S. Deprele et Jl. Montchamp, Triethylborane-initiated room temperature radical addition of hypophosphites to olefins: Synthesis of monosubstituted phosphinic acids and esters, J ORG CHEM, 66(20), 2001, pp. 6745-6755
A novel and practical approach to monosubstituted phosphinic acid (alkylpho
sphonous acid) derivatives from hypophosphite salts or esters is described.
Phosphorus-centered radical formation is initiated with Et3B/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 hy
pophosphorous acid and sodium hypophosphite (peroxide initiators, acid cata
lysis, heat), the method proceeds under neutral conditions and therefore to
lerates a wide range of functional groups. Previously inaccessible phosphin
ic acids can be prepared in a single step from cheap starting materials. Ex
cellent selectivity is observed for monoaddition, and symmetrical dialkyl p
hosphinates 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 pola
r. Because radicals derived from hypophosphites are electrophilic, the reac
tion is limited to the use of electron-rich olefins. The reaction condition
s can also be employed in the room temperature radical reduction of alkyl h
alides and provide an exceptionally mild and environmentally friendly alter
native to the use of tributyltin hydride. The remarkable mild nature of the
reaction conditions allows for the radical reaction of sensitive alkyl hyp
ophosphites to occur, in which case, a catalytic amount of Et3B suffices to
deliver alkyl phosphinate esters in reasonable yield.