SYNTHESIS OF DE NOVO CHIRAL γ-AMINO-YNAMIDES USING LITHIATED YNAMIDES. OBSERVATION OF A UNIQUE 5-ENDO-DIG CYCLIZATION WITH AN INVERSION OF S-CENTER.

We describe herein details of our efforts in developing a highly stereoselective synthesis of de novo chiral γ-amino-ynamides through additions of lithiated ynamides to Ellman-Davis chiral N-tert-butanesulfinyl imines. While additions of ynamides could be highly stereoselective even without Lewis acids, the use of BF3-OEt2 completely reversed the stereoselectivity. On the other hand, additions of oxazolidinone-substituted, oxazinanone-substituted and tetrahydropyrimidinone-substituted ynamides behaved quite differently and functioned better with BF3-OEt2. The chirality of the oxazolidinone ring exerts no impact on the selectivity. This work also features a unique 5-endo-dig cyclization of oxazolidinone-substituted γ-amino-ynamides that could be promoted with acid, leading to isothiazoles and 2,3-dihydro-isothiazole S-oxides.

A highly stereoselective addition of lithiated ynamides to Ellman-Davis chiral N-tert-butanesulfinyl imines.

A highly diastereoselective addition of lithiated ynamides to Ellman-Davis chiral imines is described. While additions of N-sulfonyl ynamides are highly stereoselective even without Lewis acids, the use of BF3-OEt2 completely reversed the stereoselectivity. In addition, oxazolidinone-substituted ynamides behaved differently and functioned better with BF3-OEt2, and the chirality of the oxazolidinone ring exerts no impact on the selectivity.