A novel and convenient preparation of hypophosphite esters

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

“…We found that similar conditions can be applied to esterify hypophosphorous acid (and some salts) to provide alkyl phosphinates in high yield and in a variety of solvents (Eq. (2)) [9]. In addition, the alkyl phosphinates (which are used in situ) displayed unusual thermal stability, with only 10-20% decomposition at 85°C for more than 20 h [9].…”

“…(2)) [9]. In addition, the alkyl phosphinates (which are used in situ) displayed unusual thermal stability, with only 10-20% decomposition at 85°C for more than 20 h [9]. In fact, stock solutions of EtOP(O)H 2 in CH 3 CN, THF, or toluene, were found to be stable at room temperature under nitrogen for over a month (less than 10% decomposition).…”

“…In subsequent work, the use of t-BuOP(O)H 2 was also demonstrated [16b]. Since our method to prepare alkyl phosphinates results in enhanced thermal stability, [9] the prospect of extending the Schwabacher cross-coupling seemed excellent. The combination of the AHP cross-coupling [18] with our selective esterification of H-phosphinic acids [8] would provide the same overall transformation.…”

“…Alkyl phosphinates prepared by the alkoxysilane method react uneventfully with carbonyl compounds and Michael acceptors (Scheme 3) [9]. Gallagher has reported the only examples of alkylation with alkyl halides using i-PrOP(O)H 2 /i-PrONa (Scheme 2, method 5) [6].…”

“…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]. 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.…”