Reduction reactions chiral auxiliaries

Moreover, this two-step equivalent of an aldol condensation can proceed with high enantioselectivity in the presence of a chiral auxiliary. Thus reaction of the enolate of chiral silyl ketene acetal (5) with isobutyryl chloride gives 6 in 89% yield and 94% ee after reduction of the intermediate. 

Chiral oxazolines developed by Albert I. Meyers and coworkers have been employed as activating groups and/or chiral auxiliaries in nucleophilic addition and substitution reactions that lead to the asymmetric construction of carbon-carbon bonds. For example, metalation of chiral oxazoline 1 followed by alkylation and hydrolysis affords enantioenriched carboxylic acid 2. Enantioenriched dihydronaphthalenes are produced via addition of alkyllithium reagents to 1-naphthyloxazoline 3 followed by alkylation of the resulting anion with an alkyl halide to give 4, which is subjected to reductive cleavage of the oxazoline moiety to yield aldehyde 5. Chiral oxazolines have also found numerous applications as ligands in asymmetric catalysis these applications have been recently reviewed, and are not discussed in this chapter. ... 

Scheme 5 details the asymmetric synthesis of dimethylhydrazone 14. The synthesis of this fragment commences with an Evans asymmetric aldol condensation between the boron enolate derived from 21 and trans-2-pentenal (20). Syn aldol adduct 29 is obtained in diastereomerically pure form through a process which defines both the relative and absolute stereochemistry of the newly generated stereogenic centers at carbons 29 and 30 (92 % yield). After reductive removal of the chiral auxiliary, selective silylation of the primary alcohol furnishes 30 in 71 % overall yield. The method employed to achieve the reduction of the C-28 carbonyl is interesting and worthy of comment. The reaction between tri-n-butylbor-... 

Alkaline hydrolysis of the crude adduct formed with benzaldehyde, followed by treatment with diazomethane and column chromatography, affords methyl (2R,3S)-3-hydroxy-2-methyl-3-phenylpropanoate in 96% ee. Reduction of the crude products formed in the reactions with 2-inethylpropanal and 2,2-dimethylpropanal leads to the corresponding 1,3-diols with >96% ee. In both the hydrolysis and the reduction procedures, the chiral auxiliary reagent, 1,1,2-triphenyl-1,2-ethanediol, can be recovered and reused72. 

Substituted 3-hydroxy-2-pyrrolidinones were synthesised via 1,3-DC reactions of furfuryl nitrones with acrylates and subsequent intramolecular cyclisation after N-0 bond reduction. Addition of iV-acryloyl-(2/()-bomane-10,2-sultam to Z-nitrone 83 gave the endo/exo cycloadducts in 85 15 ratio with complete stereoface discrimination <00JOC1590>. The 1,3-DC of pyrroline A-oxide to chiral pentenoates using (-)-/rans-2-phenylcyclohexanol and (-)-8-phenylmenthol as chiral auxiliaries occurred with moderate stereocontrol (39% de and 57% de, respectively) and opposite sense of diastereoselectivity <00EJO3595>. The... 

Hydride reductions of C = N groups are well known in organic chemistry. It was therefore obvious to try to use chiral auxiliaries in order to render the reducing agent enantioselective [88]. The chiral catalyst is prepared by addition of a chiral diol or amino alcohol, and the active species is formed by reaction of OH or NH groups of the chiral auxiliary with the metal hydride. A major drawback of most hydride reduction methods is the fact that stoichiometric or higher amounts of chiral material are needed and that the hydrolyzed borates and aluminates must be disposed of, which leads to increased costs for the reduction step. 

The chiral auxiliaries anchored to the substrate, which is subjected to diastereoselective catalysis, is another factor that can control these reactions. These chiral auxiliaries should be easily removed after reduction without damaging the hydrogenated substrate. A representative example in this sense is given by Gallezot and coworkers [268], They used (-)mentoxyacetic acid and various (S)-proline derivates as chiral auxiliaries for the reduction of o-cresol and o-toluic acid on Rh/C. A successful use of proline derivates in asymmetric catalysis has also been reported by Harada and coworkers [269,270], The nature of the solvent only has a slight influence on the d.e. [271],... 

Recently, Schaumann et al. 153,154 an(j Bienz et tf/.155,156 have developed dependable routes for the resolution of racemic functionalized organosilanes with Si-centered chirality using chiral auxiliaries, such as binaphthol (BINOL), 2-aminobutanol, and phenylethane-l,2-diol (Scheme 2). For instance, the successive reaction of BINOL with butyllithium and the chiral triorganochlorosilanes RPhMeSiCl (R = /-Pr, -Bu, /-Bu) affords the BINOL monosilyl ethers 9-11, which can be resolved into the pure enantiomers (A)-9-ll and (7 )-9-11, respectively. Reduction with LiAlFF produces the enantiomerically pure triorgano-H-silanes (A)- and (R)-RPhMeSiH (12, R = /-Pr 13, -Bu 14, /-Bu), respectively (Scheme 2). Tamao et al. have used chiral amines to prepare optically active organosilanes.157... 

