Oxazaphospholidine derivatives

A series of 2-chloro-l,3,2-oxazaphospholidine derivatives 131a-f were prepared by reaction of six enantio-pure alcohols 129a-f with phosphorus trichloride carried out in the presence of an organic base as HC1 scavenger (Scheme 38) [69], The 31P and II-NMR spectra of crude 131a, d, e containing a small amount of the HC1 salt produced during the synthesis of 131, as well as the distilled samples, indicated that the formed chloro derivatives were ca. 1 1 mixtures of the cis and trans isomers. 

Scheme 38 Synthesis of the nucleoside 3 -0-oxazaphospholidine derivatives 132a-f...

The basic hydrolysis of acyclic phosphoramidates occurs with a mixture of C-0 and P-0 bond cleavage (l, 2) however similar treatment of l,3>2-oxazaphospholidines can result in substantial P-N cleavage ( 1, 3). 1,3,2-Oxazaphospholidines derived from (-)-ephedrine react with solutions of alkoxides in alcohol to give only the products of P-N cleavage and with inversion of configuration at phosphorus. Scheme I ( +, 5). ... 

Carbon-13 NMR. - Specific NMR data of 1,3,2-oxazaphospholidine derivatives (79) are reported. The use of phosphorus J-scaled proton-carbon 2D NMR for coupling constant measurements is also reported, for example in the J-scaled correlation spectra of the DNA aptamer... 

Thirdly, oxazaphospholidines derived from ephedrine are the starting point for one of the principal methods to prepare enantiopure P-stereogenic phosphines, discussed in Chapter 4. ... 

During the 1970s Inch and co-workers ° published a series of detailed papers where they studied many 1,3,2-oxazaphospholidines derived from (—)-ephedrine, prepared from common P(V) precursors (Scheme 3.18). 

Oxazaphospholidines derived from (5)-prolinol have also been used to prepare some P-stereogenic compounds (Scheme 4.53). 

Stereodefined PS-ORNs were manually synthesized on solid supports by using the oxazaphospholidine derivatives as monomer units according to the synthetic cycle shown in Scheme 4. Finally, all-(/ p)-[Us]9U (4) and all-(Sp)-[Us]9U (5) were... 

Oka N, Yamamoto M, Sato T et al (2008) Solid-phase synthesis of stereoregular oligodeox-yribonucleoside phosphorothioates using bicyclic oxazaphospholidine derivatives as monomer units. J Am Chem Soc 130 16031-16037... 

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