CsOH-promoted direct mono-p-alkylation of primary phosphines: A mild and highly chemoselective synthetic route toward secondary and disecondary phosphines

ORGN 149

Ralph N. Salvatore, ralph.salvatore@umb.edu, Matthew T. Honaker, Benjamin J. Sandefur, and Bo Hargett. Department of Chemistry, University of Massachusetts-Boston, 100 Morrissey Blvd., Boston, MA 02125
Secondary phosphines are a preeminent class of organic compounds that are widely employed as catalysts, useful reagents in asymmetric processes, and as robust ligands for transition metal complexes. Despite burgeoning interest in these compounds, general procedures for the synthesis of these compounds are often difficult usually requiring tedious steps, generally resulting in poor product yields, and are often concomitantly accompanied by oxidation side products. These facts prompted us to develop an improved method which circumvents these chronic problems. Previously, we reported a general synthetic method for the synthesis of tertiary and ditertiary phosphines, respectively. Based on these successful results, we report here a mild and efficient method for the synthesis of secondary phosphines. In the presence of CsOH, 4 activated molecular sieves, DMF, primary phosphines smoothly coupled with alkyl halides at room temperature in moderate to high yields. Various structurally diverse primary phosphines and alkyl halides were examined and the results demonstrated this methodology was highly chemoselective in favor of monoalkylation. Moreover, CsOH was determined not only to promote the monoalkylation of primary phosphines, but also suppressed overalkylations of the produced secondary phosphines. This pivotal finding, therefore, may eliminate the commonly utilized phosphine-borane protecting group. Moreover, we also envisioned bis-secondary phosphines would serve as crucial building blocks in the preparation of phosphine macrocycles. Thus, an improved synthesis of disecondary phosphines has also been achieved using the aforementioned conditions. In a similar fashion, PhPH2, CsOH, 4 molecular sieves, DMF and dialkyl halides reacted expeditiously to produce various disecondary phosphines exclusively demonstrating the efficacy of this general protocol. Efforts toward novel phosphine macrocycle synthesis will be presented.