the synthesis of biphenyls or biphenyl derivatives by forming a CC bond. This palladium- catalyzed cross-coupling was discovered in 1979 by A. Suzuki (* 1930) and N. Miyaura (* 1946). Suzuki received the Nobel Prize in Chemistry in 2010 for his research on this cross-coupling .

Overview reaction

Here, organoborane compounds (e.g. boronic acid ) with halogen aromatic compounds or halogen-substituted vinyl compounds with the catalytic use of palladium (0) -phosphine complexes [such as Pd (PPh 3 ) 4 , Pd (PPh 3 ) 3 etc.] and implemented in the presence of a base (such as sodium carbonate , caustic soda , barium hydroxide , etc.):

Overview reaction of the Suzuki coupling

The radical R 1 here represents an alkyl , alkenyl , alkynyl or aryl group and the radical R 2 represents an alkyl, alkenyl or aryl group. Bromide , chloride, iodide or triflates can be used as halides and alkyl, O-alkyl or hydroxy groups can be used as Y.

In the early days of the Suzuki coupling, tetrakis (triphenylphosphine) palladium (0), Pd (PPh 3 ) 4 , as a catalyst, only halogen aromatic compounds with high reactivity ( leaving group X rising from bromine via triflate to iodine ) could be converted. Weakly reactive chloroaromatics can only be made to react with special palladium-phosphine catalysts in recent years. It has also been possible to convert unactivated alkyl bromides at room temperature without β- hydride elimination . In addition, to simplify the work-up, the catalyst ligands have been modified many times in order to enable work in easily separable multi-phase systems (aqueous / organic, organic / perfluorinated). In 2018 the Suzuki reaction was successfully carried out as a heterogeneously catalyzed reaction.

In addition to the Suzuki coupling, there are other palladium-catalyzed coupling reactions; they only differ in the use of organometallic compounds . So when will Stille coupling instead of Bororganylen on organotin compounds resorted which are due to their high toxicity hard to handle.

mechanism

The reaction is closely related to the Heck reaction and accordingly has a similar reaction mechanism that is based on benzene boronic acid and 4-bromotoluene through the use of the catalyst tetrakis (triphenylphosphine) palladium (0), Pd (PPh 3 ) 4 , 1 and the base Sodium hydroxide , NaOH, is to be shown. This catalytic cycle begins with an oxidative addition of 4-bromotoluene to the palladium (0) catalyst, a palladium (II) species 3 being formed. In the next step, the resulting complex is prepared for transmetalation . The addition of NaOH creates an electrophilic organopalladium hydroxide 4 . Its Pd-O bond is even more polar than the Pd-Br bond, so that transmetalation is facilitated. 4 reacts with the benzene boronic acid sodium salt 6 to form a palladium (II) complex 7 in which the hydroxide ion has been replaced by a phenyl group. 6 is obtained by the reaction of benzene boronic acid 5 with sodium hydroxide and is added to the catalytic cycle during transmetalation.

Mechanism of the Suzuki coupling

The final step is reductive elimination , in which the catalyst is regenerated and a CC bond is formed between the benzene and the toluene ligand, so that 4-methylbiphenyl ( 8 ) is formed.

Applications

The Suzuki coupling is most important in the synthesis of natural products . Examples are the synthesis of the antibiotic vancomycin or the fungicide boscalid . Boron compounds are less toxic than alternative process compounds. The Suzuki coupling can also save enormous synthetic effort in the synthesis of liquid crystals, which mostly consist of biphenyl structures, since it is very selective.

A second major application of the Suzuki coupling is the synthesis of substance libraries as part of the search for active substances in pharmaceutical chemistry . The advantage here is the simple reaction procedure which can be applied to a large number of substrates in order to synthesize biphenyl compounds.

See also

literature

  • Christoph Elschenbroich : Organometallic chemistry . 5th edition, Teubner Verlag, Wiesbaden 2005, ISBN 3-519-53501-7 .
  • A. Suzuki, PJ Stang (Ed.), F. Diedrich (Ed.): Metal-Catalyzed Cross-coupling Reactions . Wiley-VCH, Weinheim 1998.

Web links

Individual evidence

  1. ↑ T. Laue, A. Plagens: Name and catchword reactions of organic chemistry . 5th edition. Teubner, Wiesbaden 2006, ISBN 3-8351-0091-2 , p. 320-324 .
  2. ↑ Norio Miyaura, Akira Suzuki : Stereoselective synthesis of arylated (E) -alkenes by the reaction of alk-1-enylboranes with aryl halides in the presence of palladium catalyst . In: J. Chem. Soc., Chem. Commun. tape 19 , 1979, pp. 866-867 , doi : 10.1039 / C39790000866 .
  3. ↑ Norio Miyaura, Kinji Yamada, Akira Suzuki: A new stereospecific cross-coupling by the palladium-catalyzed reaction of 1-alkenylboranes with 1-alkenyl or 1-alkynyl halides . In: Tetrahedron Letters . tape 20 , no. 36 , 1979, pp. 3437-3440 , doi : 10.1016 / S0040-4039 (01) 95429-2 .
  4. ↑ L. Kürti, B. Czakó: Strategic Applications of Named Reactions in Organic Synthesis - Background and Detailed Mechanisms . Elsevier Inc., 2005, ISBN 978-0-12-369483-6 , pp. 448-449 .
  5. ^ V. Wittmann: News from the Suzuki reaction . In: News from chemistry . tape 50 , 2002, pp. 1122-1127 .
  6. ^ Zerong Wang: Comprehensive Organic Name Reactions and Reagents . John Wiley & Sons, 2009, ISBN 978-0-471-70450-8 , pp. 2733-2738 .
  7. ↑ Zupeng Chen, Evgeniya Vorobyeva, Sharon Mitchell, Edvin Fako, Manuel A. Ortuño, Núria López, Sean M. Collins, Paul A. Midgley, Sylvia Richard, Gianvito Vilé & Javier Pérez-Ramírez: A heterogeneous single-atom palladium catalyst surpassing homogeneous systems for Suzuki coupling . In: Nature Nanotechnology . June 25, 2018, doi : 10.1038 / s41565-018-0167-2 .
  8. ^ V. Wittmann: News from the Suzuki reaction . In: News from chemistry . tape 50 , 2002, pp. 1122-1127 .
  9. ↑ R. Brückner: reaction mechanisms: organic reactions, stereochemistry, modern synthesis methods . 3. Edition. Elsevier, Munich 2004, ISBN 3-8274-1579-9 , pp. 701-702 .
  10. ^ Zerong Wang: Comprehensive Organic Name Reactions and Reagents . John Wiley & Sons, 2009, ISBN 978-0-471-70450-8 , pp. 2733-2738 .