Stereochemical control and specificity is essential in many applications, including natural products synthesis and medicinal design. Methods for inverting configuration are useful for situations where the desired stereochemistry is not achieved in a particular reaction. We present synthetic methodology for inverting configuration at alcohol centers in a two-step reaction, not involving metal catalysis. The procedure involves tosylation of the alkoxide from the alcohol with p-toluenesulfonyl anhydride to provide a derivative with an excellent leaving group for subsequent S<sub>N</sub>2 substitution. Reaction with potassium hydroxide in hot DMSO solution results in stereospecific displacement of the tosylate anion by hydroxide with complete inversion of configuration at the stereo center. This synthetic procedure can be used to convert alcohols in the R-configuration to S-configuration and vice versa. It is also useful for changing the cis or trans configuration of non-chiral molecules such as 4-substituted cyclohexanols. This procedure is relatively simple to carry out and can be completed in situ. The general applicability of this method is explored with a series of alcohols. In addition, reactions with other nucleophiles, e.g. cyanide, halides, etc., are also investigated.

Simple, stereospecific method for inversion of alcohols

253rd National Meeting (2017)

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