Cyclohexene oxide stereoselective deprotonation

Investigation of site selectivity of the stereoselective deprotonation of cyclohexene oxide has been performed using kinetic resolution of isotopic enantiomers in natural abundance.40... 

Computational chemistry has been employed to calculate energy differences between diastereomeric activated complexes in the stereoselective deprotonations of cyclohexene oxide by monomeric, homo- and heterodimeric lithium amides (see Section II.A.2). Computational chemistry has also been used as a tool for design of highly stereoselective amides. Such a design approach has resulted in the homochiral base 20 and its enantiomer. These are readily available from both enantiomers of norephedrine, by inexpensive routes... 

Lithium amides derived from secondary amines like lithium diisopro-pylamide (1) appear to be strong enough bases to deprotonate epoxides, ketones, etc. However, when 1, which is a non-chiral base, deprotonates the non-chiral epoxide cyclohexene oxide (2), equal amounts of the two enantiomeric products (5)- and (/ )-cyclohex-2-enol (3) are formed in the abstraction of a proton from carbon 2 and 5, respectively, with accompanying opening of the epoxide ring (Scheme 1). Thus, none of the two enantiomeric products is formed in enantiomeric excess (ee), i.e., the reaction shows no stereoselectivity (Scheme 1). 

During the last decades, a number of chiral lithium amides have been developed for stereoselective deprotonation of, e.g., epoxides. For example, the lithium amide lithium (5 )-2-(pyrrolidin-l-yl-methyl)pyrroli-dide (4) was for a long time the most stereoselective base used in epoxide deprotonations. It gives 90% of the (5 )-enantiomer and 10% of the (/ )-enantiomer upon deprotonation of cyclohexene oxide 2 in THF solution (Scheme 2) [4-6]. 

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