Kinetic resolution conditions

C-chiral racemic y-hydroxy sulfides were also resolved using PEL under kinetic resolution conditions. The products were transformed into optically active 3-(alkanesulfonyloxy)thiolane salts (Scheme 1). Similarly, 1,2-cyclic sulfite glycerol derivatives cis and trans) were resolved into enantiomers via a Pseudomonas cepacia-catalysed acylation with vinyl butyrate. The E values depended on the solvent used and varied from 2 to 26. ... 

However, when subtilisin E was replaced by subtilisin Carlsberg, the hydrolysis of the S-N bond in some A(-acyl arenesulfinamides 34 unexpectedly became the main hydrolytic process giving under the kinetic resolution conditions, in addition to the unreacted substrates, the corresponding sulfinic acids and... 

However, the most common and important method of synthesis of chiral non-racemic hydroxy phosphoryl compounds has been the resolution of racemic substrates via a hydrolytic enzyme-promoted acylation of the hydroxy group or hydrolysis of the 0-acyl derivatives, both carried out under kinetic resolution conditions. The first attempts date from the early 1990s and have since been followed by a number of papers describing the use of a variety of enzymes and various types of organophosphorus substrates, differing both by the substituents at phosphorus and by the kind of hydroxy (acetoxy)-containing side chain. 

Two types of racemic 3-hydroxy phosphonates, in which the phosphono and hydroxy moiehes are separated hy double bond, were successfully resolved using a common enzyme-catalysed acetylation. Both acyclic 52 (Equation 28) and cyclic 54 (Equation 29) derivatives underwent easy acetylation under the kinetic resolution conditions to give the products in high yield and with almost full stereoselechvity. 

Stereoselective hydrolysis of racemic l-(//-phenylacetylamino) alkanephos-phonic acids performed in the presence of penicillin acylase under the kinetic resolution conditions gave both the unreacted substrates and the products - the corresponding 1-aminophosphonic acids in high yields and with full enantioselec-tivity. The unreacted A -acyl derivatives were hydrolysed chemically and in this way each enantiomer of the free acid was obtained (Scheme 5). ... 

Phosphotriesterase from P. diminuta (PTE) was found to exhibit high hydrolytic activity towards various types of tetracoordinated phosphorus acid esters. Apart from the phosphonothionate 92, phosphoric acid triesters 94 (Equation 45), °" benzenephosphonic acid diester 95 (Equation 46) ° and methyl-phenylphosphinic acid ester 96 (Equation 47) were also stereoselectively hydrolysed under kinetic resolution conditions. Of course, in the case of the latter three kinds of substrates, half of the reacting ester was irreversibly lost due to the formation of achiral phosphorus acids. 

The same authors also studied the alkylation of alkynyl epoxides for formation of optically active a-allenic alcohols under kinetic resolution conditions (Scheme 8.29) [54]. 

The pentanoates 32-37 are obtained with fair enanhoselectivity (E > 47) (Scheme 4.17, bottom half) [74]. When the kinetic resolution conditions were established, efficient conditions for dynamic kinetic resolutions (DKR) were also established (see Chapter 6) [74]. 

Scheme 1. Original Pd(ll)-catalyzed aerobic kinetic resolution conditions [4],...

Ru-salen Kinetic Resolution Conditions (R)-4-Phenyl-3-butyn-2-ol [9]... 

Nitrilase l-Catalyzed Production of Mandelic Acid Derivatives Under Dynamic Kinetic Resolution Conditions (Scheme 20.1)... 

Lipase-mediated acylation of racemic P-chiral hydroxymethanephosphinates (243) was performed in ionic liquids under kinetic resolution conditions. Lipase AK (Amano) and lipase from Pseudomonas fluorescens were up to six time more enantioselective in BMIM PFe solutions than in common organic solvents. ... 

An additional strategy employed by Sih and co-workers involved sequential enzyme-catalyzed reactions. Pseudomonas lipases were found to tolerate a wide range of substrates although the enantioselectivity was generally only moderate. However, by first performing a methanolysis of the oxazolinone followed by a separate enzyme-catalyzed hydrolysis under kinetic resolution conditions, a highly enantio-merically enriched product could be obtained, as shown in Fig. 9-211491. 