High asymmetric induction by amphiphilic dendrimers was reported by Rico-Lattes and co-workers [32]. These water-soluble but THF-insoluble dendrimers (e.g. 22, Scheme 23) consist of useful, readily available chiral auxiliaries and can be used in the homogeneous (when H20 is the solvent) or heterogeneous (in the case of THF as the reaction medium) catalyzed reduction of prochiral aromatic... 

Brimble and coworkers176 studied the asymmetric Diels-Alder reactions of cyclopentadiene with chiral naphthoquinones 272 bearing different chiral auxiliaries. The highest endo and facial selectivities were obtained using zinc dichloride as the Lewis acid catalyst and (—)-pantolactone as the chiral auxiliary. Thus, the reaction between cyclopentadiene and 272 afforded a 98 2 mixture of 273 and 274 (equation 76). The chiral auxiliary was removed easily by lithium borohydride reduction. 

The optical yield was found to be very sensitive to structural modifications of the achiral agent. For example, use of the more bulky FV or Bu substituents in the 3,5-positions of phenol resulted in lower optical yields. In some cases a reversal of the sense of asymmetric induction was observed. Systematic variation of reaction conditions using the best achiral component, 3,5-xylenol, established that optimum results were obtained in ether solvent at about - 15°C. There was also a minor but definite influence of the rate of addition of ketone as well as an effect of concentration on optical yield, with a slower rate being advantageous. The results of reduction of aryl alkyl ketones are shown in Table 9, along with comparative results of reduction with similar chiral auxiliary reagents. 

Access to the corresponding enantiopure hydroxy esters 133 and 134 of smaller fragments 2 with R =Me employed a highly stereoselective (ds>95%) Evans aldol reaction of allenic aldehydes 113 and rac-114 with boron enolate 124 followed by silylation to arrive at the y-trimethylsilyloxy allene substrates 125 and 126, respectively, for the crucial oxymercuration/methoxycarbonylation process (Scheme 19). Again, this operation provided the desired tetrahydrofurans 127 and 128 with excellent diastereoselectivity (dr=95 5). Chemoselective hydrolytic cleavage of the chiral auxiliary, chemoselective carboxylic acid reduction, and subsequent diastereoselective chelation-controlled enoate reduction (133 dr of crude product=80 20, 134 dr of crude product=84 16) eventually provided the pure stereoisomers 133 and 134 after preparative HPLC. 

Perlmutter used an oxymercuration/demercuration of a y-hydroxy alkene as the key transformation in an enantioselective synthesis of the C(8 ) epimeric smaller fragment of lb (and many more pamamycin homologs cf. Fig. 1) [36]. Preparation of substrate 164 for the crucial cyclization event commenced with silylation and reduction of hydroxy ester 158 (85-89% ee) [37] to give aldehyde 159, which was converted to alkenal 162 by (Z)-selective olefination with ylide 160 (dr=89 l 1) and another diisobutylaluminum hydride reduction (Scheme 22). An Oppolzer aldol reaction with boron enolate 163 then provided 164 as the major product. Upon successive treatment of 164 with mercury(II) acetate and sodium chloride, organomercurial compound 165 and a second minor diastereomer (dr=6 l) were formed, which could be easily separated. Reductive demercuration, hydrolytic cleavage of the chiral auxiliary, methyl ester formation, and desilylation eventually led to 166, the C(8 ) epimer of the... 

Chiral benzamides I and the pyrrolobenzodiazepine-5,11-dio-nes n have proven to be effective substrates for asymmetric organic synthesis. Although the scale of reaction in our studies has rarely exceeded the 50 to 60 g range, there is no reason to believe that considerably larger-scale synthesis will be impractical. Applications of the method to more complex aromatic substrates and to the potentially important domain of polymer supported synthesis are currently under study. We also are developing complementary processes that do not depend on a removable chiral auxiliary but rather utilize stereogenic centers from the chiral pool as integral stereodirectors within the substrate for Birch reduction-alkylation. 

Another aspect of the chemical properties of mixmres of enantiomers has been reported by Wynberg and Feringa in 1976. These authors have smdied some dia-stereoselective reactions on chiral molecules (such as the LiAlH4 reduction of camphor) in the absence of chiral auxiliaries. They found that the product distribution was significantly different if the substrate was enantiopure or racemic. Similarly, it is known that reduction of enantiopure or racemic camphor by K/liquid NH3 gives rise to different isobomeol/bomeol ratios, a detailed mechanistic analysis has been done by Rautenstrauch. °... 

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