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Asymmetric Synthesis of α‐Substituted β‐Amino Sulfones by Aza‐Michael Addition to Alkenyl Sulfones and Subsequent α‐Alkylation
Author(s) -
Enders Dieter,
Müller Stephan Frank,
Raabe Gerhard,
Runsink Jan
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/(sici)1099-0690(200003)2000:6<879::aid-ejoc879>3.0.co;2-e
Subject(s) - chemistry , alkylation , enantiopure drug , trifluoromethanesulfonate , racemization , diastereomer , stereocenter , michael reaction , electrophile , enantioselective synthesis , medicinal chemistry , enantiomer , bromide , stereochemistry , organic chemistry , catalysis
Abstract The aza‐Michael addition of enantiopure 1‐aminopyrrolidines to ( E )‐alkenyl sulfones in the presence of a catalytic amount of ytterbium trifluoromethanesulfonate [Yb(OTf) 3 ] yields β‐hydrazino sulfones in moderate to good yields and with diastereoselectivities of up to ≥ 98%. The latter undergo reductive N‐N bond cleavage with BH 3 · THF and, after N ‐protection with Boc 2 O or benzyl bromide, afford N ‐protected β‐amino sulfones with moderate to high enantiomeric excesses ( ee = 42 to ≥96%) without racemization. Subsequent α‐alkylation of the N , N ‐dibenzyl protected β‐amino sulfones with various electrophiles yields α‐alkyl‐β‐amino sulfones in excellent yields (88‐97%) with high diastereomeric ( de ≥96 to ≥98%) and enantiomeric purity ( ee = 94 to ≥96%). The absolute configuration of the new stereogenic centre was determined by X‐ray structural analysis and confirmed by NMR spectroscopy (NOE experiments). Possible reaction mechanisms for the conjugate addition and α‐alkylation are presented.