Josiphos ligands

structure of [(josiphos)Ir(cod)]+. In the early 1990s, Antonio Togni began studying at the Ciba (now Novartis) Central Research Laboratories The same ligand proved useful in production of (S)-metolachlor, active ingredient in the most common herbicide in the United States. Synthesis requires enantioselective hydrogenation of an imine; after introduction of the catalyst, the reaction proceeds with 100% conversion, turnover number (TON) >7mil, and turnover frequency >0.5 ms−1. This process is the largest-scale application of enantioselective hydrogenation, producing over 10 kilotons/year of the desired product with 79% e.e. Josiphos ligands also serve in non-enantioselective reactions: a Pd-catalyzed reaction of aryl chlorides and aryl vinyl tosylates with TON of 20,000 or higher, catalytic carbonylation, or Grignard and Negishi couplings A variety of Josiphos ligands are commercially available under licence from Solvias. The (R-S) and its enantiomer provide higher yields and enantioselectivities than the diastereomer (R,R). The consensus for the naming is abbreviating the individual ligand as (R)-(S)-R2PF-PR'2. The substituent on the Cp is written in front of the F and the R on the chiral center after the F. ==Reactions using Josiphos ligands==

Some reactions that are accomplished using M-Josiphos complexes as catalyst are listed below. Other reactions where Josiphos ligands can be used are: hydrogenation of C=N, C=C and C=O bonds, catalyzed allylic substitution, hydrocarboxylation, Michael addition, allylic alkylation, Heck-type reactions, oxabicycle ring-opening, and allylamine isomerization. ; Hydroboration of styrene : :Conducted at -78 °C, the above reaction has e.e.'s up to 92% and TOF of 5-10 h−1. Hayashi's Rh-binap complex gives better yield. ; Hydroformylation of Styrene : :This reaction scheme yields of up to 78% ee of the (R) product, but low TON and TOF of 10-210 and 1-14h−1 (respectively). ;Reductive amination : :Above is the preparation of (S)-metolachlor. Good yields and a 100% conversion crucially require AcOH solvent. ;Asymmetric synthesis of chromanoylpyridine derivatives : :This reaction, for an intermediate in synthesis of an antihypertensive and anti-alopecic chromanoylpyridine derivative, exhibits high enantioselectivity, but low activity. ==Modified Josiphos ligands==

The ferrocene scaffold has proved to be versatile. Many variations of Josiphos ligands have been reported. One family is prepared from Ugi's amine. An important improvement on initial syntheses has been using N(CH3)2 as a leaving group over acetate, although an acetic acid solvent gives better yields. ==Further reading==