Chiral phosphine ligand libraries based on the Bull–James three-component supramolecular assembly

ABSTRACT

An approach to the synthesis of libraries of chiral phosphine ligands is described, using condensations of 2-formylarylboronic acids, diols or related compounds, and aminophosphines. The three-component nature of this condensation, along with the ready availability of the building blocks, enables the rapid generation of diverse structures. From a library of iminoboronate-derived phosphines, three ligands that gave 90% ee or greater in a benchmark palladium-catalyzed allylic substitution reaction were identified. Significant variation of selectivity as a function of the structure of each component was observed. ¹¹B NMR spectroscopy was used to evaluate the existence of B–N interactions in the free ligands as well as their Pd-derived complexes. A bidentate P,N-coordination mode was inferred for ligands that gave high enantioselectivity in the allylic substitution reaction.

Abbreviation: BINOL: 1,1'-bi-2-naphthol; BSA: N,O-bis(trimethylsilyl)acetamide; DIOP: (2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane; HPLC: high-performance liquid chromatography; NMR: nuclear magnetic resonance; THF: tetrahydrofuran

KEYWORDS:

• Boronic acids
• combinatorial chemistry
• enantioselective catalysis
• phosphine ligands

Acknowledgments

Dr. Alan J. Lough (University of Toronto) is gratefully acknowledged for carrying out the single crystal X-ray diffraction experiment and solving the structure of 14.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplementary material

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Additional information

Funding

Acknowledgment is made to the donors of the American Chemical Society Petroleum Research Fund for partial support of this research. Funding was also provided by NSERC (Discovery Grants and Canada Research Chairs Programs) and the Canada Foundation for Innovation (Project nos. 17545 and 19119).