1.3.2- Oxazaphospholidines chiral

The stereochemistry of the first step was ascertained by an X-ray analysis [8] of an isolated oxazaphospholidine 3 (R = Ph). The overall sequence from oxi-rane to aziridine takes place with an excellent retention of chiral integrity. As the stereochemistry of the oxirane esters is determined by the chiral inductor during the Sharpless epoxidation, both enantiomers of aziridine esters can be readily obtained by choosing the desired antipodal tartrate inductor during the epoxidation reaction. It is relevant to note that the required starting allylic alcohols are conveniently prepared by chain elongation of propargyl alcohol as a C3 synthon followed by an appropriate reduction of the triple bond, e. g., with lithium aluminum hydride [6b]. 

A-trityl-(l/ ,2S)-norephedrine (58), the corresponding allyl phosphonates 62a,b were obtained via the Arbusov rearrangement of 2-ethoxy-1,3,2-oxazaphospholidine 60. The absolute configuration of the major diastereomer, 62a was determined by X-ray as (2S1,45,51 ).The reaction of the major diastereomer of allyl phosphonates 61a and 62a with DBU afforded the corresponding vinylphosphonates 63a,b (Scheme 21) [48], Nucleophilic addition to these resulted in induction of chirality at the [1-position of the stereogenic phosphorus atom in the initially produced diastereomeric phosphonates 64 or 65 (Scheme 21) [48],... 

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... 

A chiral O-phosphinylhydroxylamine-type reagent, such as (2R,4S,5R)-2-[0- N,N-dimethylhydroxylamino)]-3,4-dimethyl-5-phenyl-l,3,2-oxazaphospholidin-2-one 4e, was also used for stereoselective amination of carbanions (equation 23)"°. 

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... 

Chiral [160, l70, l80]phosphomonoesters and ATPy[l60, l70, lsO] have been synthesized by Knowles and associates, who devised the procedure outlined in Fig. 19 [51-55], The procedure has been used to synthesize phenyl[160, l70, l80]phos-phate and 2-[160,170,180]phospho-D-glycerate as well as the propylene glycol ester shown. The starting cyclic adduct was prepared by reaction of (— )-ephedrine with P17OCl3, giving a separable mixture of 2-chloro-l,3,2-oxazaphospholidin-2-ones whose chemistry had been described [56], The major isomer was converted to (/ p)-l-[160, nO,180]phospho-1,2-propanediol and (Sp)-ATPy[l60, nO, lsO] by the reactions shown. The stereochemistry at each step of the synthesis was well prece-dented in the literature nevertheless, the configurations were verified by independent methods described in the next section. 

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). ... 

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. 

Routes to the chiral ferrocenyldiphosphines 113 have been developed, via the use of the chiral oxazaphospholidine borane 114. Routes to other chiral ferrocenylphosphines have also been developed, including the boranato-functio-nalised systems 115, and the C2-symmetric diphosphine 116, having only the planar chirality of the ferrocene system. Full details have now appeared of the palladium-promoted asymmetric Diels-Alder reaction between l-phenyI-3,4-di-... 

Phosphorus-containing Ring Systems. - A range of new chiral oxazaphospholidine oxides 266 and 267 have been synthesised and used as catalysts in asymmetric reductions of ketones with diborane. Mannich-type cyclisation reactions of 5-amino-3-benzylthio-4-cyano(ethoxycarbonyl)pyrazoles with dichlorophenylphosphine and aromatic aldehydes in the presence of cation exchange resin have been used to prepare a number of 6-oxo-6-phospha-4,5,6-trihydroimidazolo[l,2-b]pyrazoles, e.g. 268. Some of these compounds have herbicidal activity and this report is typical of a number of similar ones in the Chinese literature. A number of metallocycles, e.g. 269, have been reported as products from reactions of transient zirconocene-benzyne intermediates with phosphaimines followed by sulfuration or selenation. ... 

A preliminary report on a study of the displacability of alkylseleno-groups from chiral quinquevalent phosphorus selenoesters has appeared. The substrates were prepared from 2-seleno-l,3,2-oxazaphospholidines (54) (Scheme 13), the latter in... 

Oxazaphospholidines such as 3.85 [BP6, CFl, PMl] and (3-hydroxysulfoximines 3.86 [BF3] have been proposed as chiral additives in borane reductions. With 3.86,... 

Recently Buono has reported a new class of efficient catalyst systems which contains a chiral oxazaphospholidine-borane complex as a catalyst in the borane reduction of ketones[115, 116]. The oxazaphospholidine-borane complex 75 is easily prepared by action of 1.3 equiv. of BH3 THF on (2R, 5S)-2-phenyl-3-oxa-... 

The method chosen was that of Johnson and coworkers (ref. 66) which involves the use of a chiral oxazaphospholidine-2-thione as a chiral derivatising agent for Ip NMR analysis of... 

