A novel and practical approach to monosubstituted phosphinic acid (alkylphosphonous acid) derivatives from hypophosphite salts or esters is described. Phosphorus-centered radical formation is initiated with Et(3)B/O(2), and the reaction is conveniently conducted at room temperature in an open flask. In contrast to previously reported conditions for the radical reaction of hypophosphorous acid and sodium hypophosphite (peroxide initiators, acid catalysis, heat), the method proceeds under neutral conditions and therefore tolerates a wide range of functional groups. Previously inaccessible phosphinic acids can be prepared in a single step from cheap starting materials. Excellent selectivity is observed for monoaddition, and symmetrical dialkyl phosphinates do not form in significant amounts. Monosubstituted phosphinic acids are usually obtained in better than 90% purity by a simple extractive workup; however, isolated yields are diminished if the substituent is polar. Because radicals derived from hypophosphites are electrophilic, the reaction is limited to the use of electron-rich olefins. The reaction conditions can also be employed in the room temperature radical reduction of alkyl halides and provide an exceptionally mild and environmentally friendly alternative to the use of tributyltin hydride. The remarkable mild nature of the reaction conditions allows for the radical reaction of sensitive alkyl hypophosphites to occur, in which case, a catalytic amount of Et(3)B suffices to deliver alkyl phosphinate esters in reasonable yield.

Various palladium catalysts promote the addition of hypophosphorous derivatives ROP(O)H(2) to alkenes and alkynes in good yields and under mild conditions. Particularly, Cl(2)Pd(PPh(3))(2)/2 MeLi, and Pd(2)dba(3)/xantphos allow for phosphorus-carbon bond formation instead of transfer hydrogenation. Commercial aqueous solutions of hypophosphorous acid can be employed successfully at ambient temperature. With styrene and terminal alkynes, the regioselectivity (linear versus branched products) can be controlled to some extent with the catalytic system employed. The methodology considerably extends upon previous routes for the preparation of H-phosphinic acids and other organophosphorus compounds.

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[reaction: see text] A reusable polymer-supported hydrophosphinylation catalyst is described for the preparation of H-phosphinic acids. The polystyrene-based ligand is prepared in one step from commercially available compounds. The polymeric catalyst generally gives good yields for a variety of substrates and is water- and air-tolerant, although the scope of alkenes and alkynes which can be employed is somewhat narrower than with our original xantphos/Pd(2)dba(3) catalyst.

The room temperature radical addition of sodium hypophosphite to terminal alkynes produces the previously unknown 1-alkyl-1,1-bis-H-phosphinates in moderate yield. The reaction is initiated by R 3 B and air and proceeds under mild conditions in an open container. The bis-sodium salts precipitate spontaneously from the reaction mixtures, thus providing a simple purification procedure and the opportunity for multigram synthesis. The 1,1-bis-H-phosphinate products are novel precursors of the biologically important 1,1-bisphosphonates. We recently reported a novel and general approach towards H-phosphinate derivatives, based on the room temperature radical addition of hypophosphorous compounds to alkenes (Equation 1). 1 Since then, we have studied the reactions of alkynes with sodium hypophosphite under similar conditions and discovered the formation of a new class of compounds: 1-alkyl-1,1-bis-H-phosphinates. 2 We now report the results of this study. The thermal, peroxide-initiated radical reaction of hypophosphorous acid with alkynes has been studied by Nifant'ev and coworkers. 3 Several products were identified depending on the conditions employed (Equation 2). A mixture of trans-and cis-alkenyl-H-phosphinic acids were produced as the major components, along with minor amounts of disubstituted 1,2-bis-H-phosphinic acids. Nifant'ev had also investigated alkenes under the same conditions. 4 Previously, we found that our milder reaction conditions considerably expanded the scope of H-phosphinates which could be produced both in terms of functional group tolerance on the alkene, and hypophosphorous reagent employed. 1 These differences prompted the study of alkynes as substrates under our R 3 B/air and room temperature conditions. As a model study, the reaction of sodium hypophosphite with 1-hexyne was investigated using Et 3 B/air to promote radical formation. The results are summarized in Table 1. Methanol was initially selected as solvent, since sodium hypophosphite has no significant solubility in other common organic solvents at room temperature. Interestingly, the novel 1,1-bis-H-phosphinate was always obtained as the major product (the remaining filtrate contains some unreacted