Premium
Asymmetric β‐Aminoethylation of Ketones and Nitriles with Tosylaziridines Employing the SAMP‐Hydrazone Method
Author(s) -
Enders Dieter,
Janeck Carsten F.,
Raabe Gerhard
Publication year - 2000
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 - 10.1002/1099-0690(200010)2000:19<3337::aid-ejoc3337>3.0.co;2-v
Subject(s) - chemistry , enantiopure drug , stereocenter , nitrile , hydrazone , ketone , chiral auxiliary , enantiomer , ring (chemistry) , stereochemistry , amide , absolute configuration , nucleophile , nucleophilic addition , carbon atom , asymmetric carbon , enantioselective synthesis , medicinal chemistry , organic chemistry , catalysis , optically active
The nucleophilic ring‐opening of tosylaziridines with chiral aza‐enolates is reported. The SAMP‐/ RAMP‐hydrazones 1a−h derived from aldehydes or ketones were reacted with tosylaziridine 2a to give the β‐aminoethylated hydrazones 3a−h with good diastereoselectivity. Removal of the chiral auxiliary resulted in the formation of the γ‐amino nitriles 4a−e or γ‐amino ketones 6f−h in good yields and excellent enantiomeric excesses ( ee ⩾ 98%). Ring‐opening of the enantiopure, benzyl‐substituted tosylaziridine 2b with aza‐enolates was achieved selectively at the less‐substituted ring‐carbon atom, again with excellent diastereoselectivity. Subsequent cleavage of the chiral auxiliary yielded the γ‐benzyl‐substituted γ‐amino nitrile 4j or γ‐amino ketone 6i with de , ee ⩾ 98%, respectively. The relative and absolute configuration of the new stereogenic centre of the aminoethylated hydrazones 3a−j was determined by NOE measurements and confirmed by X‐ray structure analysis on the Mosher amide of 6h .