Catalysts constituting a C2-symmetric 1,2-diamine have been used to hydrogenate a-aryl aldehydes to yield chiral alcohols, under dynamic kinetic resolution conditions. Hydrogenation of the carbonyl group of acylsilanes with 3 (presence of f-AmOK or NaBHr as activator) is apphcable to acquisition of a-silyl aUylc alcohols from conjugated acylsilanes. ... 

We applied a similar approach under kinetic resolution conditions (Figure 5) (19). First a mixture of 2 and racemic 4-methylcaprolactone (4-MeCL) was reacted until all (S)-4-MeCL had been converted, i.e., to about 50 % total monomer conversion. Subsequently, oxygen was removed from the reaction medium by several consecutive freeze-pump-thaw cycles. The ATRP was initiated by adding MMA and Ni(PPh3)2Br2 and raising the reaction temperature to 80 C. In this case the nickel complex acts as both ATRP initiator and enzyme inhibitor thereby preventing any side reactions caused by the enzyme. Chiral block copolymers were obtained by this approach as evident from SEC analysis. 

Although no mechanism was proposed, the Pd(Me-DuPhos)-catalyzed asymmetric hydrophosphination of an alkyne with a phosphine-borane under kinetic resolution conditions (Scheme 6) presumably involves similar insertion and reductive elimination steps [14]. 

Pd-catalyzed asymmetric arylation of a phosphine-borane, under kinetic resolution conditions, gave enantioenriched phosphine-borane 36. Slowing reductive elimination with a Pd-CsFs group enabled isolation and separation of the diaster-eomers of an analog of the key intermediate (Scheme 56) [94]. The stereochemical details of Pd-P bond formation and P-C reductive elimination, which both proceed with retention at phosphorus, had been elucidated earlier in related Pd(Chiraphos) complexes [95, 96]. 

Examples of electrophilic addition of secondary phosphines to alkenes or alkynes were described. [114, 124, 125, 135]. Glueck [124-126] reported enantioselective tandem reaction of alkylated/arylation of primary phosphines catalyzed by platinum complex, proceeding with formation of chiral phosphaace-naphthenes. Palladium-catalyzed hydrophosphination of alkynes 219 tmder kinetic resolution conditions gave access to 1,1-disubstituted vinylphosphine boranes 220. However, despite screening several chiral ligands, temperatures, and solvents, the... 

The reaction was performed under kinetic resolution conditions (with a ratio 41a alkyne of 1 0.5) for a variety of diphosphines and other bidentate ligands with different stereogenic elements (Table 6.5). 

As early as 1973, Zemer and Dudman reported the kinetic resolution of a P-stereogenic phosphate triester (butylmethyl(p-nitrophenyl)phosphate) by hydrolysis with beef and horse serums, albeit with very low efficiency. The first efficient resolutions of phosphorus stereocentres with enzymes were independently reported in 1994 by two groups. Serreqi and Kazlauskas studied the enantioselective hydrolysis of pendant acetate groups in chiral racemic phosphines and phosphine oxides mediated by several commercially available lipases and esterases, under kinetic resolution conditions i.e. the reaction was stopped at 50% conversion). In general, enantioselectivities were low to moderate, but for one substrate promising results were obtained (Scheme 6.54). 

Another interesting example of asymmetric induction on the nucleophile was described by Hou et al. in 2009 [56]. Under kinetic resolution conditions, racemic nucleophiles rac-66 were enantio- and diastereoselectively allylated yielding the enantioenriched trans-configured allylation products 67 along with the residual enantiomer of the nucleophile (Scheme 12.33). 

Thus, in 2008, List and coworkers published the first enantioselective version of Kabachnik-Fields reaction [214a]. They found that chiral binol-derived phosphoric acids were efficient in inducing chirality under dynamic kinetic resolution conditions when bulky a-branched aldehydes (isopropyl, cyclopentyl and cyclohexyl) were used as substrate in their reaction with p-anisidine and di(3-pentyl) phosphite (Scheme 12.28). In particular, 3,3 -bis(4-anthracenyl-2,6-diisopropylphenyl)-l,l -8-binaphtyl-2, 2 -diyl hydrogenphosphate 80 allowed the synthesis of the corresponding p,p-disubstituted-a-aminophosphonates 84 in high yields with very good stereocontrol (dr up to 28 1 and er up to 97 3). 

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