A HIGHLY STEREOCONTROLLED SYNTHESIS OF -(-)-3-(4-TERT-BUTYL)PHENYL-1-N-(CIS-2,6-DIMETHYL) MORPHOLINYL-2-METHYLPROPANE VIA ASYMMETRIC MANNICH REACTION

By employing cis-2,6-dimethylmorpholinemethylene immonium tetrachloroa luminate (5) enamines 9 and 10, prepared from 4-tert-butylpropiophenon e and propiophenone with (R)-(-)-2-(methoxymethyl)pyrrolidine (8), wer e converted to chiral Mannich bases 11,12 with nearly 100% ee; optical purity of these beta-amino ketones drops significantly during isolati on. Two-step reduction of the keto group in 11,12 afforded -1-N-(cis-2 ,6-dimethyl)morpholinyl-2-methylpropane (1), (S)-enantiomer of racemic systemic fungicide, generic name fenpropimorph, and its congener 13 w ith 95.1% and 90.7% ee, respectively. A mechanistic model for asymmetr ic induction in the diastereoselective step is proposed. Copyright (C) 1996 Elsevier Science Ltd