Novel Chiral 1,3‐Diamines by a Highly Modular Umpolung Strategy Employing a Diastereoselective Fluorination–Nucleophilic Aromatic Substitution Sequence

Abstract

AbstractA 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 α‐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. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)