Josiphos

general structure of Josiphos

Xyliphos

The Josiphos ligands are a group of bidentate diphosphine ligands with axial chirality that can be used in transition-metal-catalyzed reactions with particular enantioselectivity . It was first used by Antonio Togni in the 1990s . ( R , S ) -JosiPhos or [( R ) -1 - {(S _p ) -2-diphenylphosphanylferrocenyl} ethyl-dicyclohexylphosphane] was used for the first time on an industrial scale in the synthesis of ( S ) -metolachlor for the asymmetric hydrogenation of the preformed imine.

The turnover number is more than 2,000,000 h ^-1 . The enantioselective hydrogenation for the production of ( S ) -metolachlor with 79% enantiomeric excess ( ee ) is the largest application of such.

synthesis

Josiphos can be made in several steps from an ( R ) - Ugi -Amin:

Reactions

Hydroboration of styrene

The hydroboration of styrene .

Hydroformylation of styrene

The hydroformylation of styrene.

Reductive amination

The reductive amination of S-metolachlor only leads to 100% conversion in acetic acid .

Hydrogenation of an exocyclic methylimine

The hydrogenation of an exocyclic methylimine is the most important step in the synthesis of the HIV integrase inhibitor indinavir .

Individual evidence

1. ↑ Entry on phosphine ligands. In: Römpp Online . Georg Thieme Verlag, accessed on March 5, 2014.
2. ↑ Antonio Togni, Claude Breutel, Anita Schnyder, Felix Spindler, Heidi Landert, Amina Tijani: A Novel Easily Accessible Chiral ferrocenyldiphosphines for Highly Enantioselective Hydrogenation, allylic alkylation, and hydroboration Reactions . In: Journal of the American Chemical Society . tape 116 , no. 9 May 1994, pp. 4062-4066 , doi : 10.1021 / ja00088a047 .
3. ↑ Hans-Ulrich Blaser: Industrial asymmetric hydrogenation “Made in Switzerland” , Nachrichten aus der Chemie 58 ( 2010 ) 864–867.
4. ↑ Hans-Ulrich Blaser, Walter Brieden, Benoit Pugin, Felix Spindler, Martin Studer, Antonio Togni: Solvias Josiphos ligands: from discovery to technical applications . In: Topics in Catalysis . tape 19 , no. 1 , March 2002, p. 3-16 , doi : 10.1023 / A: 1013832630565 ( PDF ).