Article pubs.acs.org/Organometallics
Improved Synthetic Route to Heteroleptic Alkylphosphine Oxides Alexander J. Kendall, Daniel T. Seidenkranz, and David R. Tyler* University of Oregon, Department of Chemistry and Biochemistry, 1253 University of Oregon, Eugene, Oregon 97403, United States S Supporting Information *
ABSTRACT: A new method for the synthesis of heteroleptic alkylphosphine oxides (R2R1PO, where R ≠ R1) from secondary phosphine oxides (or SPOs, R2HPO) is presented. These reactions were fast at room temperature, sterically selective, high yielding, and >95% pure after an aqueous wash. Deprotonation of an SPO generates a phosphinite anion ([R2P− O]−) that was found to be highly selective for nucleophilic P−C bond formation (as opposed to O−C bond formation) with alkyl halides. Surprisingly, most strong organometallic bases failed to deprotonate SPOs to their respective phosphinite anions (pKas for most SPOs are Br > Cl). In agreement with this assessment, no reactivity was observed with D
DOI: 10.1021/acs.organomet.7b00304 Organometallics XXXX, XXX, XXX−XXX
Article
Organometallics tert-butyl iodide (Table 2, entry 12), indicating that an SN1 mechanism is not operating under the reaction conditions.
Patrick F. Martino, and Chase A. Salazar are acknowledged for their contributions to this project.
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CONCLUSIONS In summary, the result of this methodology is a simple benchtop synthesis of tertiary phosphine oxides that is exceptionally amenable to a diverse range of alkyl halide precursors. The extraordinary selectivity, clean reactivity, and ease of isolation cannot be overstated for this method, especially in comparison to traditional phosphine syntheses for similar compounds. The synthetic utility of this method was demonstrated with the synthesis of dimethylphosphine oxide derivatives and unsymmetrical bis(phosphine oxides); however, the simplicity of the synthesis makes this synthetic method applicable to many more complicated systems other than those described here. Examples where this synthetic method might be applied include the preparation of tri- or tetradentate phosphines, chiral SPOs, and chiral electrophiles. The facile selectivity of phosphinite anions to form tertiary phosphine oxides cleanly could be easily adapted using high-throughput screening methods to quickly generate many new unsymmetrical mono- or polydentate phosphines. We are currently investigating the mechanism of the phosphinite attack on electrophiles in more detail as well as developing a library of new unsymmetrical phosphines using this method.
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EXPERIMENTAL SECTION
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ASSOCIATED CONTENT
General Synthesis of Tertiary Phosphine Oxide. Sodium bis(trimethylsilyl)amide (1.0 equiv per dialkylphosphine oxide, ca. 1.9 M in THF) was added dropwise at room temperature to a solution of dialkylphosphine oxide (1.0 equiv per electrophile, 0.2 M in THF), and the mixture was stirred for 15 min. The solution became turbid. To a solution of alkyl halide (1.0 equiv, 0.2 M in THF) was added the turbid phosphinite anion solution dropwise, and this mixture was stirred for 2−16 h. An equivalent volume of H2O was added to the crude reaction mixture, which was then extracted five times with equal volumes of dichloromethane. The combined organics were dried over Na2SO4 and filtered, and the solvent was removed under vacuum to yield the tertiary phosphine oxide. Adventitious salts were removed using a chloroform/hexane wash, and residual water was removed using toluene as an azeotrope. S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.organomet.7b00304. Detailed experimental procedures, syntheses of SPOs, characterization data, and additional spectra (PDF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail for D.R.T.:
[email protected]. ORCID
David R. Tyler: 0000-0002-5032-7533 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We greatly acknowledge the donors of the American Chemical Society Petroleum Research Fund, as well as NSF CHE1503550 and NSF GRFP DGE-0829517. Justin T. Barry, E
DOI: 10.1021/acs.organomet.7b00304 Organometallics XXXX, XXX, XXX−XXX
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DOI: 10.1021/acs.organomet.7b00304 Organometallics XXXX, XXX, XXX−XXX
