ChiralQuest Phosphine Ligands and Complexes

By: William Sommer and Daniel Weibel, Aldrich ChemFiles 2008, 8.2, 47.

Aldrich ChemFiles 2008, 8.2, 47.

Professor Xumu Zhang at Penn State has made remarkable advances by creating a toolbox of chiral phosphines which can be used on a variety of substrates, some of which have been historically resistant to facile hydrogenation. Furthermore, an additional benefit in some reductions is reduced catalyst loading, due to increased turnover numbers (TON).1

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(S)-C3‑TunePhos

C3‑TunePhos, a member of the atropisomeric aryl bisphosphine ligand family with tunable dihedral angles, provides comparable or superior enantioselectivities and catalytic abilities to BINAP in Ru-catalyzed asymmetric hydrogenation of β-keto esters (Scheme 1),2 cyclic β-(acylamino) acrylates (Scheme 2),3 and α-phthalimide ketones (Scheme 3).4

Ru-catalyzed asymmetric hydrogenation of β-keto esters

Scheme 1

cyclic β-(acylamino) acrylates

Scheme 2

α-phthalimide ketones

Scheme 3

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(1S,1S',2R,2R')-TangPhos

A highly electron-donating, low molecular weight, and rigid P-chiral bisphospholane ligand, TangPhos proved to be incredibly efficient in the rhodium-catalyzed hydrogenation of a variety of functionalized olefins such as α-dehydroamino acids,5 arylenamides,5 β-(acylamino)acrylates,6 itaconic acids,7 and N-tosylimines8 (Scheme 4). 

α-dehydroamino acids, arylenamides, β-(acylamino)acrylates, itaconic acids, and N-tosylimines

Scheme 4

This P-chiral phosphorus ligand represents a superior ligand for asymmetric catalysis including hydrogenation because of its ability to force the chiral environment to encompass the substrate in close proximity to the reactive metal center. TangPhos exhibits substantial conformational rigidity allowing for high enantioselectivities in the hydrogenation of a wide variety of densely functionalized prochiral olefins, with some reaction examples approaching 100% ee.

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(S)-BINAPINE

BINAPINE, a highly electron-donating rigid ligand, demonstrates excellent enantioselectivity and reactivity, with TON up to 10,000 for the asymmetric hydrogenation of Z-β-aryl(β-acylamino) acrylates (Scheme 5).9 Interestingly, BINAPINE is a rare example of a bisbinaphthophosphepine ligand with P-chiral phosphine atoms. High enantioselectivities have been obtained with substrates that contain diverse substituents ranging from electron-rich and electron-poor aryl groups to heteroaryl components. This catalyst system illustrates the incredible effects of rigidity on the stereocontrol in the hydrogenation reaction.

asymmetric hydrogenation of Z-β-aryl(β-acylamino) acrylates

Scheme 5

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(R)-BINAPHANE

BINAPHANE incorporates a bisphosphinite backbone that displays restricted orientation of the aromatic groups proximate to the phosphines. Zhang and co-workers can tune BINAPHANE by modifying the groups on the aromatic and/or the phosphine, thus creating a general catalytic system useful for obtaining high enantioselectivities in the asymmetric hydrogenation reaction. This ligand demonstrated excellent enantioselectivity (up to >99% ee) for hydrogenation of E/Z-isomeric mixtures of β-substituted arylenamides (Scheme 6).10

hydrogenation of E/Z-isomeric mixtures of β-substituted arylenamides

Scheme 6

BINAPHANE also proved to be a very good ligand for the palladium catalyzed enantioselective cyclization of silyloxy-1,6‑enynes.11 This novel reaction allows for the synthesis of precursors for naturally occurring molecules. Using mild conditions and 5 mol% of catalyst, Toste et al. reported good yields and good selectivities (Scheme 7).

Using mild conditions and 5 mol% of catalyst, Toste et al. reported good yields and good selectivities

Scheme 7

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(1R,1'R,2S,2'S)-DuanPhos

DuanPhos is more rigid than the related TangPhos ligand, due to the fused phenyl rings on the phospholane architecture. This self-imposed conformational stability improves the enantioselectivity in the hydrogenations of a diverse array of functionalized olefins. Furthermore, Zhang and co-workers have successfully synthesized both enantiomers of this electron-rich ligand through a trivial resolution process. Even highly electron-rich prochiral olefins are readily hydrogenated with exceptional stereocontrol by this productive Rh-catalyst system (Scheme 8).

Even highly electron-rich prochiral olefins are readily hydrogenated with exceptional stereocontrol by this productive Rh-catalyst system

Scheme 8

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Materials

     

References

  1. Zhang, W. et al. Acc. Chem. Res. 2007 40, 1278.
  2. Zhang, Z. et al. J. Org. Chem. 2000, 65, 6223.
  3. Tang, W. et al. J. Am. Chem. Soc. 2003, 125, 9570.
  4. Lei, A. et al. J. Am. Chem. Soc. 2004, 126, 1626.
  5. Tang, W.; Zhang, X. Angew. Chem., Int. Ed. Engl. 2002, 41, 1612.
  6. Tang, W.; Zhang, X. Org. Lett. 2002, 4, 4159.
  7. Tang, W. et al. Org. Lett. 2003, 5, 205.
  8. Yang, Q. et al. Angew. Chem., Int. Ed. 2006, 45, 3832.
  9. Tang, W. et al. Angew. Chem., Int. Ed. Engl. 2003, 42, 3509.
  10. Xiao, D. et al. Org. Lett. 1999, 1, 1679.
  11. Corkey, B. K.; Toste, F. D. J. Am. Chem. Soc. 2007, 129, 2764.

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