Cinchona Alkaloid-Catalyzed Enantioselective Monofluoromethylation Reaction Based on Fluorobis(phenylsulfonyl)methane Chemistry Combined with a Mannic

Cinchona Alkaloid-Catalyzed Enantioselective Monofluoromethylation Reaction Based on Fluorobis(phenylsulfonyl)methane Chemistry Combined with a Mannich-type Reaction

Link: JACS ASAP

Satoshi Mizuta, Norio Shibata,* Yosuke Goto, Tatsuya Furukawa, Shuichi Nakamura, and Takeshi Toru*

Department of Applied Chemistry, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555, Japan

A new method for the overall alpha-monofluoromethylation of alpha-amino sulfone. After desulfonation, enantio-enriched compound of type 4 was obtained.

First, the catalysts were screened as shown in Table 1. The most optimal conditions were found to be in runs 10 and 11.

After the optimal conditions were identified, the reaction was screened with different substrates and results are summarized in Table 2 with yields of compounds of type 3.

The compounds of type 3 could be desulfonated under a variety of conditions. All of these conditions are summarized in Table 3, giving the final monofluoromethyl compounds of type 4 in excellent yields.

This is a quite nice two-step protocol to install monofluoromethyl group to alpha-amino sulfone in a quite good to excellent enantioselective manner using 1 effectively as a monofluoromethyl transferring reagent.