Stereoselective Monofluoromethylation of Primary and Secondary Alcohols by Using a Fluorocarbon Nucleophile in a Mitsunobu Reaction «

Stereoselective Monofluoromethylation of Primary and Secondary Alcohols by Using a Fluorocarbon Nucleophile in a Mitsunobu Reaction

G. K. Surya Prakash^*, Sujith Chacko, Steevens Alconcel, Timothy Stewart, Thomas Mathew, George A. Olah^*

Loker Hydrocarbon Research Institute and, Department of Chemistry, University of Southern California, University Park, Los Angeles, CA 90089-1661, USA

The following method is very similar to this one, that it demonstrates a strategy to synthesize monofluoromethyl derivative compounds, at least in the purpose of the research. The products are different type as the one cited in the link above are amino fluoro methyl derivatives, but this one here, the method seems to be applicable to primary and secondary alcohols (via Mitsunobu), giving a wider variety of products. The reagent used in both papers is the same one, however (1).

The initial products after the Mitsunobu step show an agreeable inversion of configuration at the former carbinol centers as shown in the table below.

Applicability is general as shown in the table below.

The bis-sulfonyl products could be di-hydrodesulfonated to give the monoflouoromethyl products in good to execellent yields.

This method could be successfully applied to natural compounds such as vitamin D3 and the tetraacetyl glucopyranose as shown in Schemes 2 and 3.

In addition to 1, a different fluoromethylating agent such as 6, possessing appropriate pKa, also smoothly participated in the current Mitsunobu strategy.