The Josiphos ligand family offers a number of chiral catalysts with steric and electronic modularity

The Josiphos ligand family offers a number of chiral catalysts with steric and electronic modularity

Josiphos Ligand Kits for a Variety of Asymmetric Applications

The Josiphos ligand was first reported in 19941 by Dr. Antonio Togni and coworkers of the Ciba-Geigy catalysis group (currently Solvias). The ligand is characterized by a ferrocene core containing two phosphine substituents on one of the cyclopentadienyl rings, with the other ring remaining unsubstituted.2  The two phosphine functionalities are installed in separate steps, using electrophilic and nucleophilic phosphine sources respectively. This synthetic strategy allows for a wide variety of phosphorus substituents to be placed in either position, granting this ligand class substantial flexibility in tuning both steric and electronic parameters.3 As chiral compounds, Josiphos-type ligands find frequent application in asymmetric catalytic transformations.

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In Togni and coworkers’ seminal report, the Josiphos ligand was applied in Rh-catalyzed asymmetric hydrogenation, alkylation, and hydroboration reactions, resulting in very high yields and enantioselectivities..1 In addition the di-tert-butyl variant of the ligand was found  especially effective in the hydrogenation of a sterically crowded biotin precursor, the synthesis of which was applied commercially.4

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Today, ligands in the Josiphos family still have widespread use in the development of novel asymmetric transformations.  In general, the ligand system has been popularized for hydrogenation5 and other H-X addition reactions such as hydroboration6, hydroalkylation7, and hydrosilylation8  The ligand  has also been applied to C–C9 and C–N10 bond formation reactions.

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The high functional group tolerance, ease of synthesis, and effectiveness in asymmetric catalysis, combined with wide availability through suppliers, such as Strem, has led the Josiphos ligand class to be described as a “privileged” ligand set.2 Josiphos and its derivatives have been used in a staggering amount of asymmetric transformations, an impressive variety of metal partners, and thus provide an excellent starting point for chiral ligand screening.

Strem provides several derivatives of the Josiphos ligand differentiated by a range of functionalities off both phosphine substituents. Nickel complexes of some of these ligands are also available.

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References:

  1. J. Am. Chem. Soc. 1994116, 4062–4066.
  2. Topics in Catalysis 2002, Vol. 19, No. 1, 3.
  3. Chimia 1996, 50, 86-93.
  4. Chem. Abstr. 1995, 122, 81369q.
  5. Angew. Chem. Int. Ed. 2000, 39, 1992.
  6. J. Am. Chem. Soc2004126, 9200–9201.
  7. Org. Lett. 20079, 5123–5126.
  8. Org. Lett. 20068, 1963–1966.
  9. J. Am. Chem. Soc. 2012134, 7305–7308.
  10. J. Am. Chem. Soc. 2006128, 10028–10029.

 

Products mentioned in this blog:

96-3650: Solvias Josiphos Ligand Kit
26-1150:R)-(-)-1-{(S)-2-[Bis(3,5-dimethyl-4-methoxyphenyl)phosphino]ferrocenyl}
ethyldicyclohexylphosphine, min. 97%

26-0960: (R)-(-)-1-{(S)-2-[Bis(3,5-di-trifluoromethylphenyl)phosphino]ferrocenyl}
ethyldicyclohexylphosphine, min. 97%

26-0965: (R)-(-)-1-{(S)-2-[Bis(3,5-di-trifluoromethylphenyl)phosphino]ferrocenyl}
ethyldi-3,5-xylylphosphine, min. 97%

26-0650: (R)-(-)-1-{(S)-2-[Bis(4-trifluoromethylphenyl)phosphino]ferrocenyl}ethyl-
di-t-butylphosphine, min. 97%

26-0975: (R)-(-)-1-[(S)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-
t-butylphosphine, min. 97%

26-1000: (R)-(-)-1-[(S)-2-(Dicyclohexylphosphino)ferrocenyl]
ethyldicyclohexylphosphine, min. 97%

26-1170: (S)-(+)-1-[(R)-2-(Di-2-furylphosphino)ferrocenyl]ethyldi-3,
5-xylylphosphine, min. 97%

26-1200: (Diphenylphosphino)ferrocenyl]ethyldi-t-butylphosphine, min. 97%
26-1210: (Diphenylphosphino)ferrocenyl]ethyldicyclohexylphosphine ethanol adduct, min. 97% (R)-(S)-JOSIPHOS
26-1255: (Diphenylphosphino)ferrocenyl]ethyldi-3,5-xylylphosphine, min. 97%

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