Here is an interesting article for efficient synthesis of fluorinated pyrrolidin synthesis from pfizer.
Fluorine containing building blocks are often used medicinal chemistry. So efficient synthetic route is very useful for us.
Some years ago, I synthesized similar compounds 1-fluoro-2-amino cyclic amine derivatives. I tried to use almost same synthetic scheme described in scheme1. 1) Epoxydation 2) Epoxy opening with sodium azide, 3) DAST-Fluorination, 4) Azide reduction.
The scheme is stereo selective if epoxyde is chiral. I like substrate controlled synthetic rote like this.
The scheme 1 is first generation which uses mCPBA, NaN3 and DAST it is not suitable for large scale production. Then the authors group developed very efficient synthetic route. They used modified burgess type reagent. The reaction with the reagent and 1,2-trans-diol makes cis-cyclic sulfamate intermediate. Key point of the strategy transform trans diol to sys amino alcohol as protected form. And also the its hydroxyl group protected SO2NR, it means the hydroxyl group is leaving group.
So the cyclic sulfamate reacts with TBAF and give trans-Fluoro protected amine. You can check the over view of the synthesis in the online abstract.
The merit of the scheme is that switching fluorination reagent from DAST to TBAF, switching nitrogen source from sodium azide to burgess reagent I think (of course there are more advantages and it described in the article).
Thanks the authors for publishing nice synthetic approach.