Novel Sulfoxide Catalysts for the Nucleophilic Substitution of Alcohols

Alcohols are the most abundant functional group in organic chemistry, both in natural products and commercially available chemicals, making them an important raw material for organic synthesis. One of the most widely used methods for the conversion of alcohols to other functional groups is the Mitsunobu reaction, which is stereospecific and high yielding, however, is problematic from a sustainability perspective as it uses hazardous reagents and produces stoichiometric waste. The development of a redox-neutral, catalytic version of the Mitsunobu reaction, reported in 2019 by Denton and coworkers, removes the need for the toxic reagent and negates the problem of waste. This method works well for simple, unfunctionalized secondary alcohols and high levels of inversion are observed, however, applications are currently limited.

Building on this work to develop a general, robust and stereospecific method for the direct substitution of unactivated alcohols is a valuable research objective, and has been highlighted as one of the top 10 key green chemistry research areas by the ACS Green Chemistry Institute Pharmaceutical Roundtable.