Phosphonates, chiral

This material is converted to bryostatin 1 in 11 steps, including Yamaguchi macrolactonization, installation of the B-ring enoate using Fuji s chiral phosphonate [38] and, remarkably, selective hydrolysis of the C20 acetate in the presence of Cl-macrolide, C7 acetate, as well as the Cl3 and C21 enoate moieties (Scheme 5.6). 

Chodkiewicz, W., One-pot synthesis of chiral phosphonous esters, conversion into asymmetric phosphines, ]. Organomet. Chem., 273, C55, 1984. 

A novel chiral phosphonic amide-SiCl4 complex has also been found to serve as a catalyst for additions of allenyltributyltin to aldehydes (Table 9.45) [78], The reaction is limited to aromatic aldehydes because of competing formation of silylated chloro-hydrins from aliphatic aldehydes and the SiCI4 reagent. 

More recently, the chiral phosphonate 85 has been used as a CDA with chiral amines to form diastereomeric phosphonic amides (86)79 which are analyzed by 31P-NMR spectroscopy for the determination of enantiomeric ratios. The reagent is readily prepared from (5)-2-butanol and phosphorous trichloride, and all a-amino acids and amines thus far examined react quantitatively in a few hours at room temperature in aqueous ethanol79. 

An asymmetric Horner-Wadsworth-Emmons reaction has been developed which uses an external chiral ligand to avoid the need to prepare chiral phosphonate derivatives. ... 

Highly enantioselective Mannich-type reactions of A-(2-hydroxyphenyl) aldi-mines with ketene trimethylsilyl acetals and of A-Boc-aldimines with acetyl acetone or furan are catalyzed by chiral phosphonic acids 9 derived from 3,3 -diaryl-(l )-BlNOL and POCI3 (Scheme 12.7). ... 

Somewhat better results are obtained by employing a chiral phosphonate in reactions with alkyl(phenyl)ketenes, which results in destruction of the chiral phosphonate and in the enantioselective formation of allenecarboxylic esters with 15-20% optical purity114-115. 

One of the most investigated type of reaction in the field of catalytic imprinted polymers, as indicated by the large number of publications available, is certainly ester hydrolysis. In particular, a great deal of work has been carried out on systems inspired by hydrolytic enzymes since 1987. In 2000, Shea et al. [37] reported the preparation of enantioselective imprinted polymers for the hydrolysis of N-tert-butoxycarbonyl phenylalanine-p-nitrophenyl ester (55), using a system already developed by the same group in 1994 [19]. The system was inspired by the natural hydrolytic enzyme chymotrypsin and polymerisable imidazole units (27) were used as functional monomers coupled via ester linkages to a chiral phosphonate (56), analogue of (d)- or (L)-phenyl-alanine. After template removal, the imprinted polymers showed selectivity towards the hydrolysis of the enantiomer with which they were imprinted. The ratio of the rate constants, k /k, was 1.9 for the polymer imprinted with the D-enantiomer and kjku was 1.2 for that imprinted with the L-enantiomer. Moreover, the imprinted polymer showed a 2.5-fold increase in the rate of the reaction when compared with the control polymer, imprinted with a... 

A different approach was used by Emgenbroich and Wulff [42] to develop imprinted polymers with enantioselective esterase activity. The system was based on the use of an amidinium functional monomer (33), already developed earlier by the same group, but in this case a chiral phosphonate (62) was used as imprinting TSA in order to catalyse the hydrolysis of the corresponding chiral ester (63). The polymer imprinted with the L-enantiomer was able to enhance the esterolytic activity 325-fold when compared with the background and 80 times compared to the non-imprinted polymer. The ratio between the two rates constant, Lai-i/L ii-i) = 1 -4, can be taken as a measure of the enantioselective efficiency of the reaction. 

We now analyze the Still-Gennari reaction of Figure 11.17. The reagents there are the enantiomerically pure chiral phosphonate A, with which you are familiar from Figure 11.16,... 

Figure 9.17 shows what happens when the achiral aldehyde B from Figure 9.16 is olefinated with an enantiomerically pure chiral phosphonate ion A. Of course, a cis-olefin (formula D) is again formed preferentially, and in principle it can again be produced in two ways via the alkoxide C or via its diastereomer iso-C. If (only) a simple... 

We now analyze the Still-Gennari olefination of Figure 9.18. The reagents there are the enantiomerically pure chiral phosphonate A, with which you are familiar from Figure 9.17, and an enantiomerically pure a-chiral aldehyde B. The diastereoselectivity of the formation of the crucial alkoxide intermediate(s) is in this case determined by the interplay of three factors ... 

The meso-dialdehydes 4.43 and 4.46 undergo the HWE reaction with chiral phosphonate 4.44 in the presence of the base KHMDS and 18-crown-6 followed by the treatment with NaBH4 to give major amounts of monoaddition products 4.45 and 4.47, respectively, with good diastereoselectivities and high -selectivities. Similarly, meso-diketone 4.48 reacts with chiral phosphonate 4.49 to give a,(3-unsaturated ester 4.50 in 95% yield with high E-selectivity (98% ee). ... 

A chiral phosphonate-substituted azirine was prepared and its Diels-Alder reactions studied <20020L655>. Azirine 105 is prepared by the Swern oxidation of the corresponding aziridine as shown in Scheme 18. The Diels-Alder reaction of azirine 105 with Danishefsky s diene provides aziridine 106 in excellent yield as a single diastereomer. Note that the reaction time for azirines such as used by Gilchrist is only 15 min as compared to 8h with the phosphonate substituted azirines suggesting that the carboxylate-substituted azirines are much more reactive than the phosphonate-substituted azirines <19978271, 2001J(P1)2969, 2005S555>. 

The asymmetric synthesis of chiral phosphonic acids has been accomplished starting from alkyl phosphonamides 5 derived from MiV -dimethyl-diaminocyclohexane, which are easily prepared by condensation with alkyl phosphonic dichlorides (eq 7). Upon... 

CM has also been applied in the immobilization of biologically active molecules. Thus, [230] Reetz and co-workers supported chiral phosphonate as a potential suicide enzyme inhibitor by reacting alkenyl phosphonates with either allyl-modified SIRAN (a porous glass) or allyl-modified TentaGel in the presence of the Grubbs catalyst in CH2CI2 at reflux. 

Several reports show that it is possible to carry out a transesterification selectively at the carboxylic ester moiety of dialkyl l-(alkoxycarbonyl)methyIphosphonates rather than at the phosphonic ester moiety with primary and secondary alcohols in the presence of NaH or DMAPP For example, a number of chiral phosphonates have been prepared in high yields (80-96%) by DMAP-catalyzed transesterification of dialkyl l-(alkoxycarbonyl)methylphospho-nates with 8-phenytmenthol in toluene at reflux." " -" ... 

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). ... 

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