Phosphoramidate rearrangement

Phosphoramidates rearrange into a-aminophosphonates using chiral lithium amide bases e.g. 31 afforded aminophosphonate 86 from phosphoramidate 85 in 13% ee and 65% yield (Scheme 61)104. A slightly higher optical purity of 26% (55% yield) was obtained with chiral (R. R)-3 as base. The application of (—)-sparteine and BuLi gave 13% ee and a yield of 30%. A higher level of enantioselectivity was reached when a bisphosphonate (87) was reacted with (R,R) 3 in THF. Although the yield was only 30%, aminophosphonate 88 was obtained in 35% ee (Scheme 61). 

The same phosphorimidate phosphoramidate rearrangement has been applied to the preparation of allylie amines starting from the phosphoroimidate (121) (e.g. Seheme 33). " ... 

A series of N-allyl sulfamates, phosphoramides, and phosphorimidates was prepared to explore the possibility of O- N rearrangements via the intermediacy of the contact alkene radical cation/anion pair, followed by 5-exo-trigonal radical cyclizations (Fig. 4) [142],... 

This rearrangement may clarify some of the experimental difficulties encountered in studies of phosphoramides. A rearrangement of the A-oxide after reaction with the enzyme might also contribute to the prolonged cholinesterase inhibition in vivo often occurring with phosphoramide poisoning in animals. 

No reaction occurs with Mel, or with Me3SiCl. Thermally induced rearrangements of phosphazenes to phosphoramidates (38)80 and (39)81 have also been reported. 

Smith et al. have developed a very elegant route to complex polyol structures by sequential dithiane-epoxide coupling reactions (Scheme 7) [16]. Following the work of Tietze [17], 2-silyl-1,3-dithianes 42 are deprotonated with /BuLi in ether and converted into the stable lithium alk-oxides 43 with enantiomerically pure epoxides. A fast 1,4-Brook rearrangement occurs only after the addition of 0.3 equivalents of hexamethyl-phosphoramide (HMPA) or 1,3-dimethylhexahy-dro-2-pyrimidone (DMPU) to the reaction mixture. A new lithiated dithiane 44 that can undergo... 

The arylsulfonyl carbanion accelerated Claisen rearrangement is completely regioselective and has also been found to be highly diastereoselective (Scheme 2). The stereochemical course of the reaction conforms to the familiar chair-like transition state model usually invoked for the classic thermal process. Recently, high degrees of asymmetric induction have been observed in tlie rearrangements of chiral cyclic phosphoramidate stabilized carbanion derivatives. ... 

New synthetic pathways for the preparation of chiral cyclic oxaza- and diaza-phosphoramidates suitable for use in asymmetric chemistry were studied with respect to the imide-amide rearrangement of cyclic phosphorimidates (Scheme 23). New types of oligomeric organophosphorus compounds (112), formed by a novel ring opening polymerisation, have been identified. These compounds are stable intermediates in the imide-amide rearrangement. 

A new perspective was opened up recently when Denmark demonstrated diat with chirally modified phosphoryl-activated allenes an asymmetric induction could be effected. From easily generated allenyl phosphoramidates containing an optically active amino alcohol, the diastereomeric adducts (37) and (39) could be obtained by addition of dlyl alcohol. When the separated adducts were employed in the carb-anionic Claisen rearrangement, a remarkable asymmetric induction (90 10) could be achieved with preferential formation of the diastereomers (38) or (40) respectively, whereas in a thermal reaction no stereoselection was observed (Scheme 63). Another example of an asymmetric induction in Claisen rearrangements is reported by Welch. ... 

The influence of an external stereogenic center P to position 2 has been intensively studied in the rearrangement of cyclic phosphoramidates 2 and 6105-517-634 (see also p 3304). 

In the presence of sodium methoxide, alkyl N-alkyl-(1-chloroalkyl)phosphonamidates rearrange to (1-aminoalkyl)-phosphonates ( a reaction previously observed) together with phosphoramidates-the latter a new feature of mechanistic significance.The use of methoxide did lead, however, to complications due to the further degradation of the products, and the use of benzyltrlmethylammonium methoxide was found to be more satisfactory. This brought about the conversion of... 

The highly reactive nitrenes derived from phosphoryl azides do not readily undergo rearrangement. They also appear to have a low selectivity with respect to —H insertion reactions. Thus, irradiation of diethylphosphoryl azide (143 R = Et) in cyclohexane, for example, led to formation of diethyl cyclohexyl-phosphoramidate (144 R = Et) in 88% yield.83 A lower yield (67%) of insertion product, diphenyl cyclophosphoramidate (144 R = Ph), was obtained on... 

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