Novel Chiral 1,3-Diamines by a highly-modular Umpolung Strategy employing a Diastereoselective Fluorination Nucleophilic Aromatic Substitution Sequence

A new highly modular synthesis for the rare class of chiral 1,3-diamines has been devised. It is accessible through nucleophilic aromatic ipso-substitution of fluorine in [(R,R)-1-fluoro-2-{(1-dimethylamino)ethyl}benzene]tricarbonylchromium and related complexes by secondary as well as primary amines. The precursor is accessible by a new diastereoselective electrophilic fluorination using N-fluorobenzenesulfonimide (NFSI), and the method is of potential interest for the synthesis of fluorinated pharmaceuticals. The protocol allows for the straightforward, modular synthesis of a broad library of diamines. A stock of 21 diamines has been synthesized. Primary amines bearing a stereogenic ?-center can be introduced without loss of optical purity, yielding planar-chiral diamines with two stereogenic centers in close proximity. An extended number of X-ray structures of these diamines is presented and discussed along with NMR experiments which show them to be "chiral proton-donors". The 1,3-diaminoarene moiety can easily be liberated from the chromium complex by decomplexation with I2 as exemplified in four examples. The new methodology adds a powerful tool to the synthesis of organic diamines, and opens a new way to the formerly difficult-to-access class of chiral 1,3-diamines.