Synthesis and Wittig Rearrangement of 3- and 4-Benzyloxyphenylphosphonamidates

Abstract

A series of seven O-ethyl-N-butylphenylphosphonamidates with benzyl ether substituents at the para or meta position have been prepared and fully characterised. Upon treatment with n-butyllithium in THF at RT, these undergo Wittig rearrangement in six cases to give the novel phosphonamidate-substituted diarylmethanols in moderate to good yield.

Synthesis and Butyllithium-Induced Cyclisation of 2-Benzyloxyphenylphosphonamidates Giving 2,3-Dihydrobenzo[d][1,3]oxaphospholes

“…The diethyl phosphonate 14 was treated with phosphorus pentachloride in toluene to afford 15, which reacted directly with two equivalents of butylamine, giving phosphonamidate 16. As previously observed in the para and meta series [9], the reaction sequence was accompanied by distinctive changes in the 31 P NMR shift: from +17.1 ppm for 14 to +26.5 ppm for 15 to +21.3 ppm for 16. Compound 16 showed an interesting and highly informative pattern of phosphorus couplings in the 13 C NMR spectrum (Figure 1), with coupling observed to all carbons of the phosphorus-bearing benzene ring and both carbons of the O-ethyl group, but only to C-2 of the N-butyl group.…”

“…In an earlier paper, we described the synthesis of aryl benzyl ethers bearing the phosphonamidate group EtO-P(=O)-NHBu on the aryl ring, either para- (7) or meta- (9) to a benzylic ether, and their successful Wittig rearrangement to afford the corresponding phosphonamidate-functionalised diarylmethanols 8 and 10, respectively (Scheme 2) [9]. In this paper, we describe the synthesis of a series of the isomeric aryl benzyl ethers 11 bearing an ortho-phosphonamidate group and their reaction with butyllithium, which leads not to Wittig rearrangement but rather to cyclisation, giving 2,3-dihydrobenzo[d] [1,3]oxaphospholes 12.…”

A tribute to Professor Aitken

“…62 Finally the n-butyl amide group was found to promote the rearrangement in moderate to high yield and was effective in ortho-, meta-, and para-positions giving diarylmethanol products 70. 63 This method has since been extended to the phosphonamide directing group giving 71, 64 and further studies on oxazoline-based systems have also been reported. 65 Arising from a fundamental study on FVP of a-functionalised carboxylic acid derivatives, dioxolanones derived from lactic or mandelic acid were found to be effective chiral acyl anion equivalents.…”