Phosphorus chiral auxiliary

Chiral Phosphorus Compounds Koizumi et al. 251 have prepared a series of chiral organophosphorus compounds (256) in which the phosphorus atom is the asymmetric center, whereby amino acid derivatives were used as chiral auxiliary reagents. 

In continuation of our efforts to explore the utility of the SAMP/RAMP hydra-zone methodology, we developed the first asymmetric synthesis of a-phosphino ketones via formation of a carbon-phosphorus bond in the a-position to the carbonyl group [70]. The key step of this asymmetric C—P bond formation is the electrophilic phosphinylation of the ketone SAMP hydrazone 87, giving rise to the borane-adduct of the phosphino hydrazone 88 with excellent diastereoselectiv-ity (de = 95-98%). Since these phosphane-borane adducts are stable with respect to oxidation, the chemoselective cleavage of the chiral auxiliary by ozonolysis leading to the a-phosphino ketones (R)-89 could be accomplished with virtually no racemization. Using RAMP as a chiral auxiliary, the synthesis of the enantiomer (S)-89 was possible (Scheme 1.1.25). 

Another important source of chiral auxiliaries for the synthesis of optically active phosphorus derivates are the C2 symmetric diamines such as 1,2-diaminocyclohex-anes. In 1994, Hanessian and co-workers described the use of A,/V -dimethyl-(R,R)-1,2-diaminocyclohexane 93 as a chiral auxiliary in the synthesis of optically pure or enantiomerically enriched a-alkyl a-amino phosphonic acids [49], Starting from easily accessible optically pure diamine 93, they synthesized in good yield (75 %) enantiomerically pure (R,R)-ethylphosphonamide 94 by condensation with ethyl phosphonic dichloride in benzene in the presence of triethylamine (Scheme 43). 

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. 

Once the methods for electrophilic azidation of phosphorus-stabilized carbanions were established a variety of chiral auxiliaries were surveyed to obtain nonraccmic a-aminophosphonic acids. All the compounds tested with the exception of 9 were used in optically active form. (The precursor of 9 was more readily available in racemic form.) The results of electrophilic azidation of these substrates are summarized in Tablet, together with those of ( )-l. Where possible, both methods A and B were tested. 

Phosphorus-Containing Ring Systems. - The chiral a-diazophosphonic acid derivatives (289), (290) and (291) have been prepared from (-) ephedrine and (S,S)-N,N -dimethyl-l,2-diaminocyclohexane. Preliminary experiments suggest that the new chiral auxiliaries investigated exert little influence over the subsequent reactions of the derived rhodium (II) acetate-catalysed O-H and N-H insertion reactions. ... 

The synthesis of allylic and non-allylic cyclic N-phosphoryliminium ions (130) based on N,0-acetals (131) and their application in C-C bond formation (132) has been reported. In addition, the influence of a chiral auxiliary on the phosphorus atom has been also investigated (Scheme 38). ... 

Many chiral phosphorus-based auxiliary ligands are available for transition metals in asymmetric, catalytic, homogeneous reductions of alkenes. ParticulaiTy noteworthy are... 

Since these pioneering works, Wills et al. have widely developed the synthesis of different phosphine oxide compounds 32-44, varying the structure of the chiral auxiliary bound to the phosphorus atom [41 -44]. 

The ready alkylation of sodium phosphonate carbanions with chloro- or bromoacetates in THF provides a useful access to dialkyl 2-(alkoxycarbonyl)ethylphosphonates bearing a variety of alkyl, aryl, cyano, keto, or phosphoryl groups at the cx-carbon (Scheme 8.43). By using a chiral auxiliary, the alkylation of phosphorus-stabilized benzylic carbanions with bromoacetate proceeds with high diastereoselectivity to provide an easy access to optically active alkylphosphonic acids. ... 

The biphosphole (370) has been obtained in enantiomerically pure form by spontaneous resolution in the crystallisation of a racemic mixture, without the use of chiral auxiliaries. A new approach to -functionalised phospholes is afforded by metallation at a methyl group of l-phenyl-3,4-dimethylphosphole(in which both phosphorus and the diene unit are protected by coordination to an iron carbonyl acceptor), followed by treatment with electrophiles, to give C-substituted products, e.g., (371). Copper(II) oxidation of the intermediate lith-iomethyl derivative leads to the formation of bridged systems, e.g., (372). ... 

The most obvious approach was to introduce chiral ligands around rhodium. Horner et al. [20] and Knowles et al. [21],in 1968,independently selected monophosphine 5 as the chiral auxiliary. Phosphorus itself was the center of chirality, located in close proximity to the alkene coordinated to rhodium. Unfortunately, the asymmetric induction was very small, not over 10% ee (Scheme 4). Nevertheless, these experiments established the possibility of transforming the Wilkin-... 

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 (—)-menthyl ester group has been employed as a chiral auxiliary in electrophilic glycine derivatives. Modified Swem oxidation of (—)-menthyl glycolate 1879 using phosphorus pentoxide for activation of DMSO instead of oxalyl chloride gave... 

Cation and solvent hydrogen bonding to the hydrophilic phosphate group of the anion BNPPA (l,l-binaphthyl-2-diyl phosphate) (71) leads to bilayers with an interior hydrophilic region and with hydrophobic binaphthyl groups on both exterior sides.A simple thiophosphate-based method for 2-alkylidenation of lactones has been described. Phosphorus-derived chiral auxiliaries for a-alkylation of secondary amines by anodic oxidation has been elaborated. lodotrimethyl-sUane, which is routinely used for the dealkylation of ethers and esters, may be used to iodinate allyl or benzyl diethyl phosphates. ... 

P. S. Pregosin, Phosphorus-Olefin Chelation in Coordinated Atropisomeric Chiral Auxiliaries , Chem. Commun. (Cambridge, U. K.), 2008, (40), 4875. 

Generally, arsonium ylides [62] are more reactive but less accessible than phos-phonium ylides. Recently, the chiral arsonium reagent 30 has appeared, and has been applied in asymmetric Wittig-type carbonyl olefinations. This first chiral arsonium reagent also bears 8-phenylmenthyl as a chiral auxiliary on its carboalkoxy portion [63], and gave moderate chemical yields and diastereoselectivities in the conversion of 4-substituted cyclohexanone derivatives to axially chiral non-racemic alkylidene cyclohexanes under the same reaction conditions as used for the related reactions with phosphorus reagents (Scheme 7.15). On the other hand, the corre-... 

This compilation embraces a wide variety of subjects, such as solid-phase and microwave stereoselective synthesis asymmetric phase-transfer asymmetric catalysis and application of chiral auxiliaries and microreactor technology stereoselective reduction and oxidation methods stereoselective additions cyclizations metatheses and different types of rearrangements asymmetric transition-metal-catalyzed, organocatalyzed, and biocatalytic reactions methods for the formation of carbon-heteroatom and heteroatom-heteroatom bonds like asymmetric hydroamina-tion and reductive amination, carboamination and alkylative cyclization, cycloadditions with carbon-heteroatom bond formation, and stereoselective halogenations and methods for the formation of carbon-sulfur and carbon-phosphorus bonds, asymmetric sulfoxidation, and so on. 

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