Phosphonic diamides chiral

Given a sufficiently strong base, the activation produced by the phosphoryl group next to an adjacent C—H bond will allow deprotonation and the generation of a highly reactive carbanion. Butyllithium has been commonly used for this purpose, but a preference has been shown in recent work for Ida. Treatment of the anion from methyl methyl(4-morpholinyl)phosphinate (284) with farnesyl chloride yields 285, which, on acidolysis, affords the phosphonic acid 286, employed in the synthesis of a pyrophosphonate analogue of farnesyl pyrophosphate ". Alkylation of the carbanion from the chiral phosphonic diamide 287 (X = Me or higher alkyl) leads to the diastereoisomeric phosphonic... 

New developments in the synthesis of a-hydroxy phosphonic acids and their derivatives have concentrated on their asymmetric formation. The chiral phosphonic diamides (629) (in which R = isopropyl, 2,2-dimethylpropyl, or benzyl or a derivative thereof) in either racemic or optically active forms were converted into their anions and allowed to react with aldehydes to give the products (630) the diastereoisomeric composition of the latter could be ascertained by the use of P NMR spectroscopy, and after acidic hydrolysis and subsequent methylation (diazomethane) it was possible to isolate optically active forms of the dimethyl esters of (l-hydroxyalkyl)phos-phonic acids, the (/ ,R)-diamide giving rise to the (5)-acids as their esters. The best results were achieved when R = Bu CFl2, and enantiomeric excesses were generally above 85% . 

In the 1,4-addition of carbanions from the diastereoisomeric l,3,2-oxazaphosph(V)-olidines 381 to cyclopent-2-enone the replacement of R = Me by R = Pr increased the enantioselectivity considerably good enantioselectivity was also achieved in additions to a didehydropiperidone to give 382. A more fully exemplified study of the conjugate addition of carbanions derived from the chiral phosphonic diamides 383 to cyclopentenones, cyclohexenones, lactones, lactams and conjugated unsaturated carboxylic demonstrated, once again, the high stereocontrol (with product ratios never less than 90 10 and often > 99 1) in the formation of the adducts 384 ( = 1 or 2 X = CH2,0 or NR). ... 

In reactions between the chiral phosphonic diamide (112), LiNPr 2, cuid the aldehydes RCHO, the ratios of diastereoisomeric or-hydroxy phosphonic diamides ranged from 29 1 (R = 1-naphthalenyl) to as low as 3.4 1 ( with isovaleraldehyde), with the (S)... 

Chiral phosphorus(III) reagents undergo the Pudovik reaction51,88 with good diastereoselectivity being achieved by the reaction of Spilling and co-workers diamide 52 with aldehydes (Scheme 26),107 however, research on this chiral auxiliary approach to ct-hydroxy phosphonates is now surpassed by chiral catalysis. 

The classical reaction between a (haloalkyl)phosphonic diester and NaN3, best carried out in a polar solvent, e.g dmf has been developed into an asymmetric synthesis. The reaction between (chloromethyl)phosphonic dichloride and the chiral auxiliary (5)-(phenylaminomethyl)pyrrolidine (314) is followed by separation of the product 1,3,2-diazaphosph(V)olidines 315 (R = H X = Cl) and 316 (R = H X = Cl), obtained in yields of 36 and 45%. Alkylation (BuLi, RX) of the cyclic diamides and reaction between the products and NaN3, to give 315 and 316 (R = alkyl X = N3), is then followed by acidoly-... 

Blazis VJ, Koeller KJ, Spilling CD (1995) Reactions of chiral phosphorus acid diamides the asymmetric synthesis of chiral alpha-hydroxy phosphonamides, phosphonates, and phosphonic acids. J Org Chem 60 931-940... 

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