Chiral alcohols directive groups

Modena and colleagues47 have developed use of some chiral, non-racemic terpene alcohols as directing groups for highly diastereoselective m-chloroperbenzoic oxidation of sulfides into sulfoxides. Specifically the isobornyl vinylic sulfides 8 undergo hydroxyl-directed oxidation to give a 9 1 ratio of diastereomeric sulfoxides (equation 11). 

As oxidation also converts the original chiral terpene-derived group to an alcohol, it is not directly reusable as a chiral auxiliary. Although this is not a problem with inexpensive materials, the overall efficiency of generation of enantiomerically pure product is improved by procedures that can regenerate the original terpene. This can be done by heating the dialkylborane intermediate with acetaldehyde. The a-pinene is released and a diethoxyborane is produced.204... 

Acid-induced wagner-meerwein rearrangements in chiral alcohols. In view of the considerable interest on ion-molecule complexes involved in gas-phase analogues of solvolytic reactions," ° " a sustained research effort has been directed to the study of Wagner-Meerwein rearrangements in cationized )8-arylaIkyl systems, under conditions excluding nucleophilic assistance by the solvent which in these systems normally interferes with anchimeric assistance of groups adjacent to the... 

Polysaccharide-based CSPs also exhibit a chiral recognition for alcohols and a large number of resolutions have been reported. Chiral alcohols can usually be directly resolved with hexane containing a small amount of an alcohol as the eluent. For aliphatic alcohols, which cannot be directly resolved, their resolution is often efficiently attained as phenylcarbamate or benzoate derivatives on OD (Figure 17).85 For example, 2-butanol and 2-pentanol are completely resolved with a very high selectivity on OD as their phenylcarbamates. The derivatization of alcohols to phenylcarbamates and benzoates can be easily achieved by the reaction with phenyl isocyanates and benzoyl chlorides, respectively. In most cases, the phenylcarbamates are better resolved than the benzoates. For chiral compounds bearing phenolic hydroxy groups, the addition of a small amount of an acid to an eluent is recommended to depress its dissociation. 

Enantiomeric cyclic amides and imides, esters, ketones, 8- and 7-lactones, and alkyl-substituted indenes can be resolved on CTA-I without derivatization. Chiral alcohols can also be resolved without deiivatiza-tion, but the best results are obtained when they are converted to esters. In general, para-nitrobenzoic esters are recommended if the hydroxyl group is directly attached to the stereogenic center benzoate or para-biomobenzoate... 

Although a multicomponent [4+2] cycloaddition/allylbo-ration reaction is not a new protocol [44] and this sequence has been explored to trap the apparently unstable intermediate with an aldehyde to afford the corresponding alcohols directly after hydrolysis, the pioneering chiral catalytic example was independently reported by Hall s [45] and Carreaux s [46] groups in 2003, and afterward. Hall s research group has extended the methodology (Scheme 4.25) [47],... 

Inversion of Chiral Alcohols. One of the most common applications for cesium acetate is its use in the inversion of the stereochemistry of secondary alcohols that have been converted into better leaving groups. Once the acetate is substituted via a direct SN2-fike displacement, it can then be easily converted back to the alcohol. Some attribute the enhanced nucleophilicity of cesium acetate to a cesium effect. Previously, cesium propionate had been used with alkyl mesylates. The use of this reagent generally resulted in good yields and was preferred to other methods, but it could lead to complicated interpretation of resulting H NMR spectra, whereas an acetate product could be more easily carried forward into further synthetic modification. 

The same RuH(CO)(PCy3)(C6H6)]BF4 catalyst precursor has been used for the ortho sp C-H bond monoalkylation of phenols with both primary and secondary alcohols, in which the hydroxyl phenol group is a directing group for C-H bond activation [(Eq. 44)] [130]. The alkylation with chiral (R)-PhCH(Me)CH20H occurs without racemization. 

In an efficient synthesis of GSK966587, 129, another broad spectrum antibiotic, Voight and co-workers utilised SAE as a way to install a key chiral tertiary alcohol. After the preparation of naphthpyridine 130, SAE was used to generate spiro epoxide 131 in 90% ee. Subsequent treatment with cone. HCl led to in situ formation of 132 which cyclised upon heating to provide 133. Two additional steps were required to elaborate 133 to the final target (Scheme 14.52). While there are numerous other examples in the industrial literature " which utilise SAE, it was the Jacobsen catalyst system that subsequently allowed pharmaceutical chemists to get away from allylic alcohols and epoxidise directing group-free olefins. 

Hydroxy group directivity in the epoxidation of chiral allylic alcohols 99ACR703. 

The landmark report by Winstein et al. (Scheme 3.6) on the powerful accelerating and directing effect of a proximal hydroxyl group would become one of the most critical in the development of the Simmons-Smith cyclopropanation reactions [11]. A clear syw directing effect is observed, implying coordination of the reagent to the alcohol before methylene transfer. This characteristic served as the basis of subsequent developments for stereocontrolled reactions with many classes of chiral allylic cycloalkenols and indirectly for chiral auxiliaries and catalysts. A full understanding of this phenomenon would not only be informative, but it would have practical applications in the rationalization of asymmetric catalytic reactions. 

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