1.3.2- Oxazaphospholidine 2-oxides synthesis

A similar synthesis of chiral (o-hydroxyaryl)oxazaphospholidine oxides 166a-b, 167a-b, and 169a-d derived from (5)-prolinol 127 and its diphenyl derivative 163 was achieved from precursors 164a-b, 165a-b, and 168 which were easily available from two different procedures as outlined in Scheme 46 [77], The first pathway gave the two expected diastereomers of 164 and 165 in a ratio... 

Scheme 46 Synthesis of (ohydroxyaryl)oxazaphospholidine oxides 166a-b and 167a-b and (ohydroxyaryl)oxazaphospholidine oxides 169a-d...

The synthesis of various new chiral (o-hydroxyaryl)oxazaphospholidine oxides (139), derived from (S)-proline derivatives, from precursors (140) have been elaborated. This two-step reaction involves an unstable metallated intermediate that undergoes a fast 1,3-rearrangement with the formation of phosphorus-carbon bond. These catalysts have been successfully applied to the catalytic asymmetric borane reduction of numerous prochiral ketones with enantiomeric excess up to 84% ee (Scheme 35). ... 

A modification of this procedure allowed the isolation of 1,3,2-oxazaphospholidine 52a as a single diastereomer [41] and its application to asymmetric synthesis of enantiomerically and diastereomerically pure phosphinic acid derivatives 53 and 54 and tertiary phosphine oxides 55 (Scheme 20) [45], A few years later, a similar approach for the synthesis of enantiomerically pure tertiary phosphine oxides 55... 

The first report on the reaction of D-pseudoephedrine 66 with phosphoryl chloride appeared as early as 1962 [49], More recently it was found that this condensation gave 2-chloro-l,3,2-oxazaphospholidine 2-oxides 67 as a single diastereomer which was subsequently esterified with racemic aldehyde cyanohydrins 68 without racemization at the phosphorus atom. The prepared diastereomeric esters 69 were used as substrates for the asymmetric synthesis of optically active cyanohydrins 72, which involves the intermediate formation of the tertiary esters 70, as shown in Scheme 22 [50],... 

Scheme 47 Synthesis of 2-phenyl-1,3,2 oxazaphospholidine-2-oxides 170a and 170b...

Scheme 49 Synthesis of 2-alkoxy-l,3,2 oxazaphospholidine-2-oxides 176a and 176b...

Scheme 51 Synthesis of 2-chloromethyl-l,3.2-oxazaphospholidine-2-oxide 182 and its conver-tion into the cyano derivative 183...

Brown and co-workers synthesized optically active phosphine oxides from phosphorus trichloride by sequential addition of nucleophiles to chiral oxazaphospholidine [Eq. (24)]. The key step in this synthesis is control of the stereochemistry of the oxazaphospholidine, since the stereochemistry from the other steps is well characterized. The overall result is a greater than 94% e.e. 

Buono developed a very effective synthesis of chiral tertiary phosphine oxide starting from oxazaphospholidines. The enantiomerically pure oxazaphospholidine (Rp)-122 was prepared from PhP(NMe2)2 and (,S)-(+)-prolinol. Subsequent treatment of 122 with a variety of acids followed by hydrolysis gave both enantiomers of tert-butylphenylphosphine oxide 4c. It was found that the acid controlled the stereochemistry of the enantiomer obtained. By using acids of high acidity or Amberlyst 15 resin, (-h)-(R)-4c was obtained with good yields and enantioselec-tivities. When acids of low acidity were used, ( )-(,S)-4c was the preferred enantiomer. For example, / -toluenesulfonic acid (PTSA) afforded (R)-4c in 88% yield and 91% ee. After a recrystaUization the optically pure compound (/ )-(-t)-4c was obtained with >99% ee (Scheme 37) [67]. 

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