Chiral compounds tertiary alcohols

Various chiral derivatizing agents have been reported for the determination of enantiomer compositions. One example is determining the enantiomeric purity of alcohols using 31P NMR.28 As shown in Scheme 1-8, reagent 20 can be readily prepared and conveniently stored in tetrahydrofuran (THF) for long periods. This compound shows excellent activity toward primary, secondary, and tertiary alcohols. To evaluate the utility of compound 20 for determining enantiomer composition, some racemic alcohols were chosen and allowed to react with 20. The diastereomeric pairs of derivative 21 exhibit clear differences in their 31P NMR spectra, and the enantiomer composition of a compound can then be easily measured (Scheme 1-8). 

Two principal approaches to the synthesis of an optically pure chiral secondary or tertiary alcohol from the reaction of an organometallic reagent with an aldehyde or ketone respectively are of current interest. In the first approach an alkyllithium or dialkylmagnesium is initially complexed with a chiral reagent which then reacts with the carbonyl compound. In this way two diastereo-isomeric transition states are generated, the more stable of which leads to an enantiometic excess of the optically active alcohol. This approach is similar in principle to the asymmetric reductions discussed in Section 5.4.1 (see also p. 15). Two chiral catalysts may be noted as successful examples, (10) derived... 

Enantioselective Butylation of Carbonyl Compounds with Lithium Tetra-n-butylaluminate Modified with (1). The reaction between lithium tetra-n-butylaluminate and (1) forms the chiral lithium alkoxytri-n-butylaluminate. This chiral ate complex reduces carbonyl compounds to form secondary and tertiary alcohols in 8-31 % ee (eq 6). ... 

The bulk of oxidations with tert-butyl hydroperoxide consists of epoxidations of alkenes in the presence of transition metals [147, 215, 216, 217, 218]. In this way, a,p-unsaturated aldehydes [219] and ketones [220] are selectively oxidized to epoxides without the involvement of the carbonyl function. Other applications of tert-butyl hydroperoxide such as the oxidation of lactams to imides [225], of tertiary amines to amine oxides [226, 227], of phosphites to phosphates [228], and of sulfides to sulfoxides [224] are rare. In the presence of a chiral compound, enantioselective epoxidations of alcohols are successfully accomplished with moderate to high enantiomeric excesses [221, 222, 223]. 

Chiral auxiliary-bound substrates have also been used for the asymmetric process. The aldol reaction of chiral pyruvates such as 46 is a reliable method for highly enantioselective synthesis of functionalized tertiary alcohols (Scheme 10.38) [112]. The Lewis acid-catalyzed aldol-type reactions of chiral acetals with silyl enolates are valuable for the asymmetric synthesis of -alkoxy carbonyl compounds ]113, 114]. 

The reactions of enolates bearing chiral auxiliaries with formaldehyde or symmetrical ketones can be stereoselective. After removal of the auxiliary, nonra-cemic primary or tertiary alcohols are obtained. The reaction of lithium enolates of Schollkopfs lactim ethers 1.114 with symmetrical carbonyl compounds are highly stereoselective, as are the reactions of enolates of Seebach s imidazolidinone S.39 (R = Ph). In both cases, the enolate reacts from its least hindered face [154, 261] (Figure 6.11). After acidic hydrolysis, P-hydroxy-a-aminoacids are obtained with a high enantiomeric excess. However, when R = H, some unwanted epimerization can take place. 

An optically active acetylenic alcohol is an useful starting material to prepare various chiral compounds, because it has two functional groups. However, the optical resolution of an acetylenic alcohol by the diastereomeric method for its phthalic acid half-ester is complicated and successful only in a few cases,1 Recently, the preparation of optically active secondary acetylenic alcohol by the enantioselective reduction of ethynyl ketone or by the enantioselective addition of lithium acetylide to aldehyde has been reported. However, these methods are not applicable to the preparation of optically active tertiary acetylenic alcohols. 

Although the enantioselective stoichiometric addition of chiral aryltitanium reagents have been reported in 1987 [66], the catalytic enantioselective aryl addition to carbonyl compounds with titanium catalyst was realized by Walsh using the catalyst prepared from bis(sulfonamide) ligand and Ti(OTr)4 with diarylzinc as the nucleophiles, to afford the tertiary alcohol in good to excellent enantioselectivities for a range of ketone substrates [67]. Very recently, Gau reported that... 

Fig. 3 Examples of marketed drugs and biologically active compounds bearing chiral tertiary alcohols...

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