Chiral compounds Alcohols

Other methods to form carboxylic acids Cyanotrimethylsilane, 87 a-Substituted carboxylic acids (see also Amino acids, Halo carbonyl compounds, Hydroxy acids) Camphor-10-sulfonic acid, 62 Chiral compounds Alcohols... 

The remarkable stereospecificity of TBHP-transition metal epoxidations of allylic alcohols has been exploited by Sharpless group for the synthesis of chiral oxiranes from prochiral allylic alcohols (Scheme 76) (81JA464) and for diastereoselective oxirane synthesis from chiral allylic alcohols (Scheme 77) (81JA6237). It has been suggested that this latter reaction may enable the preparation of chiral compounds of complete enantiomeric purity cf. Scheme 78) ... 

The most successful of the Lewis acid catalysts are oxazaborolidines prepared from chiral amino alcohols and boranes. These compounds lead to enantioselective reduction of acetophenone by an external reductant, usually diborane. The chiral environment established in the complex leads to facial selectivity. The most widely known example of these reagents is derived from the amino acid proline. Several other examples of this type of reagent have been developed, and these will be discussed more completely in Section 5.2 of part B. 

The major application of the Mitsunobu reaction is the conversion of a chiral secondary alcohol 1 into an ester 3 with concomitant inversion of configuration at the secondary carbon center. In a second step the ester can be hydrolyzed to yield the inverted alcohol 4, which is enantiomeric to 1. By using appropriate nucleophiles, alcohols can be converted to other classes of compounds—e.g. azides, amines or ethers. 

Baker s yeast reducdon of y-nitroketones offers the corresponding chiral nitro alcohols, which areusefid bndding blocks for the synthesis of chiral naniral compounds. For example, opdcally acdve 2-subsdnited pyrrolidine can be prepared using the chiral nitro alcohol fEq. 10.751. ... 

A reiterative application of a two-carbon elongation reaction of a chiral carbonyl compound (Homer-Emmonds reaction), reduction (DIBAL) of the obtained trans unsaturated ester, asymmetric epoxidation (SAE or MCPBA) of the resulting allylic alcohol, and then C-2 regioselective addition of a cuprate (Me2CuLi) to the corresponding chiral epoxy alcohol has been utilized for the construction of the polypropionate-derived chain ]R-CH(Me)CH(OH)CH(Me)-R ], present as a partial structure in important natural products such as polyether, ansamycin, or macro-lide antibiotics [52]. A seminal application of this procedure is offered by Kishi s synthesis of the C19-C26 polyketide-type aliphatic segment of rifamycin S, starting from aldehyde 105 (Scheme 8.29) [53]. 

As with the reduction of aldehydes and ketones (16-23), the addition of organometallic compounds to these substrates can be carried out enantioselectively and diastereoselectively. Chiral secondary alcohols have been obtained with high ee values by addition to aromatic aldehydes of Grignard and organolithium compounds in the presence of optically active amino alcohols as ligands. ... 

Synthesis of optically pure compounds via transition metal mediated chiral catalysis is very useful from an industrial point of view. We can produce large amounts of chiral compounds with the use of very small quantities of a chiral source. The advantage of transition metal catalysed asymmetric transformation is that there is a possibility of improving the catalyst by modification of the ligands. Recently, olefinic compounds have been transformed into the corresponding optically active alcohols (ee 94-97%) by a catalytic hydroxylation-oxidation procedure. 

A number of ketones, pharmaceutical compounds, alcohols and hydroxy acids have also been resolved on this phase [724,765-767]. A chiral polysiloxane phase with tartramide substituents has been used for the separation of enantiomers capable of hydrogen bonding interactions with the stationary phase, such as enantiomers containing carboxylic, hydroxyl and amine functional groups [768]. 

Tandem transesterification and diastereoselective intramolecular 1,3-dipolar cycloaddition of a-methoxycarbonylnitrones with chiral allyl alcohols give polycyclic compounds in one step with high stereoselectivity (Scheme 8.14).76 Transition state Ain Scheme 8.14 is more favorable than B because B has severe steric interaction (allylic 1,3-strain).77... 

Hummel, W. (1997) New alcohol dehydrogenases for the synthesis of chiral compounds. Advances in Biochemical Engineering/Biotechnology, 58, 145-184. 

The synthetic utility of chiral epoxy alcohol synthons produced by the Sharpless asymmetric epoxidation has been demonstrated in enantioselective syntheses of many important compounds. 

