Imide–Amide Rearrangement of Cyclic Phosphorimidates: A Mechanistic Study

Abstract

Studies aimed at the development of new synthetic pathways for the preparation of chiral cyclic oxaza and diaza phosphoramides suitable for use in asymmetric chemistry led us to the investigation of the imide ± amide rearrangement of cyclic phosphorimidates. As a result of this work new types of oligomeric organophosphorus compounds, formed by a novel 1,4-addition type ring opening polymerisation, were identified. These compounds are the stable intermediates of the imide ± amide rearrangement, which upon heating yield the previously reported rearranged product. A detailed study of the mechanism of the Lewis acid catalysed imide ± amide rearrangement and stereochemical control of the final products is reported. As a result, the full mechanism was elucidated and evidence of retention of configuration at the rearranged carbon atom is presented. Substituent effects were rationalised based on molecular modelling calculations.

Palladium-Catalyzed Allylic Transposition of (Allyloxy) Iminodiazaphospholidines: A Formal [3,3]-Aza-phospha-oxa-Cope Sigmatropic Rearrangement for the Stereoselective Synthesis of Allylic Amines

“…Similarly, the [2,3]-sigmatropic rearrangement of allyl phosphites is a valuable approach to the synthesis of allylphosphonates . Furthermore, thermal rearrangements of phosphorimidates to phosphoramides in which formal [1,3]-alkyl migration from oxygen to nitrogen concomitant with P(V)N to P(V)O interconversion have also been described . The thermodynamic driving force of the phospholidine−phosphoramide interconversion of 3 into 4 can be estimated by considering the model system of (allyl-O)(NH 2 ) 2 PNH, which on [3,3]-sigmatropic rearrangement is converted into (allyl-NH)(NH 2 ) 2 PO .…”

Imide–amide rearrangement of oxazaphosphorimidates: studies towards the application to the synthesis of chiral Lewis bases

“…This result is in accordance with the mechanism proposed for the oligomer-monomer conversion of the parent oligomer 3 and evidences that a phosphorous bonded oxygen is needed in the oligomeric chain for the reaction to occur. 9 As we have shown before for dioxaphosphorimidate substracts, the steric hindrance introduced by a methyl substituent at the carbon atom in the ring is sufficient to prevent the ROP to occur; the same seems to be valid for oxazaphosphorimidates. However, the most striking difference in the behaviour of these two classes of compounds is that for the oxazaphosphorimidates the conversion to a diazaphosphoramide can only be achieved by blocking the polymerization mechanism.…”

“…In the case of monosubstituted compounds, the polymerisation proceeds through the non-substituted carbon atom and, when a di-substituted compound is used, there is no reaction even under prolonged heating. 9 To probe the behaviour of structurally related oxazaphosphorimidates towards the imide-amide rearrangement, compounds 7a and 7b were prepared and subjected to Lewis acid catalysis (Scheme 3, Table 1). The formation of oligomer 8 was only detected for oxazaphosphorimidate 7a, while for compound 7b the cyclic rearranged product 9b was directly obtained.…”

“…For these compounds the reactivity towards polymerization could be explained in terms of differences in the nucleophilic character of the imidic nitrogen atom and by the steric hindrance of the ring alkoxide carbon atom. 9 The same should be true for the oxazaphosphorimidates when concerning the polymerization reaction only. Nevertheless these effects do not explain the observed direct conversion to diazaphosphoramide and suggest that a different type of reaction might be involved.…”

“…An intermolecular mechanism was found for this system and an oligomeric material 3, resulting from a 1,4-addition-type ring-opening polymerisation (ROP) of the cyclic phosphorimidate 1, was identified as being a stable intermediate of the rearrangement reaction, which occurs with retention of configuration at the carbon atom (Scheme 1). 8,9 We have also established that the most probable mechanism for the 'oligomer-monomer' conversion involves an intramolecular nucleophilic attack of the chain oxygen to the phosphorus atom in a SNi chain reaction with P-O bond cleavage and formation of the cyclic product 2. 9 The aim of the work now reported was to further explore the synthetic possibilities of the imide-amide rearrangement as a key step to the preparation of interesting cyclic chiral diazaphosphoramides.…”