Bicyclic secondary alcohol resolution

High enantiomeric excess in organocatalytic desymmetrization of meso-diols using chiral phosphines as nucleophilic catalysts was achieved for the first time by Vedejs et al. (Scheme 13.21) [36a], In this approach selectivity factors up to 5.5 were achieved when the C2-symmetric phospholane 42a was employed (application of chiral phosphines in the kinetic resolution of racemic secondary alcohols is discussed in Section 12.1). A later study compared the performance of the phos-pholanes 42b-d with that of the phosphabicyclooctanes 43a-c in the desymmetrization of meso-hydrobenzoin (Scheme 13.21) [36b], Improved enantioselectivity was observed for phospholanes 42b-d (86% for 42c) but reactions were usually slow. Currently the bicyclic compound 43a seems to be the best compromise between catalyst accessibility, reactivity, and enantioselectivity - the monobenzoate of hydrobenzoin has been obtained with a yield of 97% and up to 94% ee [36b]. 

One of the typical applications of chiral DMAP catalysts is the atylative kinetic resolution of racemic secondary alcohols. Two landmark catalj ts, planer chiral DMAP catalyst 7 and chiral bicyclic PPY catalyst 10, were developed independently by Fu and Kawabata, respectively (Schemes 22.1 and 22.2). Catalysts 7 showed excellent properties as chiral nucleophilic catalysts. In the presence of 2 mol% of 7b, a variety of racemic secondaiy alcohols possessing aryl (or vinyl) and allg l groups such as 8 and 9 were kinetically resolved with acetic anhydride to give the acetates and the recovered starting materials in high enantioselectivity (s = 12-52) (Scheme 22.1). ... 

Axially chiral carboxylic acids such as [2] and [3] can be used to prepare diastereoisomers of secondary alcohols. The NMR spectra of the diastereoisomers show enantiomeric resolution and it is possible to assign absolute configurations. Monocyclic, chiral carboxylic acid compounds such as tetrahydro-5-oxo-2-furancarboxylic acid and 2,2-diphenylcyclo-propane-carboxylic acid have been used to derivatize secondary alcohols for the purpose of enantiomeric resolution. Similarly, bicyclic derivatizing agents such as camphanic acid, camphanic acid chloride, or camphor sulfonyl chloride have been used to derivatize amines or alcohols to their respective amides or esters for the purpose of enantiomeric resolution. 

The efficient enzymatic resolution of racemic cyclic secondary alcohols can be extended to several bicyclic alcohols of different structures. These can be tetralols, indanols. 

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