Stereocontrolled alkylation of chiral pyridinium salt toward a short enantioselective access to 2-alkyl- and 2,6-dialkyl-1,2,5,6-tetrahydropyridines

Treatment of salts 1a-b with Grignard reagents gives, after reduction of th e resulting unstable dihydropyridines 7, the tetrahydropyridines 8a-c, with modest selectivities but in very few steps and under practical conditions. Higher stereo- and regioselectivities are obtained with salt Ic which give s the tetrahydropyridines 15a-e. In addition, the dihydropyridine intermedi ates 11b cyclize to give the new oxazolidine derivatives 12a-e, which turn out to be good precursors of the 2,6-trans-disubstituted tetrahydropyridine s 21a-e. Selective syntheses of (-)-lupetidin, (+)-solenopsin, and indolizi dines (-)-5 and (-)-6 are presented as representative examples of applicati ons.