Nucleophilic chiral phosphine

Subsequently, Shi and Li synthesized a more nucleophilic chiral phosphine 19i and subjected it to the aza MBH reaction of N sulfonyl imines with 2 cyclohexen 1 one or 2 cyclopenten 1 one [28]. The resulting adducts could be obtained in good yields, but with moderate enantiomeric excess (Scheme 13.16). 

Asymmetric allylation of carbon nucleophiles has been carried out extensively using Pd catalysts coordinated by various chiral phosphine ligands and even with nitrogen ligands, and ee > 90% has been achieved in several cases. However, in most cases, a high ee has been achieved only with the l,3-diaryl-substitiitcd allylic compounds 217, and the synthetic usefulness of the reaction is limited. Therefore, only references are cited[24,133]. 

In the presence of chiral phosphine ligands, there is also rapid epimerization to the most stable diastereomeric -rr-allyl complex. The stereoselectivity arises in the reaction with the nucleophile.119... 

Triisopropylsilyloxyfurans were effective nucleophiles for the vinylogous Mannich addition to iminium ions that were formed by Rh2(cap)4-catalyzed oxidation of N-alkyl groups by THYDRO <06JA5648>. A stereoselective addition of 2-trimethylsilyloxyfurans to aryl aldehydes-derived aldimines employing a chiral phosphine/Ag complex as catalyst was developed <06AG(I)7230>. The prototypical example is shown below. 

Haynes, R.K., Lam, W.W.-L., and Yeung, L.-L., Stereoselective preparation of functionalized tertiary P-chiral phosphine oxides by nucleophilic addition of lithiated tert-butylphenylphosphine oxide to carbonyl compounds, Tetrahedron Lett., 37, 4729, 1996. 

Zhang et al. developed the enantioselective chiral phosphine-catalyzed addition of 2,3-allenoates with carbon-centered nucleophiles and electron-deficient olefins leading to efficient enantioselective C-C bond formation [248, 249]. 

By contrast, the use of phosphines as catalysts is a more recent phenomenon and the development of chiral phosphines has been less well explored, possibly also because of synthetic difficulties associated with developing chiral nucleophilic phosphorus-containing scaffolds. 

The chiral ir-allyl-Pd(II) intermediates shown in Scheme 84 undergo epimerization. The efficiency of this step and the regiochemistry of the nucleophilic attack to the exo face are very important for obtaining enantioface selection (Scheme 89). Bosnich analyzed the general characteristics of the asymmetric alkylation in terms of the properties of the allylic acetate substrates and of the 7T-allyl-Pd(II) intermediates, which undergo facile o-tc-o rearrangement, readily switching the face of Pd coordination (208). Examination of the dynamic equilibria of a series of cationic ir-allyl-Pd-chiral phosphine complexes has indicated that the 7r-allyl intermediates epimerize 10-100 times faster than the nucleo-... 

A variation on this asymmetric catalytic allylation scheme employed (3-diketones or (3-keto ester nucleophiles with allyl ethers and a palladium-DIOP catalyst.434 The chiral center generated is now one carbon removed from the allyl ligand. As a result, somewhat lower optical yields were observed (-10% equation 353). A variety of chiral phosphines were evaluated in the cyclization of (3-keto esters. Optical yields up to 48% were measured in these reactions435... 

Allylic alkylations using a benzophenone imine of glycine methyl ester as a prochiral nucleophile and chiral phosphine ligands on palladium produced optical yields up to 57% (equation 354).436... 

High enantiomeric excess in organocatalytic desymmetrization of meso-diols using chiral phosphines as nucleophilic catalysts was achieved for the first time by Vedejs et al. (Scheme 13.21) [36a], In this approach selectivity factors up to 5.5 were achieved when the C2-symmetric phospholane 42a was employed (application of chiral phosphines in the kinetic resolution of racemic secondary alcohols is discussed in Section 12.1). A later study compared the performance of the phos-pholanes 42b-d with that of the phosphabicyclooctanes 43a-c in the desymmetrization of meso-hydrobenzoin (Scheme 13.21) [36b], Improved enantioselectivity was observed for phospholanes 42b-d (86% for 42c) but reactions were usually slow. Currently the bicyclic compound 43a seems to be the best compromise between catalyst accessibility, reactivity, and enantioselectivity - the monobenzoate of hydrobenzoin has been obtained with a yield of 97% and up to 94% ee [36b]. 

Preparative Methods prepared in four steps starting from p-xylene. Birch reduction of p-xylene followed by asymmetic hydroboration-oxidation provides an optically pure diol. The diol is subsequently converted to the chiral phosphine by formation of the corresponding dimesylate and nucleophilic addition ofLizPPh. 

Similarly, a Pd[(S,S)-N0RPH0S]( 7 -C3H5) Cl04 precursor prepared from 2-acetoxy-4,4-diphenylbut-3-ene has been shown to react with sodium dimethylmalonate, a soft nucleophile. The corresponding [Pd (chiral phosphine)] species is thereby generated in situ, which serves to initiate the catalytic cycle that results in allylic alkylation of the nucleophile. The resulting allylation product is formed in 76% ee (eq 8). ... 

In the allylic substitution of racemic 2-propenyl acetates or related substrates with the same substituents at 1 and 3 positions, the jt-allylpalladium intermediate containing a meso type 7r-allyl group is formed from both enantiomers of the allylic substrate. Two jt-allyl carbons at the 1- and 3-positions are diastereotopic on coordination of a chiral phosphine ligand to palladium. The asymmetric induction arises from preferential attack by the nucleophile on either of the two diastereotopic TT-allyl carbon atoms (Scheme 2-28). 

A most spectacular stereochemical aspect of the Pd-catalyzed reactions is the possibility of creating new stereogenic centers in the allylic substrate or in the nucleophile when chiral phosphine-palladium complexes are employed. Although the full potential of these reactions has still to be exploited, the results thus far are promising and the first successful applications have become known e.g. equation... 

Lithiophosphide reagents have also found application in the synthesis of a range of chiral phosphines based on carbohydrate systems, e.g., (43), the key step being nucleophilic ring-opening of epoxide derivatives with lithium diphenyl-phosphide. A lithiophosphide-tosylate route has been used in the synthesis of the carbohydrate-based diphosphine (44). Conjugate addition of lithium diphenyl-phosphide to a,P-unsaturated carboxylic esters is the key step in the synthesis of... 

Nucleophilic Attack at Other Atoms. - Trifluoromethanesulfonyloxyboron derivatives of tricyclohexylphosphine-borane have been prepared. Two enantiomerically pure borane complexes of chiral dihydrobenzazaphosphole systems, e.g., (128), have been structurally characterised. The synthesis of phosphinoboranes bearing an L-menthyloxy group is a key strategy in the synthesis of chiral phosphines, e.g., (129). Treatment of the phosphines... 

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