In reactions of chiral aldehydes, TiIV compounds work well as both activators and chelation control agents, a- or A-oxygcnated chiral aldehydes react with allylsilanes to afford chiral homoallylic alcohols with high selectivity (Scheme 22).85 These chiral alcohols are useful synthetic units for the synthesis of highly functionalized chiral compounds. Cyclic chiral 0,0- and A/O-acetals react with allylsilanes in the same way.86,87 Allenylsilanes have also been reported as allylation agents. 

Perhaps the most investigated reaction of organozinc compounds is their addition to the carbonyl group of aldehydes. A broad range of simple and functionalized diorganozincs and a great variety of aldehydes have been studied in this transformation. The reaction furnishes chiral secondary alcohols, which are essential building blocks in the synthesis of natural products and other important compounds. Recent studies of this transformation have been devoted to its asymmetric catalytic versions (Scheme 103). 

Nucleophilic addition of metal alkyls to carbonyl compounds in the presence of a chiral catalyst has been one of the most extensively explored reactions in asymmetric synthesis. Various chiral amino alcohols as well as diamines with C2 symmetry have been developed as excellent chiral ligands in the enantiose-lective catalytic alkylation of aldehydes with organozincs. Although dialkylzinc compounds are inert to ordinary carbonyl substrates, certain additives can be used to enhance their reactivity. Particularly noteworthy is the finding by Oguni and Omi103 that a small amount of (S)-leucinol catalyzes the reaction of diethylzinc to form (R)-l-phenyl-1 -propanol in 49% ee. This is a case where the... 

Since the discovery of the CBS catalyst system, many chiral //-amino alcohols have been prepared for the synthesis of new oxazoborolidine catalysts. Compounds 95 and 96 have been prepared93 from L-cysteine. Aziridine carbi-nols 97a and 97b have been prepared94 from L-serine and L-threonine, respectively. When applied in the catalytic borane reduction of prochiral ketones, good to excellent enantioselectivity can be attained (Schemes 6-42 and 6-43). 

The earliest enantioselective Reformatsky reaction was reported in 1973.52 Compound (-)-spartein was used as the chiral ligand, but the reaction gave rather low yield. Almost 20 years later, in 1991, Soai and Kawase53 reported an enantioselective Reformatsky reaction in which chiral amino alcohol 58 or 59 was used as the ligand. Aliphatic and aromatic //-hydroxy esters were obtained with moderate to good yields. 

Fluorine-containing compounds can also be synthesized via enantioselective Reformatsky reaction using bromo-difluoroacetate as the nucleophile and chiral amino alcohol as the chiral-inducing agent.86 As shown in Scheme 8-41, 1 equivalent of benzaldehyde is treated with 3 equivalents of 111 in the presence of 2 equivalents of 113, providing a,a-difluoro-/ -hydroxy ester 112 at 61% yield with 84% ee. Poor results are observed for aliphatic aldehyde substrates. For example, product 116 is obtained in only 46% ee. 

Acid-induced mcemization and isomerization of chiral allylic alcohols. Bimolecular nucleophilic displacements in allylic compounds are known to proceed via the four possible pathways shown in Scheme 19. 

The chiral compounds (/ )- and (5)-bis(trifluoromethyl)phenylethanol are particularly useful synthetic intermediates for the pharmaceutical industry, as the alcohol functionality can be easily transformed without a loss of stereospecificity and biological activity, and the trifluoromethyl functionalities slow the degradation of the compound by human metabolism. A very efficient process was recently demonstrated for the production of the (5)-enantiomer at >99% ee through ketone reduction catalyzed by the commercially available isolated alcohol dehydrogenase enzyme from Rhodococcus erythropolis (Figure 9.1). The (7 )-enantiomer could be generated at >99% ee as well using the isolated ketone reductase enzyme KRED-101. 

Relatively little attention has been paid to the conversion of racemic compounds into their enantiomerically pure versions in a single process, in other words a deracemization. For certain classes of chiral compounds such as secondary alcohols, this approach should provide many benefits, particularly to the pharmaceutical industry. Existing routes to high value intermediates in their racemic form may be modified to provide the equivalent homochiral product, thus reducing the extent of development chemistry required. In addition, the... 

Enzymes are natural biocatalysts that are becoming increasingly popular tools in synthetic organic chemistry [1]. The major areas of exploration have involved the use of hydrolases, particularly esterases and lipases [2]. These enzymes are readily available, robust and inexpensive. The second most popular area of investigation has been the reduction of carbonyl compounds to chiral secondary alcohols using either dehydrogenases (with co-factors) or a whole-cell system such as bakers yeast [3]. 

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