Tsuji–Trost reaction

The Tsuji -Trost reaction or Trost allylation, also often called simply allylic alkylation reaction is a name in the field of organic chemistry. It involves a palladium-catalyzed alkylation of allyl compounds. It serves mostly the introduction of alcohols, amines, or derivatives of phenol. The reactants connections are required, which possess a leaving group in the allylic position. It was named after Jiro Tsuji and Barry Trost.

Reaction mechanism

First, the alkene is used with the palladium catalyst has a π - complex. In an oxidative addition of a η3 - π - allyl complex is formed with inversion and cleavage of the leaving group. This step is also referred to as ionization. Depending on the hardness of the nucleophile then one of two other reaction pathways takes place:

In soft nucleophiles, which are formed by conjugate acids with a pKa of less than 25, the nucleophile adds usually right on the allyl. The nucleophilic addition will again be held under inversion. In the subsequent ligand dissociation, the alkylated allyl is released and the catalyst regressed.

Reactants and catalysts

The palladium catalyst is required in the oxidation state 0 is generated in situ. As ligands, phosphine ligands, such as the Trost ligand or triphenylphosphine are.

As allylic starting materials allyls all come with electron-deficient, so good leaving groups such as acetates or bromides in question. With the use of carbonates as leaving group may also be dispensed with the use of an additional base (build in base). As a nucleophile, for example, activated methylenes, enolates, amines or phenols may be used.

The introduction of hydroxyl groups, water may be used as nucleophile, ether can be obtained with the use of alcohols. For the introduction of amines to Phthalimidsalze are. From the product obtained the desired amine can be liberated in a further reaction step.

Asymmetric reaction

For asymmetric Tsuji -Trost reaction, also called Trostsche asymmetric allylic alkylation, metal complexes are used with enantiomerically pure chiral ligands as catalysts. In the reaction occurs at the stereogenic center for inversion.

The reaction was used inter alia as a key step in the enantioselective total synthesis of galantamine and morphine.

Modification of the asymmetric reaction

The complementary reaction was developed by Günter Helmchen. By using iridium catalysts with chiral phosphoramidite ligands can be synthesized from achiral internal alkenes chiral terminal alkenes. The nucleophile attacks in this case as opposed to Trost allylation not at the position, which has borne the leaving group, which is due to the different electronic properties of palladium and iridium. Suitable leaving groups to carboxylic acid can also be used, but mostly organic carbonates are used. Similar reactions can be carried out with molybdenum and iridium catalysts. These reactions also provide access to branched regioisomers in contrast to the Tsuji-Trost reaction.