Suzuki reaction

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

Overview reaction

Here are Organoborane compounds (eg boronic acid) with aromatic halogen compounds or halogen -substituted vinyl compounds under catalytic use of palladium ( 0) phosphine complexes ( such as Pd (PPh3 ) 4, Pd ( PPh3) 3, etc.) and in presence of a base (such as sodium carbonate, sodium hydroxide, barium hydroxide, etc. ) is reacted:

The radical R 1 stands for an alkyl, alkenyl, alkynyl or aryl group, and the radical R 2 is alkyl, alkenyl or aryl group. Halides as bromide, chloride, iodide, or triflate can be used, and as the Y - alkyl, O- alkyl or hydroxyl group.

In the early days of the Suzuki coupling could with the help of tetrakis (triphenylphosphine ) palladium ( 0), Pd ( PPh3) 4 as catalyst only haloaromatics with high reactivity ( leaving group X in ascending order of bromine via triflate after iodine) are implemented. Weakly reactive chlorinated aromatic compounds can be brought only in recent years with special palladium -phosphine catalysts for the reaction. Likewise, it is able to convert inactive bromides at room temperature, without there being a β -hydride elimination. To simplify the workup, the catalyst ligands were also frequently modified to work in easily separable multi-phase systems ( aqueous / organic, organic / perfluorinated ) allow.

In addition to the Suzuki coupling, there are other palladium-catalyzed coupling reactions, they differ only in the use of organylmetal. So is being introduced in the Stille coupling instead of Bororganylen on organotin compounds due to their high toxicity difficult to handle.

Mechanism

The reaction is closely related to the Heck reaction and has, accordingly, a similar reaction mechanism based on 4 - tolueneboronic acid and 4- bromotoluene by the use of the catalyst tetrakis (triphenylphosphine ) palladium ( 0), Pd (PPh3) 4, 1 and base is sodium hydroxide, NaOH, will be shown. This catalytic cycle begins with an oxidative addition of 4- Bromtoluols to the palladium ( 0) catalyst, a palladium (II ) species 3 is formed. In the next step, the resulting complex is prepared for transmetalation. By the addition of NaOH electrophilic organopalladium hydroxide produced 4 His Pd -O bond in comparison to Pd - Br bond still polar, so that a transmetalation is facilitated. This reacts with the 4- 4 Toluolboronsäuresalz 6 to a palladium ( II) complex, 7, in which the hydroxide ion has been replaced by a phenyl group. The 4- Toluolboronsäuresalz is obtained by the reaction of 4 - tolueneboronic acid 5 with NaOH and will be added in the transmetalation to the catalytic cycle.

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

Applications

The Suzuki coupling has its greatest importance in the synthesis of natural products. As an example, led the synthesis of the antibiotic vancomycin or the fungicide boscalid. Boron compounds are less toxic than compounds of alternative methods. Also in the synthesis of liquid crystals, which usually consist of Biphenylstrukturen, the Suzuki coupling can save huge synthetic effort since it is very selective.

A second major application of the Suzuki reaction is the synthesis of compound libraries in the context of drug discovery in the pharmaceutical chemistry. The advantage here is the simple reaction which is applicable to a variety of substrates to synthesize biphenyl compounds.