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Diastereo‐ and Enantioselective Synthesis of Vicinal Amino Alcohols by Oxa Michael Addition of N ‐Formylnorephedrine to Nitro Alkenes
Author(s) -
Enders Dieter,
Haertwig Andreas,
Raabe Gerhard,
Runsink Jan
Publication year - 1998
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/(sici)1099-0690(199809)1998:9<1771::aid-ejoc1771>3.0.co;2-p
Subject(s) - chemistry , diastereomer , enantiopure drug , enantioselective synthesis , nitro , vicinal , chirality (physics) , enantiomer , stereochemistry , nucleophile , chiral auxiliary , absolute configuration , michael reaction , medicinal chemistry , organic chemistry , catalysis , alkyl , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics , quark
The first intermolecular asymmetric oxa Michael additions with removable chirality information within the hydroxide source are reported. As enantiopure oxygen nucleophile functioning as chiral hydroxide equivalent N ‐formylnorephedrine ( 7 ) was used and conjugate additions to aliphatic ( E )‐nitro alkenes 2a – j were carried out in good yields (35‐87%) and excellent diastereomeric excesses ( de = 94–≥98%). After reduction of the nitro group and protection of the amino function ( 11a – h , 73‐87%, both steps), the cleavage of the auxiliary occurred without epimerisation (69‐99%) using Na/NH 3 . The Boc‐protected 2‐amino alcohols 12a – h could be obtained in good overall yields (30‐58 %, four steps) and excellent diastereomeric and enantiomeric excesses ( de , ee = 94–≥98%). Transition states explaining the overall stereochemical outcome are presented based on the absolute configuration determined by X‐ray structure analysis on 8b .