The use of a chiral template of an entirely different nature also provided useful stereochemical data the phosphoroamidic chloride 166 and prop-2-enylmagnesium bromide provide a product which consists entirely of (25)p-3-isopropyl-4-methyl-5-phenyl-2-(prop-2-enyl)-l,3,2-oxazaphospholidine 2-oxide (167). ... 

Various approaches are currently being made to the asymmetric synthesis of silyl ethers of (oc-hydroxyalkyl)phosphonic acids. One approach consists of the use of chiral 1,3,2-oxazaphospholidines (216 R = Et or Ph, R 3 = Bu Mc2), as a mixture of diastereoisomers, which react smoothly at room temperature with an aldehyde to give the diastereoisomer-ic silyl ethers 217 with retention of configuration at phosphorus ". In a second approach, the reaction between benzaldehyde and (EtO)2POSiMe2Bu was carried out in the presence of the chiral Lewis acids 187 (R = Me or Ph, X = Cl) a higher reaction yield accompanied a lower enantiomeric excess in the product, and vice versa, but the enantiomeric excess was never higher than about 25% ". ... 

Chirality in the phosphorus-containing dienophile induces a preferential mode of approach to the diene the (2R,45)-l,3,2-oxazaphospholidine 2-oxide 480 reacts with cyclopentadiene to give a 10 19 ratio (96% total yield) of the endo (structure confirmed by X-ray crystallography) and exo adducts, and a similar reaction with the IS, 45)-1,3,2-oxazaphospholidine 2-oxide gave endo and exo products in the ratio 2 3, with considerable diastereoisomeric excesses (80-88%) ... 

The oxazaphospholidine-based methodology has been developed to provide syntheses of chiral (chloromethyl)-, (dichloromethyl)-and (trichloromethyl)-phosphonic esters, and those of the corresponding phosphonothioic acids , and also chiral derivatives of (fluo-romethyl)phosphonic acid and (fluoromethyl)phosphonothioic acid ... 

A number of oxazaphospholidines (69) have found use as ligands in the preparation of chiral catalyst systems which promote a variety of enantioselective reactions. Examples include the use of palladium complexes for the asymmetric carbonylation of a-methylbenzyl bromide <880M59>,... 

Juge developed a powerful method (Juge-Stephan method) [1, 51] for the preparation of / -stereogenic phosphines based on the use of ephedrine as a chiral auxiliary. The key reactants in this methodology are 1,3,2-oxazaphospholidine boranes 78, prepared by a one-pot reaction from bis(diethylamino)phenylphosphine and (—)-ephedrine, followed by protection with BH3. The cyclization of the (—)-ephedrine takes place stereoselectively, with preferential formation of the (/ p)-diastereoisomer in 90% de [52, 53]. The absolute configuration at the phosphorus atom has been determined by chemical correlations and NMR analysis, and proved by X-ray analysis [54]. Oxazaphospholidines react readily with electrophiles or nucleophiles to provide various chiral phosphorus compounds. Enantiomeric antipodes of tertiary phosphines (Sp)-79 and (Rp)-81 were obtained from (-1-)- or (-)-ephedrine, as shown in Scheme 25. The configuration at the E-atom is controlled by the configuration at the Ph-substituted Cj of (-i-)-pseudoephedrine or ( )-ephedrine, respectively. This was confirmed by X-ray crystal-structure analyses of two intermediate compounds in the synthetic route to the chiral triarylborane-phosphine adducts [54]. 

The synthesis of P-chiral diarylphosphinocarboxylic acids 120 was achieved with excellent enantiopurity starting from the oxazaphospholidine boranes 82. Amido- and amino-diphosphine ligands 121, containing an L-proline backbone, were also derived from 82. The catalytic activities of the ligands 121 were evaluated in the Pd-catalyzed allylic alkylation reaction of 1,3-diphenylpropenyl acetate (Scheme 36) [66]. 

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]. 

The opening of oxazaphospholidine rings (/ p)-122 with tert-butyllithium occurred diastereoselectively with retention of absolute configuration on the phosphorus atom, affording the borane complex of aminophosphine (Rp)-124 [67, 68]. The reaction possibly proceeds via formation of chiral o X -phosphenium cation 126, which was obtained from (Sc)-chlorophosphine 125 and then isolated as borane complex 127 (Scheme 38). 

Pastor and co-workers prepared a series of extremely bulky biarylic oxazaphospholidines (Figure 3.5) using chiral and achiral amino alcohols. 

As the NMR spectra of the phospholidine-thiones 2a and 2b do not permit to assign the configuration of the phosphorous chiral center,we have tried to grow crystals suitable for X-ray diffraction. We were successful only for a homologue of 2a with a shorter chain the crystal structure of the major (2-butanoxy-4-phenyl)1,3f2-oxazaphospholidine-2-thione (2a, R = Ci Hg), shows the relative S, R configurations on positions 2 and 4.° As the acid cleavage is expected to proceed with... 

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