Enantioselective nucleophilic aromatic substitution with small-molecule chiral selectors

Article abstract of DOI:10.1002/1522-2675(200211)85:11<3605::AID-HLCA3605>3.0.CO;2-W

Small-molecule rationally designed chiral selectors have been shown to influence the stereochemical outcome of a variety of organic transformations. For instance, in a recent report, we demonstrated that a chiral selector (in conjunction with an achiral phase-transfer catalyst) could selectively inhibit one enantiomer of electron-deficient aromatic amides from forming Meisenheimer adducts (Scheme 2). We now extend this methodology to performing enantioselective nucleophilic aromatic substitutions. Initial studies involved biphasic kinetic resolutions with a chiral selector in conjunction with an achiral phase-transfer catalyst (Scheme 3). The results are consistent with previous data taken for biphasic reactions (e.g., Scheme 1) where the chiral selector effectively shields the more highly complexed enantiomer from reaction. With neutral nucleophiles such as amines, the enantioselective nucleophilic aromatic substitutions can also be conducted in single-phase systems. Several examples are given.