Broken Promises? On the Continued Challenges Faced in Catalytic Hydrophosphination

Abstract

In this Perspective, we discuss what we perceive to be the continued challenges faced in catalytic hydrophosphination chemistry. Currently the literature is dominated by catalysts, many of which are highly effective, that generate the same phosphorus architectures, e.g., anti-Markovnikov products from the reaction of activated alkenes and alkynes with diarylphosphines. We highlight the state of the art in stereoselective hydrophosphination and the scope and limitations of chemoselective hydrophosphination with primary phosphines and PH 3 . We also highlight the progress in the chemistry of the heavier homologues. In general, we have tried to emphasize what is missing from our hydrophosphination armament, with the aim of guiding future research targets.

Divergent Mechanistic Pathways for Copper(I) Hydrophosphination Catalysis: Understanding that Allows for Diastereoselective Hydrophosphination of a Tri-substituted Styrene

“…Additional primary phosphines and sterically hindered alkenes were also demonstrated as viable substrates, in recognition of the limitations of scope in hydrophosphination catalysis. 7 Throughout this study multiple light sources are demonstrated to be effective for this system and illustrate that commercially available bulbs are effective rather than specialty photoreactors, increasing the utility of this catalyst in exploratory reactions.…”

“…A more thorough understanding of mechanism would inform a transition to a prefabricated copper(I) catalysts that may promote additional reactivity to address specific challenges in hydrophosphination catalysis. 7,12 Herein, we report direct evidence of a catalytically active copper(I)-phosphido intermediate and that divergent mechanistic steps occur in the catalysis depending on the alkene substrate. Data in support of these mechanisms include a Hammett analysis, modified catalytic reactions with radical traps, a comparison of copper precursors, catalytic reactions of proxy intermediates, isotopic labeling experiments, a zwitterionic trapping experiment, and stoichiometric model reactions.…”

“…Known catalysts also have limitations in reactivity, often stymied by unactivated or highly substituted substrates, especially in intermolecular reactions. 7,12 As reported in 2020, commercially available and benchstable Cu(acac)2 (1) addresses many challenges in exploratory hydrophosphination catalysis. 37 Compound 1 is highly active, effective for a range of activated and unactivated alkenes and alkyne substrates, tolerates primary and secondary phosphines, does not require an ancillary ligand, and operates at ambient temperature under photolysis in either the UV or visible, though thermal conditions also provide reactivity.…”

“…1,2,3 Metalcatalyzed hydrophosphination, the addition of a P-H bond across an unsaturated substrate, is one of the most promising, and atom-economical, P-C bond forming reactions. [4][5][6][7][8][9][10][11][12][13][14] Progress has been made in expanding the available catalysts, scope, and selectivity of hydrophosphination in recent years. However, limitations remain that hamper the synthetic utility of hydrophosphination.…”

“…However, limitations remain that hamper the synthetic utility of hydrophosphination. 7,12 Among the most notable limitations with known catalysts is that they often require special preparation and/or complex ancillary ligands and that most precatalysts are not air-and water-stable (i.e., not convenient). Known catalysts also have limitations in reactivity, often stymied by unactivated or highly substituted substrates, especially in intermolecular reactions.…”