Chiral p-hydroxy

E. V. Dehmlow, P. Singh, J. Heider, A Cautionary Note on Optical Inductions by Chiral P-Hydroxy-Ammonium Catalysts , J. Chem. Res. (S) 1981,292-293. 

Reduction of an optically active epoxy ketone gives a chiral p-hydroxy ketone (equation I). 

Diastereoselective reduction of chiral fl-keto sulfoxides1 (13, 115-116). This reaction, which can be controlled to provide either diastereomer of a chiral P hydroxy sulfoxide, has been used to obtain (R)- or (S)-4-hydroxy-2-cyclohexenones from the monoketal (2) of 1,4-cyclohexanedione. Sulfinylation of 2 with (S)-( —)-... 

Chiral P-hydroxy esters and l,3-dioxan-4-ones are well-known substrates for diaster-oselective a-alkylation reactions developed by Frater [20] and Seebach [21]. These chiral compounds are available in both enantiomeric forms, and have been also ami-nated at the a-carbon with high stereoselectivity. 

In 1993, Bolm reported that these reactions could be performed using catalytic quantities (10 mol%) of the chiral P-hydroxy sulfoximine.132 The enantiomeric purities of the product alcohols ranged from 52% (1-indanone) to 93% (PhCOCHjOSiRj). In many cases the enantiomeric purities were enhanced using sodium borohydride as reductant in the presence of chlorotrimethylsilane.133 These methods have been extended to the asymmetric reductions of imines.134 /V-SPh-substituted imines gave the highest enantioselectivities and these reductions proceeded in the same stereochemical sense as the reductions of ketones. 

The substrates are available by diastereoselective alkylation of chiral p-hydroxy acids followed by conversion to the aldehyde and Wittig olefination. The overall process provides a diastereoselective synthesis of compounds with three consecutive asymmetric centers. Tetrahydropyridines.5 Danishefsky has used an intramolecular version of the Giese... 

Chiral P-Hydroxy-a-Aminophosphonic Acids. An enan-tioselective synthesis of substituted dihydrooxazolin-4-yl phos-phonates was reported by the reaction of an aldehyde with a-isocyanomethylphosphonate ester catalyzed by (i )-(5)-(l) (eq 12). The enantiomeric purity of the product was determined by P H NMR spectroscopy using the chiral solvating reagent (.S)-(+)-2,2,2-trifluoro-l-(9-anthryl)ethanol. Independently, an asymmetric synthesis of ot-aminophosphonic acids was reported using the chiral ferrocenylamine catalyst (R)-(S)-(3) (eq 13). ... 

The second, effective heterogeneous enantioselective catalytic system is nickel modified with tartaric acid and sodium bromide. This system is most effective for the hydrogenation of P keto esters giving chiral P hydroxy esters, 41, with ee s as high as 95% (Eqn. 14.29). 0,72,84,85 n also been used for the enantioselective hydrogenation of p diketones (Eqn. 14.30) and methyl ketones. ... 

Deprotonation of a-silyloxy ketones with LDA furnishes (Z)-lithium enolates, whereas treatment of ketones with n-Bu2BOTf in the presence of /-Pr2EtN gives the corresponding (Z)-(0)-boron enolates. Interestingly, reaction of the Li-enolates with r-PrCHO proceeds with opposite facial preference to that of the boron enolates. Thus, the Si face of the Li-enolate adds to the Si face of the aldehyde and the Si face of the boron enolate adds to the Re face of the aldehyde to furnish the chiral P-hydroxy ketone enantiomers shown below. The reason for the different face selectivity between the lithium enolate and the boron enolate is that lithium can coordinate with three oxygens in the aldol Zimmerman-Traxler transition state, whereas boron has only two coordination sites for oxygen. 

Aldol-type condensation of chiral a-sulfinyl hydrazones with aldehydes also provides a route leading to chiral p-hydroxy ketones. This is exemplified by the synthesis of (-)-(/ )-[6]-gingerol (98 equation 24). ... 

