Phosphoric chiral

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... 

In peptide syntheses, where partial racemization of the chiral a-carbon centers is a serious problem, the application of 1-hydroxy-1 H-benzotriazole ( HBT") and DCC has been very successful in increasing yields and decreasing racemization (W. Kdnig, 1970 G.C. Windridge, 1971 H.R. Bosshard, 1973), l-(Acyloxy)-lif-benzotriazoles or l-acyl-17f-benzo-triazole 3-oxides are formed as reactive intermediates. If carboxylic or phosphoric esters are to be formed from the acids and alcohols using DCC, 4-(pyrrolidin-l -yl)pyridine ( PPY A. Hassner, 1978 K.M. Patel, 1979) and HBT are efficient catalysts even with tert-alkyl, choles-teryl, aryl, and other unreactive alcohols as well as with highly bulky or labile acids. 

Phosphine(s), chirality of, 314 Phosphite, DNA synthesis and, 1115 oxidation of, 1116 Phospholipid, 1066-1067 classification of, 1066 Phosphopantetheine, coenzyme A from. 817 structure of, 1127 Phosphoramidite, DNA synthesis and, 1115 Phosphoranc, 720 Phosphoric acid, pKa of, 51 Phosphoric acid anhydride, 1127 Phosphorus, hybridization of, 20 Phosphorus oxychloride, alcohol dehydration with. 620-622 Phosphorus tribromide, reaction with alcohols. 344. 618 Photochemical reaction, 1181 Photolithography, 505-506 resists for, 505-506 Photon, 419 energy- of. 420 Photosynthesis, 973-974 Phthalic acid, structure of, 753 Phthalimide, Gabriel amine synthesis and, 929... 

The adjacent iodine and lactone groupings in 16 constitute the structural prerequisite, or retron, for the iodolactonization transform.15 It was anticipated that the action of iodine on unsaturated carboxylic acid 17 would induce iodolactonization16 to give iodo-lactone 16. The cis C20-C21 double bond in 17 provides a convenient opportunity for molecular simplification. In the synthetic direction, a Wittig reaction17 between the nonstabilized phosphorous ylide derived from 19 and aldehyde 18 could result in the formation of cis alkene 17. Enantiomerically pure (/ )-citronellic acid (20) and (+)-/ -hydroxyisobutyric acid (11) are readily available sources of chirality that could be converted in a straightforward manner into optically active building blocks 18 and 19, respectively. 

Pd-catalyzed nucleophilic allylic substitutions perform efficiently in an enan-tioselective way by using chiral phosphorous-containing ligands. Due to their high stability and convenient handling, M-containing ligands have recently... 

In 1993, Alexakis et al. reported the first copper-catalyzed asymmetric conjugate addition of diethylzinc to 2-cyclohexenone using phosphorous ligand 28 (32% ee).36 An important breakthrough was achieved by Feringa et al. with chiral phosphoramidite (S,R,R)-29 (Figure 1), which showed excellent selectivity (over 98% ee) for the addition of 2-cyclohexenone.37 Since then, efficient protocols for the conversion of both cyclic and acyclic enones, as well as lactones and nitroalkenes, have been developed featuring excellent stereocontrol. 

At the same time, however, the iridium-catalyzed hydrogenation of 80 was reported using chiral phosphoric acid diester 17be based on BINOL [47a]. Full conversion and a maximum e.e. of 50% was observed, again in a slow reaction. Interestingly, a catalyst based on palladium and 17be afforded 39% e.e. and full conversion in the hydrogenation of aryl imine 87. 

In this chapter, we will focus on the rhodium-catalyzed hydrogenation of functionalized ketones and the development of chiral phosphorous ligands for this process. Although there are other chiral phosphorous ligands which are effective for ruthenium-, iridium-, platinum-, titanium-, zirconium-, and palladium-catalyzed hydrogenation, they will not be discussed here. For details of these chemistries, the reader should refer to other chapters of this book. 

Various chiral centers, such as the chiral carbon center, chiral nitrogen center, chiral phosphorous center, and chiral sulfur center are depicted in Figure 12. 

Transition metal complexes with chiral phosphorous and nitrogen ligands have also been used for promoting asymmetric transfer hydrogenation. Moderate to good results have been obtained.114... 

For general application of these chiral ligands, see (a) Kagan, H. B. Chiral Ligands for Asymmetric Catalysis in Morrison, J. D. ed. Asymmetric Synthesis, vol. 5, Chap. 1, Academic Press, New York, 1985. (b) Kagan, H. B., Sasaki, M. Optically Active Phosphines Preparation, Uses and Chiroptical Properties in Hartley, F. R. ed. The Chemistry of Organo Phosphorous Compounds, John Wiley Sons, New York, 1990, vol. 1, Chap. 3. 

Based on the fact that hexamethylphosphoric triamide can greatly enhance the stereoselectivity of the reaction, chiral phosphorous amidites of type 90 have been synthesized and tested for inducing asymmetric conjugate additions, and indeed good results have been obtained. For example, Scheme 8-31 shows that product was obtained with 87% ee.72... 

The broad range of alkenes undergoing asymmetric hydrogenation using ruthenium-based systems as catalysts has attracted the attention of chemists engaged in the synthesis of chiral biologically active natural products (Scheme 13)[60] and other pharmaceuticals (Scheme 14)[61]. a, (3-Unsaturated phosphoric acids and esters have also proved to be suitable substrates for Ru(II)-catalysed asymmetric hydrogenation [62]. 

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. 

Another phosphorus containing CDA (87) has also been described for the estimation of the enantiomeric excess of chiral amines80. The phosphorus CDA 87 is formed quantitatively and instantaneously in situ in an NMR tube by reaction of phosphorus trichloride (PCI3) with the chiral diamine 88. Addition to the NMR tube of the chiral amine (IC-NIIo) for which the ee is to be determined gives the diastereomeric phosphorous derivatives ... 

The absolute configurations of the products have now been determined (23) and the reaction promises to be of considerable interest, since Jacques and his colleagues have shown that chiral phosphoric acids are useful resolving agents (86). 

The first application of a copper-catalyzed conjugate addition of diethylzinc to 2-cyclohexenone, using chiral phosphorous ligand 12, was reported by AlexaHs (Fig. 7.1) [35]. An ee of 32% was obtained. 

As a true testament to the potential long-term impact of H-bonding activation, a number of ureas, thioureas, and acid catalysts are now finding broad application in a large number of classical and modem carbon-carbon bond-forming processes. On one hand, Johnston s chiral amidinium ion 28 was elegantly applied to the asymmetric aza-Henry reactions (Scheme 11.12d). On the other hand, chiral phosphoric acids (e.g., 29 and 30), initially developed by Akiyama and Terada, have been successfully employed in Mannich reactions, hydrophosphonylation reac-tions, aza-Friedel-Crafts alkylations (Scheme 11.12e), and in the first example... 

Keywords Asymmetric catalysis BINOL Dicarboxylic acids A-Triflyl phosphoramides Phosphoric acids Strong chiral Brpnsted acids... 

In this review, we present asymmetric reactions catalyzed by stronger Brpnsted acids. The scope and limitations of chiral phosphoric acids, iV-triflyl phosphoramides, and dicarboxylic acids are described considering articles published until the middle of 2008. Although the mechanisms of a few transformations have been investigated in some detail, they are not the focus of this review. 

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