title: Betti's base for crystallization-induced deracemization of substituted aldehydes: synthesis of enantiopure amorolfine and fenpropimorph.
abstract: The acid-promoted crystallization-induced diastereoisomer transformation (CIDT) of naphthoxazines derived from racemic O-protected 2-substituted 4-hydroxybutyraldehydes and enantiopure Betti's base allows the deracemization of the starting aldehydes with ee up to 96%. As an alternative, reduction with lithium aluminum hydride of the diastereoisomerically enriched naphthoxazines leads to enantioenriched primary amines. The utility of the latter strategy was demonstrated by applying it to the synthesis of enantioenriched fenpropimorph and to the first synthesis of enantiopure amorolfine, with ee up to 99.5%.
authors.affiliation: Dipartimento di Chimica Industriale "Toso Montanari" - Alma Mater Studiorum - Università di Bologna - Viale del Risorgimento, 4 - I-40136 Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Carella
authors.affiliation: Dipartimento di Chimica Industriale "Toso Montanari" - Alma Mater Studiorum - Università di Bologna - Viale del Risorgimento, 4 - I-40136 Bologna, Italy.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Ramos Ferronatto
authors.affiliation: Dipartimento di Chimica Industriale "Toso Montanari" - Alma Mater Studiorum - Università di Bologna - Viale del Risorgimento, 4 - I-40136 Bologna, Italy.
authors.forename: Emanuela
authors.identifier: http://orcid.org/0000-0002-9269-3507
authors.initials: E
authors.lastname: Marotta
authors.affiliation: Dipartimento di Chimica Industriale "Toso Montanari" - Alma Mater Studiorum - Università di Bologna - Viale del Risorgimento, 4 - I-40136 Bologna, Italy.
authors.forename: Andrea
authors.identifier: http://orcid.org/0000-0003-1819-8863
authors.initials: A
authors.lastname: Mazzanti
authors.affiliation: Dipartimento di Chimica Industriale "Toso Montanari" - Alma Mater Studiorum - Università di Bologna - Viale del Risorgimento, 4 - I-40136 Bologna, Italy.
authors.forename: Paolo
authors.identifier: http://orcid.org/0000-0003-1419-2560
authors.initials: P
authors.lastname: Righi
authors.affiliation: Dipartimento di Chimica Industriale "Toso Montanari" - Alma Mater Studiorum - Università di Bologna - Viale del Risorgimento, 4 - I-40136 Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Paolucci
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D003460:Crystallization; D008958:Models, Molecular; D008968:Molecular Conformation; D009025:Morpholines / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000447:Aldehydes; D009025:Morpholines; C050435:fenpropimorph; C038974:amorolfine