Triethylborane-Initiated Room Temperature Radical Addition of Hypophosphites to Olefins:  Synthesis of Monosubstituted Phosphinic Acids and Esters

Abstract

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.

Tin-Free Radical Reactions Mediated by Organoboron Compounds

“…In this last case, basic or acidic treatment of the main syn β-siloxygermane furnishes the corresponding E-or Z-alkene, respectively [24]. The addition of hypophosphites to alkenes under Et 3 B initiation is also reported [27]. Piettre described recently the addition of diethylthiophosphite to alkenes leading to the formation of thiophosphonates (Scheme 9, Eq.…”

Recent advances in phosphorus–carbon bond formation: synthesis of H-phosphinic acid derivatives from hypophosphorous compounds

“…In spite of the modern improvements in the reaction conditions [4] (AIBN initiator, refluxing EtOH), the medium is always strongly acidic and therefore not compatible with functionalized molecules. To solve this significant limitation, we have developed a room-temperature radical hydrophosphinylation reaction, which proceeds under very mild conditions and has a broad scope [27]. Our process is based on the initiation of the radical reaction through trialkylboranes autooxidation.…”

“…Hypophosphorous acid, its salts (including AHP and NaH 2 PO 2 ), and even alkyl phosphinates can be added to alkenes at room temperature [27]. With alkyl phosphinates, a substoichiometric amount of R 3 B is sufficient to achieve good yields of addition, but the other starting materials are best used with 0.5-1.0 equivalent of R 3 B.…”

“…With alkyl phosphinates, a substoichiometric amount of R 3 B is sufficient to achieve good yields of addition, but the other starting materials are best used with 0.5-1.0 equivalent of R 3 B. In our initial work [27], the alkyl phosphinates were prepared by the orthoformate method [28] (Fitch), or by the Dean-Stark method [29] (NifantÕev), and thus were more sensitive to decomposition, or limited to a small set of solvents. Since then, we found our alkoxysilane method to be superior, both in terms of convenience and generality (alkyl group, reaction solvent) [9].…”

“…Since then, we found our alkoxysilane method to be superior, both in terms of convenience and generality (alkyl group, reaction solvent) [9]. The radical-based hydrophosphinylation [27] has a very broad scope (Table 2) and is conveniently run at room temperature and in an open flask, thus making it an experimentally straightforward reaction which can be easily scaled-up. The reactions are usually complete in less than two hours.…”