As shown in Scheme 8.2, chiral P-hydroxy-a-amino adds can be obtained by the Mukaiyama-type aldol reaction of aldehydes with glycine-derived enol silyl ethers using cinchona-based quaternary ammonium salts. In 2004, Castle and coworkers [9] found that dnchona-based quaternary ammonium salts such as 13 are also able to catalyze the dired aldol readion of aldehydes with the glydne donor 14 in the presence of a phosphazene base such as BTTP (t-butyliminotri(pyrrolidino)phos-... 

Scheme 15 illustrates the asymmetric hydrogenation of 3-keto phosphonates catalyzed by a BINAP-Ru complex, giving P-hydroxy phosphonates in up to 99% ee [61]. The sense of enantioface differentiation is the same as that of hydrogenation of P-keto carboxylic esters (see table of Scheme 3). The reactivity of the phosphonates is much higher than that of the carboxylic esters so that the hydrogenation proceeds even at 1 to 4 atm of hydrogen and at room temperature. A Ru complex of BDPP also shows high enantioselectivity [46b]. Chiral P-hydroxy phosphonates thus obtained are useful intermediates for the syntheses of phosphonic acid-based antibiotics as well as haptens of catalytic antibodies. Similarly, P-keto thiophosphates are hydrogenated enantioselectively with a MeO-BIPHEP-Ru catalyst [61b].

The Cu(n)-catalyzed reaction of silyl enol ethers with oxomalonic esters in the presence of a bis(oxazoline) ligand constitutes the first step of an access to chiral p-hydroxy acids. Enantioselective Mukaiyama aldol reaction performed in the presence of 52, and that in aqueous ethanol has been accomplished to a certain degree of success (32-85% ee). ... 

The chiral 1,3-dioxanes 21 and 25 are obtained from the biopolymer poly[(i )-3-hydroxybutyric acid] (PHB) by hydrolysis providing the chiral P-hydroxy acid 26 which is condensed with aldehydes. 

Openings of mcso-epoxides to obtain chiral P-hydroxy nitrile derivatives and of A -acylaziridines to afford A-(P-sulfenylalkyl) amides have enlisted the service of ligand 23 and dicyclohexyl L-(+)-tartrate, respectively. An efficient method for acquiring chiral azido silyl ethers from epoxides and Me SiN, employs a (salenlCr-N, complex 24. "... 

Through this approach formation of chiral P-hydroxy carboxylic acids with appropriate carbon frameworks is the key step of the method. Evans [92] reported an asymmetric synthesis of the carbapenem PS-5 in which the two stereocenters of the P-lactam ring were efficiently established via an asymmetric aldol addition reaction (Scheme 34). In this approach, the boron enolate 214 was... 

Aldol reactions are ubiquitous in synthetic organic chemistry to generate intermediates of antihypertensive dmgs and calcium antagonists. Chiral p-hydroxy carbonyl compounds can readily be converted to 1, i-syn and anfr-diols and amino alcohols, which are the building blocks in many natural products such as antibiotics and pheromones and in many biologically active compounds. Aldol products have successfully been converted to key synthetic intermediates of epithilone A and bryostatin 7. ... 

Chiral P-Silyl Aldehydes as Precursors of Chiral P-Hydroxy Acids and Chiral 1 -Diols... 

The catalyst was able to differentiate and control the reactivity of both used aldehydes, allowing the synthesis of chiral P-hydroxy aldehydes bearing a quaternary stereocenter in good results (40-95%, 50-99% de, 41-98% ee) [261]. By using this reaction protocol, the total synthesis of branched-chain natural products such as pantolactone or lyxose derivatives were successfully accomplished. 

Scheme 4.40 Phase-transfer catalysis of chiral p-hydroxy-a-amino acids...

Another class of reaction for which chiral tertiary amines are privileged catalysts is the Morita-Baylis-Hillman type (477, 478). One of the first applications of Cinchona alkaloids to mediate an asymmetric Morita-Baylis-Hillman reaction in a natural product synthesis was reported by Hatakeyama et al. in 2001 (479). Using a stoichiometric amount of (3-isocupreidine (568), a stereoselective addition of hexafluoroisopropyl acrylate (569) to aldehyde 570 could be carried out in good yield and with excellent selectivity (99% ee) (Scheme 119). The chiral p-hydroxy ester 571 was converted further into the epoxide 572, a known intermediate in the synthesis of epopromycin B (573). Epopromycin B (573) is a plant cell wall... 

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