Oxazaphospholidine sulfides

Inch and co-workers reported in 1979 the preparation of P-stereogenic phosphinothioic aeids starting from 1,3,2-oxazaphospholidine sulfides derived from (-)-ephedrine (Scheme 4.48). 

I.3. 2-Chloro-4-methyl-5-phenyl-l,3,2-oxazaphospholidine 2-Sulfide for the Determination of Enantiomeric Purities of Amines by a "P-NMR Technique... 

Table 8. P-NMR Chemical Shift Differences0 for Diastereomeric 1,3,2-Oxazaphospholidine 2-Sulfide Derivatives of Amines40...

To 1 mmol of 2-chloro-4-methyl-5-phenyl-l,3,2-oxazapHospholidine 2-sulfide dissolved in 5 mL of THF and 1.5 mmol of F,t3N is added 1.00 mmol of the amine of interest. The mixture is stirred at r.t. for 24 h, then at 65 °C for 24 h and then is poured into Et.O and HzO. The organic layer is separated, dried over Na2SQ4, and concentrated. The diastereomeric amides are analyzed without further purification. 

Alternatively, the ambident oi-hetero substituted allyl anions have been utilized as homoenolate equivalents. For example, in the presence of HMPA, allyl phenyl sulfides (251),192 allyl phenyl sulfones (252)192b c and allyl phenyl selenides (253)192d e add to a,(3-enones in a l,4(0)-mode, while allyl phenyl sulfoxides (254) and allyl phosphine oxides (255) afford 1 A j-addition exclusively, irrespective of solvent used.193 Hua has shown that additions of either chiral sulfoxide (254 R1 = R2 = R3 = R4 = H, R5 = p-tolyl) or allyl oxazaphospholidine oxide (256) occur with excellent enantioselectivity (>95% ee).194 Similarly, Ahlbrecht reports that the a-azaallyl (257) adds exclusively in a 1 A j-mode to acceptor (59) to afford 1,5-diketones (Scheme 86).195... 

Treatment of 1,3,2-oxazaphospholidine 2-sulfide 176, bearing two amino residues at phosphorus, with oxaziridine 80 gave 1,3,2-oxazaphospholidine 2-oxide 177 in 92% yield <1997JOC6401>. It was interesting to note that the desulfurization occurred with complete stereoselectivity (>98% de) and with inversion of the configuration at the phosphoms, whereas use of w-chloroperbenzoic acid (MCPBA) resulted in retention of configuration affording 178 (Scheme 6). 

In the last section several oxazaphospholidine oxides, obtained by oxidation of the P(III) precursor with t-BuOOH, have already been described. There is also one report by Juge and co-workers in which they prepare oxazaphospholidine oxides and sulfides by in situ deboronation/oxidation of oxazaphospholidine boranes. This section illustrates some more derivatives, prepared directly from P(V) species and ephedrine. Chronologically, these types of compounds were studied earlier than the corresponding P(III) counterparts. Nowadays oxazaphospholidine boranes, not oxides, are the most important precursors used to prepare enantiopure phosphorus ligands. However, apart from historic interest, ephedrine-derived oxazaphospholidine oxides, sulfides and selenides occupy an important place in the study of phosphorus stereochemistry and conformational analysis. Only a few examples are described here. 

The mentioned compounds have been used in systematic studies on the regio-and stereoselectivity of substitution reactions at the phosphorus atom. ° los.iii 112 The same authors also reported a similar study on oxazaphospholidine oxides and sulfides derived from (+)-norephedrine (Figure 3.3). 

There is one example reported by Koizumi and co-workers where phosphinates were prepared from bicylic oxazaphospholidine oxides or sulfides by the sequential nucleophilic substitution and acidic methanolysis (Scheme 4.52). 

Scheme 4.52 Preparation of a phosphinate from a bicyclic oxazaphospholidine oxide/ sulfide.

The biphasic Hammett and Brpnsted plots found for the 5 2 reaction between 3-and 4-substituted pyridines and anilines and (2i ,4f ,55)-(+)-2-chloro-3,4-dimethyl-5-phenyl-l,3,2-oxazaphospholidine 2-sulfide in CH3CN at 5 C is attributed to a change from a backside to a frontside attack by the nucleophile. The Hammett p = -6.l5 and Brpnsted = 1.11 found for strongly basic pyridines was attributed to a frontside attack by the nucleophile, while the Hammett p = 4.73 and Brpnsted fl = -0.75 found with the weakly basic pyridines was thought to be for a backside attack by the nucleophile. The rate constants, AH and AS values, and the isokinetic temperature where 8 AH = T... 

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