(1R,2S,4R,5S)-2,5-Dimethyl-7-phenyl-7-phosphabicyclo[2.2.1]heptane

[189210-88-6]  · C14H19P  · (MW 217.97)

(chiral, nonracemic phosphine ligand for asymmetric transition metal-catalyzed reactions)

Solubility: soluble in common organic solvents (i.e., benzene, toluene, CH2Cl2).

Analysis of Reagent Purity: 1H-NMR.

Preparative Methods prepared in four steps starting from p-xylene.1 Birch reduction of p-xylene followed by asymmetic hydroboration-oxidation provides an optically pure diol. The diol is subsequently converted to the chiral phosphine by formation of the corresponding dimesylate and nucleophilic addition of Li2PPh.

Purification: purification was accomplished by chromatography of the corresponding borane complex. Decomplexation using HBF4·O(C2H5)2 afforded the pure phosphine.

Handling, Storage, and Precautions: sensitive to atmospheric oxidation. Should be stored and handled under an inert atmosphere.

Introduction

Chiral phosphines have played a crucial role in the development of catalytic asymmetric reactions. In particular, the coordination of a resolved, chiral phosphine to a transition metal center has been exploited to produce highly enantioselective catalysts for a variety of catalytic processes.2 Although there are many chiral monodentate and bidentate chiral phosphines available, (1R,2S,4R,5S)-2,5-dimethyl-7-phenyl-7-phosphabicyclo[2.2.1]heptane provides the advantage of a rigidified ring system that reduces the conformational flexibility present in many other phosphine ligands.

Transition Metal-Catalyzed Reactions

Application of this ligand to the Pd-catalyzed allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate provides an alkylated product in > 99.5% enantiomeric excess (1).1 The enantioselectivity of the process is dependent on the ligand:Pd ratio, the palladium precursor, and the nature of the nucleophile. Optimal conditions employed Pd(dba)3 as the Pd precursor and 2 equiv of phosphine ligand, suggesting that two phosphines coordinate to the active Pd catalyst. Replacement of 1,3-diphenyl-2-propenyl acetate with pent-3-en-2-yl acetate decreased the ee to 34% due to the reduced sterics of methyl relative to phenyl substituents. It is noteworthy that in contrast to this ligand, most monodentate ligands provide low enantioselectivity in this reaction.3

Phosphine-Catalyzed Reactions

This ligand has also been shown to be effective in the direct organocatalysis of asymmetric processes.4 For example, the phosphine-catalyzed [3 + 2] annulation reaction of ethyl 2,3-butadienoate and isobutyl acrylate produces two cyclopentene regioisomers (1 and 2) (2).5 Isomer 1 generally predominates and enantiomeric excesses ranging from 86-93% are displayed. Similarly, the ligand induces enantiomeric excesses between 43-68% in the phoshine-catalyzed g-addition reaction of 2-butynoates (3).6


1. Chen, Z.; Jiang, Q.; Zhu, G.; Xiao, D.; Cao, P.; Guo, C.; Zhang, X., J. Org. Chem. 1997, 62, 4521.
2. (a) Lee, S.; Hartwig, J. F., J. Org. Chem. 2001, 66, 3402. (b) Zhang, X., Enantiomer 1999, 4, 541. (c) Noyori, R., Asymmetric Catalysis in Organic Synthesis; Wiley: New York, 1994.
3. (a) Fiaud, J. C.; Legros, J. Y., Tetrahedron Lett. 1991, 32, 5089. (b) Fiaud, J. C.; Aribi-Zouioueche, L., J. Organomet. Chem. 1985, 295, 383.
4. Dalko, P. I.; Moisan, L., Angew. Chem. Int. Ed. 2001, 40, 3726.
5. Zhu, G.; Chen, Z.; Jiang, Q.; Xiao, D.; Cao, P.; Zhang, X., J. Am. Chem. Soc. 1997, 119, 3836.
6. Chen, Z.; Zhu, G.; Jiang, Q.; Xiao, D.; Cao, P.; Zhang, X., J. Org. Chem. 1998, 63, 5631.

Jon R. Parquette

The Ohio State University, Columbus, OH, USA



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